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Saha R, Sharma S, Mondal A, Sati HC, Khan MA, Mahajan S, Datta S, Shalimar, Acharya P. Evaluation of Acute Kidney Injury (AKI) Biomarkers FABP1, NGAL, Cystatin C and IL-18 in an Indian Cohort of Hospitalized Acute-on-chronic Liver Failure (ACLF) Patients. J Clin Exp Hepatol 2025; 15:102491. [PMID: 39901974 PMCID: PMC11787010 DOI: 10.1016/j.jceh.2024.102491] [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: 05/15/2024] [Accepted: 12/12/2024] [Indexed: 02/05/2025] Open
Abstract
Background/Aims Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis associated with systemic inflammation and organ dysfunction. In ACLF, the development of acute kidney injury (AKI) is associated with poor outcomes. FABP1, NGAL, Cys C and IL-18 have been shown to correlate with ACLF severity and mortality. Hence, our study aimed to evaluate the association of these biomarkers with organ dysfunctions, particularly AKI, in an Indian ACLF patient cohort. Methods 151 study participants including ACLF (n = 91; with AKI n = 63, no-AKI n = 28), non-liver AKI (n = 30) and healthy controls (n = 30) were recruited. Serum ELISA was performed for biomarker estimation. Data interpolation and graphical representation were performed using GraphPad Prism and statistical analyses performed using STATA 14.0. Results FABP1 and Cys C levels were higher in ACLF-AKI patients compared to ACLF no-AKI (P-value ≤ 0.0005). Serum Cys C levels were significantly increased in non-liver AKI compared to ACLF-AKI (P-value ≤ 0.001). AUROC analysis showed better performance of Cys C (AUC 0.79; 95% CI (0.68-0.89)) compared to serum creatinine (AUC 0.71; 95% CI (0.61-0.82)) in discriminating AKI and no-AKI. Correlation analysis revealed positive correlations of FABP1 with creatinine and urea, Cys C with creatinine, urea and OF-Kidney, NGAL, and IL-18 with general markers of organ dysfunction. Plasma MTs) measured in a subset of ACLF patients were elevated in progression-to-AKI. Conclusion Our study showed that in an Indian population of ACLF patients with a high short-term mortality, serum Cys C and FABP1 were elevated in ACLF-AKI, however did not have predictive potential for ACLF-AKI. Cys C levels were significantly higher in non-liver AKI patients vs. ACLF-AKI and correlated with markers of kidney dysfunction whereas NGAL and IL-18 represented higher inflammation and total organ dysfunction. Hence, we conclude that these biomarkers were elevated in ACLF-AKI but did not have predictive potential for AKI in ACLF.
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Affiliation(s)
- Rohini Saha
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | | | | | - Hem C. Sati
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Maroof A. Khan
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Mahajan
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - Sudip Datta
- Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Pragyan Acharya
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
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Jia L, He WP, Xing HC, Li J, Yu HW, Hou W, Xue R, Zhao J, Meng QH. The restoration of immunity characterized by the recovery of myeloid dendritic cells represent a favorable response to methylprednisolone therapy for HBV-ACLF patients: A prospective cohort study. Cytokine 2025; 189:156894. [PMID: 40043628 DOI: 10.1016/j.cyto.2025.156894] [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: 06/28/2024] [Revised: 08/04/2024] [Accepted: 02/12/2025] [Indexed: 03/18/2025]
Abstract
BACKGROUND The use of methylprednisolone (MP) is still controversial for hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF). We aimed to explore the change in dendritic cells (DCs) during MP treatment in HBV-ACLF to guide the use of MP to improve patient's prognosis. METHODS Patients with HBV-ACLF were prospectively allocated to groups given methylprednisolone intravenously (1.5 mg/kg/day for the first 3 days, 1 mg/kg/day for the second 2 days, and 0.5 mg/kg/day for the last 2 days, MP group, n = 36) plus standard treatment or standard treatment only (CM group, n = 34). The phenotype [myeloid and plasmacytoid DCs (mDCs, pDCs)] and function of DCs (IL-12 and IFN-α production) were measured at baseline (0d), 3d, 7d, 10d, 14d, 28d, and then monthly until 3 months. Patients' survival was assessed until day 90. RESULTS The 3-month survival rate was significantly higher in the MP group than the control (72.0 % vs. 35.5 %，P < 0.01). The phenotype and function of DCs were suppressed in the MP group. The mDCs counts was lower in non-survivors compared to survivors at baseline. Patients with a decline in mDCs counts at the 7th day and a continuous increase in mDCs counts from the 10th day presented a better outcome for patients with MP treatment. Bilirubin was the only relative factor for the restoration of mDCs in the MP group (odds ratio, 0.991; 95 % confidence interval, 0.984-0.999; P = 0.023). CONCLUSIONS Methylprednisolone could improve the outcome of HBV-ACLF by inhibiting the circulating mDCs counts. And the recovery of mDCs counts after methylprednisolone treatment could represent a favorable response. We can consider monitoring the circulating DCs counts to guide the use of MP in HBV-ACLF in order to improve patient outcomes.
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Affiliation(s)
- Lin Jia
- Department of Infection and Immunity, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Wei-Ping He
- 302 Hospital of People's Liberation Army, Liver Disease Center for Military Staff, Beijing, China
| | - Hui-Chun Xing
- Institute of Infectious Diseases, Beijing DiTan Hospital, Capital Medical University, Beijing, China
| | - Juan Li
- Department of Medical Oncology, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Hong-Wei Yu
- Outpatient Department, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Wei Hou
- Department I, Center for Liver Diseases, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Ran Xue
- Key laboratory of Carcinogenesis and Translational Research, Department of phase I clinical trial, Peking University Cancer Hospital & Institute, Beijing, China
| | - Juan Zhao
- Department II, Center for Liver Diseases, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Qing-Hua Meng
- Department of Medical Oncology, Beijing You-An Hospital, No. 8 You An Men Wai Street, Fengtai District, Beijing 100069, China.
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Lemmer P, Sowa JP, Bulut Y, Strnad P, Canbay A. Mechanisms and aetiology-dependent treatment of acute liver failure. Liver Int 2025; 45:e15739. [PMID: 37752801 DOI: 10.1111/liv.15739] [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: 05/19/2023] [Revised: 09/01/2023] [Accepted: 09/05/2023] [Indexed: 09/28/2023]
Abstract
This review compiles the mechanisms of acute liver failure (ALF) as well as the current and potential therapeutic approaches, including aetiology-specific treatment, and the issues encountered with such approaches. On a cellular level, ALF is characterized by massive hepatocyte death due to different types of cellular demise. Compensatory hyperplasia and functional recovery are possible when the regenerative capacity is sufficient to sustain hepatic function. ALF has a high mortality of about 30% and can lead to death in a very short time despite maximum therapeutic intervention. Besides aetiology-specific therapy and intensive care, the therapeutic option of emergency liver transplantation has significantly improved the prognosis of patients with ALF. However, due to limiting factors such as organ shortage, many patients die on the waiting list. In addition to graft assessment, machine perfusion may have the potential to recondition marginal organs and thus expand the organ donor pool.
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Affiliation(s)
- Peter Lemmer
- Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Jan-Peter Sowa
- Department of Medicine, Universitätsklinikum Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany
| | - Yesim Bulut
- Department of Medicine, Universitätsklinikum Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany
| | - Pavel Strnad
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Ali Canbay
- Department of Medicine, Universitätsklinikum Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany
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Patel P, Lodh A, Beasley TM, Gupta U, Forrister N, Hegazy Y, Evers C, Xie S, Shoreibah M. Optimizing treatment outcomes in acute-on-chronic liver failure: The role of T2 candida panel in detecting invasive candidiasis. Am J Med Sci 2025; 369:366-372. [PMID: 39510501 DOI: 10.1016/j.amjms.2024.10.009] [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: 03/21/2024] [Revised: 10/22/2024] [Accepted: 10/25/2024] [Indexed: 11/15/2024]
Abstract
INTRODUCTION Acute-on-Chronic Liver Failure(ACLF) is a syndrome characterized by organ dysfunction and high mortality in cirrhotic patients. ACLF has multiple triggers but those precipitated by fungal infection have higher mortality. Early detection and treatment of candidemia have shown mortality benefits in ACLF. The sensitivity of blood cultures ranged from 21 % - 71 %. Given the increase in mortality, it is vital to have a quick yet reliable diagnostic test for the detection of candida. This study examines the risk of developing ACLF and its impact on survival in hospitalized cirrhotic patients with invasive fungal infection via a positive T2 Candida Panel. We also examine the effects of earlier treatment on mortality in those with a positive T2 Candida Panel. METHODS We performed a retrospective study and included cirrhotic patients admitted from 2017 to 2021. Data collected includes baseline characteristics, labs, progression to ACLF, and mortality outcomes. The stages of ACLF were determined through the use of the CLIF-Consortium ACLF score. RESULTS Of the 489 patients sampled, 95 patients developed ACLF during the time of the T2 panel collection, of which 60 (63.2 %) (p ≤ 0.001) patients had a positive T2 Candida Panel. The data also demonstrates that patients who had earlier antifungal initiation had a decrease in mortality (6.15 ± 5.23 versus 13.53 ± 11.42)(p ≤ 001). CONCLUSION Our study shows that a positive T2 Panel leads to more frequent progression of ACLF and worsening survival outcomes. This study shows that earlier treatment of candidiasis via the T2 Panel leads to mortality benefits.
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Affiliation(s)
- P Patel
- University of Alabama at Birmingham, Birmingham, AL, USA; Princeton Baptist Medical Center, Birmingham, AL, USA.
| | - A Lodh
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - T M Beasley
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - U Gupta
- University of New Mexico, Albuquerque, NM, USA
| | - N Forrister
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - Y Hegazy
- University of Mississippi, Jackson, MS, USA
| | - C Evers
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - S Xie
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - M Shoreibah
- University of Alabama at Birmingham, Birmingham, AL, USA
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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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Zhao X, Xue H, Fu C, Li S, Wang Z, Xiao Z, Ye J, Cai J, Yang Y, Zhao Q, Zhu F, Wang T, Huang W. Incidence and risk factors for acute kidney injury after traumatic hemorrhagic shock: A 10-year retrospective cohort study. J Nephrol 2024; 37:2337-2346. [PMID: 39172314 PMCID: PMC11649738 DOI: 10.1007/s40620-024-02035-1] [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: 02/17/2024] [Accepted: 07/10/2024] [Indexed: 08/23/2024]
Abstract
BACKGROUND Acute kidney injury (AKI) is a common complication of traumatic hemorrhagic shock. The risk factors for AKI after traumatic hemorrhagic shock remain unclear. The aim of this study was to investigate the risk factors for AKI after traumatic hemorrhagic shock. METHODS This was a ten-year retrospective cohort study of patients who experienced traumatic hemorrhagic shock between January 2013 and April 2023. Patient characteristics and clinical data were recorded for 417 patients. The outcome was the occurrence of AKI, defined as a serum creatinine increase of ≥ 0.3 mg/dL (≥ 26.5 μmol/L) within 48 h, or an increase to 1.5 times the baseline, or a urine volume of < 0.5 mL/(kg h.). Risk factors for AKI were tested by logistic regression models. RESULTS The incidence of AKI after traumatic hemorrhagic shock was 29.3% (122/417 patients). Multivariable analysis revealed that the independent risk factors for AKI included age (OR, 1.048; 95% CI, 1.022-1.074; p < 0.001), B-type natriuretic peptide (OR, 1.002; 95% CI, 1.000-1.004; p = 0.041), sepsis (OR, 4.536; 95% CI, 1.651-12.462; p = 0.030) and acute myocardial injury (OR, 2.745; 95% CI, 1.027-7.342; p = 0.044). Road traffic accidents (OR, 0.202; 95% CI, 0.076-0.541; p = 0.001), mean arterial pressure (OR, 0.972; 95% CI, 0.950-0.995; p = 0.017), and base excess (OR, 0.842; 95% CI, 0.764-0.929; p = 0.001) were negatively correlated with AKI. The area under the receiver operating characteristic (ROC) curve for prediction by this model was 0.85 (95% CI, 0.81-0.90). CONCLUSION The incidence of AKI after traumatic hemorrhagic shock was 29.3% in our series. Indicators of blood perfusion, sepsis and acute myocardial injury may be independent risk factors for AKI after traumatic hemorrhagic shock. Early detection and effective intervention on these risk factors could reduce the occurrence of AKI and improve outcomes.
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Affiliation(s)
- Xiujuan Zhao
- Department of Critical Care Medicine, Peking University People's Hospital, Beijing, 100044, China
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China
| | - Haiyan Xue
- Department of Critical Care Medicine, Peking University People's Hospital, Beijing, 100044, China
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China
| | - Chun Fu
- Department of Critical Care Medicine, Peking University People's Hospital, Beijing, 100044, China
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China
| | - Shu Li
- Department of Critical Care Medicine, Peking University People's Hospital, Beijing, 100044, China
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China
| | - Zhenzhou Wang
- Department of Critical Care Medicine, Peking University People's Hospital, Beijing, 100044, China
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China
| | - Ziyan Xiao
- Department of Critical Care Medicine, Peking University People's Hospital, Beijing, 100044, China
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China
| | - Jingjing Ye
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China
- Key Laboratory of Trauma and Neural Regeneration (Peking University), Ministry of Education, Beijing, 100044, China
- National Center for Trauma Medicine of China, Beijing, 100044, China
| | - Jie Cai
- Department of Critical Care Medicine, Shenzhen Nanshan People's Hospital, Shenzhen, 518052, China
| | - Yucun Yang
- Department of Internal Medicine, Wudi Hospital of Traditional Chinese Medicine, Binzhou, 251900, China
| | - Qiong Zhao
- Emergency Department, First People's Hospital of Jinghong, Xishuangbanna, 666100, China
| | - Fengxue Zhu
- Department of Critical Care Medicine, Peking University People's Hospital, Beijing, 100044, China
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China
| | - Tianbing Wang
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China
- Key Laboratory of Trauma and Neural Regeneration (Peking University), Ministry of Education, Beijing, 100044, China
- National Center for Trauma Medicine of China, Beijing, 100044, China
| | - Wei Huang
- Trauma Medicine Center, Peking University People's Hospital, Beijing, 100044, China.
- Key Laboratory of Trauma and Neural Regeneration (Peking University), Ministry of Education, Beijing, 100044, China.
- National Center for Trauma Medicine of China, Beijing, 100044, China.
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Brochado-Kith O, Rava M, Berenguer J, González-García J, Rojo D, Díez C, Hontañon V, Virseda-Berdices A, Ibañez-Samaniego L, Llop-Herrera E, Olveira A, Pérez-Latorre L, Barbas C, Fernández-Rodríguez A, Resino S, Jiménez-Sousa MA. Altered blood microbiome in patients with HCV-related Child-Pugh class B cirrhosis. J Infect Public Health 2024; 17:102524. [PMID: 39241484 DOI: 10.1016/j.jiph.2024.102524] [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: 08/01/2024] [Accepted: 08/22/2024] [Indexed: 09/09/2024] Open
Abstract
BACKGROUND Altered bacterial translocation is associated with changes in hepatic function and the progression from compensated to decompensated cirrhosis. Child-Turcotte-Pugh (CTP) score is an essential indicator of liver severity. Thus, we aimed to study differences in the blood microbiome together with metabolome profile between HCV-infected patients with CTP class B (CTP-B, significant functional compromise) and patients with CTP class A (CTP-A, well-compensated cirrhosis). METHODS We conducted a cross-sectional study in patients with advanced HCV-related cirrhosis (n = 88) stratified by CTP-B and CTP-A. Bacterial 16S rRNA sequencing was sequenced by MiSeq Illumina technology and non-targeted metabolomics was performed by GC-MS and LC-MS ESI+ and ESI- to complement the analysis. RESULTS Patients with CTP-B had lower levels of richness (Chao1), and alpha diversity (Shannon and Simpson indexes) at phylum level than patients with CTP-A. Likewise, we observed significant differences in beta diversity between groups at phylum, class, and order levels, showing lower diversity in patients with CTP-B. Higher relative abundance of Proteobacteria (p = 0.012), Alphaproteobacteria (p = 0.005), Sphingomonadales (p = 0.012) and Sphingomonadaceae (p = 0.016) were significantly associated with CTP-B. The phylum Proteobacteria was positively correlated with ethanolamine and oleic acid (p = 0.005 and p = 0.004, respectively) and negatively with p-cresol (p = 0.006). In addition, the order Sphingomonadales and the family Sphingomonadaceae was also negatively correlated with p-cresol (p = 0.001 and p = 0.001). CONCLUSIONS Blood microbial diversity was significantly decreased in patients with CTP-B, who presented an enrichment of Proteobacteria, Alphaproteobacteria, Sphingomonadales and Sphingomonadaceae compared to patients with CTP-A.
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Affiliation(s)
- Oscar Brochado-Kith
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid. Spain.
| | - Marta Rava
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid. Spain; Unidad de la Cohorte de la Red de Investigación en Sida (CoRIS). Centro Nacional de Epidemiologia (CNE), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
| | - Juan Berenguer
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid. Spain; Unidad de Enfermedades Infecciosas/VIH; Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
| | - Juan González-García
- Servicio de Medicina Interna-Unidad de VIH. Hospital Universitario La Paz, Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain.
| | - David Rojo
- Centre of Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28060 Boadilla del Monte, Spain.
| | - Cristina Díez
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid. Spain; Unidad de Enfermedades Infecciosas/VIH; Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
| | - Victor Hontañon
- Servicio de Medicina Interna-Unidad de VIH. Hospital Universitario La Paz, Madrid, Spain; Instituto de Investigación Sanitaria La Paz (IdiPAZ), Madrid, Spain.
| | - Ana Virseda-Berdices
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid. Spain.
| | - Luis Ibañez-Samaniego
- Servicio de Aparato Digestivo, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.
| | - Elba Llop-Herrera
- Departamento de Gastroenterología; Hospital Universitario Puerta de Hierro-Majadahonda; Majadahonda, Madrid; Spain.
| | - Antonio Olveira
- Servicio de Aparato Digestivo, Hospital Universitario La Paz, Madrid, Spain.
| | - Leire Pérez-Latorre
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid. Spain; Unidad de Enfermedades Infecciosas/VIH; Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
| | - Coral Barbas
- Centre of Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28060 Boadilla del Monte, Spain.
| | - Amanda Fernández-Rodríguez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid. Spain.
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid. Spain.
| | - María Angeles Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid. Spain.
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Roedl K, Fuhrmann V. [Liver diseases in the intensive care unit]. Med Klin Intensivmed Notfmed 2024; 119:449-457. [PMID: 38937335 DOI: 10.1007/s00063-024-01157-5] [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: 05/22/2024] [Accepted: 06/04/2024] [Indexed: 06/29/2024]
Abstract
The frequency of liver diseases in the intensive care unit has increased significantly in recent years and is now observed in up to 20% of critically ill patients. The occurrence of liver disease is associated with significantly increased morbidity and mortality. Two groups of liver diseases in the intensive care unit can be distinguished. First, the group of "primary hepatic dysfunctions", which includes primary acute liver failure as well as acute-on-chronic liver failure in patients with pre-existing liver cirrhosis. The second group of "secondary or acquired liver diseases" includes cholestatic liver diseases, as well as hypoxic liver injury and mixed forms, as well as other rarer liver diseases. Due to the diversity of liver diseases and the very different triggers, sufficient knowledge of the underlying changes (including hemodynamic changes, inflammatory states or drug-related) is essential. Early recognition, diagnosis, and treatment of the underlying disease are essential for all liver dysfunction in critically ill patients in the intensive care unit. This review article aims to take a closer look at liver diseases in the intensive care unit and provides insight into diagnostics and treatment options.
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Affiliation(s)
- Kevin Roedl
- Klinik für Intensivmedizin, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Deutschland.
| | - Valentin Fuhrmann
- Abteilung für Innere Medizin und Gastroenterologie, Heilig-Geist-Krankenhaus, Köln, Deutschland
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Sun J, Yang F, Zheng Y, Huang C, Fan X, Yang L. Pathogenesis and interaction of neutrophils and extracellular vesicles in noncancer liver diseases. Int Immunopharmacol 2024; 137:112442. [PMID: 38889508 DOI: 10.1016/j.intimp.2024.112442] [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: 02/29/2024] [Revised: 06/04/2024] [Accepted: 06/05/2024] [Indexed: 06/20/2024]
Abstract
Liver disease ranks as the eleventh leading cause of mortality, leading to approximately 2 million deaths annually worldwide. Neutrophils are a type of immune cell that are abundant in peripheral blood and play a vital role in innate immunity by quickly reaching the site of liver injury. They exert their influence on liver diseases through autocrine, paracrine, and immunomodulatory mechanisms. Extracellular vesicles, phospholipid bilayer vesicles, transport a variety of substances, such as proteins, nucleic acids, lipids, and pathogenic factors, for intercellular communication. They regulate cell communication and perform their functions by delivering biological information. Current research has revealed the involvement of the interaction between neutrophils and extracellular vesicles in the pathogenesis of liver disease. Moreover, more research has focused on targeting neutrophils as a therapeutic strategy to attenuate disease progression. Therefore, this article summarizes the roles of neutrophils, extracellular vesicles, and their interactions in noncancerous liver diseases.
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Affiliation(s)
- Jie Sun
- Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, China; Medical College, Tibet University, Lhasa, China
| | - Fan Yang
- Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Yanyi Zheng
- Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Chen Huang
- Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoli Fan
- Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, China.
| | - Li Yang
- Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, China.
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10
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Gananandan K, Wiese S, Møller S, Mookerjee RP. Cardiac dysfunction in patients with cirrhosis and acute decompensation. Liver Int 2024; 44:1832-1841. [PMID: 38712826 DOI: 10.1111/liv.15896] [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: 01/22/2024] [Revised: 02/25/2024] [Accepted: 03/04/2024] [Indexed: 05/08/2024]
Abstract
The prevalence of cirrhotic cardiomyopathy (CCM) has been reported as high as 60%-70% in patients with liver cirrhosis and is associated with various negative outcomes. There has been a growing understanding of CCM over recent years. Indeed, the development of imaging techniques has enabled new diagnostic criteria to be proposed by the Cirrhotic Cardiomyopathy Consortium. However, important unanswered questions remain over pathophysiological mechanisms, optimal diagnostic modalities and potential treatment options. While there has been an increasing volume of literature evaluating CCM, there is a lack of clarity on its implications in acute decompensation, acute-on-chronic liver failure and following interventions such as transjugular intrahepatic portosystemic shunt insertion and liver transplantation. This review aims to summarise the literature in these challenging domains and suggest where future research should focus. We conclude that systemic inflammation and structural myocardial changes are likely to be crucial in the pathophysiology of the disease, but the relative contribution of different components remains elusive. Furthermore, future studies need to use standardised diagnostic criteria for CCM as well as incorporate newer imaging techniques assessing both myocardial structure and function. Finally, while specific treatments are currently lacking, therapeutics targeting systemic inflammation, microbial dysbiosis and bacterial translocation are promising targets and warrant further research.
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Affiliation(s)
- Kohilan Gananandan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, London, UK
| | - Signe Wiese
- Centre of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, University of Copenhagen, Copenhagen, Denmark
- Gastroenterology Unit, Medical Division, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Søren Møller
- Centre of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Rajeshwar P Mookerjee
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, London, UK
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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11
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Song DS, Kim HY, Jung YK, Kim TH, Yim HJ, Yoon EL, Suk KT, Yoo JJ, Kim SG, Kim MY, Chang Y, Jeong SW, Jang JY, Kim SE, Kim JH, Park JG, Kim W, Yang JM, Kim DJ, Choudhury AK, Arora V, Sarin SK. Dynamic analysis of acute deterioration in chronic liver disease patients using modified quick sequential organ failure assessment. Clin Mol Hepatol 2024; 30:388-405. [PMID: 38600873 PMCID: PMC11261223 DOI: 10.3350/cmh.2023.0563] [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: 12/27/2023] [Revised: 03/23/2024] [Accepted: 04/09/2024] [Indexed: 04/12/2024] Open
Abstract
BACKGROUND/AIMS Quick sequential organ failure assessment (qSOFA) is believed to identify patients at risk of poor outcomes in those with suspected infection. We aimed to evaluate the ability of modified qSOFA (m-qSOFA) to identify high-risk patients among those with acutely deteriorated chronic liver disease (CLD), especially those with acute-onchronic liver failure (ACLF). METHODS We used data from both the Korean Acute-on-Chronic Liver Failure (KACLiF) and the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and an m-qSOFA ≥2 was considered high. RESULTS Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than those with low m-qSOFA (Ps<0.05). Subgroup analysis by ACLF showed that patients with high m-qSOFA had lower TFS than those with low m-qSOFA. m-qSOFA was an independent prognostic factor (hazard ratios, HR=2.604, 95% confidence interval, CI 1.353-5.013, P=0.004 in KACLiF and HR=1.904, 95% CI 1.484- 2.442, P<0.001 in AARC). The patients with low m-qSOFA at baseline but high m-qSOFA on day 7 had a significantly lower 1-month TFS than those with high m-qSOFA at baseline but low m-qSOFA on day 7 (52.6% vs. 89.4%, P<0.001 in KACLiF and 26.9% vs. 61.5%, P<0.001 in AARC). CONCLUSION Baseline and dynamic changes in m-qSOFA may identify patients with a high risk of developing organ failure and short-term mortality among CLD patients with acute deterioration.
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Affiliation(s)
- Do Seon Song
- Department of Internal Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Hee Yeon Kim
- Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Young Kul Jung
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Tae Hyung Kim
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Hyung Joon Yim
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Eileen L Yoon
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Ki Tae Suk
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Jeong-ju Yoo
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Young Chang
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Jae Young Jang
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Sung-Eun Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Jung-Hee Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Jung Gil Park
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Jin Mo Yang
- Department of Internal Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Korean Acute-on-Chronic Liver Failure (KACLiF) study group
- Department of Internal Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Seoul, Korea
- Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - APASL ACLF Research Consortium (AARC) for APASL ACLF working party
- Department of Internal Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Seoul, Korea
- Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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12
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Orosz L, Sárvári KP, Dernovics Á, Rosztóczy A, Megyeri K. Pathogenesis and clinical features of severe hepatitis E virus infection. World J Virol 2024; 13:91580. [PMID: 38984076 PMCID: PMC11229844 DOI: 10.5501/wjv.v13.i2.91580] [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: 12/31/2023] [Revised: 02/08/2024] [Accepted: 04/15/2024] [Indexed: 06/24/2024] Open
Abstract
The hepatitis E virus (HEV), a member of the Hepeviridae family, is a small, non-enveloped icosahedral virus divided into eight distinct genotypes (HEV-1 to HEV-8). Only genotypes 1 to 4 are known to cause diseases in humans. Genotypes 1 and 2 commonly spread via fecal-oral transmission, often through the consumption of contaminated water. Genotypes 3 and 4 are known to infect pigs, deer, and wild boars, often transferring to humans through inadequately cooked meat. Acute hepatitis caused by HEV in healthy individuals is mostly asymptomatic or associated with minor symptoms, such as jaundice. However, in immunosuppressed individuals, the disease can progress to chronic hepatitis and even escalate to cirrhosis. For pregnant women, an HEV infection can cause fulminant liver failure, with a potential mortality rate of 25%. Mortality rates also rise amongst cirrhotic patients when they contract an acute HEV infection, which can even trigger acute-on-chronic liver failure if layered onto pre-existing chronic liver disease. As the prevalence of HEV infection continues to rise worldwide, highlighting the particular risks associated with severe HEV infection is of major medical interest. This text offers a brief summary of the characteristics of hepatitis developed by patient groups at an elevated risk of severe HEV infection.
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Affiliation(s)
- László Orosz
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - Károly Péter Sárvári
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - Áron Dernovics
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
| | - András Rosztóczy
- Department of Internal Medicine, Division of Gastroenterology, University of Szeged, Szeged 6725, Csongrád-Csanád, Hungary
| | - Klára Megyeri
- Department of Medical Microbiology, University of Szeged, Szeged 6720, Csongrád-Csanád, Hungary
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13
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Jafree SR, Naveed A, Ahsan H, Burhan SK, Khan MA, Khawar A, Fischer F. Mental health and quality of life in patients with chronic liver disease: a single-center structural equation model. BMC Gastroenterol 2024; 24:193. [PMID: 38840079 PMCID: PMC11155103 DOI: 10.1186/s12876-024-03268-x] [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: 06/11/2023] [Accepted: 05/15/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND Chronic liver disease (CLD) is one of the leading disease burdens in Pakistan. Until now, there has only been limited focus in the country on providing health services through tertiary services in urban cities, whereas there is almost no research in Pakistan on the mental health and quality of life of CLD patients. This study aimed to understand which predictors influence the mental health and quality of life of CLD patients in order to advise better policy protection. METHODS Data was collected from CLD patients at the Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan. A total of 850 respondents were part of the final sample. The age of respondents ranged from 18 to 79 years and included the following diagnosis: (i) Chronic Viral Hepatitis (n = 271), (ii) Cirrhosis (n = 259), (iii) Hepatocellular Carcinoma (n = 193), and (iv) Non-viral Liver Disease (n = 127). RESULTS Mean results reveal that females as well as illiterate patients need more support for mental health and communication with their physician; whereas men need more support to develop coping strategies. Structural equation modelling results reveal that the severity of symptoms (β = 0.24, p < 0.001), coping strategies (β=-0.51, p < 0.001), and doctor communication (β=-0.35, p < 0.001) predict mental health. Quality of life is associated with the severity of symptoms (β=-0.36, p < 0.001), coping strategies (β = 0.26, p < 0.05), and doctor communication (β = 0.09, p < 0.05). CONCLUSIONS A 'bio-psycho-social-spiritual' model is recommended for Pakistan's CLD patients which includes the integration of social officers to provide support in four key areas to secure mental health and quality of life of patients.
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Affiliation(s)
- Sara Rizvi Jafree
- Department of Sociology, Forman Christian College University, Lahore, Pakistan
| | - Ammara Naveed
- Pakistan Kidney Liver Institute and Research Centre, Lahore, Pakistan
| | - Humna Ahsan
- Department of Economics, Forman Christian College University, Lahore, Pakistan
| | | | - Masha Asad Khan
- Academic Dean of Humanities and Social Sciences, Kinnaird College for Women, Lahore, Pakistan
| | - Amna Khawar
- Department of Psychology, Lahore College of Women University, Lahore, Pakistan
| | - Florian Fischer
- Institute of Public Health, Charité - Universitätsmedizin Berlin, Berlin, Germany.
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Batra N, Gaidhane SA, Kumar S, Acharya S. Outcome Predictors of Acute-on-Chronic Liver Failure: A Narrative Review. Cureus 2024; 16:e61655. [PMID: 38966452 PMCID: PMC11223737 DOI: 10.7759/cureus.61655] [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: 03/02/2024] [Accepted: 06/04/2024] [Indexed: 07/06/2024] Open
Abstract
Complications of acute-on-chronic liver failure (ACLF) include increased short-term mortality. Extrahepatic organ failures result from chronic liver disease and acute hepatic injury. This combination characterizes end-stage liver disease. Its rapid progression makes it challenging for hepatologists and intensivists to treat. The varied definitions of this condition lead to varied clinical presentations. Hepatic or extrahepatic failures are more prevalent in chronic hepatitis B or cirrhosis patients who receive an additional injury. Numerous intensity parameters and prognosis ratings, including those for hepatitis B virus (HBV), have been developed and verified for various patients and causes of the disease. Liver regeneration, liver transplantation (LT), or antiviral therapy for HBV-related ACLF are the main treatment aims for various organ failures. LT is the best treatment for HBV-ACLF. In some HBV-related ACLF patients, nucleos(t)ide analogs and artificial liver assistance may enhance survival. Combining epidemiological and clinical studies, this review updates our understanding of HBV-ACLF's definition, diagnosis, epidemiology, etiology, therapy, and prognosis.
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Affiliation(s)
- Nitish Batra
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Shilpa A Gaidhane
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sunil Kumar
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sourya Acharya
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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15
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Colak M, Ocak I. Management of pediatric liver failure with therapeutic plasma exchange and continuous renal replacement therapy: A retrospective observational study. Medicine (Baltimore) 2024; 103:e38093. [PMID: 38728496 PMCID: PMC11081591 DOI: 10.1097/md.0000000000038093] [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: 01/09/2024] [Accepted: 04/11/2024] [Indexed: 05/12/2024] Open
Abstract
Liver failure represents a critical medical condition, marked by the rapid decline of hepatic functions. Emerging therapies, notably therapeutic plasma exchange (TPE) and continuous venovenous hemodiafiltration (CVVHDF), have demonstrated potential in mitigating these conditions through their roles in detoxification and hepatic support. The utility of these treatments, whether applied individually or in tandem, constitutes a significant area of research concerning the management of liver failure in pediatric patients. This study aims to evaluate the role and efficacy of TPE or TPE combined with CVVHDF in the treatment of liver failure among children. This retrospective study was conducted in a LTICU by reviewing the medical history of pediatric patients aged 1 month to 18 years. Patients were admitted between January 1, 2021 and December 1, 2023 due to acute liver failure or acute-chronic liver failure. The study evaluated those who received TPE or continuous renal replacement therapy combined with TPE. In statistical analyses, a P-value of <.05 was considered statistically significant. The study involved 24 patients with liver failure, comprising 13 males and 11 females. Sixteen patients (66.6%) received only TPE, while 8 patients (33.4%) were treated with TPE and CVVHDF. For patients treated only with TPE, the median INR reduced from 3.1 to 1.26, alanine aminotransferase from 1255 to 148, and aspartate aminotransferase from 2189 to 62. Similar significant reductions were observed in the TPE and CVVHDF group: INR from 3.9 to 1.26, alanine aminotransferase from 1749 to 1148, and aspartate aminotransferase from 1489 to 62. These changes were statistically significant with P-values of .01 for each parameter in both groups. Overall, 14 patients survived without requiring a liver transplant, while 4 patients underwent liver transplantation. Our study on pediatric liver failure treatment shows that both standalone TPE and its combination with CVVHDF are effective, especially as a bridge to transplantation. With 58% transplant-free survival, these therapies demonstrate significant clinical improvements. Future multicentric studies are needed for broader validation of these findings in liver failure management.
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Affiliation(s)
- Mustafa Colak
- Department of Liver Transplantation Intensive Care Unit, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - Ilhan Ocak
- Department of Liver Transplantation Intensive Care Unit, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
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16
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Abstract
Acute-on-chronic liver failure (ACLF) is characterized by an acute hepatic insult happening in a patient with underlying cirrhosis with compromised hepatic reserve leading to development of systemic inflammation, sepsis, and organ failure resulting in poor outcome in majority. While Asia Pacific Association for Study of Liver Diseases (APASL) emphasizes on early diagnosis before development of organ failure, European Association for Study of Liver Diseases (EASL) mandates the presence of organ failures to define ACLF. There is a lack of consensus definition of pediatric ACLF although recent APASL guidelines have tried to address the issue. While Wilson disease (WD) and autoimmune hepatitis (AIH) are the most common cause of underlying cirrhosis in children, acute viral hepatitis and flares of WD and AIH are the commonest acute precipitating events. Poor outcomes [death and liver transplantation (LT)] ranging from 19 to 59% have been reported. Prognosis in pediatric ACLF is usually better than that in adults due to greater proportion of treatable etiologies, lesser organ failures, comorbidities and better hepatic reserves. APASL ACLF Research Consortium (AARC) score more than or equal to 11 is predictive of poor 28-90 d mortality. Treatment of pediatric ACLF relies mainly on prompt diagnosis and medical management of a potentially treatable etiology of underlying cirrhosis. Bridging therapies, especially high volume plasma exchange can be initiated early as a bridge to LT or native liver recovery. Those with no improvement in 4-7 d should undergo LT before development of sepsis or multi-organ failure.
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Affiliation(s)
- Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
| | - Bikrant Bihari Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
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17
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Hassan HM, Liang X, Xin J, Lu Y, Cai Q, Shi D, Ren K, Li J, Chen Q, Li J, Li P, Guo B, Yang H, Luo J, Yao H, Zhou X, Hu W, Jiang J, Li J. Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure. BMC Med 2024; 22:95. [PMID: 38439091 PMCID: PMC10913480 DOI: 10.1186/s12916-024-03318-x] [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: 10/31/2023] [Accepted: 02/23/2024] [Indexed: 03/06/2024] Open
Abstract
BACKGROUND The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate THBS1 as a potential biomarker in ACLF disease pathogenesis. METHODS Biobanked peripheral blood mononuclear cells (PBMCs) from 330 subjects with hepatitis B virus (HBV)-related etiologies, including HBV-ACLF, liver cirrhosis (LC), and chronic hepatitis B (CHB), and normal controls (NC) randomly selected from the Chinese Group on the Study of Severe Hepatitis B (COSSH) prospective multicenter cohort underwent transcriptome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15); the findings were externally validated in participants from COSSH cohort, an ACLF rat model and hepatocyte-specific THBS1 knockout mice. RESULTS THBS1 was the top significantly differentially expressed gene in the PBMC transcriptome, with the most significant upregulation in ACLF, and quantitative polymerase chain reaction (ACLF = 110; LC = 60; CHB = 60; NC = 45) was used to verify that THBS1 expression corresponded to ACLF disease severity outcome, including inflammation and hepatocellular apoptosis. THBS1 showed good predictive ability for ACLF short-term mortality, with an area under the receiver operating characteristic curve (AUROC) of 0.8438 and 0.7778 at 28 and 90 days, respectively. Enzyme-linked immunosorbent assay validation of the plasma THBS1 using an expanded COSSH cohort subjects (ACLF = 198; LC = 50; CHB = 50; NC = 50) showed significant correlation between THBS1 with ALT and γ-GT (P = 0.01), and offered a similarly good prognostication predictive ability (AUROC = 0.7445 and 0.7175) at 28 and 90 days, respectively. ACLF patients with high-risk short-term mortality were identified based on plasma THBS1 optimal cut-off value (< 28 µg/ml). External validation in ACLF rat serum and livers confirmed the functional association between THBS1, the immune response and hepatocellular apoptosis. Hepatocyte-specific THBS1 knockout improved mouse survival, significantly repressed major inflammatory cytokines, enhanced the expression of several anti-inflammatory mediators and impeded hepatocellular apoptosis. CONCLUSIONS THBS1 might be an ACLF disease development-related biomarker, promoting inflammatory responses and hepatocellular apoptosis, that could provide clinicians with a new molecular target for improving diagnostic and therapeutic strategies.
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Affiliation(s)
- Hozeifa Mohamed Hassan
- Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, China
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Xi Liang
- Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, China
| | - Jiaojiao Xin
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Yingyan Lu
- Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Qun Cai
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Dongyan Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Keke Ren
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Jun Li
- Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qi Chen
- Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, China
| | - Jiang Li
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Peng Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Beibei Guo
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Hui Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Jinjin Luo
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Heng Yao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Xingping Zhou
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Wen Hu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Jing Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China.
| | - Jun Li
- Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, China.
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China.
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Vu QV, Le TV, Le HT, Nguyen AHN, Nguyen DT. Adult-to-adult right lobe graft living donor liver transplantation for acute-on-chronic liver failure: a single-centre retrospective study in Vietnam. Ann Med Surg (Lond) 2024; 86:1261-1267. [PMID: 38463078 PMCID: PMC10923391 DOI: 10.1097/ms9.0000000000001708] [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: 10/16/2023] [Accepted: 12/30/2023] [Indexed: 03/12/2024] Open
Abstract
Introduction Acute-on-chronic liver failure (ACLF) has a high mortality rate, and liver transplantation is considered a definite treatment for patients with this condition. This study aims to evaluate the outcomes of living donor liver transplantation (LDLT) in ACLF patients in a single centre in a lower middle-income country, Vietnam. Materials and methods This was a retrospective study at the 108 Military Central Hospital (Hanoi, Vietnam), enroling 51 patients diagnosed with ACLF based on Asian Pacific Association for the Study of the Liver (APASL) criteria who underwent LDLT with a right lobe graft from December 2019 to December 2022. The authors utilize the model for end-stage liver disease (MELD) and APASL ACLF Research Consortium (AARC) scores to evaluate and stratify the severity of ACLF. Results The average age of all patients was 47.27±13.61, with 88.24% being male. The average BMI was 22.78±2.61. The most common underlying liver disease was chronic viral hepatitis B (88.2%). The average MELD score of the patients was 34.90±5.61, with 33.3% having MELD score greater than or equal to 40. In terms of ACLF severity, five patients (9.8%) had grade I ACLF, 35 patients (68.6%) had grade II ACLF, and 11 patients (21.6%) had grade III ACLF. The average AARC score was 9.43±1.68. The duration of treatment in the ICU was 8.59±7.27 days, and the length of hospital stay was 28.02±13.45 days. The most common post-transplant complication was biliary complication (19.61%). Death occurred in 7 patients (13.7%). The survival rates at 6 months, 1 year, and 3 years were 84%, 81.7%, and 81.7%, respectively. Conclusion Living donor liver transplantation for ACLF patients is safe and has a high post-transplant survival rate. Multidisciplinary care before, during, and after surgery, and the decision to do a liver transplant early, is essential in saving the lives of ACLF patients.
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Affiliation(s)
- Quang V. Vu
- Department of Hepatopancreatobiliary Surgery, Institute of Digestive Surgery, 108 Military Central Hospital
| | - Thanh V. Le
- Department of Hepatopancreatobiliary Surgery, Institute of Digestive Surgery, 108 Military Central Hospital
| | - Hieu T. Le
- Department of Hepatopancreatobiliary Surgery, Institute of Digestive Surgery, 108 Military Central Hospital
| | - Anh H N. Nguyen
- Department of Hepatopancreatobiliary Surgery, Institute of Digestive Surgery, 108 Military Central Hospital
| | - Duy T. Nguyen
- College of Health Sciences, VinUniversity, Hanoi, Vietnam
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19
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Qiu B, Liang JX, Romero Gómez M. The efficacy and safety of granulocyte colony-stimulating factor in the treatment of acute-on-chronic liver failure: A systematic review and meta-analysis. PLoS One 2023; 18:e0294818. [PMID: 38033111 PMCID: PMC10688871 DOI: 10.1371/journal.pone.0294818] [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: 05/22/2023] [Accepted: 11/09/2023] [Indexed: 12/02/2023] Open
Abstract
BACKGROUND AND OBJECTIVES The safety and efficacy of granulocyte-colony stimulating factor (G-CSF) for the treatment of acute-on-chronic liver failure (ACLF) remain controversial. This meta-analysis aimed to evaluate the effectiveness and safety of G-CSF in treating ACLF. METHODS The estimated pooled risk ratio (RR) and 95% confidence interval (CI) assessed the treatment effects of G-CSF. Mean differences (MD) and 95% confidence intervals were used to analyze continuous data. Heterogeneity was explored by sensitivity analysis. Potential publication bias was assessed using Egger's test. RESULTS Ten studies, comprising a total of 603 participants, were included in the analysis. The G-CSF group showed significantly lower MELD scores at 7-day (MD = -2.39, 95%CI: -3.95 to -0.82), CTP scores at 7-day (MD = -0.77, 95%CI: -1.41 to -0.14), and MELD scores at 30-day (MD = -3.01, 95%CI: -5.36 to -0.67) compared to the control group. Furthermore, the G-CSF group was associated with a reduced risk of sepsis (RR = 0.53, 95%CI: 0.35-0.80). The 30-day survival (RR = 1.26, 95%CI:1.10-1.43), 60-day survival (RR = 1.47, 95%CI:1.17-1.84, and 90-day survival (RR = 1.73, 95%CI: 1.27-2.35) of patients with ACLF treated with G-CSF were significantly higher than those of the control group. CONCLUSIONS Our meta-analysis suggests that G-CSF therapy may be a promising treatment for ACLF, with significant improvements in liver function and survival rates, however, further studies are needed to verify this conclusion.
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Affiliation(s)
- Bo Qiu
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, HaiNan, China
| | - Jia Xu Liang
- Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, HaiNan, China
- Department of Diagnostic Radiology, People’s Hospital of Zhengzhou, Zhengzhou, China
| | - Manuel Romero Gómez
- Department of Digestive, Hospital Universitario de Virgen Rocio, Seville, Spain
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Saeidinejad M, Elshabrawi A, Sriphoosanaphan S, Andreola F, Mehta G, Agarwal B, Jalan R. Novel Therapeutic Approaches in Treatment of Acute-on-Chronic Liver Failure. Semin Liver Dis 2023; 43:429-445. [PMID: 38101419 PMCID: PMC10723941 DOI: 10.1055/s-0043-1776773] [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] [Indexed: 12/17/2023]
Abstract
Acute-on-chronic liver failure (ACLF), a clinical syndrome that can develop at any stage in the progression of cirrhotic liver disease, is characterized by an acute decompensation in liver function with associated multiorgan failure and high short-term mortality. Current evidence points to ACLF being reversible, particularly in those at the lower end of the severity spectrum. However, there are no specific treatments for ACLF, and overall outcomes remain poor. Expedited liver transplantation as a treatment option is limited by organ shortage and a lack of priority allocation for this indication. Other options are therefore urgently needed, and our improved understanding of the condition has led to significant efforts to develop novel therapies. In conclusion, this review aims to summarize the current understanding of the pathophysiological processes involved in the onset, progression, and recovery of ACLF and discuss novel therapies under development.
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Affiliation(s)
- MohammadMahdi Saeidinejad
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Ahmed Elshabrawi
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
- Intensive Care Unit, Endemic Hepatology and Gastroenterology Department, Mansoura University, Mansoura, Egypt
| | - Supachaya Sriphoosanaphan
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok
| | - Fausto Andreola
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Gautam Mehta
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Banwari Agarwal
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
- Intensive Care Unit, Royal Free Hospital, London, United Kingdom
| | - Rajiv Jalan
- Liver Failure Group, Department of Medicine, Institute for Liver and Digestive Health, University College London, London, United Kingdom
- Hepatology Department, Royal Free Hospital, London, United Kingdom
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
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21
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Li ZH, Wang JY, Li XL, Meng SB, Zheng HY, Wang JL, Lei ZY, Lin BL, Zhang J. Mesenchymal stem cell-regulated miRNA-mRNA landscape in acute-on-chronic liver failure. Genomics 2023; 115:110737. [PMID: 37926353 DOI: 10.1016/j.ygeno.2023.110737] [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: 08/30/2023] [Revised: 10/20/2023] [Accepted: 10/30/2023] [Indexed: 11/07/2023]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a major challenge in the field of hepatology. While mesenchymal stem cell (MSC) therapy can improve the prognosis of patients with ACLF, the molecular mechanisms through which MSCs attenuate ACLF remain poorly understood. We performed global miRNA and mRNA expression profiling via next-generation sequencing of liver tissues from MSC-treated ACLF mice to identify important signaling pathways and major factors implicated in ACLF alleviation by MSCs. METHODS Carbon tetrachloride-induced ACLF mice were treated with saline or mouse bone marrow-derived MSCs. Mouse livers were subjected to miRNA and mRNA sequencing. Related signal transduction pathways were obtained through Gene Set Enrichment Analysis. Functional enrichment, protein-protein interaction, and immune infiltration analyses were performed for the differentially expressed miRNA target genes (DETs). Hub miRNA and mRNA associated with liver injury were analyzed using LASSO regression. The expression levels of hub genes were subjected to Pearson's correlation analysis and verified using RT-qPCR. The biological functions of hub genes were verified in vitro. RESULTS The tricarboxylic acid cycle and peroxisome proliferator-activated receptor pathways were activated in the MSC-treated groups. The proportions of liver-infiltrating NK resting cells, M2 macrophages, follicular helper T cells, and other immune cells were altered after MSC treatment. The expression levels of six miRNAs and 10 transcripts correlated with the degree of liver injury. miR-27a-5p was downregulated in the mouse liver after MSC treatment, while its target gene E2f2 was upregulated. miR-27a-5p inhibited E2F2 expression, suppressed G1/S phase transition and proliferation of hepatocytes, in addition to promoting their apoptosis. CONCLUSIONS This is the first comprehensive analysis of miRNA and mRNA expression in the liver tissue of ACLF mice after MSC treatment. The results revealed global changes in hepatic pathways and immune subpopulations. The miR-27a-5p/E2F2 axis emerged as a central regulator of the MSC-induced attenuation of ACLF. The current findings improve our understanding of the molecular mechanisms through which MSCs alleviate ACLF.
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Affiliation(s)
- Zhi-Hui Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, People's Republic of China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People's Republic of China
| | - Jun-Yi Wang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, People's Republic of China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People's Republic of China
| | - Xian-Long Li
- Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People's Republic of China
| | - Shi-Bo Meng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, People's Republic of China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People's Republic of China
| | - Hui-Yuan Zheng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, People's Republic of China
| | - Jia-Lei Wang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, People's Republic of China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People's Republic of China
| | - Zi-Ying Lei
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, People's Republic of China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People's Republic of China.
| | - Bing-Liang Lin
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, People's Republic of China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong 510080, People's Republic of China.
| | - Jing Zhang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, People's Republic of China; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People's Republic of China.
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22
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Dellbrügge F, Jesse LD, Medyukhina A, Liu N, Neugebauer S, Freißmuth M, Höppener S, Figge MT, Morrison H, Riecken LB, Press AT. Contribution of radixin and ezrin to the maintenance of hepatocytes' excretory function in health and disease. Heliyon 2023; 9:e21009. [PMID: 37928027 PMCID: PMC10623174 DOI: 10.1016/j.heliyon.2023.e21009] [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: 08/31/2023] [Revised: 09/29/2023] [Accepted: 10/12/2023] [Indexed: 11/07/2023] Open
Abstract
Background & aims Excretory liver failure is frequently associated with poor prognosis in critically ill patients. It is characterized by the loss of canalicular membrane export pumps at the hepatocyte membrane. The membrane export pump Multidrug resistant-associated protein (MRP) 2 is pivotal in hepatocytes for brushed membrane morphology and transport of various metabolites. In addition, MRP2 anchoring proteins of the Ezrin/Radixin/Moesin (ERM) family are crucial for the correct MRP2 location, integration, and function in different tissues. In hepatocytes, altered ERM signaling is elementary for developing excretory liver failure. Methods Polarized human HepaRG cells, primary human hepatocytes, and hepatocyte-specific Ezrin knockout mice are employed to investigate ERM expression and function in health and the bile duct ligation model of obstructive cholestasis. Results ERM-scaffolding protein Ezrin has no relevant function in maintaining the canalicular structure in hepatocytes during health and disease. Conclusions Homeostasis of the canalicular pole in hepatocytes is maintained exclusively by Radixin but not Ezrin, and Radixin dysfunction promotes cholestasis.
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Affiliation(s)
- Friederike Dellbrügge
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07740, Jena, Germany
- Center for Sepsis Control and Care, Jena University Hospital, Am Klinikum 1, 07740, Jena, Germany
| | - Lena D. Jesse
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07740, Jena, Germany
- Center for Sepsis Control and Care, Jena University Hospital, Am Klinikum 1, 07740, Jena, Germany
| | - Anna Medyukhina
- Research Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute, Beutenbergstraße 11a, 07745, Jena, Germany
| | - Na Liu
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07740, Jena, Germany
| | - Sophie Neugebauer
- Department of Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, Am Klinikum 1, 07740, Jena, Germany
| | - Markus Freißmuth
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07740, Jena, Germany
| | - Stephanie Höppener
- Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich-Schiller University, Fürstengraben 1, 07737, Jena, Germany
| | - Marc T. Figge
- Research Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute, Beutenbergstraße 11a, 07745, Jena, Germany
- Faculty of Biological Sciences, Friedrich-Schiller University, Fürstengraben 1, 07737, Jena, Germany
| | - Helen Morrison
- Faculty of Biological Sciences, Friedrich-Schiller University, Fürstengraben 1, 07737, Jena, Germany
- Leibniz Institute on Aging, Beutenbergstraße 11, 07745, Jena, Germany
| | - Lars B. Riecken
- Leibniz Institute on Aging, Beutenbergstraße 11, 07745, Jena, Germany
| | - Adrian T. Press
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07740, Jena, Germany
- Center for Sepsis Control and Care, Jena University Hospital, Am Klinikum 1, 07740, Jena, Germany
- Medical Faculty, Friedrich-Schiller University, Fürstengraben 1, 07737, Jena, Germany
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23
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Essing T, Bock H, Wieland B, Fluegen G, Bednarsch J, Bode JG, Neumann UP, Roderburg C, Loosen SH, Luedde T. Clinical determinants of hospital mortality in liver failure: a comprehensive analysis of 62,717 patients. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1472-1483. [PMID: 36972596 DOI: 10.1055/a-2016-9061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/29/2023]
Abstract
BACKGROUND Liver failure (LF) is characterised by a loss of the synthetic and metabolic liver function and is associated with a high mortality. Large-scale data on recent developments and hospital mortality of LF in Germany are missing. A systematic analysis and careful interpretation of these datasets could help to optimise outcomes of LF. METHODS We used standardised hospital discharge data of the Federal Statistical Office to evaluate current trends, hospital mortality and factors associated with an unfavourable course of LF in Germany between 2010 and 2019. RESULTS A total of 62,717 hospitalised LF cases were identified. Annual LF frequency decreased from 6716 (2010) to 5855 (2019) cases and was higher among males (60.51%). Hospital mortality was 38.08% and significantly declined over the observation period. Mortality significantly correlated with patients' age and was highest among individuals with (sub)acute LF (47.5%). Multivariate regression analyses revealed pulmonary (ORARDS: 2.76, ORmechanical ventilation: 6.46) and renal complications (ORacute kidney failure: 2.04, ORhepatorenal syndrome: 2.92) and sepsis (OR: 1.92) as factors for increased mortality. Liver transplantation reduced mortality in patients with (sub)acute LF. Hospital mortality significantly decreased with the annual LF case volume and ranged from 47.46% to 29.87% in low- or high-case-volume hospitals, respectively. CONCLUSIONS Although incidence rates and hospital mortality of LF in Germany have constantly decreased, hospital mortality has remained at a very high level. We identified a number of variables associated with increased mortality that could help to improve framework conditions for the treatment of LF in the future.
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Affiliation(s)
- Tobias Essing
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Paracelsus Medical University, Klinikum Nürnberg, Nürnberg, Germany
| | - Hans Bock
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Björn Wieland
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Georg Fluegen
- Department of Surgery (A), University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Jan Bednarsch
- Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany
| | - Johannes G Bode
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Ulf P Neumann
- Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany
| | - Christoph Roderburg
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Sven H Loosen
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Tom Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
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24
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Butt MF, Jalan R. Review article: Emerging and current management of acute-on-chronic liver failure. Aliment Pharmacol Ther 2023; 58:774-794. [PMID: 37589507 DOI: 10.1111/apt.17659] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/02/2023] [Accepted: 07/24/2023] [Indexed: 08/18/2023]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a clinically and pathophysiologically distinct condition from acutely decompensated cirrhosis and is characterised by systemic inflammation, extrahepatic organ failure, and high short-term mortality. AIMS To provide a narrative review of the diagnostic criteria, prognosis, epidemiology, and general management principles of ACLF. Four specific interventions that are explored in detail are intravenous albumin, extracorporeal liver assist devices, granulocyte-colony stimulating factor, and liver transplantation. METHODS We searched PubMed and Cochrane databases for articles published up to July 2023. RESULTS Approximately 35% of hospital inpatients with decompensated cirrhosis have ACLF. There is significant heterogeneity in the criteria used to diagnose ACLF; different definitions identify different phenotypes with varying mortality. Criteria established by the European Association for the Study of the Liver were developed in prospective patient cohorts and are, to-date, the most well validated internationally. Systemic haemodynamic instability, renal dysfunction, coagulopathy, neurological dysfunction, and respiratory failure are key considerations when managing ACLF in the intensive care unit. Apart from liver transplantation, there are no accepted evidence-based treatments for ACLF, but several different approaches are under investigation. CONCLUSION The recognition of ACLF as a distinct entity from acutely decompensated cirrhosis has allowed for better patient stratification in clinical settings, facilitating earlier engagement with the intensive care unit and liver transplantation teams. Research priorities over the next decade should focus on exploring novel treatment strategies with a particular focus on which, when, and how patients with ACLF should be treated.
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Affiliation(s)
- Mohsin F Butt
- Centre for Neuroscience, Trauma and Surgery, Wingate Institute of Neurogastroenterology, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Liver Failure Group, University College London Medical School, Royal Free Hospital Campus, London, UK
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottinghamshire, UK
| | - Rajiv Jalan
- Liver Failure Group, University College London Medical School, Royal Free Hospital Campus, London, UK
- European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium, Barcelona, Spain
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25
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Gülcicegi DE, Goeser T, Kasper P. Prognostic assessment of liver cirrhosis and its complications: current concepts and future perspectives. Front Med (Lausanne) 2023; 10:1268102. [PMID: 37780566 PMCID: PMC10537916 DOI: 10.3389/fmed.2023.1268102] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 08/28/2023] [Indexed: 10/03/2023] Open
Abstract
Liver cirrhosis is an irreversible stage of chronic liver disease with varying clinical course. Acute decompensation of liver cirrhosis represents a watershed in prognosis and is characterized by the occurrence of clinical complications such as ascites, jaundice, hepatic encephalopathy, infections, or portal-hypertensive hemorrhages. Emergent data indicate that an acute decompensation can be subdivided into stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre-acute-on chronic liver failure (pre-ACLF) and acute-on chronic liver failure (ACLF), while the mortality risk varies greatly between the respective subgroups. ACLF is the most severe form of acutely decompensated cirrhosis and characterized by the development of organ failure(s) and a high short-term mortality. Due to the dynamic disease course of acute decompensation, it is paramount to detect patients at particular risk for severe complications those at high risk for developing ACLF as early as possible in order to initiate optimal management. This review describes new concepts and perspectives in the definition and classification of decompensated cirrhosis and provides on overview on emerging predictive scoring systems, non-invasive measurement methods and new biomarkers, which allow an early identification of patients with acute decompensation at risk.
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Affiliation(s)
- Dilan Elcin Gülcicegi
- Department of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | | | - Philipp Kasper
- Department of Gastroenterology and Hepatology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
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Crocombe D, O’Brien A. Antimicrobial prophylaxis in decompensated cirrhosis: friend or foe? Hepatol Commun 2023; 7:e0228. [PMID: 37655979 PMCID: PMC10476838 DOI: 10.1097/hc9.0000000000000228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 06/21/2023] [Indexed: 09/02/2023] Open
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Fu M, He F, Jiang Z, Chen X, Xie Z, Hu JF. Development of a novel near-infrared molecule rotator for early diagnosis and visualization of viscosity changes in acute liver injury models. RSC Adv 2023; 13:26247-26251. [PMID: 37670994 PMCID: PMC10475972 DOI: 10.1039/d3ra04391f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 08/03/2023] [Indexed: 09/07/2023] Open
Abstract
Acute liver injury leading to acute liver failure can be a life-threatening condition. Therefore, timely and accurate early diagnosis of the onset of acute liver injury in vivo is critical. Viscosity is one of the key parameters that can accurately reflect the levels of relevant active analytes at the cellular level. Herein, a novel near-infrared molecule rotator, DJM, was designed and synthesized. This probe exhibited a highly sensitive (461-fold from PBS solution to 95% glycerol solution) and selective response to viscosity with a maximum emission wavelength of 760 nm and a Stokes shift of 240 nm. Furthermore, DJM has exhibited a remarkable capacity to discern viscosity changes induced by nystatin in viable cells with sensitivity and selectivity and further applied in the zebrafish and mouse model of acute liver injury. Additionally, DJM may potentially offer direction for the timely observation and visualization of viscosity in more relevant disease models in the future.
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Affiliation(s)
- Manlin Fu
- Institute of Natural Medicine and Health Products, School of Pharmaceutical Sciences, Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, Taizhou University Zhejiang 318000 China
| | - Fenglin He
- Institute of Natural Medicine and Health Products, School of Pharmaceutical Sciences, Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, Taizhou University Zhejiang 318000 China
| | - Zhelu Jiang
- Institute of Natural Medicine and Health Products, School of Pharmaceutical Sciences, Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, Taizhou University Zhejiang 318000 China
| | - Xue Chen
- Institute of Natural Medicine and Health Products, School of Pharmaceutical Sciences, Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, Taizhou University Zhejiang 318000 China
| | - Zhenda Xie
- Institute of Natural Medicine and Health Products, School of Pharmaceutical Sciences, Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, Taizhou University Zhejiang 318000 China
| | - Jin-Feng Hu
- Institute of Natural Medicine and Health Products, School of Pharmaceutical Sciences, Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, Taizhou University Zhejiang 318000 China
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Amer K, Flikshteyn B, Lingiah V, Tafesh Z, Pyrsopoulos NT. Mechanisms of Disease and Multisystemic Involvement. Clin Liver Dis 2023; 27:563-579. [PMID: 37380283 DOI: 10.1016/j.cld.2023.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2023]
Affiliation(s)
- Kamal Amer
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers University, 185 South Orange Avenue, MSB H Room - 538, Newark, NJ 07101-1709, USA
| | - Ben Flikshteyn
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers University, 185 South Orange Avenue, MSB H Room - 538, Newark, NJ 07101-1709, USA
| | - Vivek Lingiah
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers University, 185 South Orange Avenue, MSB H Room - 538, Newark, NJ 07101-1709, USA
| | - Zaid Tafesh
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers University, 185 South Orange Avenue, MSB H Room - 53, Newark, NJ 07101-1709, USA
| | - Nikolaos T Pyrsopoulos
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers University, 185 South Orange Avenue, MSB H Room - 536, Newark, NJ 07101-1709, USA.
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Kezer CA, Simonetto DA, Shah VH. Acute on Chronic Liver Failure in Patients with Alcohol-Associated Hepatitis: A Review. Clin Liver Dis 2023; 27:659-670. [PMID: 37380289 DOI: 10.1016/j.cld.2023.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2023]
Abstract
Acute on chronic liver failure (ACLF) is a unique disease process associated with significant short-term mortality wherein patients with either chronic liver disease or cirrhosis suffer rapid decompensation in hepatic function accompanied by extrahepatic organ failures. Alcohol-associated hepatitis (AH) is a common precipitant of ACLF and has been shown to uniquely affect the pathophysiology of systemic and hepatic immune responses in patients with ACLF. Treatment of AH-associated ACLF includes supportive measures as well as treatment directed at AH; however, AH-directed therapies unfortunately remain limited and are of suboptimal efficacy.
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Affiliation(s)
- Camille A Kezer
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN, USA
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN, USA
| | - Vijay H Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN, USA.
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Tourkochristou E, Tsounis EP, Tzoupis H, Aggeletopoulou I, Tsintoni A, Lourida T, Diamantopoulou G, Zisimopoulos K, Kafentzi T, de Lastic AL, Rodi M, Tselios T, Thomopoulos K, Mouzaki A, Triantos C. The Influence of Single Nucleotide Polymorphisms on Vitamin D Receptor Protein Levels and Function in Chronic Liver Disease. Int J Mol Sci 2023; 24:11404. [PMID: 37511164 PMCID: PMC10380285 DOI: 10.3390/ijms241411404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/29/2023] [Accepted: 07/11/2023] [Indexed: 07/30/2023] Open
Abstract
Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been associated with chronic liver disease. We investigated the role of VDR SNPs on VDR protein levels and function in patients with chronic liver disease. VDR expression levels were determined in peripheral T lymphocytes (CD3+VDR+), monocytes (CD14+VDR+), and plasma from patients (n = 66) and healthy controls (n = 38). Genotyping of SNPs and the determination of expression of VDR/vitamin D-related genes were performed by using qPCR. The effect of FokI SNP on vitamin D-binding to VDR was investigated by molecular dynamics simulations. CD14+VDR+ cells were correlated with the MELD score. The ApaI SNP was associated with decreased CD3+VDR+ levels in cirrhotic patients and with higher liver stiffness in HCV patients. The BsmI and TaqI SNPs were associated with increased VDR plasma concentrations in cirrhotic patients and decreased CD14+VDR+ levels in HCV patients. The FokI SNP was associated with increased CD3+VDR+ levels in cirrhotic patients and controls. VDR polymorphisms were significantly related to the expression of genes critical for normal hepatocyte function and immune homeostasis. VDR expression levels were related to the clinical severity of liver disease. VDR SNPs may be related to the progression of chronic liver disease by affecting VDR expression levels.
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Affiliation(s)
- Evanthia Tourkochristou
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
| | - Efthymios P Tsounis
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece
| | | | - Ioanna Aggeletopoulou
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
| | - Aggeliki Tsintoni
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece
| | - Theoni Lourida
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece
| | - Georgia Diamantopoulou
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece
| | - Konstantinos Zisimopoulos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece
| | - Theodora Kafentzi
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece
| | - Anne-Lise de Lastic
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
| | - Maria Rodi
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
| | - Theodore Tselios
- Department of Chemistry, University of Patras, 26504 Patras, Greece
| | - Konstantinos Thomopoulos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece
| | - Athanasia Mouzaki
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece
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Bajaj JS, Choudhury AK, Xie Q, Kamath PS, Topazian M, Hayes PC, Torre A, Desalegn H, Idilman R, Cao Z, Alvares-da-Silva MR, George J, Bush BJ, Thacker LR, Wong F. Global disparities in mortality and liver transplantation in hospitalised patients with cirrhosis: a prospective cohort study for the CLEARED Consortium. Lancet Gastroenterol Hepatol 2023; 8:611-622. [PMID: 37230109 PMCID: PMC10330833 DOI: 10.1016/s2468-1253(23)00098-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 03/27/2023] [Accepted: 03/29/2023] [Indexed: 05/27/2023]
Abstract
BACKGROUND Cirrhosis, the end result of liver injury, has high mortality globally. The effect of country-level income on mortality from cirrhosis is unclear. We aimed to assess predictors of death in inpatients with cirrhosis using a global consortium focusing on cirrhosis-related and access-related variables. METHODS In this prospective observational cohort study, the CLEARED Consortium followed up inpatients with cirrhosis at 90 tertiary care hospitals in 25 countries across six continents. Consecutive patients older than 18 years who were admitted non-electively, without COVID-19 or advanced hepatocellular carcinoma, were enrolled. We ensured equitable participation by limiting enrolment to a maximum of 50 patients per site. Data were collected from patients and their medical records, and included demographic characteristics; country; disease severity (MELD-Na score); cirrhosis cause; medications used; reasons for admission; transplantation listing; cirrhosis-related history in the past 6 months; and clinical course and management while hospitalised and for 30 days post discharge. Primary outcomes were death and receipt of liver transplant during index hospitalisation or within 30 days post discharge. Sites were surveyed regarding availability of and access to diagnostic and treatment services. Outcomes were compared by country income level of participating sites, defined according to World Bank income classifications (high-income countries [HICs], upper-middle-income countries [UMICs], and low-income or lower-middle-income countries [LICs or LMICs]). Multivariable models controlling for demographic variables, disease cause, and disease severity were used to analyse the odds of each outcome associated with variables of interest. FINDINGS Patients were recruited between Nov 5, 2021, and Aug 31, 2022. Complete inpatient data were obtained for 3884 patients (mean age 55·9 years [SD 13·3]; 2493 (64·2%) men and 1391 (35·8%) women; 1413 [36·4%] from HICs, 1757 [45·2%] from UMICs, and 714 [18·4%] from LICs or LMICs), with 410 lost to follow-up within 30 days after hospital discharge. The number of patients who died while hospitalised was 110 (7·8%) of 1413 in HICs, 182 (10·4%) of 1757 in UMICs, and 158 (22·1%) of 714 in LICs and LMICs (p<0·0001), and within 30 days post discharge these values were 179 (14·4%) of 1244 in HICs, 267 (17·2%) of 1556 in UMICs, and 204 (30·3%) of 674 in LICs and LMICs (p<0·0001). Compared with patients from HICs, increased risk of death during hospitalisation was found for patients from UMICs (adjusted odds ratio [aOR] 2·14 [95% CI 1·61-2·84]) and from LICs or LMICs (2·54 [1·82-3·54]), in addition to increased risk of death within 30 days post discharge (1·95 [1·44-2·65] in UMICs and 1·84 [1·24-2·72] in LICs or LMICs). Receipt of a liver transplant was recorded in 59 (4·2%) of 1413 patients from HICs, 28 (1·6%) of 1757 from UMICs (aOR 0·41 [95% CI 0·24-0·69] vs HICs), and 14 (2·0%) of 714 from LICs and LMICs (0·21 [0·10-0·41] vs HICs) during index hospitalisation (p<0·0001), and in 105 (9·2%) of 1137 patients from HICs, 55 (4·0%) of 1372 from UMICs (0·58 [0·39-0·85] vs HICs), and 16 (3·1%) of 509 from LICs or LMICs (0·21 [0·11-0·40] vs HICs) by 30 days post discharge (p<0·0001). Site survey results showed that access to important medications (rifaximin, albumin, and terlipressin) and interventions (emergency endoscopy, liver transplantation, intensive care, and palliative care) varied geographically. INTERPRETATION Inpatients with cirrhosis in LICs, LMICs, or UMICs have significantly higher mortality than inpatients in HICs independent of medical risk factors, and this might be due to disparities in access to essential diagnostic and treatment services. These results should encourage researchers and policy makers to consider access to services and medications when evaluating cirrhosis-related outcomes. FUNDING National Institutes of Health and US Department of Veterans Affairs.
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Affiliation(s)
- Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, VA, USA.
| | - Ashok K Choudhury
- Department of Hepatology, Institute for Liver and Biliary Sciences, New Delhi, India
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Mark Topazian
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Gastroenterology and Hepatology Unit, St Paul's Hospital, Millennium Medical College, Addis Ababa, Ethiopia
| | - Peter C Hayes
- Hepatology, Division of Health Sciences, Deanery of Clinical Sciences, University of Edinburgh, Edinburgh, UK
| | - Aldo Torre
- Department of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Hailemichael Desalegn
- Gastroenterology and Hepatology Unit, St Paul's Hospital, Millennium Medical College, Addis Ababa, Ethiopia
| | - Ramazan Idilman
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Zhujun Cao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mario R Alvares-da-Silva
- Department of Hepatology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Jacob George
- Storr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, Sydney, NSW, Australia
| | - Brian J Bush
- Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA
| | - Leroy R Thacker
- Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA
| | - Florence Wong
- Department of Medicine, University of Toronto, Toronto, ON, Canada
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Terres AZ, Balbinot RS, Muscope ALF, Longen ML, Schena B, Cini BT, Rost Jr GL, Balensiefer JIL, Eberhardt LZ, Balbinot RA, Balbinot SS, Soldera J. Acute-on-chronic liver failure is independently associated with higher mortality for cirrhotic patients with acute esophageal variceal hemorrhage: Retrospective cohort study. World J Clin Cases 2023; 11:4003-4018. [PMID: 37388802 PMCID: PMC10303600 DOI: 10.12998/wjcc.v11.i17.4003] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/15/2023] [Accepted: 05/11/2023] [Indexed: 06/12/2023] Open
Abstract
BACKGROUND Acute esophageal variceal hemorrhage (AEVH) is a common complication of cirrhosis and might precipitate multi-organ failure, causing acute-on-chronic liver failure (ACLF).
AIM To analyze if the presence and grading of ACLF as defined by European Society for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) is able to predict mortality in cirrhotic patients presenting AEVH.
METHODS Retrospective cohort study executed in Hospital Geral de Caxias do Sul. Data from medical records from 2010 to 2016 were obtained by searching the hospital electronic database for patients who received terlipressin. Medical records were reviewed in order to determine the diagnosis of cirrhosis and AEVH, including 97 patients. Kaplan-Meier survival analysis was used for univariate analysis and a stepwise approach to the Cox regression for multivariate analysis.
RESULTS All- cause mortality for AEVH patients was 36%, 40.2% and 49.4% for 30-, 90- and 365-day, respectively. The prevalence of ACLF was 41.3%. Of these, 35% grade 1, 50% grade 2 and 15% grade 3. In multivariate analysis, the non-use of non-selective beta-blockers, presence and higher grading of ACLF and higher Model for End-Stage Liver Disease scores were independently associated with higher mortality for 30-day with the addition of higher Child-Pugh scores for 90-day period.
CONCLUSION Presence and grading of ACLF according to the EASL-CLIF criteria was independently associated with higher 30- and 90-day mortality in cirrhotic patients admitted due to AEVH.
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Affiliation(s)
- Alana Zulian Terres
- Clinical Gastroenterology, Universidade de Caxias do Sul, Caxias do Sul 95020-002, Brazil
| | | | | | - Morgana Luisa Longen
- School of Medicine, Universidade de Caxias do Sul, Caxias do Sul 95020-002, Brazil
| | - Bruna Schena
- School of Medicine, Universidade de Caxias do Sul, Caxias do Sul 95020-002, Brazil
| | - Bruna Teston Cini
- School of Medicine, Universidade de Caxias do Sul, Caxias do Sul 95020-002, Brazil
| | | | | | | | - Raul Angelo Balbinot
- Clinical Gastroenterology, Universidade de Caxias do Sul, Caxias do Sul 95020-002, Brazil
| | | | - Jonathan Soldera
- Department of Gastroenterology, University of South Wales, Cardiff CF37 1DL, United Kingdom
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Chaudhry H, Sohal A, Iqbal H, Roytman M. Alcohol-related hepatitis: A review article. World J Gastroenterol 2023; 29:2551-2570. [PMID: 37213401 PMCID: PMC10198060 DOI: 10.3748/wjg.v29.i17.2551] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 03/10/2023] [Accepted: 04/13/2023] [Indexed: 05/23/2023] Open
Abstract
Alcohol-related hepatitis (ARH) is a unique type of alcohol-associated liver disease characterized by acute liver inflammation caused by significant alcohol use. It ranges in severity from mild to severe and carries significant morbidity and mortality. The refinement of scoring systems has enhanced prognostication and guidance of clinical decision-making in the treatment of this complex disease. Although treatment focuses on supportive care, steroids have shown benefit in select circumstances. There has been a recent interest in this disease process, as coronavirus disease 2019 pandemic led to substantial rise in cases. Although much is known regarding the pathogenesis, prognosis remains grim due to limited treatment options. This article summarizes the epidemiology, genetics, pathogenesis, diagnosis and treatment of ARH.
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Affiliation(s)
- Hunza Chaudhry
- Department of Internal Medicine, University of California, San Francisco, Fresno, CA 93701, United States
| | - Aalam Sohal
- Department of Hepatology, Liver Institute Northwest, Seattle, WA 98105, United States
| | - Humzah Iqbal
- Department of Internal Medicine, University of California, San Francisco, Fresno, CA 93701, United States
| | - Marina Roytman
- Department of Gastroenterology and Hepatology, University of California, San Francisco, Fresno, CA 93701, United States
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Li F, Zhang Y, Wang ZH, Gao S, Fan YC, Wang K. SOCS1 methylation level is associated with prognosis in patients with acute-on-chronic hepatitis B liver failure. Clin Epigenetics 2023; 15:79. [PMID: 37149648 PMCID: PMC10163770 DOI: 10.1186/s13148-023-01495-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 04/28/2023] [Indexed: 05/08/2023] Open
Abstract
BACKGROUND Glucocorticoids could greatly improve the prognosis of patients with acute-on-chronic hepatitis B liver failure (ACHBLF). Suppressor of cytokine signaling (SOCS) 1 methylation has been shown to be associated with mortality in ACHBLF. METHODS Eighty patients with ACHBLF were divided into group glucocorticoid (GC) and group conservative medical (CM). Sixty patients with chronic hepatitis B (CHB), and Thirty healthy controls (HCs) served as control group. SOCS1 methylation levels in peripheral mononuclear cells (PBMCs) was detected by MethyLight. RESULTS SOCS1 methylation levels were significantly higher in patients with ACHBLF than those with CHB and HCs (P < 0.01, respectively). Nonsurvivors showed significantly higher SOCS1 methylation levels (P < 0.05) than survivors in both GC and CM groups in ACHBLF patients. Furthermore, the survival rates of the SOCS1 methylation-negative group were significantly higher than that of the methylation-positive group at 1 month (P = 0.014) and 3 months (P = 0.003) follow-up. Meanwhile, GC group and CM group had significantly lower mortality at 3 months, which may be related to application of glucocorticoid. In the SOCS1 methylation-positive group, the 1-month survival rate was significantly improved, which may be related to GC treatment (P = 0.020). However, no significant difference could be observed between the GC group and CM group in the methylation-negative group (P = 0.190). CONCLUSIONS GC treatment could decrease the mortality of ACHBLF and SOCS1 methylation levels might serve as prognostic marker for favorable response to glucocorticoid treatment.
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Affiliation(s)
- Feng Li
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, Shandong, China
| | - Ying Zhang
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, Shandong, China
| | - Zhao-Hui Wang
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, Shandong, China
| | - Shuai Gao
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, Shandong, China
- Hepatology Institute of Shandong University, Jinan, 250012, China
| | - Yu-Chen Fan
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, Shandong, China
- Hepatology Institute of Shandong University, Jinan, 250012, China
| | - Kai Wang
- Department of Hepatology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, Shandong, China.
- Hepatology Institute of Shandong University, Jinan, 250012, China.
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Patnaik SK, Mohanty S, Mishra D, Kanungo M, Patil S, Teja RG, Uthansingh K, Narayan J, Sahu MK, Pati GK. A Prospective Study on the Clinical Significance of Infections in a Hospital Setting Among the Cirrhotic Patients and Their Outcomes. Cureus 2023; 15:e37912. [PMID: 37220470 PMCID: PMC10200015 DOI: 10.7759/cureus.37912] [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] [Accepted: 04/16/2023] [Indexed: 05/25/2023] Open
Abstract
Aim and objectives The infection of microbial agents in cirrhosis has increased due to poor immunity, which increases morbidities and mortalities worldwide. The present study aimed to assess the incidence, the type of infections, the pattern of resistance, and the course of hospitalization among cirrhotic patients in the Eastern coastal region. Methodology The study was a descriptive cross-sectional study, and the current study was undertaken for 24 months at the Department of Gastroenterology and Hepatobiliary Sciences, IMS, and SUM. Hospital, Bhubaneswar. Consecutive cirrhotic patients admitted with bacterial infection were prospectively evaluated, and the infection patterns were accessed. The data were collected in a well-structured proforma designed by our study team. Results Out of the total 200 cases, a fraction of 72.5% of males outnumbered the females; the mean age of presentation was 59 ± 12 years. A fraction of 59% of cases had the habit of consuming alcohol which amounted to the predominant etiological factor for cirrhosis, followed by non-alcoholic steatohepatitis (NASH). Urinary tract infection (UTI) and spontaneous bacterial peritonitis (SBP) were more common types of infections in the healthcare-associated (HCA) group; however, pneumonia and skin and soft tissue infections (SSTI) were predominant types of infections in community-acquired (CA) group. The model for end-stage liver disease (MELD) scores were not significantly different amongst the three groups with infections at the time of Diagnosis infection and at the time of hospitalization. However, the MELD scores were substantially higher at the time of infection diagnosis than the MELD scores at the time of admission amongst the three groups with infection. Conclusion The present study showed that infections in cirrhosis were relatively common. Due to increasing resistance patterns, the judicious usage of antibiotics in cirrhosis could be the need of the hour.
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Affiliation(s)
- Swarup K Patnaik
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Sambedana Mohanty
- Community Medicine, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Debakanta Mishra
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Manjit Kanungo
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Srinith Patil
- Gastroenterology, ESIC Medical College, Gulbarga, IND
| | | | - Kanishka Uthansingh
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Jimmy Narayan
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Manoj K Sahu
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
| | - Girish K Pati
- Gastroenterology, Siksha 'O' Anusandhan Deemed to be University Institute of Medical Sciences and SUM Hospital, Bhubaneswar, IND
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Wang S, Feng R, Wang SS, Liu H, Shao C, Li Y, Link F, Munker S, Liebe R, Meyer C, Burgermeister E, Ebert M, Dooley S, Ding H, Weng H. FOXA2 prevents hyperbilirubinaemia in acute liver failure by maintaining apical MRP2 expression. Gut 2023; 72:549-559. [PMID: 35444014 DOI: 10.1136/gutjnl-2022-326987] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 04/04/2022] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Multidrug resistance protein 2 (MRP2) is a bottleneck in bilirubin excretion. Its loss is sufficient to induce hyperbilirubinaemia, a prevailing characteristic of acute liver failure (ALF) that is closely associated with clinical outcome. This study scrutinises the transcriptional regulation of MRP2 under different pathophysiological conditions. DESIGN Hepatic MRP2, farnesoid X receptor (FXR) and Forkhead box A2 (FOXA2) expression and clinicopathologic associations were examined by immunohistochemistry in 14 patients with cirrhosis and 22 patients with ALF. MRP2 regulatory mechanisms were investigated in primary hepatocytes, Fxr -/- mice and lipopolysaccharide (LPS)-treated mice. RESULTS Physiologically, homeostatic MRP2 transcription is mediated by the nuclear receptor FXR/retinoid X receptor complex. Fxr-/- mice lack apical MRP2 expression and rapidly progress into hyperbilirubinaemia. In patients with ALF, hepatic FXR expression is undetectable, however, patients without infection maintain apical MRP2 expression and do not suffer from hyperbilirubinaemia. These patients express FOXA2 in hepatocytes. FOXA2 upregulates MRP2 transcription through binding to its promoter. Physiologically, nuclear FOXA2 translocation is inhibited by insulin. In ALF, high levels of glucagon and tumour necrosis factor α induce FOXA2 expression and nuclear translocation in hepatocytes. Impressively, ALF patients with sepsis express low levels of FOXA2, lose MRP2 expression and develop severe hyperbilirubinaemia. In this case, LPS inhibits FXR expression, induces FOXA2 nuclear exclusion and thus abrogates the compensatory MRP2 upregulation. In both Fxr -/- and LPS-treated mice, ectopic FOXA2 expression restored apical MRP2 expression and normalised serum bilirubin levels. CONCLUSION FOXA2 replaces FXR to maintain MRP2 expression in ALF without sepsis. Ectopic FOXA2 expression to maintain MRP2 represents a potential strategy to prevent hyperbilirubinaemia in septic ALF.
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Affiliation(s)
- Sai Wang
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Rilu Feng
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Shan Shan Wang
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Beijing Institute of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Hui Liu
- Department of Pathology, Beijing You'an Hospital, Affiliated with Capital Medical University, Beijing, China
| | - Chen Shao
- Department of Pathology, Beijing You'an Hospital, Affiliated with Capital Medical University, Beijing, China
| | - Yujia Li
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Frederik Link
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Stefan Munker
- Department of Medicine II, University Hospital, LMU, Munich, Germany
- Liver Center Munich, University Hospital, LMU, Munich, Germany
| | - Roman Liebe
- Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich Heine University, Düsseldorf, Germany
- Department of Medicine II, Saarland University Medical Centre, Saarland University, Homburg, Germany
| | - Christoph Meyer
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Elke Burgermeister
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Matthias Ebert
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Clinical Cooperation Unit Healthy Metabolism, Center of Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Steven Dooley
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Huiguo Ding
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital, Affiliated with Capital Medical University, Beijing, China
| | - Honglei Weng
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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Alshehri FS, Alorfi NM. Protective role of resveratrol against VCM-induced hepatotoxicity in male wistar rats. Front Pharmacol 2023; 14:1130670. [PMID: 36825158 PMCID: PMC9941161 DOI: 10.3389/fphar.2023.1130670] [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: 12/23/2022] [Accepted: 01/30/2023] [Indexed: 02/10/2023] Open
Abstract
Background: Vancomycin is a glycopeptide antibiotic with a high risk of acute liver injury. Resveratrol is believed to protect the liver against toxicity. Aim: To investigate the ability of resveratrol to attenuate vancomycin-induced liver toxicity in rats injected with vancomycin. Method: Twenty-four adult male Wistar rats were distributed into three groups. The control group received only a vehicle, while the treated group received either vancomycin 200 (mg/kg, i. p.) only or vancomycin (200 mg/kg, i. p.) with resveratrol (20 mg/kg, oral gavage). All groups received their dose once daily for 7 days. Hepatic damage was assessed by measuring biochemical parameter levels in serum, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). Also, antioxidants and inflammation biomarkers such as Interleukin-6 (IL-6), malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH) were measured. Furthermore, the vancomycin-induced pathological changes in the liver were evaluated by histopathological studies. Results: In the vancomycin-treated group, hepatic serum biomarkers such as AST, ALT, ALP, IL-6, and MDA were elevated, while NO and GSH were depleted. However, resveratrol co-treatment with vancomycin prevented the elevation of AST, ALT, ALP, IL-6, and MDA and it protected the liver from NO and GSH depletion. Also, regarding vancomycin-induced degeneration of hepatocytes, resveratrol co-treatment with vancomycin prevented such degeneration and improved mononuclear cells in the liver. Conclusion: The results showed that oral administration of resveratrol has a significant hepatoprotective effect against vancomycin-induced hepatotoxicity.
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Affiliation(s)
| | - Nasser M. Alorfi
- Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
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Abstract
Patients with cirrhosis frequently require admission to the intensive care unit as complications arise in the course of their disease. These admissions are associated with high short- and long-term morbidity and mortality. Thus, understanding and characterizing complications and unique needs of patients with cirrhosis and acute-on-chronic liver failure helps providers identify appropriate level of care and evidence-based treatments. While there is no widely accepted critical care admission criteria for patients with cirrhosis, the presence of organ failure and primary or nosocomial infections are associated with particularly high in-hospital mortality. Optimal management of patients with cirrhosis in the critical care setting requires a system-based approach that acknowledges deviations from canonical pathophysiology. In this review, we discuss appropriate considerations and evidence-based practices for the general care of patients with cirrhosis and critical illness.
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Affiliation(s)
- Thomas N Smith
- Department of Internal Medicine, Mayo Clinic Rochester, Rochester, Minnesota
| | - Alice Gallo de Moraes
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic Rochester, Rochester, Minnesota
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, Minnesota
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Driever EG, Lisman T. Fibrin clot properties and thrombus composition in cirrhosis. Res Pract Thromb Haemost 2023; 7:100055. [PMID: 36798901 PMCID: PMC9925609 DOI: 10.1016/j.rpth.2023.100055] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 11/28/2022] [Accepted: 11/30/2022] [Indexed: 01/21/2023] Open
Abstract
Patients with cirrhosis frequently acquire profound hemostatic alterations, which may affect thrombus quality and composition-factors that determine the susceptibility to embolization and fibrinolysis. In this narrative review, we describe in vitro studies on fibrin clot formation and quantitative and qualitative changes in fibrinogen in patients with cirrhosis, and describe recent findings on the composition of portal vein thrombi in patients with cirrhosis. Patients with mild cirrhosis have increased thrombin generation capacity and plasma fibrinogen levels, which may be balanced by delayed fibrin polymerization and decreased factor XIII levels. With progressing illness, plasma fibrinogen levels decrease, but thrombin generation capacity remains elevated. Fibrinogen is susceptible to posttranslational protein modifications and is, for example, hypersialylated and carbonylated in patients with cirrhosis. Despite changes in thrombin generation, factor XIII levels and the fibrinogen molecule, fibrin fiber thickness, and density are normal in patients with cirrhosis. Paradoxically, fibrin clot permeability in patients with cirrhosis is decreased, possibly because of posttranslational protein modifications. Most patients have normal fibrinolytic potential. We have recently demonstrated that portal vein thrombosis is likely a misnomer as the material that may obstruct the cirrhotic portal vein frequently consists of a thickened portal vein wall, rather than a true thrombus. Patients with cirrhosis often have thrombocytopenia and anemia, which may also affect clot stability and composition, but the role of cellular components in clot quality in cirrhosis has not been extensively studied. Finally, we summarize abstracts on fibrin formation and clot quality that were presented at the ISTH 2022 meeting in London.
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Affiliation(s)
| | - Ton Lisman
- Correspondence Ton Lisman, University Medical Center Groningen, Department of Surgery, BA33, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
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Watanabe Y, Abe H, Kimura N, Arao Y, Ishikawa N, Yuichiro M, Setsu T, Sakamaki A, Kamimura H, Yokoo T, Kamimura K, Tsuchiya A, Terai S. Navitoclax improves acute-on-chronic liver failure by eliminating senescent cells in mice. Hepatol Res 2023; 53:460-472. [PMID: 36628578 DOI: 10.1111/hepr.13879] [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: 09/10/2022] [Revised: 12/21/2022] [Accepted: 12/25/2022] [Indexed: 01/12/2023]
Abstract
AIM Acute-on-chronic liver failure (ACLF), a disease with poor prognosis, is reportedly caused by cellular senescence due to mitochondrial dysfunction. In this study, we described and analyzed the underlying mechanism of a novel approach for ACLF using ABT263/navitoclax (Navi) that selectively eliminates senescent cells. METHODS Irradiation-induced senescent hepatocytes were used for in vitro evaluation of the effects of Navi on ACLF (n = 6 for each group). Lipopolysaccharide- and carbon tetrachloride-induced ACLF mouse model was used for in vivo evaluation of the effects of Navi administration compared with the control using one-way or two-way analysis of variance, followed by Student's t-test or Kruskal-Wallis test. The effects on the senescence-associated secretory phenotype (n = 8 for each group) and mitochondrial functions, including adenosine triphosphate concentration and membrane potential (n = 8 for each group), were investigated using real-time polymerase chain reaction, immunohistochemistry, and enzyme analysis. RESULTS Navi eliminated irradiation-induced senescent hepatocytes in vitro, leading to non-senescent hepatocyte proliferation. Navi eliminated senescent cells in the liver in vivo, resulting in downregulation of mRNA expression of senescence-associated secretory phenotype factors, a decrease of liver enzymes, and upregulated proliferation of non-senescent cells in the liver. Regarding mitochondrial functional assessment in the liver, adenosine triphosphate concentration and membrane potential were upregulated after Navi administration in vitro and in vivo. CONCLUSIONS Navi may ameliorate ACLF damage by eliminating senescent cells in the liver, downregulating senescence-associated secretory phenotype factors, and upregulating mitochondrial functions. We believe that this novel approach using Navi will pave the way for ACLF treatment.
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Affiliation(s)
- Yusuke Watanabe
- Division of Preemptive Medicine for Digestive Disease and Healthy Active Life, School of Medicine, Niigata University, Niigata, Japan.,Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Hiroyuki Abe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Naruhiro Kimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Yoshihisa Arao
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Natsuki Ishikawa
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Maeda Yuichiro
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Toru Setsu
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Takeshi Yokoo
- Division of Preemptive Medicine for Digestive Disease and Healthy Active Life, School of Medicine, Niigata University, Niigata, Japan.,Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
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Im GY. Emerging Biomarkers in Alcohol-associated Hepatitis. J Clin Exp Hepatol 2023; 13:103-115. [PMID: 36647419 PMCID: PMC9840081 DOI: 10.1016/j.jceh.2022.07.246] [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: 03/13/2022] [Revised: 07/14/2022] [Accepted: 07/17/2022] [Indexed: 01/19/2023] Open
Abstract
Alcohol-associated hepatitis (AH) is a clinical syndrome of jaundice, abdominal pain, and anorexia due to prolonged heavy alcohol intake. AH is associated with changes in gene expression, cytokines, immune response, and the gut microbiome. There are limited biomarkers to diagnose and prognosticate in AH, but several non-invasive biomarkers are emerging. In this review, clinical risk-stratifying algorithms, promising AH biomarkers like cytokeratin-18 fragments, genetic polymorphisms, and microRNAs will be reviewed.
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Key Words
- AH, Alcohol-associated hepatitis
- ALD, alcohol-associated liver disease
- ASCA, anti–Saccharomyces cerevisiae antibodies
- AUC, area under the curve
- FGF, fibroblast growth factor
- GAHS, Glasgow alcohol-associated hepatitis score
- HCC, hepatocellular carcinoma
- MELD, model for end-stage liver disease
- NASH, non-alcohol-associated steatohepatitis
- PPV, positive predictive value
- PT, prothrombin time
- VCTE, vibration-controlled transient elastography
- alcohol-associated hepatitis
- biomarkers
- cytokines
- miRNAs, MicroRNAs
- microRNA
- microbiome
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Affiliation(s)
- Gene Y. Im
- Icahn School of Medicine at Mount Sinai, Division of Liver Diseases, Recanati/Miller Transplantation Institute, New York, NY, USA
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Rashed E, Soldera J. CLIF-SOFA and CLIF-C scores for the prognostication of acute-on-chronic liver failure and acute decompensation of cirrhosis: A systematic review. World J Hepatol 2022; 14:2025-2043. [PMID: 36618331 PMCID: PMC9813844 DOI: 10.4254/wjh.v14.i12.2025] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/18/2022] [Accepted: 11/07/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a syndrome characterized by decompensation in individuals with chronic liver disease, generally secondary to one or more extra-hepatic organ failures, implying an elevated mortality rate. Acute decompensation (AD) is the term used for one or more significant consequences of liver disease in a short time and is the most common reason for hospital admission in cirrhotic patients. The European Association for the Study of Liver-Chronic-Liver Failure (EASL-CLIF) Group modified the intensive care Sequential Organ Failure Assessment score into CLIF-SOFA, which detects the presence of ACLF in patients with or without AD, classifying it into three grades.
AIM To investigate the role of the EASL-CLIF definition for ACLF and the ability of CLIF-SOFA, CLIF-C ACLF, and CLIF-C AD scores for prognosticating ACLF or AD.
METHODS This study is a literature review using a standardized search method, conducted using the steps following the guidelines for reporting systematic reviews set out by the PRISMA statement. For specific keywords, relevant articles were found by searching PubMed, ScienceDirect, and BioMed Central-BMC. The databases were searched using the search terms by one reviewer, and a list of potentially eligible studies was generated based on the titles and abstracts screened. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/).
RESULTS Most of the included studies used the EASL-CLIF definition for ACLF to identify cirrhotic patients with a significant risk of short-term mortality. The primary outcome in all reviewed studies was mortality. Most of the study findings were based on an area under the receiver operating characteristic curve (AUROC) analysis, which revealed that CLIF-SOFA, CLIF-C ACLF, and CLIF-C AD scores were preferable to other models predicting 28-d mortality. Their AUROC scores were higher and able to predict all-cause mortality at 90, 180, and 365 d. A total of 50 articles were included in this study, which found that the CLIF-SOFA, CLIF-C ACLF and CLIF-C AD scores in more than half of the articles were able to predict short-term and long-term mortality in patients with either ACLF or AD.
CONCLUSION CLIF-SOFA score surpasses other models in predicting mortality in ACLF patients, especially in the short-term. CLIF-SOFA, CLIF-C ACLF, and CLIF-C AD are accurate short-term and long-term mortality prognosticating scores.
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Affiliation(s)
- Ebrahim Rashed
- Acute Medicine, University of South Wales, Cardiff CF37 1DL, United Kingdom
| | - Jonathan Soldera
- Acute Medicine, University of South Wales, Cardiff CF37 1DL, United Kingdom
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Watanabe Y, Osaki A, Waguri N, Tsuchiya A, Terai S. Prognostic study of acute-on-chronic liver failure patients: Usefulness of the fibrosis-4 index. Medicine (Baltimore) 2022; 101:e31328. [PMID: 36343064 PMCID: PMC9646499 DOI: 10.1097/md.0000000000031328] [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] [Indexed: 11/09/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome characterized by an acute deterioration of liver function in cirrhotic patients. Since treatment of this condition is difficult, its prevention is of paramount importance. The predictors of ACLF are yet to be identified. To determine the prognosis of cirrhotic and ACLF patients, we conducted a retrospective study to analyze each parameter in ACLF patients. Cirrhotic patients with serum total-bilirubin level ≥5.0 mg/dL and prothrombin time (PT) value ≤40% after acute insults were diagnosed with ACLF, whereas patients who met one of the above criteria were diagnosed with extended type of ACLF (EX-ACLF). Overall, in this study, 18 ACLF and 16 EX-ACLF patients retrospectively investigated between 2008 and 2020, and each data was analyzed during and before acute insults. In the analysis during acute insults, renal and coagulation functions showed significant differences between the ACLF and EX-ACLF groups. Furthermore, the mortality rate in the ACLF group was higher than that in the EX-ACLF group. In the analysis before acute insults, aspartate aminotransferase (AST), Fibrosis-4 (FIB-4) index score, and AST to platelet ratio index (APRI) showed significant differences between the two groups. Among these, the FIB-4 index score correlated best with ACLF severity for identifying cirrhotic patients with poor prognosis. The FIB-4 index is the most useful predictor of ACLF severity. Careful management of cirrhotic patients with a high FIB-4 index score is considered beneficial to prevent ACLF occurrence.
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Affiliation(s)
- Yusuke Watanabe
- Division of Preemptive Medicine for Digestive Disease and Healthy Active Life, School of Medicine, Niigata University, Niigata, Japan
- Division of Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, Japan
- *Correspondence: Yusuke Watanabe, Division of Preemptive Medicine for Digestive Disease and Healthy Active Life, School of Medicine, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan (e-mail: )
| | - Akihiko Osaki
- Division of Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, Japan
| | - Nobuo Waguri
- Division of Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
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Kwon HM, Kim JH, Kim JY, Hwang GS. Five-year all-cause mortality in critically ill liver transplant patients with coronary artery disease: analysis of acute-on chronic liver failure. Anesth Pain Med (Seoul) 2022; 17:412-419. [DOI: 10.17085/apm.22168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 08/01/2022] [Indexed: 11/07/2022] Open
Abstract
Background: Patients with acute-on-chronic liver failure (ACLF) are critically ill and have high waiting-list mortality. Although studies demonstrated that appropriately treated coronary artery disease (CAD) should not be regarded as a contraindication to liver transplant (LT), data regarding long-term outcomes in critically ill liver LT recipients are lacking. The aim of this study was to compare the rates of all-cause death at 5 years following LT in patients with ACLF with or without CAD.Methods: Between 2010 and 2020, we evaluated 921 consecutive LT patients (MELD score, 32 ± 9) and ACLF classified by CLIF-C ACLF score. Up to 5-year all-cause death according to the CAD status was examined. CAD was defined as a preoperative history of coronary artery bypass graft or a percutaneous intervention and old myocardial infarction. Kaplan-Meier survival analysis was used.Results: Up to 5 years, 212 (23.0%) of all ACLF patients (n = 921) in whom 17 (29.3%) of 58 CAD patients died. In patients with CAD (6.3%, 58/921), the Kaplan-Meier cumulative mortality rate at 5 years was numerically higher but was not statistically significant when compared with those without CAD (32.9% vs. 23.5%, log-rank, P = 0.25). In subgr oup analysis, there were comparable risks of cumulative mortalities at 5 years across the stratification of ACLF grade 1, 2, and 3 (log-rank P = 0.062, P = 0.72, and P = 0.999, respectively).Conclusions: All-cause mortality is high in patients with ACLF after LT but is not related to the presence of revascularized or treated CAD, across the stratification of ACLF grades.
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Haurylenka D, Silivontchik N. Applicability of the Chronic Liver Failure-Consortium score in patients with cirrhosis and bacterial infections: a single-clinic experience. Gastroenterology 2022; 55:239-245. [DOI: 10.22141/2308-2097.55.4.2021.247915] [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] [Indexed: 01/16/2025]
Abstract
Background. The frequency and characteristics of acute-on-chronic liver failure (ACLF) are reported in numerous articles from different countries. The aim of the study was to assess the cirrhosis decompensation in patients with bacterial infections based on the Chronic Liver Failure-Consortium (CLIF-C) score in one of the city clinics in Belarus. Materials and methods. The patients underwent laboratory and instrumental studies during the hospitalization. The assessment of the syndrome of acute-on-chronic liver failure was performed using the CLIF-C score. Bacterial infections were diagnosed on the basis of standard criteria. Results. The study included 151 cirrhotic patients, 87 males and 64 females. Median age was 55 years (Q1=43; Q3=61). Cirrhosis was predominantly due to alcohol addiction— 83 patients (55%). ACLF was diagnosed in 44 of 151 patients with cirrhosis (29.1%; 95% confidence interval (CI) 22.0–37.1). Bacterial infections were detected in 67 people (44.4%; 95% CI 36.3–52.7). Most often patients had liver failure that was detected by an increase in serum bilirubin level. Among individuals with upper gastrointestinal bleedings, number needed to harm for developing ACLF was 3.3 (95% CI 2.2–4.4). The risk of developing ACLF grade 2 and 3 in cirrhotic patients with infections was 8.2, with 95% CI 1.0–69.6 (number needed to harm was 12.9; 95% CI 10.7–15.0). Bacterial infections increase the risk of acute decompensation in patients with cirrhosis (odds ratio=2.0, p=0.048). Conclusions. The CLIF-C score is quite applicable in our cohort of patients with cirrhosis.
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Vogg J, Maier-Stocker C, Munker S, Mehrl A, Schlosser S, Tews HC, Gülow K, Müller M, Schmid S. Hepatic perfusion as a new predictor of prognosis and mortality in critical care patients with acute-on-chronic liver failure. Front Med (Lausanne) 2022; 9:1008450. [PMID: 36300192 PMCID: PMC9589036 DOI: 10.3389/fmed.2022.1008450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 09/20/2022] [Indexed: 12/07/2022] Open
Abstract
Background and aims Liver diseases are frequent causes of morbidity and mortality worldwide. Liver diseases can lead to cirrhosis, with the risk of acute-on-chronic liver failure (ACLF). For the detection of changes in hepatic hemodynamics, Doppler ultrasonography is a well-established method. We investigated hepatic hemodynamics via serial Doppler ultrasonography to determine the predictive value of changes in hepatic perfusion for the outcome in patients with severe liver diseases compared to established prognostic models such as the MELD (Model for End-Stage Liver Disease) or CLIF-C (Chronic Liver Failure-Consortium) ACLF score. Methods In this prospective cohort study, hepatic perfusion was quantified at baseline before the initiation of treatment and every third day by means of serial measurements of the hepatic artery resistance index (HARI) and the maximum portal vein velocity (PVv) using Doppler ultrasonography in 50 consecutive patients with severe liver diseases admitted to a medical intensive care unit (MICU). The recorded hemodynamic parameters were compared to the MELD score, and the CLIF-C ACLF score to analyze their utility for the prediction of the outcome of patients with severe liver diseases, liver cirrhosis, and ACLF. Results The changes (delta) obtained by serial measurements of the MELD score, HARI, and PVv were analyzed through scatter plots. Bivariate correlation analysis yielded a new positive linear correlation between the delta-HARI and the delta-MELD score (r = 0.469; p < 0.001). In addition, our data revealed a new negative linear correlation between delta-PVv and the delta-MELD score (r = -0.279, p = 0.001). The leading cause of MICU mortality was acute-on-chronic liver failure (ACLF). A subgroup analysis of patients with liver cirrhosis revealed a positive linear correlation between the delta-HARI and the delta-CLIF-C-ACLF score (r = 0.252, p = 0.005). Of clinical relevance, non-survivors of ACLF exhibited a significantly higher mean value for the delta-HARI (0.010 vs. -0.005; p = 0.015) and a lower mean value for the delta-PVv (-0.7 vs. 1.9 cm/s; p = 0.037) in comparison to survivors of ACLF. Conclusion This study shows the prognostic value of the assessment of hepatic perfusion in critical care patients with severe liver diseases by bedside Doppler ultrasound examination and its utility as an accurate predictor of the outcome in patients with ACLF. Increasing HARI and a decreasing PVv are predictors of an adverse outcome. Delta-HARI and delta-PVv are new biomarkers of prognosis and ACLF-related mortality in patients with liver diseases. Delta-HARI and delta-PVv may be helpful in guiding clinical decision-making, especially in catecholamine and fluid management.
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Affiliation(s)
- Johannes Vogg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
- Department of Anesthesiology and Critical Care, School of Medicine, Technical University of Munich, Munich, Germany
| | - Constantin Maier-Stocker
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
| | - Stefan Munker
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Alexander Mehrl
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
| | - Sophie Schlosser
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
| | - Hauke Christian Tews
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, Regensburg, Germany
| | - Karsten Gülow
- 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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Immunomodulation by Hemoadsorption—Changes in Hepatic Biotransformation Capacity in Sepsis and Septic Shock: A Prospective Study. Biomedicines 2022; 10:biomedicines10102340. [PMID: 36289602 PMCID: PMC9598581 DOI: 10.3390/biomedicines10102340] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/13/2022] [Accepted: 09/14/2022] [Indexed: 11/26/2022] Open
Abstract
Background: Sepsis is often associated with liver dysfunction, which is an indicator of poor outcomes. Specific diagnostic tools that detect hepatic dysfunction in its early stages are scarce. So far, the immune modulatory effects of hemoadsorption with CytoSorb® on liver function are unclear. Method: We assessed the hepatic function by using the dynamic LiMAx® test and biochemical parameters in 21 patients with sepsis or septic shock receiving CytoSorb® in a prospective, observational study. Points of measurement: T1: diagnosis of sepsis or septic shock; T2 and T3: 24 h and 48 h after the start of CytoSorb®; T4: 24 h after termination of CytoSorb®. Results: The hepatic biotransformation capacity measured by LiMAx® was severely impaired in up to 95 % of patients. Despite a rapid shock reversal under CytoSorb®, a significant improvement in LiMAx® values appeared from T3 to T4. This decline and recovery of liver function were not reflected by common parameters of hepatic metabolism that remained mostly within the normal range. Conclusions: Hepatic dysfunction can effectively and safely be diagnosed with LiMAx® in ventilated ICU patients under CytoSorb®. Various static liver parameters are of limited use since they do not adequately reflect hepatic dysfunction and impaired hepatic metabolism.
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Roth S, Flint E, Ghataore L, Patel VC, Singanayagam A, Vincent RP, Triantafyllou E, Ma Y, Bernal W, Auzinger G, Heneghan M, Antoniades C, Christ-Crain M, McPhail MJ, Taylor DR, Wendon J, Bernsmeier C. Low Baseline but Not Delta Cortisol Relates to 28-Day Transplant-Free Survival in Acute and Acute-on-Chronic Liver Failure. GASTRO HEP ADVANCES 2022; 2:72-82. [PMID: 39130154 PMCID: PMC11308052 DOI: 10.1016/j.gastha.2022.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 08/19/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims The clinical, prognostic, and therapeutic impact of adrenal insufficiency in acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) remains controversial and exact diagnostic criteria are lacking. We sought to determine the diagnostic and therapeutic value of cortisol measurement and glucocorticoid (GC) treatment in ALF and ACLF. Methods 28-day transplant-free survival (TFS) was studied in relation to absolute cortisol concentrations and to GC treatment in ALF (n = 30) and ACLF (n = 34) patients. Cortisol concentrations and short synacthen test were assessed by chemiluminescence immunoassay and liquid chromatography-mass spectrometry. Clinicians decided independently on GC treatment. In relation, phenotypic and functional characteristics of circulating monocytes were assessed. Results In ALF, baseline cortisol concentrations <387 nmol/L predicted TFS (sensitivity 83%, specificity 53%). In ACLF, baseline cortisol <392 nmol/L correlated with TFS (sensitivity 80%, specificity 61%). In both, ALF and ACLF, GC treatment did not influence 28-day TFS in patients with low baseline cortisol. However, in patients with baseline cortisol exceeding 387 and 392 nmol/L, respectively, TFS was higher if they had been treated with GC. High baseline cortisol was associated with low HLA-DR expression on monocytes. Conclusion Our data suggest a prognostic value of baseline cortisol measurement in ALF and ACLF. Overall, strong activation of the hypothalamic-pituitary-adrenal axis indicated poor prognosis. Furthermore, baseline cortisol deserves prospective evaluation as a guide for GC treatment decision-making.
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Affiliation(s)
- Sofia Roth
- Department of Biomedicine, University of Basel and University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Emilio Flint
- Department of Biomedicine, University of Basel and University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
| | - Lea Ghataore
- Department of Clinical Biochemistry, King's College Hospital NHS Foundation Trust, London, UK
| | - Vishal C. Patel
- Liver Intensive Therapy Unit and Institute of Liver Studies, King's College London, King's College Hospital, London, UK
| | - Arjuna Singanayagam
- Liver Intensive Therapy Unit and Institute of Liver Studies, King's College London, King's College Hospital, London, UK
- Hepatology Department, Imperial College London, St. Mary’s Hospital, London, UK
| | - Royce P. Vincent
- Department of Clinical Biochemistry, King's College Hospital NHS Foundation Trust, London, UK
| | - Evangelos Triantafyllou
- Liver Intensive Therapy Unit and Institute of Liver Studies, King's College London, King's College Hospital, London, UK
- Hepatology Department, Imperial College London, St. Mary’s Hospital, London, UK
| | - Yun Ma
- Liver Intensive Therapy Unit and Institute of Liver Studies, King's College London, King's College Hospital, London, UK
| | - William Bernal
- Liver Intensive Therapy Unit and Institute of Liver Studies, King's College London, King's College Hospital, London, UK
| | - Georg Auzinger
- Liver Intensive Therapy Unit and Institute of Liver Studies, King's College London, King's College Hospital, London, UK
| | - Michael Heneghan
- Liver Intensive Therapy Unit and Institute of Liver Studies, King's College London, King's College Hospital, London, UK
| | - Charalambos Antoniades
- Liver Intensive Therapy Unit and Institute of Liver Studies, King's College London, King's College Hospital, London, UK
- Hepatology Department, Imperial College London, St. Mary’s Hospital, London, UK
| | - Mirjam Christ-Crain
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, Switzerland
| | - Mark J.W. McPhail
- Liver Intensive Therapy Unit and Institute of Liver Studies, King's College London, King's College Hospital, London, UK
| | - David R. Taylor
- Department of Clinical Biochemistry, King's College Hospital NHS Foundation Trust, London, UK
| | - Julia Wendon
- Liver Intensive Therapy Unit and Institute of Liver Studies, King's College London, King's College Hospital, London, UK
| | - Christine Bernsmeier
- Department of Biomedicine, University of Basel and University Centre for Gastrointestinal and Liver Diseases, Basel, Switzerland
- Liver Intensive Therapy Unit and Institute of Liver Studies, King's College London, King's College Hospital, London, UK
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Zhang L, Zhao Y, Xie Z, Xiao L, Hu Q, Li Q, Tang S, Wang J, Li L. 1,5-Anhydroglucitol Predicts Mortality in Patients with HBV-Related Acute-on-chronic Liver Failure. J Clin Transl Hepatol 2022; 10:651-659. [PMID: 36062285 PMCID: PMC9396314 DOI: 10.14218/jcth.2021.00347] [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: 08/19/2021] [Revised: 10/18/2021] [Accepted: 11/03/2021] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS 1,5-Anhydroglucitol (1,5AG) activity has been reported in chronic liver disease. Hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF) patients have a high mortality. We aimed to discover the relationship between serum 1,5AG and the prognosis of HBV-ACLF. METHODS Serum 1,5AG levels were determined in 333 patients with HBV-ACLF, 300 without diabetes were allocated to derivation (n=206) and validation cohorts (n=94), and 33 were recruited to evaluate 1,5AG in those with diabetes. Forty patients with chronic hepatitis B, 40 with liver cirrhosis, and 40 healthy people were controls in the validation cohort. RESULTS In the derivation and validation cohorts, serum 1,5AG levels were significantly lower in nonsurvivors than in survivors. The AUC of 1,5AG for 28-day mortality was 0.811. In patients with diabetes, serum 1,5AG levels were also significantly lower in nonsurvivors than in survivors. In multivariate Cox regression analysis, serum 1,5AG levels were independently associated with 28-day mortality. A novel predictive model (ACTIG) based on 1,5AG, age, TB, cholesterol, and INR was derived to predict mortality. In ACTIG, the AUC for 28-day mortality was 0.914, which was superior to some prognostic score models. ACTIG was also comparable to those prognostic score models in predicting 6-month mortality. In mice with D-galactosamine/lipopolysaccharide-induced liver failure, 1,5AG levels were significantly reduced in serum and significantly increased in urine and liver tissue. CONCLUSIONS Serum 1,5AG levels are a promising predictor of short-term mortality in HBV-ACLF patients. The 1,5AG distribution changed in mice with D-galactosamine/ lipopolysaccharide-induced liver failure.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Lanjuan Li
- Correspondence to: Lanjuan Li, Chief of Key Laboratory of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China. ORCID: https://orcid.org/0000-0001-6945-0593. Tel/Fax: +86-571-87236459, E-mail:
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Characteristics and Risk Factors of Myocardial Injury after Traumatic Hemorrhagic Shock. J Clin Med 2022; 11:jcm11164799. [PMID: 36013038 PMCID: PMC9409653 DOI: 10.3390/jcm11164799] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/05/2022] [Accepted: 08/15/2022] [Indexed: 11/16/2022] Open
Abstract
Myocardial injury increases major adverse cardiovascular events and mortality in patients with traumatic hemorrhagic shock, but its prevalence and risk factors remain unclear. This study aimed to assess the prevalence and risk factors of myocardial injury after traumatic hemorrhagic shock. This was an observational, retrospective cohort study of patients with traumatic hemorrhagic shock at a tertiary university hospital from November 2012 to July 2021. Patient characteristics and clinical variables were recorded in 314 patients. The outcome was the occurrence of myocardial injury after traumatic hemorrhagic shock. Risk factors for myocardial injury were identified using logistic regression. The incidence of myocardial injury after the traumatic hemorrhagic shock was 42.4%, and 95.5% of myocardial injuries occurred within the first three days after trauma. In the multivariate analysis, the independent risk factors for myocardial injury after traumatic hemorrhagic shock included heart rate of >100 beats/min (OR [odds ratio], 3.33; 95% confidence interval [CI], 1.56−7.09; p = 0.002), hemoglobin level of <70 g/L (OR, 3.50; 95% CI, 1.15−10.60; p = 0.027), prothrombin time of >15 s (OR, 2.39; 95% CI, 1.12−5.10; p = 0.024), acute kidney injury (OR, 2.75; 95% CI, 1.27−5.93; p = 0.01), and a higher APACHE II score (OR, 1.08; 95% CI, 1.01−1.15; p = 0.018). The area under the receiver operating characteristic curve for the prediction of myocardial injury after a traumatic hemorrhagic shock was 0.67 (95% CI, 0.68−0.79) for a heart rate of >100 beats/min, 0.67 (95% CI, 0.61−0.73) for hemoglobin level of <70 g/L, 0.66 (95% CI, 0.60−0.73) for prothrombin time of >15 s, 0.70 (95% CI, 0.64−0.76) for acute kidney injury, and 0.78 (95% CI, 0.73−0.83) for APACHE II scores. The incidence rate of myocardial injury in traumatic hemorrhagic shock is high, and heart rates of >100 beats/min, hemoglobin levels of <70 g/L, prothrombin times of >15 s, AKI and higher APACHE II scores are independent risk factors for myocardial injury after traumatic hemorrhagic shock. These findings may help clinicians to identify myocardial injury after traumatic hemorrhagic shock early and initiate appropriate treatment.
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