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Arora A, Sharma P, Kumar A, Acharya S, Sarin SK, Duseja A, Puri P, Shah S, Chawla Y, Rao P, Saraya A, Mohanka R, Singh S, Saighal S, Rela M, Vij V, Asthana S, Shukla A, Bhangui P, Saraf N, Maiwall R, Mandot A, Saraswat V, Madan K, Shalimar, Kapoor D, Anand AC, Gupta S, Varghese J, Mehta N. Indian National Association for the Study of Liver (INASL) Guidance Statements for Determining Futility in Liver Transplantation. J Clin Exp Hepatol 2025; 15:102539. [PMID: 40343081 PMCID: PMC12056968 DOI: 10.1016/j.jceh.2025.102539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 02/24/2025] [Indexed: 05/10/2025] Open
Abstract
Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease; however, with the growing shortage of organ donors, the need to identify futile transplants has become increasingly urgent. Futility in liver transplantation refers to situations where the expected post-transplant survival or quality of life is poor, making the procedure unlikely to yield a meaningful benefit. Various definitions of futility are used across different countries and transplant centers, with criteria often based on clinical factors such as age, comorbidities, MELD score, and functional status. For hepatologists and transplant surgeons, clearer guidelines are essential to make informed decisions and avoid unnecessary transplants that may place patients at risk without improving their prognosis. While some studies have proposed futility scores, there is currently no universal consensus on a standardized definition or set of criteria. This highlights the need for further prospective trials to evaluate the predictors of futility in liver transplantation, aiming to refine decision-making processes, optimize organ allocation, and improve patient outcomes. Future research should focus on the development of universally accepted futility criteria and explore interventions to mitigate the factors contributing to transplant futility.
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Affiliation(s)
- Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Praveen Sharma
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - S.K. Acharya
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | - Shiv K. Sarin
- Institute of Liver and Biliary Sciences, Delhi, India
| | - Ajay Duseja
- Post Institute of Medical Sciences, Chandigarh, India
| | | | - Samir Shah
- Institute of Liver Disease, HPB Surgery and Transplant, Global Hospitals, Dr E Borges Road, Parel, Mumbai, 400012, India
| | - Y.K. Chawla
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | - P.N. Rao
- Asian Institute of Gsstroenterology, Hyderabad, India
| | - Anoop Saraya
- All India Institute of Medical Sciences, New Delhi, India
| | - Ravi Mohanka
- Sir HN Reliance Foundation Hospital, Mumbai, India
| | | | | | - Mohamed Rela
- Dr. Rela Institute & Medical Centre, #7, CLC Works Road, Chromepet, Chennai, 600044, India
| | - Vivek Vij
- Fortis Hospital, Noida, Delhi, India
| | - Sonal Asthana
- Aster CMI Bangalore, Aster RV Bangalore, Aster Whitefield, Bangalore, India
| | - Akash Shukla
- Reliance Foundation Hospital and Research Centre, Mumbai, India
- Seth GSMC & KEM Hospital, Mumbai, 400022, India
| | | | | | - Rakhi Maiwall
- Institute of Liver and Biliary Sciences, Delhi, India
| | - Amit Mandot
- Institute of Liver Disease, HPB Surgery and Transplant, Global Hospitals, Dr E Borges Road, Parel, Mumbai, 400012, India
| | | | | | - Shalimar
- All India Institute of Medical Sciences, New Delhi, India
| | - Dharmesh Kapoor
- Mahatma Gandhi Medical College and Hospital, RIICO Institutional Area, Sitapura, Tonk Road, Jaipur, 302022, Rajasthan, India
- Yashoda Hospital, Hyderabad, India
| | - Anil C. Anand
- Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, 751024, Odisha, India
| | | | - Joy Varghese
- Gleneagles Global Health City, 439, Cheran Nagar, Perumbakkam, Chennai, Tamil Nadu, 600100, India
| | - Naimish Mehta
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences. Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
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Kumar R, Kumar A, Kumar S. Sepsis in liver failure patients: Diagnostic challenges and recent advancements. World J Crit Care Med 2025; 14:101587. [DOI: 10.5492/wjccm.v14.i2.101587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 01/19/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
Acute liver failure (ALF) and acute-on-chronic LF (ACLF) are prevalent hepatic emergencies characterized by an increased susceptibility to bacterial infections (BI), despite significant systemic inflammation. Literature indicates that 30%–80% of ALF patients and 55%–81% of ACLF patients develop BI, attributed to immunological dysregulation. Bacterial sepsis in these patients is associated with adverse clinical outcomes, including prolonged hospitalization and increased mortality. Early detection of bacterial sepsis is critical; however, distinguishing between sterile systemic inflammation and sepsis poses a significant challenge due to the overlapping clinical presentations of LF and sepsis. Conventional sepsis biomarkers, such as procalcitonin and C-reactive protein, have shown limited utility in LF patients due to inconsistent results. In contrast, novel biomarkers like presepsin and sTREM-1 have demonstrated promising discriminatory performance in this population, pending further validation. Moreover, emerging research highlights the potential of machine learning-based approaches to enhance sepsis detection and characterization. Although preliminary findings are encouraging, further studies are necessary to validate these results across diverse patient cohorts, including those with LF. This article provides a comprehensive review of the magnitude, impact, and diagnostic challenges associated with BI in LF patients, focusing on novel advancements in early sepsis detection and characterization.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Abhishek Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Sudhir Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
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Lin Z, Ma X, Ji H, Hou Y, He X, Zhu X, Hu A. A nomogram for predicting early biliary complications in adult liver recipients of deceased donor grafts: Integrating artery resistive index and clinical risk factors. Surgery 2025; 182:109352. [PMID: 40209401 DOI: 10.1016/j.surg.2025.109352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 02/21/2025] [Accepted: 03/14/2025] [Indexed: 04/12/2025]
Abstract
BACKGROUND This study aimed to identify predictors of biliary complications within 90 days after liver transplantation in adult recipients of deceased donor grafts. METHODS The study retrospectively analyzed adult patients who underwent liver transplantation from January 2016 to December 2021 using deceased donor grafts in our center. Patients were randomly divided into training and validation cohorts (7:3 ratio). A nomogram was developed using least absolute shrinkage and selection operator logistic regression for feature selection, followed by a 2-way stepwise approach in multivariate logistic regression. Model performance was assessed with the C-index, receiver operating characteristic area under the curve, calibration curves, and decision curve analysis. RESULTS A total of 757 patients were included, of whom 76 developed early biliary complications. Least absolute shrinkage and selection operator binary logistic analysis showed that postoperative day 1 arterial resistance index, acute rejection, acute-on-chronic liver failure, hepatic artery thrombosis, recipient body mass index, and donor age were independent predictors of biliary complications within 90 days. A nomogram was established on the basis of these factors. The C-index for the final nomogram was 0.822. The area under the curve in the training cohort was 0.837 (95% confidence interval, 0.780-0.893) and 0.771 (95% confidence interval, 0.677-0.865) in the validation cohort. Calibration curves demonstrated good agreement between predicted and actual outcomes. Decision curve analysis confirmed the clinical utility of the nomogram. CONCLUSION Low arterial resistance index (≤0.57) on the first postoperative day is a predictor of biliary complications within 90 days after liver transplantation in adult recipients of deceased donor grafts. The nomogram provides a practical tool for predicting complications and guiding clinical decisions.
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Affiliation(s)
- Zepeng Lin
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Xue Ma
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Haibin Ji
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Yibo Hou
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Xiaoshun He
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Xiaofeng Zhu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Anbin Hu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China; Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.
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Li S, Liu J, Wu J, Zheng X. Immunological Mechanisms and Effects of Bacterial Infections in Acute-on-Chronic Liver Failure. Cells 2025; 14:718. [PMID: 40422221 DOI: 10.3390/cells14100718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2025] [Revised: 05/09/2025] [Accepted: 05/10/2025] [Indexed: 05/28/2025] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome characterized by high morbidity and mortality rates. Bacterial infection is a frequent precipitating factor and complication in ACLF patients, significantly worsening patient outcomes. Elucidating the mechanisms underlying bacterial infections and their impact on ACLF pathophysiology is crucial for developing effective therapies to reduce infection rates and mortality. Current research highlights that immune suppression in ACLF increases susceptibility to bacterial infections, which in turn exacerbate immune dysfunction. However, a comprehensive review summarizing the emerging mechanisms underlying this immunosuppression is currently lacking. This review aims to provide an overview of the latest research, focusing on alterations in the immune responses of innate immune cells-including monocytes, macrophages, and neutrophils-as well as adaptive immune cells such as T and B lymphocytes during the onset and progression of bacterial infections in ACLF. In addition, recent advances in immunomodulatory therapies, including stem cell-based interventions, will also be discussed.
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Affiliation(s)
- Sumeng Li
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Jing Liu
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Jun Wu
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Xin Zheng
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China
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Gupta T, Saini A, Gaur V, Goel A. Comparative Study of Terlipressin and Noradrenaline as Vasopressors in Patients With Acute-on-chronic Liver Failure and Septic Shock: A Randomized Controlled Trial. J Clin Exp Hepatol 2025; 15:102494. [PMID: 39980577 PMCID: PMC11836504 DOI: 10.1016/j.jceh.2024.102494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 12/15/2024] [Indexed: 02/22/2025] Open
Abstract
BACKGROUND Sepsis is the most common acute insult in patients with acute-on-chronic liver failure (ACLF), and circulatory failure portends a poor prognosis in them. AIM This study aimed to compare terlipressin and noradrenaline as first-line vasopressors in patients with ACLF and septic shock. METHODS This prospective, open-label, randomized controlled study was conducted from January 2021 to June 2022 at a tertiary care center. All patients presenting with ACLF as per the chronic liver failure consortium acute on chronic liver failure in cirrhosis study and septic shock were screened. Shock was defined as a mean arterial pressure (MAP) <65 mmHg/systolic blood pressure <90 mmHg. Patients with septic shock nonresponsive to crystalloids/colloids were randomized to receive terlipressin (group I) at 2.6 μg/kg/min and noradrenaline (group II) at 0.1 μg/kg/min. The primary outcome was an MAP >65 mmHg at 6 h. The secondary outcomes were 3-, 7-, 14-, and 28-day mortality, duration of hospital stay, cumulative dose of drug, and new events such as upper gastrointestinal bleed, acute kidney injury, jaundice, and hepatic encephalopathy within 28 days. RESULTS A total of 70 patients were randomized to group I (n = 35) and group II (n = 35). According to per-protocol analysis, a higher number of patients achieved an MAP > 65 mmHg at 6 h in group II (n = 23/31, 74%) than in group I (5/34, 14%) (P < 0.001). The 3-and 7-day mortality was significantly higher in group I than in group II, with no difference at 14 and 28 days. The 28-day mortality was highest in ACLF grade-3 in both group II (22/25, 88%) and group I (15/20, 75%). CONCLUSION Terlipressin did not prove to be noninferior to norepinephrine, and therefore, norepinephrine should be the first-line vasopressor in ACLF patients with septic shock. The mortality rate was highest in ACLF grade-3 patients in both the groups, irrespective of the initial response to vasopressors. This indicates that holistic management of these patients is most important.
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Affiliation(s)
- Tarana Gupta
- Medicine, Division of Hepatology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, 124001, India
| | - Anjali Saini
- Medicine, Division of Hepatology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, 124001, India
| | - Vaibhav Gaur
- Medicine, Division of Hepatology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, 124001, India
| | - Ashank Goel
- Medicine, Division of Hepatology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, 124001, India
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6
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Allgeier J, Zeuzem N, Jamme P, Stangl M, Kur F, Guba M, Melichar J, Irlbeck M, Draenert R, Lange CM. Liver transplantation in Candida endocarditis-induced acute-on-chronic liver failure. Am J Transplant 2025:S1600-6135(25)00203-5. [PMID: 40222586 DOI: 10.1016/j.ajt.2025.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 03/11/2025] [Accepted: 04/08/2025] [Indexed: 04/15/2025]
Abstract
This case report details the clinical course of a 35-year-old patient with decompensated liver cirrhosis due to primary sclerosing cholangitis awaiting liver transplantation. The patient developed recurrent candidemia due to biliary candidiasis complicated by endotipsitis, leading to repeated hospitalizations and an eventual diagnosis of tricuspid valve Candida endocarditis. In the setting of active Candida infection and severe acute-on-chronic liver failure and lacking other suitable alternatives for infection control, an interdisciplinary team of hepatologists, transplant surgeons, and cardiologists decided to proceed with liver transplantation during a window of opportunity with repeat negative blood cultures. The patient experienced an unremarkable posttransplant recovery despite having repeated positive-result blood cultures for Candida albicans and underwent successful tricuspid valve replacement 5 months later. Our goal is to underscore the critical role of multidisciplinary collaboration in managing high-risk transplant candidates, highlighting in particular the potential benefits of liver transplantation in infection-induced acute-on-chronic liver failure, where full recovery from complex infections might not be possible before transplantation in a setting of severe cirrhosis-associated immune deficiency.
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Affiliation(s)
- Julian Allgeier
- Department of Internal Medicine II, LMU University Hospital Munich, Munich, Germany.
| | - Nicholas Zeuzem
- Department of Internal Medicine II, LMU University Hospital Munich, Munich, Germany
| | - Paul Jamme
- Department of Internal Medicine II, LMU University Hospital Munich, Munich, Germany
| | - Manfred Stangl
- Department of General, Visceral, Transplantation, Vascular, and Thoracic Surgery, LMU University Hospital Munich, Munich, Germany
| | - Felix Kur
- Department of Cardiac Surgery, LMU University Hospital Munich, Munich, Germany
| | - Markus Guba
- Department of General, Visceral, Transplantation, Vascular, and Thoracic Surgery, LMU University Hospital Munich, Munich, Germany
| | - Jan Melichar
- Department of Anesthesiology, LMU University Hospital Munich, Munich, Germany
| | - Michael Irlbeck
- Department of Anesthesiology, LMU University Hospital Munich, Munich, Germany
| | - Rika Draenert
- Interdisciplinary Antibiotic Stewardship Team, LMU University Hospital Munich, Munich, Germany
| | - Christian M Lange
- Department of Internal Medicine II, LMU University Hospital Munich, Munich, Germany
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Lee S, Arefaine B, Begum N, Stamouli M, Witherden E, Mohamad M, Harzandi A, Zamalloa A, Cai H, Williams R, Curtis MA, Edwards LA, Chokshi S, Mardinoglu A, Proctor G, Moyes DL, McPhail MJ, Shawcross DL, Uhlen M, Shoaie S, Patel VC. Oral-gut microbiome interactions in advanced cirrhosis: characterisation of pathogenic enterotypes and salivatypes, virulence factors and antimicrobial resistance. J Hepatol 2025; 82:622-633. [PMID: 39447963 DOI: 10.1016/j.jhep.2024.09.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 09/11/2024] [Accepted: 09/30/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND & AIMS Cirrhosis complications are often triggered by bacterial infections with multidrug-resistant organisms. Alterations in the gut and oral microbiome in decompensated cirrhosis (DC) influence clinical outcomes. We interrogated: (i) gut and oral microbiome community structures, (ii) virulence factors (VFs) and antimicrobial resistance genes (ARGs) and (iii) oral-gut microbial overlap in patients with differing cirrhosis severity. METHODS Fifteen healthy controls (HCs), as well as 26 patients with stable cirrhosis (SC), 46 with DC, 14 with acute-on-chronic liver failure (ACLF) and 14 with severe infection without cirrhosis participated. Metagenomic sequencing was undertaken on paired saliva and faecal samples. 'Salivatypes' and 'enterotypes' based on genera clustering were assessed against cirrhosis severity and clinical parameters. VFs and ARGs were evaluated in oral and gut niches, and distinct resistotypes identified. RESULTS Salivatypes and enterotypes revealed a greater proportion of pathobionts with concomitant reduction in autochthonous genera with increasing cirrhosis severity and hyperammonaemia. Increasing overlap between oral and gut microbiome communities was observed in DC and ACLF vs. SC and HCs, independent of antimicrobial, beta-blocker and gastric acid-suppressing therapies. Two distinct gut microbiome clusters harboured genes encoding for the PTS (phosphoenolpyruvate:sugar phosphotransferase system) and other VFs in DC and ACLF. Substantial ARGs (oral: 1,218 and gut: 672) were detected (575 common to both sites). The cirrhosis resistome was distinct, with three oral and four gut resistotypes identified, respectively. CONCLUSIONS The degree of oral-gut microbial community overlap, frequency of VFs and ARGs all increase significantly with cirrhosis severity, with progressive dominance of pathobionts and loss of commensals. Despite similar antimicrobial exposure, patients with DC and ACLF have reduced microbial richness compared to patients with severe infection without cirrhosis, supporting the additive pathobiological effect of cirrhosis. IMPACT AND IMPLICATIONS This research underscores the crucial role of microbiome alterations in the progression of cirrhosis in an era of escalating multidrug resistant infections, highlighting the association and potential impact of increased oral-gut microbial overlap, virulence factors, and antimicrobial resistance genes on clinical outcomes. These findings are particularly significant for patients with decompensated cirrhosis and acute-on-chronic liver failure, as they reveal the intricate relationship between microbiome alterations and cirrhosis complications. This is relevant in the context of multidrug-resistant organisms and reduced oral-gut microbial diversity that exacerbate cirrhosis severity, drive hepatic decompensation and complicate treatment. For practical applications, these insights could guide the development of targeted microbiome-based therapeutics and personalised antimicrobial regimens for patients with cirrhosis to mitigate infectious complications and improve clinical outcomes.
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Affiliation(s)
- Sunjae Lee
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom; School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea
| | - Bethlehem Arefaine
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
| | - Neelu Begum
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom
| | - Marilena Stamouli
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
| | - Elizabeth Witherden
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom
| | - Merianne Mohamad
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
| | - Azadeh Harzandi
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom
| | - Ane Zamalloa
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Haizhuang Cai
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom
| | - Roger Williams
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
| | - Michael A Curtis
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom; Dental Clinical Academic Group, King's Health Partners, United Kingdom
| | - Lindsey A Edwards
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom
| | - Shilpa Chokshi
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
| | - Adil Mardinoglu
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-171 21, Sweden
| | - Gordon Proctor
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom; Dental Clinical Academic Group, King's Health Partners, United Kingdom
| | - David L Moyes
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom
| | - Mark J McPhail
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Debbie L Shawcross
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Mathias Uhlen
- Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-171 21, Sweden
| | - Saeed Shoaie
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-171 21, Sweden.
| | - Vishal C Patel
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom.
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8
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Lopes D, Bandovas JP, Chumbinho B, Santo CE, Sousa M, Ferreira B, Val-Flores L, Germano N, Pereira R, Cardoso FS, Bento L, Póvoa P. Pancreatic Stone Protein in patients with liver failure: A prospective pilot cohort study. Anaesth Crit Care Pain Med 2025; 44:101486. [PMID: 39892616 DOI: 10.1016/j.accpm.2025.101486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 10/30/2024] [Accepted: 11/05/2024] [Indexed: 02/04/2025]
Abstract
BACKGROUND Pancreatic Stone Protein (PSP) seems to have higher accuracy for sepsis detection compared to other biomarkers. As PSP has never been studied in patients with liver failure (LF), our purpose was to assess its accuracy for diagnosis of infection and prognosis in this population. METHODS We conducted a prospective pilot cohort study on patients with LF consecutively admitted to the Intensive Care Unit of a liver transplant center in 2021-2023. Ongoing overt infection was an exclusion criterion. Daily measurements of biomarkers were performed until discharge, death, or for 21 days. Analysis was performed by adjusting the baseline for the first infection episode (median on D3), which was the reference for those non-infected. RESULTS Sixteen patients were included, 7 with acute and 9 with acute-on-chronic LF. Median age was 54 (interquartile range 42-64) years, half were female, with admission SOFA score of 10 (IQR 8-12). Hospital mortality was 43.8% (n = 7). An infection was observed in 8 patients, who presented non-significantly higher levels of PSP than non-infected ones during follow-up. Levels were higher in non-survivors than survivors (p < 0.05 from D4 on and since the day of infection considering only infected patients). Similarly, patients under renal replacement therapy had higher PSP levels than others (p < 0.05, D2 to D7 after admission). CONCLUSION This pilot study provides early insights into PSP kinetics, suggesting a potential role for prognosis in patients with LF. PSP rises in both ALF and ACLF to levels sustainably higher than those expected for healthy adults. Further research is needed to reassess its diagnostic accuracy for infection and redefine cut-offs in this population.
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Affiliation(s)
- Diogo Lopes
- Department of Intensive Care Medicine, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal.
| | - João Pedro Bandovas
- Department of General Surgery, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | - Beatriz Chumbinho
- Department of General Surgery, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | | | - Mónica Sousa
- Transplant Unit, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | - Bernardo Ferreira
- Department of Intensive Care Medicine, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | - Luis Val-Flores
- Department of Intensive Care Medicine, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | - Nuno Germano
- Department of Intensive Care Medicine, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | - Rui Pereira
- Department of Intensive Care Medicine, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | | | - Luís Bento
- Department of Intensive Care Medicine, São José Hospital, ULSSJ, Lisboa, Portugal; NOVA Medical School, CHRC, NOVA University of Lisbon, Lisbon, Portugal
| | - Pedro Póvoa
- NOVA Medical School, CHRC, NOVA University of Lisbon, Lisbon, Portugal; Intensive Care Unit 4, Department of Intensive Care, São Francisco Xavier Hospital, ULSLO, Lisboa, Portugal; Center for Clinical Epidemiology and Research Unit of Clinical Epidemiology, OUH Odense University Hospital, Denmark
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9
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Juanola A, Tiwari N, Solé C, Adebayo D, Wong F, Ginès P. Organ dysfunction and failure in liver disease. Liver Int 2025; 45:e15622. [PMID: 37222263 DOI: 10.1111/liv.15622] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Accepted: 05/15/2023] [Indexed: 05/25/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a complex syndrome defined by the existence of different organ failures (OFs) in patients with chronic liver disease, mainly cirrhosis. Several definitions have been proposed to define the syndrome, varying in the grade of the subjacent liver disease, the type of precipitants and the organs considered in the definition. Liver, coagulation, brain, kidney, circulatory and pulmonary are the six types of OFs proposed in the different classifications, with different prevalence worldwide. Irrespective of the definition used, patients who develop ACLF present a hyperactive immune system, profound haemodynamic disturbances and several metabolic alterations that finally lead to organ dysfunction. These disturbances are triggered by different factors such as bacterial infections, alcoholic hepatitis, gastrointestinal bleeding or hepatitis B virus flare, among others. Because patients with ACLF present high short-term mortality, a prompt recognition is needed to start treatment of the trigger event and specific organ support. Liver transplantation is also feasible in carefully selected patients and should be evaluated.
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Affiliation(s)
- Adrià Juanola
- Liver Unit, Hospital Clínic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
| | - Neha Tiwari
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Cristina Solé
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
- Department of Gastroenterology and Hepatology, Parc Tauli Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Spain
| | - Danielle Adebayo
- Department of Gastroenterology, Royal Berkshire NHS Foundation Trust, Reading, UK
| | - Florence Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Pere Ginès
- Liver Unit, Hospital Clínic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
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10
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Piano S, Mahmud N, Caraceni P, Tonon M, Mookerjee RP. Mechanisms and treatment approaches for ACLF. Liver Int 2025; 45:e15733. [PMID: 37715608 PMCID: PMC12036731 DOI: 10.1111/liv.15733] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 08/03/2023] [Accepted: 09/02/2023] [Indexed: 09/17/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by decompensation of cirrhosis, severe systemic inflammation and organ failures. ACLF is frequently triggered by intra- and/or extrahepatic insults, such as bacterial infections, alcohol-related hepatitis or flares of hepatic viruses. The imbalance between systemic inflammation and immune tolerance causes organ failures through the following mechanisms: (i) direct damage of immune cells/mediators; (ii) worsening of circulatory dysfunction resulting in organ hypoperfusion and (iii) metabolic alterations with prioritization of energetic substrates for inflammation and peripheral organ 'energetic crisis'. Currently, the management of ACLF includes the support of organ failures, the identification and treatment of precipitating factors and expedited assessment for liver transplantation (LT). Early LT should be considered in patients with ACLF grade 3, who are unlikely to recover with the available treatments and have a mortality rate > 70% at 28 days. However, the selection of transplant candidates and their prioritization on the LT waiting list need standardization. Future challenges in the ACLF field include a better understanding of pathophysiological mechanisms leading to inflammation and organ failures, the development of specific treatments for the disease and personalized treatment approaches. Herein, we reviewed the current knowledge and future perspectives on mechanisms and treatment of ACLF.
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Affiliation(s)
- Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine –DIMED, University and Hospital of Padova, Padova, Italy
| | - Nadim Mahmud
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Leonard Davis Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Unit of Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Marta Tonon
- Unit of Internal Medicine and Hepatology, Department of Medicine –DIMED, University and Hospital of Padova, Padova, Italy
| | - Rajeshwar Prosad Mookerjee
- Institute for Liver and Digestive Health, University College London, London, UK
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus C, Denmark
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11
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Karvellas CJ, Gustot T, Fernandez J. Management of the acute on chronic liver failure in the intensive care unit. Liver Int 2025; 45:e15659. [PMID: 37365997 PMCID: PMC11815614 DOI: 10.1111/liv.15659] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 06/01/2023] [Accepted: 06/15/2023] [Indexed: 06/28/2023]
Abstract
Acute on chronic liver failure (ACLF) reflects the development of organ failure(s) in a patient with cirrhosis and is associated with high short-term mortality. Given that ACLF has many different 'phenotypes', medical management needs to take into account the relationship between precipitating insult, organ systems involved and underlying physiology of chronic liver disease/cirrhosis. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (e.g. infection, severe alcoholic hepatitis and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo liver transplantation or recovery. Management of these patients is complex since they are prone to develop new organ failures and infectious or bleeding complications. ICU therapy parallels that applied in the general ICU population in some complications but differs in others. Given that liver transplantation in ACLF is an emerging and evolving field, multidisciplinary teams with expertise in critical care and transplant medicine best accomplish management of the critically ill ACLF patient. The focus of this review is to identify the common complications of ACLF and to describe the proper management in critically ill patients awaiting liver transplantation in our centres, including organ support, prognostic assessment and how to assess when recovery is unlikely.
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Affiliation(s)
- Constantine J. Karvellas
- Department of Critical Care MedicineUniversity of AlbertaEdmontonCanada
- Division of Gastroenterology (Liver Unit)University of AlbertaEdmontonCanada
| | - Thierry Gustot
- Department of Gastroenterology, Hepato‐Pancreatology and Digestive Oncology, H.U.B.CUB Hôpital ErasmeBrusselsBelgium
| | - Javier Fernandez
- Liver ICU, Liver Unit, Hospital ClinicUniversity of Barcelona, IDIBAPS and CIBERehdBarcelonaSpain
- EF CLIF, EASL‐CLIF ConsortiumBarcelonaSpain
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12
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Choudhury A, Kulkarni AV, Arora V, Soin AS, Dokmeci AK, Chowdhury A, Koshy A, Duseja A, Kumar A, Mishra AK, Patwa AK, Sood A, Roy A, Shukla A, Chan A, Krag A, Mukund A, Mandot A, Goel A, Butt AS, Sahney A, Shrestha A, Cárdenas A, Di Giorgio A, Arora A, Anand AC, Dhawan A, Jindal A, Saraya A, Srivastava A, Kumar A, Kaewdech A, Pande A, Rastogi A, Valsan A, Goel A, Kumar A, Singal AK, Tanaka A, Coilly A, Singh A, Meena BL, Jagadisan B, Sharma BC, Lal BB, Eapen CE, Yaghi C, Kedarisetty CK, Kim CW, Panackel C, Yu C, Kalal CR, Bihari C, Huang CH, Vasishtha C, Jansen C, Strassburg C, Lin CY, Karvellas CJ, Lesmana CRA, Philips CA, Shawcross D, Kapoor D, Agrawal D, Payawal DA, Praharaj DL, Jothimani D, Song DS, Kim DJ, Kim DS, Zhongping D, Karim F, Durand F, Shiha GE, D’Amico G, Lau GK, Pati GK, Narro GEC, Lee GH, Adali G, Dhakal GP, Szabo G, Lin HC, Li H, Nair HK, Devarbhavi H, Tevethia H, Ghazinian H, Ilango H, Yu HL, Hasan I, Fernandez J, George J, Behari J, Fung J, Bajaj J, Benjamin J, Lai JC, Jia J, Hu JH, et alChoudhury A, Kulkarni AV, Arora V, Soin AS, Dokmeci AK, Chowdhury A, Koshy A, Duseja A, Kumar A, Mishra AK, Patwa AK, Sood A, Roy A, Shukla A, Chan A, Krag A, Mukund A, Mandot A, Goel A, Butt AS, Sahney A, Shrestha A, Cárdenas A, Di Giorgio A, Arora A, Anand AC, Dhawan A, Jindal A, Saraya A, Srivastava A, Kumar A, Kaewdech A, Pande A, Rastogi A, Valsan A, Goel A, Kumar A, Singal AK, Tanaka A, Coilly A, Singh A, Meena BL, Jagadisan B, Sharma BC, Lal BB, Eapen CE, Yaghi C, Kedarisetty CK, Kim CW, Panackel C, Yu C, Kalal CR, Bihari C, Huang CH, Vasishtha C, Jansen C, Strassburg C, Lin CY, Karvellas CJ, Lesmana CRA, Philips CA, Shawcross D, Kapoor D, Agrawal D, Payawal DA, Praharaj DL, Jothimani D, Song DS, Kim DJ, Kim DS, Zhongping D, Karim F, Durand F, Shiha GE, D’Amico G, Lau GK, Pati GK, Narro GEC, Lee GH, Adali G, Dhakal GP, Szabo G, Lin HC, Li H, Nair HK, Devarbhavi H, Tevethia H, Ghazinian H, Ilango H, Yu HL, Hasan I, Fernandez J, George J, Behari J, Fung J, Bajaj J, Benjamin J, Lai JC, Jia J, Hu JH, Chen JJ, Hou JL, Yang JM, Chang J, Trebicka J, Kalf JC, Sollano JD, Varghese J, Arab JP, Li J, Reddy KR, Raja K, Panda K, Kajal K, Kumar K, Madan K, Kalista KF, Thanapirom K, Win KM, Suk KT, Devadas K, Lesmana LA, Kamani L, Premkumar M, Niriella MA, Al Mahtab M, Yuen MF, Sayed MHE, Alla M, Wadhawan M, Sharma MK, Sahu M, Prasad M, Muthiah MD, Schulz M, Bajpai M, Reddy MS, Praktiknjo M, Yu ML, Prasad M, Sharma M, Elbasiony M, Eslam M, Azam MG, Rela M, Desai MS, Vij M, Mahmud N, Choudhary NS, Marannan NK, Ormeci N, Saraf N, Verma N, Nakayama N, Kawada N, Oidov Baatarkhuu, Goyal O, Yokosuka O, Rao PN, Angeli P, Parikh P, Kamath PS, Thuluvath PJ, Lingohr P, Ranjan P, Bhangui P, Rathi P, Sakhuja P, Puri P, Ning Q, Dhiman RK, Kumar R, Vijayaraghavan R, Khanna R, Maiwall R, Mohanka R, Moreau R, Gani RA, Loomba R, Mehtani R, Rajaram RB, Hamid SS, Palnitkar S, Lal S, Biswas S, Chirapongsathorn S, Agarwal S, Sachdeva S, Saigal S, Kumar SE, Violeta S, Singh SP, Mochida S, Mukewar S, Alam S, Lim SG, Alam S, Shalimar, Venishetty S, Sundaram SS, Shetty S, Bhatia S, Singh SA, Kottilil S, Strasser S, Shasthry SM, Maung ST, Tan SS, Treeprasertsuk S, Asthana S, Manekeller S, Gupta S, Acharya SK, K.C. S, Maharshi S, Asrani S, Dadhich S, Taneja S, Giri S, Singh S, Chen T, Gupta T, Kanda T, Tanwandee T, Piratvishuth T, Spengler U, Prasad VGM, Midha V, Rakhmetova V, Arroyo V, Sood V, BR VK, Wong VWS, Pamecha V, Singh V, Dayal VM, Saraswat VA, Kim WR, Jafri W, Gu W, Jun WY, Qi X, Chawla YK, Kim YJ, Shi Y, Abbas Z, Kumar G, Shiina S, Wei L, Omata M, Sarin SK, APASL-ACLF Research Consortium (AARC) for APASL-ACLF working party. Acute-on-chronic liver failure (ACLF): the ‘Kyoto Consensus’—steps from Asia. Hepatol Int 2025; 19:1-69. [DOI: https:/doi.org/10.1007/s12072-024-10773-4] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Accepted: 12/29/2024] [Indexed: 04/16/2025]
Abstract
Abstract
Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the “APASL ACLF Research Consortium (AARC)” was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia–Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the ‘Golden Therapeutic Window’, the ‘transplant window’, and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The ‘Kyoto APASL Consensus’ presented below carries the final recommendations along with the relevant background information and areas requiring future studies.
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13
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Engelmann C. Rifaximin in cirrhosis: Is its microbiological spotless record under threat? J Hepatol 2025; 82:392-394. [PMID: 39681500 DOI: 10.1016/j.jhep.2024.11.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024]
Affiliation(s)
- Cornelius Engelmann
- Charité - Universitaetsmedizin Berlin, Campus Virchow Klinikum, Department of Hepatology and Gastroenterology, Berlin, Germany; University College London, Institute of Liver and Digestive Health, Royal Free Campus, London, United Kingdom.
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14
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Choudhury A, Kulkarni AV, Arora V, Soin AS, Dokmeci AK, Chowdhury A, Koshy A, Duseja A, Kumar A, Mishra AK, Patwa AK, Sood A, Roy A, Shukla A, Chan A, Krag A, Mukund A, Mandot A, Goel A, Butt AS, Sahney A, Shrestha A, Cárdenas A, Di Giorgio A, Arora A, Anand AC, Dhawan A, Jindal A, Saraya A, Srivastava A, Kumar A, Kaewdech A, Pande A, Rastogi A, Valsan A, Goel A, Kumar A, Singal AK, Tanaka A, Coilly A, Singh A, Meena BL, Jagadisan B, Sharma BC, Lal BB, Eapen CE, Yaghi C, Kedarisetty CK, Kim CW, Panackel C, Yu C, Kalal CR, Bihari C, Huang CH, Vasishtha C, Jansen C, Strassburg C, Lin CY, Karvellas CJ, Lesmana CRA, Philips CA, Shawcross D, Kapoor D, Agrawal D, Payawal DA, Praharaj DL, Jothimani D, Song DS, Kim DJ, Kim DS, Zhongping D, Karim F, Durand F, Shiha GE, D'Amico G, Lau GK, Pati GK, Narro GEC, Lee GH, Adali G, Dhakal GP, Szabo G, Lin HC, Li H, Nair HK, Devarbhavi H, Tevethia H, Ghazinian H, Ilango H, Yu HL, Hasan I, Fernandez J, George J, Behari J, Fung J, Bajaj J, Benjamin J, Lai JC, Jia J, Hu JH, et alChoudhury A, Kulkarni AV, Arora V, Soin AS, Dokmeci AK, Chowdhury A, Koshy A, Duseja A, Kumar A, Mishra AK, Patwa AK, Sood A, Roy A, Shukla A, Chan A, Krag A, Mukund A, Mandot A, Goel A, Butt AS, Sahney A, Shrestha A, Cárdenas A, Di Giorgio A, Arora A, Anand AC, Dhawan A, Jindal A, Saraya A, Srivastava A, Kumar A, Kaewdech A, Pande A, Rastogi A, Valsan A, Goel A, Kumar A, Singal AK, Tanaka A, Coilly A, Singh A, Meena BL, Jagadisan B, Sharma BC, Lal BB, Eapen CE, Yaghi C, Kedarisetty CK, Kim CW, Panackel C, Yu C, Kalal CR, Bihari C, Huang CH, Vasishtha C, Jansen C, Strassburg C, Lin CY, Karvellas CJ, Lesmana CRA, Philips CA, Shawcross D, Kapoor D, Agrawal D, Payawal DA, Praharaj DL, Jothimani D, Song DS, Kim DJ, Kim DS, Zhongping D, Karim F, Durand F, Shiha GE, D'Amico G, Lau GK, Pati GK, Narro GEC, Lee GH, Adali G, Dhakal GP, Szabo G, Lin HC, Li H, Nair HK, Devarbhavi H, Tevethia H, Ghazinian H, Ilango H, Yu HL, Hasan I, Fernandez J, George J, Behari J, Fung J, Bajaj J, Benjamin J, Lai JC, Jia J, Hu JH, Chen JJ, Hou JL, Yang JM, Chang J, Trebicka J, Kalf JC, Sollano JD, Varghese J, Arab JP, Li J, Reddy KR, Raja K, Panda K, Kajal K, Kumar K, Madan K, Kalista KF, Thanapirom K, Win KM, Suk KT, Devadas K, Lesmana LA, Kamani L, Premkumar M, Niriella MA, Al Mahtab M, Yuen MF, Sayed MHE, Alla M, Wadhawan M, Sharma MK, Sahu M, Prasad M, Muthiah MD, Schulz M, Bajpai M, Reddy MS, Praktiknjo M, Yu ML, Prasad M, Sharma M, Elbasiony M, Eslam M, Azam MG, Rela M, Desai MS, Vij M, Mahmud N, Choudhary NS, Marannan NK, Ormeci N, Saraf N, Verma N, Nakayama N, Kawada N, Oidov Baatarkhuu, Goyal O, Yokosuka O, Rao PN, Angeli P, Parikh P, Kamath PS, Thuluvath PJ, Lingohr P, Ranjan P, Bhangui P, Rathi P, Sakhuja P, Puri P, Ning Q, Dhiman RK, Kumar R, Vijayaraghavan R, Khanna R, Maiwall R, Mohanka R, Moreau R, Gani RA, Loomba R, Mehtani R, Rajaram RB, Hamid SS, Palnitkar S, Lal S, Biswas S, Chirapongsathorn S, Agarwal S, Sachdeva S, Saigal S, Kumar SE, Violeta S, Singh SP, Mochida S, Mukewar S, Alam S, Lim SG, Alam S, Shalimar, Venishetty S, Sundaram SS, Shetty S, Bhatia S, Singh SA, Kottilil S, Strasser S, Shasthry SM, Maung ST, Tan SS, Treeprasertsuk S, Asthana S, Manekeller S, Gupta S, Acharya SK, K C S, Maharshi S, Asrani S, Dadhich S, Taneja S, Giri S, Singh S, Chen T, Gupta T, Kanda T, Tanwandee T, Piratvishuth T, Spengler U, Prasad VGM, Midha V, Rakhmetova V, Arroyo V, Sood V, Br VK, Wong VWS, Pamecha V, Singh V, Dayal VM, Saraswat VA, Kim WR, Jafri W, Gu W, Jun WY, Qi X, Chawla YK, Kim YJ, Shi Y, Abbas Z, Kumar G, Shiina S, Wei L, Omata M, Sarin SK. Acute-on-chronic liver failure (ACLF): the 'Kyoto Consensus'-steps from Asia. Hepatol Int 2025; 19:1-69. [PMID: 39961976 PMCID: PMC11846769 DOI: 10.1007/s12072-024-10773-4] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Accepted: 12/29/2024] [Indexed: 02/23/2025]
Abstract
Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the 'Golden Therapeutic Window', the 'transplant window', and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The 'Kyoto APASL Consensus' presented below carries the final recommendations along with the relevant background information and areas requiring future studies.
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Affiliation(s)
- Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - A S Soin
- Medanta-The Medicity Hospital, Gurugram, Haryana, India
| | | | - Abhijeet Chowdhury
- Institute of Post-Graduate Medical Education and Research (IPGMER), Kolkata, West Bengal, India
| | - Abraham Koshy
- VPS Lakeshore Hospital and Research Center Ltd, Kochi, Kerala, India
| | - Ajay Duseja
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Ajay Kumar
- Govind Ballabh Pant Hospital, New Delhi, India
| | - Ajay Kumar Mishra
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | | | - Ajit Sood
- Dayanand Medical College, Ludhiana, India
| | - Akash Roy
- Apollo Multispeciality Hospital, Kolkata, India
| | - Akash Shukla
- Seth G S Medical College and K E M Hospital, Mumbai, Maharashtra, India
- Sir HN Reliance Foundation Hospital, Girgaon, Mumbai, Maharashtra, India
| | - Albert Chan
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Amar Mukund
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Amit Goel
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | | | | | | | - Andrés Cárdenas
- Univerity of Barcelona Institut d'Investigacions Biomèdiques August Pi-Sunyer, Barcelona, Spain
| | | | - Anil Arora
- Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, India
| | - Anil Chandra Anand
- Kalinga Institute of Medical Sciences (KIMS), Bhubaneshwar, Orissa, India
| | | | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Anoop Saraya
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Anshu Srivastava
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | - Anupam Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Apurva Pande
- Fortis Hospital, Greater Noida, Uttar Pradesh, India
| | - Archana Rastogi
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Arun Valsan
- Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, India
| | - Ashish Goel
- Christian Medical College (CMC), Vellore, India
| | - Ashish Kumar
- Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, India
| | - Ashwani K Singal
- University of Louisville School of Medicine, Trager Transplant Center and Jewish Hospital, Louisville, KY, USA
| | | | - Audrey Coilly
- Centre Hepato-Biliaire, Paul Brousse Hospital, Paris-Saclay University, Villejuif, France
| | - Ayaskanta Singh
- IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
| | - Babu Lal Meena
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | - Bikrant Bihari Lal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - C E Eapen
- Christian Medical College (CMC), Vellore, India
| | - Cesar Yaghi
- Saint Joseph University, Hôtel-Dieu de France University Medical Center, Beirut, Lebanon
| | | | | | | | - Chen Yu
- Capital Medical University, Beijing, China
| | - Chetan R Kalal
- Nanavati Max Super Specialty Hospital, Mumbai, Maharashtra, India
| | - Chhagan Bihari
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Chitranshu Vasishtha
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Christian Jansen
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | | | - Chun Yen Lin
- Linkou Medical Centre, Chang Gung Memorial Hospital, Keelung, Taiwan
| | | | - Cosmas Rinaldi Adithya Lesmana
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
- Medistra Hospital, Jakarta, Indonesia
| | | | | | | | | | | | | | | | | | | | - Dong-Sik Kim
- Korea University College of Medicine, Seoul, Republic of Korea
| | | | - Fazal Karim
- Sir Salimullah Medical College, Mitford Hospital, Dhaka, Bangladesh
| | - Francois Durand
- Université de Paris, AP-HP, C, DMU DIGEST, Centre de Référence Des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Centre de Recherche Sur L'inflammation, Inserm, Paris, France
| | | | - Gennaro D'Amico
- Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
- Clinica La Maddalena, Palermo, Italy
| | - George K Lau
- Humanity and Health Medical Center, Hongkong, SAR, China
| | | | - Graciela Elia Castro Narro
- Hospital Médica Sur, Mexico City, Mexico
- Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubiran",, Mexico City, Mexico
- Latin-American Association for the Study of the Liver (ALEH), Santiago de Chile, Chile
| | - Guan-Huei Lee
- National University Hospital, National University of Singapore, Singapore, Singapore
| | - Gupse Adali
- University of Health Sciences, Ümraniye, Istanbul, Turkey
| | | | - Gyongyi Szabo
- Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - H C Lin
- Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hai Li
- School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Hari Kumar Nair
- Ernakulam Medical Center (EMC), Kinder Multispeciality Hospital, Kochi, Kerala, India
| | | | - Harshvardhan Tevethia
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | | | - Irsan Hasan
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
| | - J Fernandez
- University of Barcelona, IDIBAPS and CIBEREHD, Barcelona, Spain
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Jaideep Behari
- Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - James Fung
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Jaya Benjamin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Jennifer C Lai
- University of California, San Francisco, San Francisco, CA, USA
| | - Jidong Jia
- Capital Medical University, Beijing, China
| | - Jin Hua Hu
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Jin Jun Chen
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Jin Lin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Jin Mo Yang
- The Catholic University of Korea, Seoul, Korea
| | - Johannes Chang
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Jonel Trebicka
- Medizinische Klinik B, Universitätsklinikum Münster, Münster, Germany
| | - Jörg C Kalf
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Jose D Sollano
- Department of Medicine, Cardinal Santos Medical Center, Manila, Philippines
| | - Joy Varghese
- Gleneagles Global Hospital, Chennai, Tamil Nadu, India
| | - Juan Pablo Arab
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Schulich School of Medicine, Western University, London, ON, Canada
| | - Jun Li
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | | | - Kaiser Raja
- King's College Hospital London, Dubai, United Arab Emirates
| | - Kalpana Panda
- IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
| | - Kamal Kajal
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Karan Kumar
- Mahatma Gandhi Medical College, Jaipur, Rajasthan, India
| | - Kaushal Madan
- Max Super Specialty Hospital Saket, New Delhi, India
| | - Kemal Fariz Kalista
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
| | | | - Khin Maung Win
- University of Medicine, Yangon Ministry of Health, Yangon, Myanmar
| | - Ki Tae Suk
- Hallym University, Chuncheon, Republic of Korea
| | | | | | - Lubna Kamani
- Liaquat National Hospital, Karachi, Sindh, Pakistan
| | - Madhumita Premkumar
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | | | - Mamun Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Man Fung Yuen
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Manasa Alla
- Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | | | - Manoj Kumar Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Manoj Sahu
- IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
| | - Manya Prasad
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Mark Dhinesh Muthiah
- National University Hospital, National University of Singapore, Singapore, Singapore
| | - Martin Schulz
- Goethe University Clinic Frankfurt, Frankfurt, Germany
| | - Meenu Bajpai
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | - Ming Lung Yu
- Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine, National Sun Yet-Sen University, Kaohsiung, Taiwan
| | | | - Mithun Sharma
- Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | | | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Mohd Golam Azam
- Endocrine and Metabolic Disorder (BIRDEM) Shahbad, Bangladesh Institute of Research and Rehabilitation in Diabetes, Dhaka, Bangladesh
| | - Mohd Rela
- Dr. Rela Institute and Medical Centre, Chennai, India
| | - Moreshwar S Desai
- Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA
| | - Mukul Vij
- Dr. Rela Institute and Medical Centre, Chennai, India
| | - Nadim Mahmud
- University of Pennsylvania, Philadelphia, PA, USA
| | | | | | - Necati Ormeci
- İstanbul Health and Technology University, Istanbul, Turkey
| | - Neeraj Saraf
- Medanta-The Medicity Hospital, Gurugram, Haryana, India
| | - Nipun Verma
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | | | - Norifumi Kawada
- Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Oidov Baatarkhuu
- Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | | | - Osamu Yokosuka
- Graduate School of Medicine, Chiba University, Chuo-Ku, Chiba, Japan
| | - P N Rao
- Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Paolo Angeli
- Department of Medicine (DIMED), University of Padova, Padua, Italy
| | | | | | | | - Philipp Lingohr
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Piyush Ranjan
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | - Pravin Rathi
- Topi Wala National (TN) Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | | | - Puneet Puri
- Virginia Commonwealth University, Richmond, VA, USA
| | - Qin Ning
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - R K Dhiman
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | - Rahul Kumar
- Changi General Hospital, Singapore, Singapore
| | - Rajan Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rajeev Khanna
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Ravi Mohanka
- Sir HN Reliance Foundation Hospital, Girgaon, Mumbai, Maharashtra, India
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
- Centre de Recherche Sur L'Inflammation (CRI), INSERM and Université Paris-Cité, Paris, France
- Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Beaujon, Service d'Hépatologie, Clichy, France
| | - Rino Alvani Gani
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
| | - Rohit Loomba
- University of California, San Diego, La Jolla, CA, USA
| | - Rohit Mehtani
- Amrita Institute of Medical Sciences and Research Centre, Faridabad, Haryana, India
| | | | - S S Hamid
- Aga Khan University Hospital, Karachi, Pakistan
| | | | - Sadhna Lal
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Sagnik Biswas
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | - Samagra Agarwal
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | - Sanjiv Saigal
- Max Super Specialty Hospital Saket, New Delhi, India
| | | | | | - Satender Pal Singh
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Saurabh Mukewar
- Midas Multispeciality Hospital Pvt. Ltd, Nagpur, Maharashtra, India
| | - Seema Alam
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Seng Gee Lim
- National University Hospital, National University of Singapore, Singapore, Singapore
| | - Shahinul Alam
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Shalimar
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | | | - Shiran Shetty
- Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Shobna Bhatia
- National Institute of Medical Sciences, Jaipur, India
| | | | - Shyam Kottilil
- University of Maryland School of Medicine, Baltimore, USA
| | | | - S M Shasthry
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Soek Siam Tan
- Selayang Hospital, University of Malaysia, Batu Caves, Selangor, Malaysia
| | | | | | | | - Subhash Gupta
- Max Super Specialty Hospital Saket, New Delhi, India
| | | | - Sudhamshu K C
- Bir Hospital, National Academy of Medical Sciences, Kathmandu, Nepal
| | - Sudhir Maharshi
- Sawai Man Singh (SMS) Medical College and Hospital, Jaipur, Rajasthan, India
| | - Sumeet Asrani
- Baylor Simmons Transplant Institute, Dallas, TX, USA
| | - Sunil Dadhich
- Dr Sampuranand Medical College (SNMC), Jodhpur, Rajasthan, India
| | - Sunil Taneja
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Suprabhat Giri
- Kalinga Institute of Medical Sciences (KIMS), Bhubaneshwar, Orissa, India
| | - Surender Singh
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | - Tao Chen
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tarana Gupta
- Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India
| | - Tatsuo Kanda
- Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | | | | | - Ulrich Spengler
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - V G Mohan Prasad
- Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA
| | | | | | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
| | - Vikrant Sood
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Vinay Kumar Br
- Mazumdar Shaw Medical Centre, Bangalore, Karnataka, India
| | | | - Viniyendra Pamecha
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Virendra Singh
- Punjab Institute of Liver and Biliary Sciences, Mohali, Punjab, India
| | - Vishwa Mohan Dayal
- Indira Gandhi Institute of Medical Sciences, (IGIMS), Bely Road Patna, Bihar, India
| | | | - WRay Kim
- Stanford University, Stanford, CA, USA
| | - Wasim Jafri
- Aga Khan University Hospital, Karachi, Pakistan
| | - Wenyi Gu
- Goethe University Clinic Frankfurt, Frankfurt, Germany
| | - Wong Yu Jun
- Changi General Hospital, Singapore, Singapore
| | - Xiaolong Qi
- Medical School, Zhongda Hospital, Southeast University, Nanjing, China
| | - Yogesh K Chawla
- Kalinga Institute of Medical Sciences (KIMS), Bhubaneshwar, Orissa, India
| | - Yoon Jun Kim
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yu Shi
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | - Zaigham Abbas
- Ziauddin University Hospital Karachi, Karachi, Pakistan
| | - Guresh Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Lai Wei
- Changgung Hospital, Tsinghua University, Beijing, China
| | - Masao Omata
- Yamanashi Central Hospital, Yamanashi, Japan
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
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15
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Cerutti E, D'Arcangelo F, Becchetti C, Cilla M, Cossiga V, Guarino M, Invernizzi F, Lapenna L, Lavezzo B, Marra F, Merli M, Morelli MC, Toniutto P, Burra P, Zanetto A. Sex disparities in acute-on-chronic liver failure: From admission to the intensive care unit to liver transplantation. Dig Liver Dis 2025; 57:355-361. [PMID: 39164168 DOI: 10.1016/j.dld.2024.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 07/01/2024] [Accepted: 08/04/2024] [Indexed: 08/22/2024]
Abstract
Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome characterized by acute liver decompensation in patients with chronic liver disease, marked by systemic inflammation and systemic organ failure. In this review, we discussed sex-related disparities in the incidence, prognosis, and access to liver transplantation (LT) for patients with ACLF, particularly during Intensive Care Unit (ICU) management. Some studies have suggested that ACLF is more prevalent among male patients admitted to the ICU, and they have higher mortality rates than females. Available prognostic scores, such as CLIF-C or TAM-score, lack sex-specific adjustments. Sarcopenia seems to enhance the accuracy of these scores though this is observed only in male individuals. LT is the only effective treatment for patients with ACLF grade 2-3 who do not respond to medical therapies. Sex-related disparities occur in both access to LT and post-transplant outcomes, although the influence of sex on the prevalence, clinical course, and listing for LT in ACLF remains largely undetermined. A sex-orientated analysis of ICU outcomes in ACLF would facilitate the development of sex-orientated management strategies, thereby improving patients' outcomes.
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Affiliation(s)
- Elisabetta Cerutti
- Department of Anesthesia, Transplant and Surgical Intensive Care, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
| | - Francesca D'Arcangelo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy
| | - Chiara Becchetti
- Hepatology and Gastroenterology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Marta Cilla
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy
| | - Valentina Cossiga
- Diseases of the Liver and Biliary System Unit, Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy
| | - Maria Guarino
- Diseases of the Liver and Biliary System Unit, Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy
| | - Federica Invernizzi
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy
| | - Lucia Lapenna
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Bruna Lavezzo
- Emergency Department, Anesthesia and Intensive Care Unit, SS Annunziata Hospital, Savigliano ASL Cuneo, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Maria Cristina Morelli
- Internal Medicine Unit for the Treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Pierluigi Toniutto
- Hepatology and Liver Transplantation Unit, Academic Hospital, University of Udine, Udine, Italy
| | - Patrizia Burra
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy.
| | - Alberto Zanetto
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy
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16
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Shi K, Zhang Y, Li Y, Wang X, Feng Y, Wang X. High-density lipoprotein cholesterol as a prognostic marker for 90-day transplant-free mortality in hepatitis B virus-related acute-on-chronic liver failure. Front Cell Infect Microbiol 2025; 14:1458818. [PMID: 39911493 PMCID: PMC11794805 DOI: 10.3389/fcimb.2024.1458818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 12/30/2024] [Indexed: 02/07/2025] Open
Abstract
Background Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is linked to dyslipidemia and inflammatory responses. This study aimed to investigate the correlation between high-density lipoprotein cholesterol (HDL-C) levels and 90-day transplant-free (TF) mortality in patients with HBV-ACLF. Methods A prospective cohort of 287 patients with HBV-ACLF from Beijing Ditan Hospital was enrolled between January 2016 and December 2019. The prognostic accuracy of lipid profile parameters was evaluated by the area under the receiver operating characteristic curve (AUC), and the association between HDL-C levels and mortality was assessed using a restricted cubic spline analysis. Correlations between lipid profile parameters and inflammatory factors were analyzed. Kaplan-Meier curves were used to assess 90-day TF mortality, and log-rank tests were used for comparison analysis. These results were internally validated between January 2020 and December 2023 (n=125). Results Patients with lower HDL-C levels exhibited higher mortality rates (adjusted hazard ratio for HDL-C < 0.13 mmol/L: 4.04, 95% confidence interval: 1.35-11.85) compared with those in the reference group (with HDL-C levels above 0.36 mmol/L). An "L-shaped" association was observed between HDL-C levels and TF mortality. The prognostic value of HDL-C (AUC at day 90: 0.732) was comparable to the model for end-stage liver disease score of 0.729. Additionally, HDL-C levels were inversely correlated with interleukin (IL)-4, IL-6, and tumor necrosis factor-α (all P<0.05). In the training cohort, the 90-day TF mortality rates were 8.3%, 15.2%, 24.0%, and 43.2% for the extremely low, low, medium, and high-risk subgroups, respectively, while in the validation cohort, they were 4.5%, 18.5%, 31.2%, and 44.7%, respectively. Conclusions HDL-C levels < 0.13 mmol/L were associated with increased 90-day transplant-free mortality in patients with HBV-ACLF. An inverse correlation was found between HDL-C levels and inflammatory markers.
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Affiliation(s)
| | | | | | | | - Ying Feng
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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17
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Kulkarni AV, Sarin SK. Reply to: "A consensus definition for ACLF - The need of the hour?". J Hepatol 2025; 82:e54-e55. [PMID: 39321927 DOI: 10.1016/j.jhep.2024.09.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 09/04/2024] [Accepted: 09/15/2024] [Indexed: 09/27/2024]
Affiliation(s)
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
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18
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Haedge F, Bruns T. Antibiotics in decompensated liver disease - who, when and for how long? Expert Rev Gastroenterol Hepatol 2025; 19:111-130. [PMID: 39921440 DOI: 10.1080/17474124.2025.2464044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 01/26/2025] [Accepted: 02/04/2025] [Indexed: 02/10/2025]
Abstract
INTRODUCTION Bacterial infections are a leading cause of hospitalization and mortality in patients with decompensated cirrhosis. Antibiotic prophylaxis in cirrhotic patients has demonstrated significant short-term reductions in bacterial infections in randomized controlled trials, but at the cost of drug resistance and with uncertain survival benefits. AREAS COVERED This review examines antibiotic use in cirrhosis, focusing on patients most likely to benefit from antibiotic prophylaxis, management strategies for infections through risk-based antibiotic selection and timely treatment initiation, challenges posed by the emergence of multidrug-resistant organisms, and principles of antimicrobial stewardship. EXPERT OPINION The efficacy of prophylaxis has decreased over time, and current registry data have questioned its use, emphasizing the need for better risk-based individualized strategies. When bacterial infections occur, the efficacy of antimicrobial therapies depends heavily on local epidemiological patterns and individual patient risk factors, necessitating tailored antibiotic selection based on regional resistance data and specific clinical scenarios. Nosocomial infections, colonization with multidrug-resistant organisms, and prior exposure to systemic antibiotics are key risk factors that should guide empirical therapy selection. Until evidence-based algorithms are available, clinicians should continue to adopt individualized approaches, guided by available evidence, local specificities, and antimicrobial stewardship principles to optimize patient outcomes.
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Affiliation(s)
- Frederic Haedge
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Tony Bruns
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
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19
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Zhang Y, Zhao H, Ji SB, Xing HC. Clinical analysis of Klebsiella pneumoniae infection in patients with liver cirrhosis in Beijing. World J Hepatol 2024; 16:1441-1449. [DOI: 10.4254/wjh.v16.i12.1441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 10/07/2024] [Accepted: 11/12/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND The incidence of Klebsiella pneumoniae (K. pneumoniae) infection in patients with cirrhosis has been increasing over recent years, posing certain difficulties in clinical treatment.
AIM To analyze the clinical features of patients with liver cirrhosis and identify the risk factors to help the early diagnosis and treatment of these diseases.
METHODS Clinical data and laboratory tests were collected from 72 patients with cirrhosis confirmed by secretion or blood culture of K. pneumoniae infection at Beijing Ditan Hospital, Capital Medical University, between May 2016 and October 2018. Data from hospitalized patients with liver cirrhosis and K. pneumoniae infections, including age, sex, antimicrobial use, length of stay, site of infection, distribution of pathogenic bacteria, complications, invasive operations, laboratory indicators, treatment, and clinical regression, were extracted and retrospectively analyzed. Clinical data and biochemical values were included in the multivariate logistic regression analysis.
RESULTS A total of 52 men and 20 women, with an age range from 29 to 85 years and an average age of 57.7 ± 12.54, were analyzed. The incidence of hospital K. pneumoniae infection in patients with cirrhosis was approximately 19.44%. The most common the infection site was the bloodstream, followed by the respiratory tract, abdominal cavity, and biliary tract. Risk factors for infection were old age, long hospital stays, gastrointestinal bleeding, and low serum albumin levels, while prophylactic antibiotics were protective factors. The multivariate analysis suggested that other infections, chronic diseases, and invasive procedures were independent factors.
CONCLUSION In clinical practice, the length of hospital stays should be shortened as much as possible, invasive operations should be reduced, antibiotics should be rationally used, and the patients’ liver function should be timely improved. This is of great significance for reducing the incidence of hospital infection.
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Affiliation(s)
- Yu Zhang
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Peking University Ditan Teaching Hospital, Beijing 100015, China
| | - Hong Zhao
- Center of Liver Diseases Division 1, Beijing Ditan Hospital, Capital Medical University, Peking University Ditan Teaching Hospital, Beijing 100015, China
| | - Shi-Bo Ji
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Peking University Ditan Teaching Hospital, Beijing 100015, China
| | - Hui-Chun Xing
- Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, Peking University Ditan Teaching Hospital, Beijing 100015, China
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20
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Zhang Y, Luo Q, Lin X, Wang L, Li Z, Chen J, Xu R, Wu L, Peng L, Xu W. Development and Validation of a New Model Including Inflammation Indexes for the Long-Term Prognosis of Hepatitis B-Related Acute-On-Chronic Liver Failure. J Med Virol 2024; 96:e70110. [PMID: 39651596 DOI: 10.1002/jmv.70110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 10/30/2024] [Accepted: 11/23/2024] [Indexed: 12/11/2024]
Abstract
Acute-on-chronic liver failure (ACLF) is a severe condition characterized by a systemic inflammatory response and associated with high mortality. Currently, there is no reliable prediction model for long-term prognosis in ACLF. This study aimed to develop and validate a prognostic model incorporating inflammation indexes to predict the long-term outcome of patients with hepatitis B virus-related ACLF (HBV-ACLF). A retrospective analysis of clinical data from HBV-ACLF patients (n = 986) treated at the Third Affiliated Hospital of Sun Yat-sen University between January 2014 and December 2018 was conducted. Patients were randomly divided into training (n = 690) and validation (n = 296) cohorts. The Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analyses were used to identify independent risk factors for long-term mortality. The following variables were identified as independent predictors of long-term mortality: age, cirrhosis, hepatic encephalopathy, total bilirubin (TBIL), international normalized ratio (INR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-platelet ratio (NPR). A novel nomogram was established by assigning weights to each variable. The C-index of the nomogram was 0.777 (95% confidence interval [CI]: 0.752-0.802). In the training set, the area under the curve (AUC) for predicting mortality at 1, 3, and 12 months was 0.841 (95% CI: 0.807-0.875), 0.827 (95% CI: 0.796-0.859), and 0.829 (95% CI: 0.798-0.859), respectively. The nomogram demonstrated superior predictive performance for 12-month survival compared to the model for end-stage liver disease (MELD) score (0.767, 95% CI: 0.730-0.804, p < 0.001) and the clinical overt sepsis in acute liver failure clinical practice Guidelines-ACLF II score (0.807, 95% CI: 0.774-0.840, p = 0.028). Finally, calibration curves and decision curve analysis (DCA) confirmed the clinical utility of the nomogram. The novel inflammation-based scoring system, incorporating MLR and NPR, effectively predicts long-term mortality in HBV-ACLF patients.
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Grants
- This study was supported by grants from the Natural Science Foundation of China (No. 82070611 to Liang Peng), Natural Science Foundation of Guangdong Province (No. 2020A1515010317 to Liang Peng), GuangDong Basic and Applied Basic Research Foundation (No. 21202104030000608 and 2021A1515220029 to Liang Peng), Guangzhou Science and Technology Plan Projects (No. 202102010204 and 2023B03J1287 to Liang Peng, and No. 202102080064 to Wenxiong Xu), Sun Yat-Sen University Clinical Research 5010 Program (No. 2020007 and 2018009 to Liang Peng), the Five-Year Plan of Third Affiliated Hospital of Sun Yat-sen University (No. K00006 and P02421 to Liang Peng), and Beijing iGandan Foundation (No. iGandanF-1082022-RGG038 to Wenxiong Xu and No. iGandanF-1082024-RGG050 to Liang Peng). All funders did not participate in the design of the study, collection, analysis, and interpretation of data, as well as in writing the manuscript.
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Affiliation(s)
- Yeqiong Zhang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qiumin Luo
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiumei Lin
- Department of Clinical Laboratory, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lu Wang
- Department of Diagnostics, Second School of Clinical Medicine, Binzhou Medical University, Yantai, China
| | - Zhipeng Li
- Department of Emergency, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jia Chen
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ruixuan Xu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lina Wu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Liang Peng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wenxiong Xu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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21
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Girish V, Maiwall R. Revisiting septic shock in cirrhosis: a call for personalized management. Expert Rev Gastroenterol Hepatol 2024; 18:795-813. [PMID: 39744868 DOI: 10.1080/17474124.2024.2443813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 12/14/2024] [Indexed: 01/12/2025]
Abstract
INTRODUCTION Patients with cirrhosis are known to be prone to infections. Infections can trigger organ failures and decompensations in cirrhosis. Septic shock can increase mortality by fourfold and cause hemodynamic imbalances, adding to the already hyperdynamic circulation. Management of septic shock in cirrhosis can be tricky due to this complex interplay of altered hemodynamics, immune function, and coagulation. AREAS COVERED In this review, we explore the pathophysiological basis, screening, monitoring and management of septic shock in cirrhosis. We also explore novel biomarkers, the growing challenge of multidrug-resistant pathogens and novel and adjunctive therapies. Finally, we propose an algorithm for the management of septic shock in cirrhosis. We conducted a comprehensive search of electronic databases such as PubMed, Web of Science, and Cochrane Library using the keywords and MeSH terms like 'septic shock,' 'cirrhosis,' 'liver disease,' 'sepsis' among others. The search was restricted to peer-reviewed articles in English. EXPERT OPINION The difficulties in managing septic shock in cirrhosis are discussed, emphasizing personalized approaches over protocol-driven care. Fluid and vasopressor management, antibiotic timing and selection, the role of adjunctive therapies, the importance of lactate clearance, gut failure, and the need for further research in this population are highlighted.
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Affiliation(s)
- Vishnu Girish
- Department of Hepatology, Institute of liver and biliary sciences, Delhi, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of liver and biliary sciences, Delhi, India
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22
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Shen Y, Xu W, Chen Y, Wen S, Chen Q, Liu S, Zhu X, Tang LL, Li L, Ju B. Early prediction of acute-on-chronic liver failure development in patients with diverse chronic liver diseases. Sci Rep 2024; 14:28245. [PMID: 39548240 PMCID: PMC11568263 DOI: 10.1038/s41598-024-79486-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 11/11/2024] [Indexed: 11/17/2024] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome characterized by the acute decompensation of chronic liver disease, resulting in organ failure and high short-term mortality. The progression of ACLF is dynamic and reversible in a considerable proportion of patients during hospitalization. Early detection and accurate assessment of ACLF are essential; however, ideal methods for this purpose are still lacking. Therefore, this study aimed to develop a new score for predicting the onset of ACLF in patients with various chronic liver diseases.A total of 6,188 patients with various chronic liver diseases were included in the study. Clinical and laboratory data were collected, and the occurrence of ACLF within 28 days was recorded. The Lasso-Cox regression method was employed to develop prediction models for the onset of ACLF at 7, 14, and 28 days. Among 5,221 patients without ACLF, 477 progressed to ACLF within 28 days. Seven predictors were identified as significantly associated with the occurrence of ACLF at 7, 14, and 28 days. A new scoring system was developed as follows: [NEUT ≥ 7, 109/L; 1 or 0] × 0.49 + [PLT < 100, 109/L; 1 or 0] × 0.44 + [TBIL ≥ 35, µmol/L; 1 or 0] × 0.05 + [HDL-C < 0.5, mmol/L; 1 or 0] × 1.04 - Ln[Hb, g/L] × 0.89 + [BUN > 7, mmol/L; 1 or 0] × 0.51 + Ln[INR] × 0.87 + 3.40. This new score demonstrated superior discrimination, with the C-indexes of 0.958, 0.944, and 0.938 at 7, 14, and 28 days, respectively, outperforming those of four other scores (CLIF-C-ACLF-Ds, MELD, MELD-Na, and CLIF-C-ADs score; all P < 0.001). Additionally, the new score improved in predictive accuracy, time-dependent receiver operating characteristics, probability density function evaluations, and calibration curves, making it highly predictive for the onset of ACLF at all time points. The optimal cut-off value of 9.6 effectively distinguished between high- and low-risk patients for ACLF onset. These findings were further validated in a separate cohort of patients. A new progressive score, based on seven predictors, has been developed to accurately forecast the occurrence of ACLF within 7, 14, and 28 days in patients with various chronic liver diseases. This tool may be utilized to identify high-risk patients, tailor follow-up management, and guide the escalation of care, prognostication, and transplant evaluation.
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Affiliation(s)
- Yuqiang Shen
- Department of Information Technology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
- School of Computer Science and Technology, Zhejiang Sci-Tech University, Hangzhou, China
| | - Wan Xu
- Hangzhou Xiaoshan District Center for Disease Control and Prevention (Hangzhou Xiaoshan District Health Supervision Institute), Hangzhou, China
| | - Yang Chen
- Department of Information Technology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
| | | | - Qijiong Chen
- Hangzhou Xiaoshan District Center for Disease Control and Prevention (Hangzhou Xiaoshan District Health Supervision Institute), Hangzhou, China
| | - Shanna Liu
- Department of Information Technology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
| | - Xinjian Zhu
- Department of Information Technology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
| | - Ling-Ling Tang
- Department of Infectious Diseases, Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China.
| | - Li Li
- Department of Hepatobiliary Surgery, The First People's Hospital of Kunming, Kunming, China.
| | - Bin Ju
- SanOmics AI Co., Ltd, Hangzhou, China.
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23
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Pompili E, Iannone G, Carrello D, Zaccherini G, Baldassarre M, Caraceni P. Managing Multiorgan Failure in Acute on Chronic Liver Failure. Semin Liver Dis 2024; 44:492-509. [PMID: 39442531 DOI: 10.1055/a-2448-0664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2024]
Abstract
Acute-on-chronic liver failure (ACLF) is defined as a clinical syndrome that develops in patients with chronic liver disease characterized by the presence of organ failure and high short-term mortality, although there is still no worldwide consensus on diagnostic criteria. Management of ACLF is mainly based on treatment of "precipitating factors" (the most common are infections, alcohol-associated hepatitis, hepatitis B flare, and bleeding) and support of organ failure, which often requires admission to the intensive care unit. Liver transplantation should be considered in patients with ACLF grades 2 to 3 as a potentially life-saving treatment. When a transplant is not indicated, palliative care should be considered after 3 to 7 days of full organ support in patients with at least four organ failures or a CLIF-C ACLF score of >70. This review summarizes the current knowledge on the management of organ failure in patients with ACLF, focusing on recent advances.
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Affiliation(s)
- Enrico Pompili
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giulia Iannone
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Daniele Carrello
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maurizio Baldassarre
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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24
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Ferrarese A, Senzolo M, Sasset L, Bassi D, Cillo U, Burra P. Multidrug-resistant bacterial infections in the liver transplant setting. Updates Surg 2024; 76:2521-2529. [PMID: 38918314 PMCID: PMC11602820 DOI: 10.1007/s13304-024-01903-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 05/21/2024] [Indexed: 06/27/2024]
Abstract
Bacterial infections pose a life-threatening complication in patients with decompensated liver cirrhosis and acute-on-chronic liver failure. An increasing prevalence of infections caused by multidrug-resistant organisms (MDROs) has been observed in these patients, significantly impacting prognosis. A growing body of evidence has identified the most common risk factors for such infections, enabling the development of preventive strategies and therapeutic interventions. MDRO infections may also occur after liver transplantation (most commonly in the early post-operative phase), affecting both graft and patient survival. This review provides an overview of MDRO infections before and after liver transplantation, discussing epidemiological aspects, risk factors, prevention strategies, and novel therapeutic approaches. Furthermore, it examines the implications of MDRO infections in the context of prioritizing liver transplantation for the most severe patients, such as those with acute-on-chronic liver failure.
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Affiliation(s)
- Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.
| | - Marco Senzolo
- Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Lolita Sasset
- Infectious Disease Unit, Padua University Hospital, Padua, Italy
| | - Domenico Bassi
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Umberto Cillo
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
- Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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25
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Li W, Liu W, Rong Y, Li D, Zhu B, Yang S, Sun S, You S, Chen Y, Li J. Development and Validation of a New Prognostic Model for Predicting Survival Outcomes in Patients with Acute-on-chronic Liver Failure. J Clin Transl Hepatol 2024; 12:834-844. [PMID: 39440220 PMCID: PMC11491505 DOI: 10.14218/jcth.2024.00316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 09/05/2024] [Accepted: 09/18/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND AND AIMS Early determination of prognosis in patients with acute-on-chronic liver failure (ACLF) is crucial for optimizing treatment options and liver allocation. This study aimed to identify risk factors associated with ACLF and to develop new prognostic models that accurately predict patient outcomes. METHODS We retrospectively selected 1,952 hospitalized patients diagnosed with ACLF between January 2010 and June 2018. This cohort was used to develop new prognostic scores, which were subsequently validated in external groups. RESULTS The study included 1,386 ACLF patients and identified six independent predictors of 28-day mortality through multivariate analysis (all p < 0.05). The new score, based on a multivariate regression model, demonstrated superior predictive accuracy for both 28-day and 90-day mortalities, with Areas under the ROC curves of 0.863 and 0.853, respectively (all p < 0.05). This score can be used to stratify the risk of mortality among ACLF patients with ACLF, showing a significant difference in survival between patients categorized by the cut-off value (log-rank (Mantel-Cox) χ2 = 487.574 and 606.441, p = 0.000). Additionally, the new model exhibited good robustness in two external cohorts. CONCLUSIONS This study presents a refined prognostic model, the Model for end-stage liver disease-complication score, which accurately predicts short-term mortality in ACLF patients. This model offers a new perspective and tool for improved clinical decision-making and short-term prognostic assessment in ACLF patients.
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Affiliation(s)
- Wende Li
- Department of Infection and Liver Diseases, Peking University International Hospital, Beijing, China
| | - Wanshu Liu
- Department of Hepatology Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yihui Rong
- Department of Infection and Liver Diseases, Peking University International Hospital, Beijing, China
| | - Dongze Li
- Department of Hepatology Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Bing Zhu
- Department of Hepatology Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shaobo Yang
- Department of Infection and Liver Diseases, Peking University International Hospital, Beijing, China
| | - Shidong Sun
- Department of Infection and Liver Diseases, Peking University International Hospital, Beijing, China
| | - Shaoli You
- Department of Hepatology Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yu Chen
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jun Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, Zhejiang, China
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Hoppmann H, Zeman F, Wittmann D, Stöckert P, Schlosser-Hupf S, Mehrl A, Pavel V, Müller M, Schmid S. The LIVERAID (LIVER And Infectious Diseases)-ICU score predicts in-hospital mortality in liver cirrhosis patients with infections in the intensive care unit. BMJ Open Gastroenterol 2024; 11:e001482. [PMID: 39384247 PMCID: PMC11481117 DOI: 10.1136/bmjgast-2024-001482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 09/24/2024] [Indexed: 10/11/2024] Open
Abstract
OBJECTIVES The admission of patients with liver cirrhosis to the intensive care unit (ICU) due to infections is a frequent occurrence, often leading to complications such as hepatic encephalopathy, renal failure and circulatory collapse, significantly elevating mortality risks. Accurate and timely diagnosis and intervention are critical for improving therapeutic outcomes. In this context, medical scoring systems in ICUs are essential for precise diagnosis, severity assessment and appropriate therapeutic strategies. There are no specific models for the prediction of mortality in ICU patients with liver cirrhosis-associated infections. This study aims to develop an improved prognostic scoring system for predicting in-hospital mortality among liver cirrhosis patients with infections in the ICU. This scoring system is designed to enhance the predictive accuracy of in-hospital mortality complementing existing sepsis and liver-specific prognostic models. METHODS A retrospective analysis was conducted in 620 patients with liver cirrhosis, treated for infections in the ICU of a German university hospital during 2017-19. Advanced statistical techniques were employed to develop and validate the LIVERAID (LIVER And Infectious Diseases)-ICU score, a novel scoring system specifically tailored for liver cirrhosis patients in the ICU with infections. The development of the multivariable logistic regression model involved selecting variables with the highest prognostic efficacy, and its predictive performance was assessed using calibration plots and the concordance statistic (c-index) to evaluate both calibration and discrimination. RESULTS The LIVERAID-ICU score integrates Child-Pugh class, serum urea levels and respiratory metrics. It is designed for bedside calculation using basic clinical and laboratory data, with no need for additional tools. In the validation cohort, the LIVERAID-ICU score exhibited enhanced sensitivity and specificity (AUC=0.83) in forecasting in-hospital mortality of patients with liver cirrhosis-associated infections when compared with established scores like Sequential Organ Failure Assessment (SOFA) (p=0.045), Model for End-Stage Liver Disease (MELD) (p=0.097), Child (p<0.001) and CLIF consortium acute-on-chronic liver failure (CLIF-C ACLF) (p<0.001). CONCLUSION The newly developed LIVERAID-ICU score represents a robust, streamlined and easy tool for predicting in-hospital mortality in liver cirrhosis patients with infections, surpassing the predictive capabilities of established liver or sepsis scores like SOFA, MELD, Child and CLIF-C ACLF. The reliance of the LIVERAID-ICU score on fundamental clinical and laboratory data facilitates its global application in ICUs, enabling immediate application at the bedside for patients with liver cirrhosis during episodes of suspected or confirmed infections.
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Affiliation(s)
- Hauke Hoppmann
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Florian Zeman
- Center for Clinical Studies, University of Regensburg, Regensburg, Germany
| | - Daniela Wittmann
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Petra Stöckert
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Sophie Schlosser-Hupf
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Alexander Mehrl
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Vlad Pavel
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Martina Müller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
| | - Stephan Schmid
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology, and Infectious diseases, University Hospital Regensburg, Regensburg, Germany
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27
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Flanagan E, Pianko S, Ho C, Saxby E, Grant J, Bell S, Stuart R, Le S. Identify, screen and treat via electronic pathway: a semiautomated approach to retriaging a liver clinic waitlist. Intern Med J 2024; 54:1678-1685. [PMID: 39078091 DOI: 10.1111/imj.16474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Accepted: 06/29/2024] [Indexed: 07/31/2024]
Abstract
BACKGROUND Long specialist outpatient waiting lists are a source of clinical risk. Triage assignment is based on subjective assessment of referrals and fails to account for dynamic changes in disease status while patients await clinical review. AIMS To pilot an innovative triage method using a trifold approach to conduct noninvasive assessment of fibrosis and to determine the feasibility of reflex hepatitis C virus (HCV) polymerase chain reaction (PCR) testing. METHODS A total of 1006 patients awaiting an initial liver clinic appointment at a tertiary Australian hospital were sent a short message service (SMS) requesting a blood test be completed. The first 60 patients received an SMS only, and the subsequent 946 patients also received a phone call from a Liver Care Guide (LCG), a nonclinician employed to increase patient engagement. Liver fibrosis assessment through noninvasive testing was performed using an aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB4) score. Patients with an APRI ≥1, FIB4 ≥3.25 or positive HCV PCR were retriaged to Category 1. RESULTS Four hundred ninety (49%) patients completed testing and 40 (4%) were triaged to Category 1. Subanalyses demonstrated increased response rates with LCG input (P = 0.012). Retriaged patients had been on the waitlist for a median of 216 days, exceeding initial category recommendations. CONCLUSION This study successfully implemented a semiautomated strategy that prioritises patients with probable advanced liver disease or active HCV, demonstrating enhanced patient engagement with LCG support. It highlights the burden of patients referred for specialist care and the need for innovative strategies for monitoring and objective risk stratification.
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Affiliation(s)
- Eliza Flanagan
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
- School of Clinical Sciences, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Melbourne, Victoria, Australia
| | - Stephen Pianko
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
- School of Clinical Sciences, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Melbourne, Victoria, Australia
| | - Cindy Ho
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Edward Saxby
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Julianne Grant
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
| | - Sally Bell
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
- School of Clinical Sciences, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Melbourne, Victoria, Australia
| | - Rhonda Stuart
- School of Clinical Sciences, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Melbourne, Victoria, Australia
- South East Public Health Unit, Monash Health, Melbourne, Victoria, Australia
| | - Suong Le
- Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia
- School of Clinical Sciences, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Melbourne, Victoria, Australia
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28
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Ferguson Toll J, Solà E, Perez MA, Piano S, Cheng A, Subramanian AK, Kim WR. Infections in decompensated cirrhosis: Pathophysiology, management, and research agenda. Hepatol Commun 2024; 8:e0539. [PMID: 39365139 PMCID: PMC11458171 DOI: 10.1097/hc9.0000000000000539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 08/01/2024] [Indexed: 10/05/2024] Open
Abstract
Bacterial infections in patients with cirrhosis lead to a 4-fold increase in mortality. Immune dysfunction in cirrhosis further increases the risk of bacterial infections, in addition to alterations in the gut microbiome, which increase the risk of pathogenic bacteria. High rates of empiric antibiotic use contribute to increased incidence of multidrug-resistant organisms and further increases in mortality. Despite continous advances in the field, major unknowns regarding interactions between the immune system and the gut microbiome and strategies to reduce infection risk and improve mortality deserve further investigation. Here, we highlight the unknowns in these major research areas and make a proposal for a research agenda to move toward improving disease progression and outcomes in patients with cirrhosis and infections.
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Affiliation(s)
- Jessica Ferguson Toll
- Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA
| | | | - Salvatore Piano
- Department of Medicine, University Hospital of Padova, Padova, Italy
| | - Alice Cheng
- Department of Medicine, University of Chicago, Chicago, Illinois, USA
| | - Aruna K. Subramanian
- Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - W. Ray Kim
- Department of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA
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Gupta T, Gaur V, Saini A, Jarpula NS, Goyal SK. Rifaximin alone vs combination with norfloxacin for secondary prophylaxis of spontaneous bacterial peritonitis with hepatic encephalopathy: randomized controlled trial. EGYPTIAN LIVER JOURNAL 2024; 14:66. [DOI: 10.1186/s43066-024-00374-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 09/08/2024] [Indexed: 04/16/2025] Open
Abstract
Abstract
Background
In liver cirrhosis, events of spontaneous bacterial peritonitis (SBP) and hepatic encephalopathy (HE) portend a poor prognosis. Gut dysbiosis remains a common pathogenetic mechanism for both SBP and HE. Recent data suggests the role of rifaximin in gut modulation and improving intestinal dysbiosis. Due to emergence of multidrug-resistant organisms, gut-selective antibiotics with minimal systemic effects are warranted for secondary prophylaxis in patients of cirrhosis. We compared rifaximin alone vs combination with norfloxacin for secondary prophylaxis of patients of cirrhosis presenting with SBP and HE. This was a prospective, open-label, RCT which included all patients of cirrhosis with SBP and HE on admission. On discharge, in addition to standard medical treatment, patients were randomized to rifaximin 400 mg three times a day (group I) and rifaximin 400 mg three times a day with norfloxacin 400 mg once a day (group II) as a secondary prophylaxis of SBP. Primary outcomes were recurrent episodes of SBP and HE at 6 months and 28-day, 90-day, and 6-month mortalities. Secondary outcomes included number of rehospitalizations, episodes of upper gastrointestinal bleed, new acute kidney injury episodes, and change in Child–Turcotte–Pugh (CTP) and model for end-stage liver disease (MELD) scores over next 6 months.
Results
After screening 87 patients of cirrhosis with SBP and HE, 12 patients had in-hospital mortality and another 25 were excluded, one patient was lost to follow-up, and, finally, 49 patients were randomized into group I (n = 24) and group II (n = 25). The HE was grade 2 (18 vs 16) and grade 3 (6 vs 9) in groups I and II respectively. Primary outcomes as recurrent SBP (3 vs 2; P = 0.67); recurrent HE at 6 months (5 vs 2; P = 0.24); and 28-day (2 vs 2; P = 1.0) and 90-day mortality (4 vs 3; P = 0.72) and 6-month mortality (6 vs 8, P = 0.52) were comparable between two groups respectively. Secondary outcomes as number of rehospitalizations (3 vs 8, P = 0.07), new episodes of UGI bleed (2 vs 3, P = 0.1), new AKI episodes (4 vs 1, P = 0.06), ∆CTP (− 4 vs − 4), and ∆MELD (− 9 vs − 8) over the next 6 months were not significantly different between two groups respectively.
Conclusions
Rifaximin was effective in secondary prevention of both SBP and HE in patients of cirrhosis.
Trial registration
The randomized controlled trial was registered in CTRI/2021/09/036321 dated September 7, 2021.
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Bevilacqua M, De Marco L, Stupia R, Cattazzo F, Zoncapé M, Paon V, Ieluzzi D, Dalbeni A, Sacerdoti D. Hepatofugal portal flow is highly predictive of acute-on-chronic liver failure: A new hemodynamic patho-physiological hypothesis. Dig Liver Dis 2024; 56:1522-1528. [PMID: 38281869 DOI: 10.1016/j.dld.2024.01.190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 12/22/2023] [Accepted: 01/10/2024] [Indexed: 01/30/2024]
Abstract
BACKGROUND AND AIMS Acute-on-chronic liver failure (ACLF) is a severe complication of advanced liver disease. A significant number of ACLF patients have not clear precipitating factors. The aim of the study was to investigate the role of alterations in porto-hepatic hemodynamics, especially non-forward portal flow (NFPF), in ACLF and liver-related mortality. METHODS 233 cirrhotic patients were included in the study with a median follow-up of 24 months. Color-Doppler ultrasound was used to assess portal vein patency, flow direction and significant porto-systemic collaterals (>8 mm). Patients with active cancer, both at baseline and during follow-up and severe non liver-related comorbidities were excluded. ACLF and liver-related mortality were recorded during follow-up. RESULTS Fifty-six patients (24%) developed ACLF; 24 (10,3%) had baseline NFPF. In survival analysis, NFPF, but not portal vein thrombosis, was independently associated with ACLF development (HR 2.85 95% C.I. [1.49-5.42], p = 0.001) and liver-related mortality (HR 2.24 95% C.I. [1.16-4.28], p = 0.015), even after adjustment for liver disease severity scores, age and etiology of liver disease. CONCLUSION NFPF is independently associated with ACLF development and liver-related mortality, regardless of etiology, severity disease scores and portal vein thrombosis. Although there is no specific measure to reverse NFPF, patients with NFPF should receive prompt intensive management and urgent prioritization for liver transplantation. CLINICAL TRIAL NUMBER 2730 CESC.
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Affiliation(s)
- Michele Bevilacqua
- General Medicine C, Department of Medicine, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Leonardo De Marco
- General Medicine C, Department of Medicine, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Roberta Stupia
- General Medicine C, Department of Medicine, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Filippo Cattazzo
- General Medicine C, Department of Medicine, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Mirko Zoncapé
- General Medicine C, Department of Medicine, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Veronica Paon
- Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Donatella Ieluzzi
- Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Andrea Dalbeni
- General Medicine C, Department of Medicine, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - David Sacerdoti
- Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
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Li S, Zhang Y, Lin Y, Zheng L, Fang K, Wu J. Development and validation of prediction models for nosocomial infection and prognosis in hospitalized patients with cirrhosis. Antimicrob Resist Infect Control 2024; 13:85. [PMID: 39113159 PMCID: PMC11304655 DOI: 10.1186/s13756-024-01444-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 07/27/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Nosocomial infections (NIs) frequently occur and adversely impact prognosis for hospitalized patients with cirrhosis. This study aims to develop and validate two machine learning models for NIs and in-hospital mortality risk prediction. METHODS The Prediction of Nosocomial Infection and Prognosis in Cirrhotic patients (PIPC) study included hospitalized patients with cirrhosis at the Qingchun Campus of the First Affiliated Hospital of Zhejiang University. We then assessed several machine learning algorithms to construct predictive models for NIs and prognosis. We validated the best-performing models with bootstrapping techniques and an external validation dataset. The accuracy of the predictions was evaluated through sensitivity, specificity, predictive values, and likelihood ratios, while predictive robustness was examined through subgroup analyses and comparisons between models. RESULTS We enrolled 1,297 patients into derivation cohort and 496 patients into external validation cohort. Among the six algorithms assessed, the Random Forest algorithm performed best. For NIs, the PIPC-NI model achieved an area under the curve (AUC) of 0.784 (95% confidence interval [CI] 0.741-0.826), a sensitivity of 0.712, and a specificity of 0.702. For in-hospital mortality, the PIPC- mortality model achieved an AUC of 0.793 (95% CI 0.749-0.836), a sensitivity of 0.769, and a specificity of 0.701. Moreover, our PIPC models demonstrated superior predictive performance compared to the existing MELD, MELD-Na, and Child-Pugh scores. CONCLUSIONS The PIPC models showed good predictive power and may facilitate healthcare providers in easily assessing the risk of NIs and prognosis among hospitalized patients with cirrhosis.
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Affiliation(s)
- Shuwen Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Yu Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Yushi Lin
- Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Luyan Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Kailu Fang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Jie Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
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de Haan J, Termorshuizen F, de Keizer N, Gommers D, Hoed CD. One-year transplant-free survival following hospital discharge after ICU admission for ACLF in the Netherlands. J Hepatol 2024; 81:238-247. [PMID: 38479613 DOI: 10.1016/j.jhep.2024.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 03/05/2024] [Accepted: 03/06/2024] [Indexed: 06/20/2024]
Abstract
BACKGROUND & AIMS Patients with acute decompensation of cirrhosis or acute-on-chronic liver failure (ACLF) often require intensive care unit (ICU) admission for organ support. Existing research, mostly from specialized liver transplant centers, largely addresses short-term outcomes. Our aim was to evaluate in-hospital mortality and 1-year transplant-free survival after hospital discharge in the Netherlands. METHODS We conducted a nationwide observational cohort study, including patients with a history of cirrhosis or first complications of cirrhotic portal hypertension admitted to ICUs in the Netherlands between 2012 and 2020. The influence of ACLF grade at ICU admission on 1-year transplant-free survival after hospital discharge among hospital survivors was evaluated using unadjusted Kaplan-Meier survival curves and an adjusted Cox proportional hazard model. RESULTS Out of the 3,035 patients, 1,819 (59.9%) had ACLF-3. 1,420 patients (46.8%) survived hospitalization after ICU admission. The overall probability of 1-year transplant-free survival after hospital discharge was 0.61 (95% CI 0.59-0.64). This rate varied with ACLF grade at ICU admission, being highest in patients without ACLF (0.71; 95% CI 0.66-0.76) and lowest in those with ACLF-3 (0.53 [95% CI 0.49-0.58]) (log-rank p <0.0001). However, after adjusting for age, malignancy status and MELD score, ACLF grade at ICU admission was not associated with an increased risk of liver transplantation or death within 1 year after hospital discharge. CONCLUSION In this nationwide cohort study, ACLF grade at ICU admission did not independently affect 1-year transplant-free survival after hospital discharge. Instead, age, presence of malignancy and the severity of liver disease played a more prominent role in influencing transplant-free survival after hospital discharge. IMPACT AND IMPLICATIONS Patients with acute-on-chronic liver failure often require intensive care unit (ICU) admission for organ support. In these patients, short-term mortality is high, but long-term outcomes of survivors remain unknown. Using a large nationwide cohort of ICU patients, we discovered that the severity of acute-on-chronic liver failure at ICU admission does not influence 1-year transplant-free survival after hospital discharge. Instead, age, malignancy status and overall severity of liver disease are more critical factors in determining their long-term survival.
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Affiliation(s)
- Jubi de Haan
- Department of Adult Intensive Care, Erasmus University Medical Center, Rotterdam, the Netherlands.
| | - Fabian Termorshuizen
- National Intensive Care Evaluation (NICE) Foundation, Amsterdam, the Netherlands; Department of Medical Informatics, Amsterdam Public Health Institute, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Nicolette de Keizer
- National Intensive Care Evaluation (NICE) Foundation, Amsterdam, the Netherlands; Department of Medical Informatics, Amsterdam Public Health Institute, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Diederik Gommers
- Department of Adult Intensive Care, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Caroline den Hoed
- Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, Erasmus University Medical Center, Rotterdam, the Netherlands
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Incicco S, Angeli P, Piano S. Infectious Complications of Portal Hypertension. Clin Liver Dis 2024; 28:525-539. [PMID: 38945641 DOI: 10.1016/j.cld.2024.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Patients with cirrhosis and clinically significant portal hypertension are at high risk of developing bacterial infections (BIs) that are the most common trigger of acute decompensation and acute-on-chronic liver failure. Furthermore, after decompensation, the risk of developing BIs further increases in an ominous vicious circle. BIs may be subtle, and they should be ruled out in all patients at admission and in case of deterioration. Timely administration of adequate empirical antibiotics is the cornerstone of treatment. Herein, we reviewed current evidences about pathogenesis, clinical implications and management of BIs in patients with cirrhosis and portal hypertension.
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Affiliation(s)
- Simone Incicco
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy.
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Piano S, Bunchorntavakul C, Marciano S, Rajender Reddy K. Infections in cirrhosis. Lancet Gastroenterol Hepatol 2024; 9:745-757. [PMID: 38754453 DOI: 10.1016/s2468-1253(24)00078-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 03/04/2024] [Accepted: 03/04/2024] [Indexed: 05/18/2024]
Abstract
Cirrhosis is an immune dysfunction state, and as such, patients with cirrhosis are susceptible to bacterial, fungal, and viral infections. Because of infection, these patients have a propensity to develop multiorgan failure, which is associated with high mortality. Bacterial infections are the most prevalent type of infection in patients with cirrhosis, with the prevalence of bacterial infections in patients admitted for an acute decompensating event ranging from 24% to 29%. Together with invasive fungal infections, bacterial infections are the most severe. Multidrug-resistant organisms have been evolving at a rapid and alarming rate around the world, which presents enormous challenges. The development of effective measures for the prevention, early detection, and treatment of infections in patients with cirrhosis is challenging, given the rising incidence of infections in this patient population.
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Affiliation(s)
- Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy
| | | | - Sebastian Marciano
- Department of Clinical Investigation, Italian Hospital, Buenos Aires, Argentina
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA.
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35
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Fernández J, Blasi A, Hidalgo E, Karvellas CJ. Bridging the critically ill patient with acute to chronic liver failure to liver transplantation. Am J Transplant 2024; 24:1348-1361. [PMID: 38548058 DOI: 10.1016/j.ajt.2024.03.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 03/16/2024] [Accepted: 03/18/2024] [Indexed: 04/14/2024]
Abstract
Liver transplantation (LT) has emerged as an effective therapy for severe forms of acute-on-chronic liver failure (ACLF), an entity characterized by the development of multiorgan failure and high short-term mortality. The aim of critical care management of ACLF patients is to rapidly treat precipitating events and aggressively support failing organs to ensure that patients may successfully undergo LT or, less frequently, recover. Malnutrition and sarcopenia are frequently present, adversely impacting the prognosis of these patients. Management of critical care patients with ACLF is complex and requires the participation of different specialties. Once the patient is stabilized, a rapid evaluation for salvage LT should be performed because the time window for LT is often narrow. The development of sepsis and prolonged organ support may preclude LT or diminish its chances of success. The current review describes strategies to bridge severe ACLF patients to LT, highlights the minimal evaluation required for listing and the currently suggested contraindications to proceed with LT, and addresses different aspects of management during the perioperative and early posttransplant period.
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Affiliation(s)
- Javier Fernández
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERehd, Spain; EF Clif, EASL-CLIF Consortium, Barcelona, Spain.
| | - Annabel Blasi
- Anesthesiology Department, Hospital Clínic, and University of Barcelona, Spain
| | - Ernest Hidalgo
- Hepatolobiliary Surgery Department, Hospital Vall d'Hebron, Barcelona, Spain
| | - Constantine J Karvellas
- Department of Critical Care Medicine, University of Alberta, Edmonton, Canada; Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada
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Xu Z, Zhang X, Chen J, Shi Y, Ji S. Bacterial Infections in Acute-on-chronic Liver Failure: Epidemiology, Diagnosis, Pathogenesis, and Management. J Clin Transl Hepatol 2024; 12:667-676. [PMID: 38993512 PMCID: PMC11233977 DOI: 10.14218/jcth.2024.00137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 05/05/2024] [Accepted: 05/27/2024] [Indexed: 07/13/2024] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease, often leading to multi-organ failures and significant short-term mortalities. Bacterial infection is one of the most frequent triggers for ACLF and a common complication following its onset. The impact of bacterial infections on the clinical course and outcome of ACLF underscores their critical role in the pathogenesis of systemic inflammation and organ failures. In addition, the evolving epidemiology and increasing prevalence of multidrug-resistant bacteria in cirrhosis and ACLF highlight the importance of appropriate empirical antibiotic use, as well as accurate and prompt microbiological diagnosis. This review provided an update on recent advances in the epidemiology, diagnosis, pathogenesis, and management of bacterial infections in ACLF.
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Affiliation(s)
- Zhaoyu Xu
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Xiuding Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jiyang Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yu Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Shangwei Ji
- Department of Infectious Diseases, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
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37
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Liu J, MacNaughtan J, Kerbert AJC, Portlock T, Martínez Gonzalez J, Jin Y, Clasen F, Habtesion A, Ji H, Jin Q, Phillips A, De Chiara F, Ingavle G, Jimenez C, Zaccherini G, Husi K, Rodriguez Gandia MA, Cordero P, Soeda J, McConaghy L, Oben J, Church K, Li JV, Wu H, Jalan A, Gines P, Solà E, Eaton S, Morgan C, Kowalski M, Green D, Gander A, Edwards LA, Cox IJ, Cortez-Pinto H, Avery T, Wiest R, Durand F, Caraceni P, Elosua R, Vila J, Pavesi M, Arroyo V, Davies N, Mookerjee RP, Vargas V, Sandeman S, Mehta G, Shoaie S, Marchesi J, Albillos A, Andreola F, Jalan R. Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis. Gut 2024; 73:1183-1198. [PMID: 38621924 DOI: 10.1136/gutjnl-2023-330699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Accepted: 03/17/2024] [Indexed: 04/17/2024]
Abstract
OBJECTIVE Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed. RESULTS Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial. CONCLUSIONS This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation. TRIAL REGISTRATION NUMBER NCT03202498.
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Affiliation(s)
- Jinxia Liu
- Liver Failure Group, UCL Institute for Liver & Digestive Health, Division of Medicine, London, UK
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Jane MacNaughtan
- Liver Failure Group, UCL Institute for Liver & Digestive Health, Division of Medicine, London, UK
| | - Annarein J C Kerbert
- Liver Failure Group, UCL Institute for Liver & Digestive Health, Division of Medicine, London, UK
| | - Theo Portlock
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK
| | - Javier Martínez Gonzalez
- Hospital Ramón y Cajal, IRYCIS, CIBEREHD, Universidad de Alcalá, Madrid, Spain
- Liver Unit, Hospital Vall d'Hebron, Universitat Autónoma, CIBERehd, Barcelona, Spain
| | - Yi Jin
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK
| | - Frederick Clasen
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK
| | - Abeba Habtesion
- Liver Failure Group, UCL Institute for Liver & Digestive Health, Division of Medicine, London, UK
| | - Huoyan Ji
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Qin Jin
- Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China
| | - Alexandra Phillips
- Liver Failure Group, UCL Institute for Liver & Digestive Health, Division of Medicine, London, UK
| | - Francesco De Chiara
- Liver Failure Group, UCL Institute for Liver & Digestive Health, Division of Medicine, London, UK
| | - Ganesh Ingavle
- Centre for Regenerative Medicine and Devices, School of Applied Sciences, University of Brighton, Brighton, UK
- Symbiosis Centre for Stem Cell Research (SCSCR), Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University), Pune, India
| | - Cesar Jimenez
- Liver Unit, Hospital Vall d'Hebron, Universitat Autónoma, CIBERehd, Barcelona, Spain
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-related Diseases, University of Bologna Hospital of Bologna Sant'Orsola-Malpighi Polyclinic, Bologna, Italy
| | - Katherine Husi
- Department of Gastroenterology, Inselspital University Hospital Bern, Bern, Switzerland
| | | | - Paul Cordero
- Symbiosis Centre for Stem Cell Research (SCSCR), Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University), Pune, India
| | - Junpei Soeda
- Liver Failure Group, UCL Institute for Liver & Digestive Health, Division of Medicine, London, UK
| | - Lynda McConaghy
- Yaqrit Discovery Limited. The Elms Courtyard, Bromesberrow, Ledbury, UK
| | - Jude Oben
- Liver Failure Group, UCL Institute for Liver & Digestive Health, Division of Medicine, London, UK
| | - Karen Church
- Yaqrit Discovery Limited. The Elms Courtyard, Bromesberrow, Ledbury, UK
| | - Jia V Li
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Haifeng Wu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | | | - Pere Gines
- Liver Unit, Hospital Clinic of Barcelona, IDIBAPS, Faculty of Medicine and Health sciences, University of Barcelona, Barcelona, Spain
| | - Elsa Solà
- Liver Unit, Hospital Clinic of Barcelona, IDIBAPS, Faculty of Medicine and Health sciences, University of Barcelona, Barcelona, Spain
| | - Simon Eaton
- Institute of Child Health, University College London, London, UK
| | - Carrie Morgan
- Yaqrit Discovery Limited. The Elms Courtyard, Bromesberrow, Ledbury, UK
| | - Michal Kowalski
- Yaqrit Discovery Limited. The Elms Courtyard, Bromesberrow, Ledbury, UK
| | - Daniel Green
- Yaqrit Discovery Limited. The Elms Courtyard, Bromesberrow, Ledbury, UK
| | - Amir Gander
- Tissue Access for Patient Benefit, University College London, London, UK
| | - Lindsey A Edwards
- Centre for Host Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, Guy's Tower, Guy's Hospital, King's College London, London, UK
- Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - I Jane Cox
- The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK
- Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Helena Cortez-Pinto
- Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | | | - Reiner Wiest
- UVCM Gastroenterology, University Bern, Bern, Switzerland
| | - Francois Durand
- Hepatology and Liver Intensive Care, Hospital Beaujon, Clichy, University paris Cité, Paris, France
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | | | | | - Marco Pavesi
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
| | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
| | - Nathan Davies
- Liver Failure Group, UCL Institute for Liver & Digestive Health, Division of Medicine, London, UK
| | - Rajeshwar P Mookerjee
- Liver Failure Group, UCL Institute for Liver & Digestive Health, Division of Medicine, London, UK
| | - Victor Vargas
- Liver Unit, Hospital Vall d'Hebron, Universitat Autónoma, CIBERehd, Barcelona, Spain
| | - Susan Sandeman
- Centre for Regenerative Medicine and Devices, School of Applied Sciences, University of Brighton, Brighton, UK
| | - Gautam Mehta
- Liver Failure Group, UCL Institute for Liver & Digestive Health, Division of Medicine, London, UK
| | - Saeed Shoaie
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK
| | - Julian Marchesi
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, St Mary's Hospital, Imperial College London, London, UK
| | - Agustín Albillos
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramon y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Fausto Andreola
- Liver Failure Group, UCL Institute for Liver & Digestive Health, Division of Medicine, London, UK
| | - Rajiv Jalan
- Liver Failure Group, UCL Institute for Liver & Digestive Health, Division of Medicine, London, UK
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
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Karvellas CJ, Bajaj JS, Kamath PS, Napolitano L, O'Leary JG, Solà E, Subramanian R, Wong F, Asrani SK. AASLD Practice Guidance on Acute-on-chronic liver failure and the management of critically ill patients with cirrhosis. Hepatology 2024; 79:1463-1502. [PMID: 37939273 DOI: 10.1097/hep.0000000000000671] [Citation(s) in RCA: 32] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 11/01/2023] [Indexed: 11/10/2023]
Affiliation(s)
- Constantine J Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, Edmonton, Canada
| | - Jasmohan S Bajaj
- Virginia Commonwealth University, Central Virginia Veterans Healthcare System, Richmond, Virginia, USA
| | - Patrick S Kamath
- Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | | | - Jacqueline G O'Leary
- Department of Medicine, Dallas Veterans Medical Center, University of Texas Southwestern Medical Center Dallas, Texas, USA
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA
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Idalsoaga F, Díaz LA, Fuentes-López E, Ayares G, Valenzuela F, Meza V, Manzur F, Sotomayor J, Rodriguez H, Chianale F, Villagrán S, Schalper M, Villafranca P, Veliz MJ, Uribe P, Puebla M, Bustamante P, Aguirre H, Busquets J, Roblero JP, Mezzano G, Hernandez-Tejero M, Arrese M, Arab JP. Active alcohol consumption is associated with acute-on-chronic liver failure in Hispanic patients. GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:562-573. [PMID: 37778718 DOI: 10.1016/j.gastrohep.2023.09.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 09/16/2023] [Accepted: 09/18/2023] [Indexed: 10/03/2023]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a severe clinical entity associated with elevated short-term mortality. We aimed to characterize patients with decompensated cirrhosis according to presence of ACLF, their association with active alcohol intake, and long-term survival in Latin America. METHODS Retrospective cohort study of decompensated cirrhotic in three Chilean university centers (2017-2019). ACLF was diagnosed according EASL-CLIF criteria. We assessed survival using competing-risk and time-to-event analyses. We evaluated the time to death using accelerated failure time (AFT) models. RESULTS We included 320 patients, median age of 65.3±11.7 years old, and 48.4% were women. 92 (28.7%) patients met ACLF criteria (ACLF-1: 29.3%, ACLF-2: 27.1%, and ACLF-3: 43.4%). The most common precipitants were infections (39.1%), and the leading organ failure was kidney (59.8%). Active alcohol consumption was frequent (27.7%), even in patients with a prior diagnosis of non-alcoholic fatty liver disease (NAFLD) (16.2%). Ninety-two (28.7%) patients had ACLF (ACLF-1: 8.4%, ACLF-2: 7.8%, and ACLF-3: 12.5%). ACLF patients had a higher MELD-Na score at admission (27 [22-31] versus 16 [12-21], p<0.0001), a higher frequency of alcohol-associated liver disease (36.7% versus 24.9%, p=0.039), and a more frequent active alcohol intake (37.2% versus 23.8%, p=0.019). In a multivariate model, ACLF was associated with higher mortality (subdistribution hazard ratio 1.735, 95%CI: 1.153-2.609; p<0.008). In the AFT models, the presence of ACLF during hospitalization correlated with a shorter time to death: ACLF-1 shortens the time to death by 4.7 times (time ratio [TR] 0.214, 95%CI: 0.075-0.615; p<0.004), ACLF-2 by 4.4 times (TR 0.224, 95%CI: 0.070-0.713; p<0.011), and ACLF-3 by 37 times (TR 0.027, 95%CI: 0.006-0.129; p<0.001). CONCLUSIONS Patients with decompensated cirrhosis and ACLF exhibited a high frequency ofactive alcohol consumption. Patients with ACLF showed higher mortality and shorter time todeath than those without ACLF.
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Affiliation(s)
- Francisco Idalsoaga
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis Antonio Díaz
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Eduardo Fuentes-López
- Departamento de Ciencias de la Salud, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Gustavo Ayares
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco Valenzuela
- Departamento de Medicina Interna, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Victor Meza
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Franco Manzur
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Joaquín Sotomayor
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Hernán Rodriguez
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Franco Chianale
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Sofía Villagrán
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | | | | | - Paz Uribe
- Escuela de Medicina, Universidad de Chile, Santiago, Chile
| | | | - Pablo Bustamante
- Departamento de Medicina, Sección Gastroenterología, Hospital Clínico Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Herman Aguirre
- Departamento de Medicina, Sección Gastroenterología, Hospital Clínico Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Javiera Busquets
- Departamento de Medicina, Sección Gastroenterología, Hospital Clínico Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Juan Pablo Roblero
- Departamento de Medicina, Sección Gastroenterología, Hospital Clínico Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Gabriel Mezzano
- Sección de Gastroenterología, Hospital del Salvador, Santiago, Chile; Centro de Enfermedades Digestivas, Universidad de los Andes, Santiago, Chile
| | - Maria Hernandez-Tejero
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Marco Arrese
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada.
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Zhang G, Pan J, Dong X, Li X, Song Z, Liu Y, Liu X, Li Y, Li Q. Construction of atom co-sharing Bi/Bi 4O 5Br 2 nanosheet heterojunction for plasmonic-enhanced visible-light-driven photocatalytic antibacterial activity. Colloids Surf B Biointerfaces 2024; 238:113923. [PMID: 38692173 DOI: 10.1016/j.colsurfb.2024.113923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 04/04/2024] [Accepted: 04/17/2024] [Indexed: 05/03/2024]
Abstract
The rapid advancement of photodynamic therapy (PDT) antibacterial materials has led to promising alternatives to antibiotics for treating bacterial infections. However, antibacterial drugs have poor light absorption and utilization rates, which limits their practical application. Constructing two-dimensional (2D) heterojunctions from materials with matching photophysical properties has emerged as a highly effective strategy for achieving high-efficiency photo-antibacterial performance. Here, we designed and prepared an atom co-sharing Bi/Bi4O5Br2 nanosheet heterojunction by a simple in situ reduction. This heterojunction material combines outstanding biocompatibility with excellent bactericidal efficiency, which exceeded 90 % against Escherichia coli (a Gram-negative bacterium) and Staphylococcus aureus (a Gram-positive bacterium) under visible light irradiation, around nine-fold higher than that with pure Bi4O5Br2 nanosheets. The results suggest that localized surface plasmon resonance (LSPR) of shared Bi atoms on the Bi4O5Br2 nanosheets promotes light utilization and the separation and transfer of photo-generated charges, thus producing more abundant reactive oxygen species (ROS), which can partake in the PDT antibacterial effect. Our study underscores the potential utility of LSPR-enhanced Bi-based nanosheet heterojunctions for safe and efficient PDT to combat bacterial infections.
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Affiliation(s)
- Guixue Zhang
- Institute of Pharmacy, Dali University, Dali, Yunnan 671000, China
| | - Jie Pan
- Department of Stomatology, The First People's Hospital of Yunnan Province, Kunming 650032, China
| | - Xiaoyi Dong
- School of Materials Science and Engineering, Kunming University of Science and Technology, Kunming 650093, China
| | - Xue Li
- Department of Pharmacy, The First People's Hospital of Yunnan Province, Kunming 650032, China
| | - Zhiguo Song
- School of Materials Science and Engineering, Kunming University of Science and Technology, Kunming 650093, China
| | - Yan Liu
- Institute of Pharmacy, Dali University, Dali, Yunnan 671000, China
| | - Xiaomeng Liu
- School of Materials Science and Engineering, Kunming University of Science and Technology, Kunming 650093, China
| | - Yongjin Li
- School of Materials Science and Engineering, Kunming University of Science and Technology, Kunming 650093, China.
| | - Qiyan Li
- Department of Stomatology, The First People's Hospital of Yunnan Province, Kunming 650032, China.
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Kosuta I, Premkumar M, Reddy KR. Review article: Evaluation and care of the critically ill patient with cirrhosis. Aliment Pharmacol Ther 2024; 59:1489-1509. [PMID: 38693712 DOI: 10.1111/apt.18016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 03/21/2024] [Accepted: 04/12/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND The increase in prevalence of liver disease globally will lead to a substantial incremental burden on intensive care requirements. While liver transplantation offers a potential life-saving intervention, not all patients are eligible due to limitations such as organ availability, resource constraints, ongoing sepsis or multiple organ failures. Consequently, the focus of critical care of patients with advanced and decompensated cirrhosis turns to liver-centric intensive care protocols, to mitigate the high mortality in such patients. AIM Provide an updated and comprehensive understanding of cirrhosis management in critical care, and which includes emergency care, secondary organ failure management (mechanical ventilation, renal replacement therapy, haemodynamic support and intensive care nutrition), use of innovative liver support systems, infection control, liver transplantation and palliative and end-of life care. METHODS We conducted a structured bibliographic search on PubMed, sourcing articles published up to 31 March 2024, to cover topics addressed. We considered data from observational studies, recommendations of society guidelines, systematic reviews, and meta-analyses, randomised controlled trials, and incorporated our clinical expertise in liver critical care. RESULTS Critical care management of the patient with cirrhosis has evolved over time while mortality remains high despite aggressive management with liver transplantation serving as a crucial but not universally available resource. CONCLUSIONS Implementation of organ support therapies, intensive care protocols, nutrition, palliative care and end-of-life discussions and decisions are an integral part of critical care of the patient with cirrhosis. A multi-disciplinary approach towards critical care management is likely to yield better outcomes.
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Affiliation(s)
- Iva Kosuta
- Department of Intensive Care Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Madhumita Premkumar
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Trad N, Mohamed G, Bizid S, Abdallah HB, Bouali R, Abdelli MN. Clinical impact of multidrug-resistant bacterial infections in patients with cirrhosis. Future Sci OA 2024; 10:FSO945. [PMID: 38813115 PMCID: PMC11131343 DOI: 10.2144/fsoa-2023-0160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 11/17/2023] [Indexed: 05/31/2024] Open
Abstract
Aim: Recently, the emergency of multidrug-resistant organisms (MDRO) has complicated the management of bacterial infections (BI) in cirrhosis. We aimed to assess their clinical impact on patients with decompensated cirrhosis. Methods: A retrospective study included consecutive cirrhotic patients hospitalized for acute decompensation (AD) between January 2010 and December 2019. Results: A total of 518 AD admissions in 219 patients were included, with 260 BI episodes (50.2%). MDRO prevalence was 38.2% of the total isolates. Recent antibiotic use (OR = 4.91), nosocomial infection (OR = 2.95), and healthcare-associated infection (OR = 3.45) were their main risk factors. MDROs were associated with empiric treatment failure (OR = 23.42), a higher prevalence of sepsis (OR = 4.93), ACLF (OR = 3.42) and mortality. Conclusion: The clinical impact of MDROs was pejorative, with an increased risk of empiric treatment failure, organ failure and death.
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Affiliation(s)
- Nouha Trad
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Ghanem Mohamed
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Sondes Bizid
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Hatem Ben Abdallah
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Riadh Bouali
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Mohamed Nabil Abdelli
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
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Maiwall R, Piano S, Singh V, Caraceni P, Alessandria C, Fernandez J, Soares EC, Kim DJ, Kim SE, Marino M, Vorobioff J, Ribeiro Barea RDC, Merli M, Elkrief L, Vargas V, Krag A, Singh SP, Lesmana LA, Toledo C, Marciano S, Verhelst X, Wong F, Intagliata N, Rabinowich L, Colombato L, Kim SG, Gerbes A, Durand F, Roblero JP, Bhamidimarri KR, Maevskaya M, Fassio E, Kim HS, Hwang JS, Gines P, Bruns T, Gadano A, Angeli P, Sarin SK. Determinants of clinical response to empirical antibiotic treatment in patients with cirrhosis and bacterial and fungal infections-Results from the ICA "Global Study" (EABCIR-Global Study). Hepatology 2024; 79:1019-1032. [PMID: 38047909 DOI: 10.1097/hep.0000000000000653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 06/30/2023] [Indexed: 12/05/2023]
Abstract
BACKGROUND The administration of an appropriate empirical antibiotic treatment is essential in cirrhosis and severe bacterial infections. We aimed to investigate the predictors of clinical response of empirical antibiotic treatment in a prospective cohort of patients with cirrhosis and bacterial and fungal infections included in the International Club of Ascites "Global Study." METHODS Patients hospitalized with cirrhosis and bacterial/fungal infection were prospectively enrolled at 46 centers. Clinical response to antibiotic treatment was defined according to changes in markers of infection/inflammation, vital signs, improvement of organ failure, and results of cultures. RESULTS From October 2015 to September 2016, 1302 patients were included at 46 centers. A clinical response was achieved in only 61% of cases. Independent predictors of lack of clinical response to empirical treatment were C-reactive protein (OR = 1.16; 95% CI = 1.02-1.31), blood leukocyte count (OR = 1.39;95% CI = 1.09-1.77), serum albumin (OR = 0.70; 95% CI = 0.55-0.88), nosocomial infections (OR = 1.96; 95% CI = 1.20-2.38), pneumonia (OR = 1.75; 95% CI = 1.22-2.53), and ineffective treatment according to antibiotic susceptibility test (OR = 5.32; 95% CI = 3.47-8.57). Patients with a lack of clinical response to first-line antibiotic treatment had a significantly lower resolution rate of infections (55% vs. 96%; p < 0.001), a higher incidence of second infections (29% vs. 15%; p < 0.001), shock (35% vs. 7%; p < 0.001) and new organ failures (52% vs. 19 %; p < 0.001) than responders. Clinical response to empirical treatment was an independent predictor of 28-day survival ( subdistribution = 0.20; 95% CI = 0.14-0.27). CONCLUSIONS Four out of 10 patients with cirrhosis do not respond to the first-line antibiotic therapy, leading to lower resolution of infections and higher mortality. Broader-spectrum antibiotics and strategies targeting systemic inflammation may improve prognosis in patients with a high degree of inflammation, low serum albumin levels, and severe liver impairment.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine, DIMED, University of Padova, Padova, Italy
| | - Virendra Singh
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Turin, Turin, Italy
| | - Javier Fernandez
- Liver ICU, Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain
- Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain
- European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain
| | - Elza Cotrim Soares
- Gastroenterology Division, Medicine Department, Faculty of Medical Sciences, University of Campinas (UNICAMP). Campinas, São Paulo, Brazil
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Sung Eun Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hallym Sacred Heart Hospital, College of Medicine, Hallym University, Anyang city, Republic of Korea
| | - Monica Marino
- Liver Unit, Hospital Dr. Carlos B. Udaondo, Buenos Aires, Argentina
| | | | | | - Manuela Merli
- Gastroenterology and Hepatology Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Laure Elkrief
- Service de Transplantation, Service d'Hépato-gastroentérologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland
| | - Victor Vargas
- Liver Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, CIBERehd, Barcelona. Spain
| | - Aleksander Krag
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | | | | | - Claudio Toledo
- Gastroenterology Unit, Hospital Valdivia, Universidad Austral de Chile, Valdivia, Chile
| | - Sebastian Marciano
- Liver Unit and Department of Research, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Xavier Verhelst
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Florence Wong
- Division of Gastroenterology, Department of Medicine, University of Toronto, Ontario, Canada
| | - Nicolas Intagliata
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Liane Rabinowich
- Liver Unit, Department of Gastroenterology, Tel-Aviv Medical Center and Tel-Aviv University, Tel-Aviv, Israel
| | - Luis Colombato
- Gastroenterology Department, Buenos Aires British Hospital, Argentine Catholic University (UCA), Buenos Aires, Argentina
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea
| | - Alexander Gerbes
- Department of Medicine II, Liver Centre Munich, University Hospital, LMU Munich, Germany
| | - Francois Durand
- Hepatology & Liver Intensive Care, Hospital Beaujon, Clichy, University Paris Diderot, Paris, France
| | - Juan Pablo Roblero
- Departamento de Medicina, Universidad de Chile Campus Centro, Hospital Clínico San Borja Arriarán, Santiago, Chile
| | | | | | - Eduardo Fassio
- Liver Unit, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Hyoung Su Kim
- Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea
| | - Jae Seok Hwang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Pere Gines
- Liver ICU, Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain
- Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain
| | - Tony Bruns
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Adrian Gadano
- Liver Unit and Department of Research, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine, DIMED, University of Padova, Padova, Italy
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Liu Y, Xu Y, Wen Q. Carbon dots for staining bacterial dead cells and distinguishing dead/alive bacteria. Anal Biochem 2024; 687:115432. [PMID: 38113980 DOI: 10.1016/j.ab.2023.115432] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 12/06/2023] [Accepted: 12/15/2023] [Indexed: 12/21/2023]
Abstract
The small molecular dyes such as propidium iodide (PI) always suffer from photo-bleaching and potential toxicity. To tackle the problems, a type of nontoxic carbon dots (CDs) was obtained for dead/alive bacterial distinguishing. This kind of carbon dots has an average size of 1.91 nm and owns carboxyl groups, emerging as excellent candidates for imaging bacterial cells. The negative charges of carboxyl groups lead their avoidance of alive cells while their small size facilitates penetration of dead cells. This kind of nontoxic CDs has effectively differentiated between and alive ones, presenting a highly promising green dye comparing with traditional small molecular dyes.
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Affiliation(s)
- Yuting Liu
- Institute of Biomedical Engineering, College of Life Science, Qingdao University, Qingdao, 266071, China
| | - Yuanhong Xu
- Institute of Biomedical Engineering, College of Life Science, Qingdao University, Qingdao, 266071, China
| | - Qin Wen
- Institute of Biomedical Engineering, College of Life Science, Qingdao University, Qingdao, 266071, China.
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45
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Mücke MM, Hernández-Tejero M, Gu W, Kuhn M, Janz M, Keller MI, Fullam A, Altepeter L, Mücke VT, Finkelmeier F, Schwarzkopf KM, Cremonese C, Hunyady PM, Heilani MW, Uschner FE, Schierwagen R, Brol MJ, Fischer J, Klein S, Peiffer KH, Hogardt M, Shoaie S, Coenraad MJ, Bojunga J, Arroyo V, Zeuzem S, Kempf VAJ, Welsch C, Laleman W, Bork P, Fernandez J, Trebicka J. Terlipressin therapy is associated with increased risk of colonisation with multidrug-resistant bacteria in patients with decompensated cirrhosis. Aliment Pharmacol Ther 2024; 59:877-888. [PMID: 38414095 DOI: 10.1111/apt.17899] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 12/20/2023] [Accepted: 01/28/2024] [Indexed: 02/29/2024]
Abstract
BACKGROUND Patients with cirrhosis are susceptible to develop bacterial infections that trigger acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Infections with multidrug-resistant organisms (MDRO) are associated with deleterious outcome. MDRO colonisation frequently proceeds MDRO infections and antibiotic therapy has been associated with MDRO colonisation. AIM The aim of the study was to assess the influence of non-antibiotic medication contributing to MDRO colonisation. METHODS Three hundred twenty-four patients with AD and ACLF admitted to the ICU of Frankfurt University Hospital with MDRO screening were included. Regression models were performed to identify drugs associated with MDRO colonisation. Another cohort (n = 129) from Barcelona was included to validate. A third multi-centre cohort (n = 203) with metagenomic sequencing data of stool was included to detect antibiotic resistance genes. RESULTS A total of 97 patients (30%) were identified to have MDRO colonisation and 35 of them (11%) developed MDRO infection. Patients with MDRO colonisation had significantly higher risk of MDRO infection than those without (p = 0.0098). Apart from antibiotic therapy (odds ratio (OR) 2.91, 95%-confidence interval (CI) 1.82-4.93, p < 0.0001), terlipressin therapy in the previous 14 days was the only independent covariate associated with MDRO colonisation in both cohorts, the overall (OR 9.47, 95%-CI 2.96-30.23, p < 0.0001) and after propensity score matching (OR 5.30, 95%-CI 1.22-23.03, p = 0.011). In the second cohort, prior terlipressin therapy was a risk factor for MDRO colonisation (OR 2.49, 95% CI 0.911-6.823, p = 0.075) and associated with risk of MDRO infection during follow-up (p = 0.017). The validation cohort demonstrated that antibiotic inactivation genes were significantly associated with terlipressin administration (p = 0.001). CONCLUSIONS Our study reports an increased risk of MDRO colonisation in patients with AD or ACLF, who recently received terlipressin therapy, while other commonly prescribed non-antibiotic co-medications had negligible influence. Future prospective trials are needed to confirm these results.
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Affiliation(s)
- Marcus M Mücke
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
| | - María Hernández-Tejero
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERehd, Barcelona, Spain
| | - Wenyi Gu
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
- Department of Internal Medicine B, Muenster University Clinic, University of Münster, Münster, Germany
| | - Michael Kuhn
- Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Malte Janz
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
| | - Marisa I Keller
- Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Anthony Fullam
- Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Laura Altepeter
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
| | - Victoria T Mücke
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
| | - Fabian Finkelmeier
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
| | - Katharina M Schwarzkopf
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
| | - Carla Cremonese
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
| | - Peter-Merton Hunyady
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
| | - Myriam W Heilani
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
| | - Frank Erhard Uschner
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
- Department of Internal Medicine B, Muenster University Clinic, University of Münster, Münster, Germany
| | - Robert Schierwagen
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
- Department of Internal Medicine B, Muenster University Clinic, University of Münster, Münster, Germany
| | - Maximilian J Brol
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
- Department of Internal Medicine B, Muenster University Clinic, University of Münster, Münster, Germany
| | - Julia Fischer
- Department of Internal Medicine B, Muenster University Clinic, University of Münster, Münster, Germany
| | - Sabine Klein
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
- Department of Internal Medicine B, Muenster University Clinic, University of Münster, Münster, Germany
| | - Kai-Henrik Peiffer
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
- Department of Internal Medicine B, Muenster University Clinic, University of Münster, Münster, Germany
| | - Michael Hogardt
- Institute of Medical Microbiology and Infection Control, Goethe University Frankfurt, Germany University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany
- University Center of Competence for Infection Control, State of Hesse, Germany
| | - Saeed Shoaie
- Centre for Host-Microbiome Interactions, Dental Institute, King's College London, London, UK
- Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden
| | - Minneke J Coenraad
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Jörg Bojunga
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
| | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Stefan Zeuzem
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
| | - Volkhard A J Kempf
- Institute of Medical Microbiology and Infection Control, Goethe University Frankfurt, Germany University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt, Germany
- University Center of Competence for Infection Control, State of Hesse, Germany
| | - Christoph Welsch
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
| | - Wim Laleman
- Department of Internal Medicine B, Muenster University Clinic, University of Münster, Münster, Germany
- Department of Gastroenterology & Hepatology, Section of Liver and Biliopancreatic Disorders, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Peer Bork
- Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Javier Fernandez
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERehd, Barcelona, Spain
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Jonel Trebicka
- Medical Clinic 1, University Hospital, Goethe-University Frankfurt, Frankfurt am Main, Germany
- Department of Internal Medicine B, Muenster University Clinic, University of Münster, Münster, Germany
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
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Dalbeni A, Cattazzo F, De Marco L, Bevilacqua M, Zoncapè M, Lombardi R, Stupia R, Mantovani A, Sacerdoti D. Bacterial infections as a risk factor for non-neoplastic portal vein thrombosis development in cirrhotic patients. Dig Liver Dis 2024; 56:477-483. [PMID: 37778894 DOI: 10.1016/j.dld.2023.09.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 08/23/2023] [Accepted: 09/07/2023] [Indexed: 10/03/2023]
Abstract
BACKGROUND Portal vein thrombosis (PVT) and sepsis are common complications in patients with liver cirrhosis. Factors that lead to PVT are not completely understood. This study aimed to investigate the possible association between bacterial infections and the development of PVT in cirrhotic patients. PATIENTS AND METHODS 202 consecutive cirrhotic patients without previous infections, followed at the Liver Unit in Verona Hospital, were enrolled from 2017 to 2021 (median follow-up 3.3 years). During the follow-up period, PVT was diagnosed by ultrasound, CT and/or MRI, and episodes of bacterial infections requiring hospitalization were recorded. Malignant PVT was an exclusion criterion. RESULTS Of the 202 patients enrolled (68.3 % males, mean age 63.8 ± 11 years), 22 (10.8 %) developed PVT during the follow up. In patients with PVT, the prevalence of previous bacterial infections was significantly higher compared to patients without PVT (63.6% vs 31.1 %; p = 0.02). Cox regression analysis revealed that a history of bacterial infection was the only variable that demonstrated a significant association with the risk of de novo PVT occurrence (HR 4.04, 95 % CI: 1.68-9.65). CONCLUSION in patients with liver cirrhosis bacterial infections are a predisposing factor for the following development of PVT. Further studies are needed to confirm this evidence.
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Affiliation(s)
- Andrea Dalbeni
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy.
| | - Filippo Cattazzo
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy
| | - Leonardo De Marco
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy
| | - Michele Bevilacqua
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy
| | - Mirko Zoncapè
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy
| | - Rosa Lombardi
- Department of Pathophysiology and Transplantation, Unit of Metabolic and Internal Medicine, University of Milan, Italy
| | - Roberta Stupia
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy
| | - Anna Mantovani
- Division of General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy; Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy.
| | - David Sacerdoti
- Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, University of Verona, Verona, Italy
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Xie H, Wang B, Hong Y. A deep learning approach for acute liver failure prediction with combined fully connected and convolutional neural networks. Technol Health Care 2024; 32:555-564. [PMID: 38759076 PMCID: PMC11191538 DOI: 10.3233/thc-248048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2024]
Abstract
BACKGROUND Acute Liver Failure (ALF) is a critical medical condition with rapid development, often caused by viral infections, hepatotoxic drug abuse, or other severe liver diseases. Timely and accurate prediction of ALF occurrence is clinically crucial. However, predicting ALF poses challenges due to the diverse physiological differences among patients and the dynamic nature of the disease. OBJECTIVE This study introduces a deep learning approach that combines fully connected and convolutional neural networks for effective ALF prediction. The goal is to overcome limitations of traditional machine learning methods and enhance predictive model performance and generalization. METHODS The proposed model integrates a fully connected neural network for handling basic patient features and a convolutional neural network dedicated to capturing temporal patterns in patient data. The combination allows automatic learning of complex patterns and abstract features present in highly dynamic medical data associated with ALF. RESULTS The model's effectiveness is demonstrated through comprehensive experiments and performance evaluations. It outperforms traditional machine learning methods, achieving 94.8% accuracy and superior generalization capabilities. CONCLUSIONS The study highlights the potential of deep learning in ALF prediction, emphasizing the importance of considering individualized medical factors. Future research should focus on improving model robustness, addressing imbalanced data, and further exploring personalized features for enhanced predictive accuracy in real-world clinical scenarios.
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Affiliation(s)
- Hefu Xie
- Xiamen University School of Information Science and Technology, Xiamen University Xiang’an Campus, Xiamen, Fujian, China
| | - Bingbing Wang
- Xiamen University School of Information Science and Technology, Xiamen University Xiang’an Campus, Xiamen, Fujian, China
- Department of Thoracic Surgery, The First Hospital Affiliated of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Yuanzhen Hong
- Hepatology Department’s Three Wards, Xiamen Hospital, Beijing University of Chinese Medicine, Xiamen, Fujian, China
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48
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Sharma M, Alla M, Kulkarni A, Nagaraja Rao P, Nageshwar Reddy D. Managing a Prospective Liver Transplant Recipient on the Waiting List. J Clin Exp Hepatol 2024; 14:101203. [PMID: 38076359 PMCID: PMC10701136 DOI: 10.1016/j.jceh.2023.06.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 06/09/2023] [Indexed: 01/05/2025] Open
Abstract
The management of a patient in the peri-transplantation period is highly challenging, and it is even more difficult while the patient is on the transplantation waitlist. Keeping the patient alive during this period involves managing the complications of liver disease and preventing the disease's progression. Based on the pre-transplantation etiology and type of liver failure, there is a difference in the management protocol. The current review is divided into different sections, which include: the management of underlying cirrhosis and complications of portal hypertension, treatment and identification of infections, portal vein thrombosis management, and particular emphasis on the management of patients of hepatocellular carcinoma and acute liver failure in the transplantation waitlist. The review highlights special concerns in the management of patients in the Asian subcontinent also. The review also addresses the issue of delisting from the transplant waitlist to see that futility does not overtake the utility of organs. The treatment modalities are primarily expressed in tabular format for quick reference. The following review integrates the vast issues in this period concisely so that the management during this crucial period is taken care of in the best possible way.
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Affiliation(s)
- Mithun Sharma
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Manasa Alla
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Anand Kulkarni
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Padaki Nagaraja Rao
- Department of Hepatology and Liver Transplantation, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Duvvur Nageshwar Reddy
- Department of Gastroenterology, Asian Institute of Gastroenterology Hospitals, Hyderabad, India
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49
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Yu X, Liu X, Tan W, Wang X, Zheng X, Huang Y, Chen J, Li B, Meng Z, Gao Y, Qian Z, Liu F, Lu X, Shang J, Yan H, Zheng Y, Zhang W, Yin S, Gu W, Deng G, Xiang X, Zhou Y, Hou Y, Zhang Q, Xiong S, Liu J, Chen R, Long L, Jiang X, Luo S, Chen Y, Jiang C, Zhao J, Ji L, Mei X, Li J, Li T, Zheng R, Zhou X, Ren H, Sheng J, Li H, Shi Y. The clinical courses of HBV-related acute-on-chronic liver failure and a multi-state model to predict disease evolution. Hepatol Commun 2024; 8:e0354. [PMID: 38180960 PMCID: PMC10781128 DOI: 10.1097/hc9.0000000000000354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 10/30/2023] [Indexed: 01/07/2024] Open
Abstract
BACKGROUND AND AIMS Acute-on-chronic liver failure (ACLF) is a highly dynamic syndrome. The objective of this study was to delineate the clinical course of patients with HBV-ACLF and to develop a model to estimate the temporal evolution of disease severity. METHODS We enrolled eligible patients from 2 large, multicenter prospective cohorts. The ACLF grade, organ failures, and outcomes were assessed at multiple time points (days 1/4/7/14/21/28). Probabilities for ACLF transitions between these disease states and to death within 28 days were calculated using a multi-state model that used baseline information and updated ACLF status. The model was validated in independent patients. RESULTS Among all the 445 patients with HBV-ACLF, 76 represented disease progression, 195 had a stable or fluctuating course, 8 with improvement, and the remaining 166 with resolution within 28-day follow-up. New coagulation (63.64%) or renal failure (45.45%) was frequently observed during early progression. Patients with disease progression had a higher incidence of new episodes of ascites [10 (13.16%) vs. 22 (5.96%), p = 0.027] and HE [13(17.11%) vs. 21 (5.69%), p = 0.001], and a significant increase in white blood cell count. The multi-state model represented dynamic areas under the receiver operating characteristic curves ranging from 0.71 to 0.84 for predicting all ACLF states and death at 4, 7, 14, 21, and 28 days post-enrollment and from 0.73 to 0.94 for predicting death alone, performing better than traditional prognostic scores. CONCLUSIONS HBV-ACLF is a highly dynamic syndrome with reversibility. The multi-state model is a tool to estimate the temporal evolution of disease severity, which may inform clinical decisions on treatment.
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Affiliation(s)
- Xia Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Xinxin Liu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Wenting Tan
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiaobo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xin Zheng
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yan Huang
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Jinjun Chen
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Beiling Li
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhongji Meng
- Department of Infectious Disease, Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Yanhang Gao
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Zhiping Qian
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Feng Liu
- Tianjin Institute of Hepatology, Nankai University Second People’s Hospital, Tianjin, China
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Xiaobo Lu
- Infectious Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Huadong Yan
- Department of Infectious Disease, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Shulan International Medical College, Hangzhou, China
| | - Yubao Zheng
- Deparment of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Weituo Zhang
- Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shan Yin
- Department of Gastroenterology, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China
| | - Wenyi Gu
- Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Gastroenterology, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Guohong Deng
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiaomei Xiang
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yi Zhou
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yixin Hou
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Qun Zhang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shue Xiong
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Liu
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ruochan Chen
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Liyuan Long
- Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, China
| | - Xiuhua Jiang
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Sen Luo
- Department of Infectious Disease, Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Yuanyuan Chen
- Department of Infectious Disease, Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Chang Jiang
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Jinming Zhao
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Liujuan Ji
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Xue Mei
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Jing Li
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Tao Li
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Rongjiong Zheng
- Infectious Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Xinyi Zhou
- Infectious Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Haotang Ren
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jifang Sheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Hai Li
- Department of Gastroenterology, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology and Hepatology, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China
| | - Yu Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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50
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Odenwald MA, Lin H, Lehmann C, Dylla NP, Cole CG, Mostad JD, Pappas TE, Ramaswamy R, Moran A, Hutchison AL, Stutz MR, Dela Cruz M, Adler E, Boissiere J, Khalid M, Cantoral J, Haro F, Oliveira RA, Waligurski E, Cotter TG, Light SH, Beavis KG, Sundararajan A, Sidebottom AM, Reddy KG, Paul S, Pillai A, Te HS, Rinella ME, Charlton MR, Pamer EG, Aronsohn AI. Bifidobacteria metabolize lactulose to optimize gut metabolites and prevent systemic infection in patients with liver disease. Nat Microbiol 2023; 8:2033-2049. [PMID: 37845315 PMCID: PMC11059310 DOI: 10.1038/s41564-023-01493-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 09/08/2023] [Indexed: 10/18/2023]
Abstract
Progression of chronic liver disease is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections and lactulose treatment for hepatic encephalopathy, can impact gut microbiome composition and metabolite production. Here, using shotgun metagenomic sequencing and targeted metabolomic analyses on 847 faecal samples from 262 patients with acute or chronic liver disease, we demonstrate that patients hospitalized for liver disease have reduced microbiome diversity and a paucity of bioactive metabolites, including short-chain fatty acids and bile acid derivatives, that impact immune defences and epithelial barrier integrity. We find that patients treated with the orally administered but non-absorbable disaccharide lactulose have increased densities of intestinal bifidobacteria and reduced incidence of systemic infections and mortality. Bifidobacteria metabolize lactulose, produce high concentrations of acetate and acidify the gut lumen in humans and mice, which, in combination, can reduce the growth of antibiotic-resistant bacteria such as vancomycin-resistant Enterococcus faecium in vitro. Our studies suggest that lactulose and bifidobacteria serve as a synbiotic to reduce rates of infection in patients with severe liver disease.
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Affiliation(s)
- Matthew A Odenwald
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA.
| | - Huaiying Lin
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA
| | - Christopher Lehmann
- Department of Medicine, Section of Infectious Diseases and Global Health, University of Chicago, Chicago, IL, USA
| | - Nicholas P Dylla
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA
| | - Cody G Cole
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA
- Department of Microbiology, University of Chicago, Chicago, IL, USA
| | - Jake D Mostad
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA
| | - Téa E Pappas
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA
| | | | - Angelica Moran
- Department of Pathology, University of Chicago, Chicago, IL, USA
| | - Alan L Hutchison
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA
| | - Matthew R Stutz
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Cook County Health, Chicago, IL, USA
| | - Mark Dela Cruz
- Section of Cardiology, Department of Medicine, University of Chicago, Chicago, IL, USA
| | - Emerald Adler
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA
| | - Jaye Boissiere
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA
| | - Maryam Khalid
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA
| | - Jackelyn Cantoral
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA
| | - Fidel Haro
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA
| | - Rita A Oliveira
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA
| | - Emily Waligurski
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA
- Department of Microbiology, University of Chicago, Chicago, IL, USA
| | - Thomas G Cotter
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, TX, USA
| | - Samuel H Light
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA
| | | | | | | | - K Gautham Reddy
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA
| | - Sonali Paul
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA
| | - Anjana Pillai
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA
| | - Helen S Te
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA
| | - Mary E Rinella
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA
| | - Michael R Charlton
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA
| | - Eric G Pamer
- Duchossois Family Institute, University of Chicago, Chicago, IL, USA.
- Department of Medicine, Section of Infectious Diseases and Global Health, University of Chicago, Chicago, IL, USA.
- Department of Microbiology, University of Chicago, Chicago, IL, USA.
| | - Andrew I Aronsohn
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, IL, USA
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