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Lopes D, Bandovas JP, Chumbinho B, Santo CE, Sousa M, Ferreira B, Val-Flores L, Germano N, Pereira R, Cardoso FS, Bento L, Póvoa P. Pancreatic Stone Protein in patients with liver failure: A prospective pilot cohort study. Anaesth Crit Care Pain Med 2025; 44:101486. [PMID: 39892616 DOI: 10.1016/j.accpm.2025.101486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 10/30/2024] [Accepted: 11/05/2024] [Indexed: 02/04/2025]
Abstract
BACKGROUND Pancreatic Stone Protein (PSP) seems to have higher accuracy for sepsis detection compared to other biomarkers. As PSP has never been studied in patients with liver failure (LF), our purpose was to assess its accuracy for diagnosis of infection and prognosis in this population. METHODS We conducted a prospective pilot cohort study on patients with LF consecutively admitted to the Intensive Care Unit of a liver transplant center in 2021-2023. Ongoing overt infection was an exclusion criterion. Daily measurements of biomarkers were performed until discharge, death, or for 21 days. Analysis was performed by adjusting the baseline for the first infection episode (median on D3), which was the reference for those non-infected. RESULTS Sixteen patients were included, 7 with acute and 9 with acute-on-chronic LF. Median age was 54 (interquartile range 42-64) years, half were female, with admission SOFA score of 10 (IQR 8-12). Hospital mortality was 43.8% (n = 7). An infection was observed in 8 patients, who presented non-significantly higher levels of PSP than non-infected ones during follow-up. Levels were higher in non-survivors than survivors (p < 0.05 from D4 on and since the day of infection considering only infected patients). Similarly, patients under renal replacement therapy had higher PSP levels than others (p < 0.05, D2 to D7 after admission). CONCLUSION This pilot study provides early insights into PSP kinetics, suggesting a potential role for prognosis in patients with LF. PSP rises in both ALF and ACLF to levels sustainably higher than those expected for healthy adults. Further research is needed to reassess its diagnostic accuracy for infection and redefine cut-offs in this population.
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Affiliation(s)
- Diogo Lopes
- Department of Intensive Care Medicine, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal.
| | - João Pedro Bandovas
- Department of General Surgery, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | - Beatriz Chumbinho
- Department of General Surgery, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | | | - Mónica Sousa
- Transplant Unit, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | - Bernardo Ferreira
- Department of Intensive Care Medicine, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | - Luis Val-Flores
- Department of Intensive Care Medicine, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | - Nuno Germano
- Department of Intensive Care Medicine, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | - Rui Pereira
- Department of Intensive Care Medicine, Curry Cabral Hospital, ULSSJ, Lisboa, Portugal
| | | | - Luís Bento
- Department of Intensive Care Medicine, São José Hospital, ULSSJ, Lisboa, Portugal; NOVA Medical School, CHRC, NOVA University of Lisbon, Lisbon, Portugal
| | - Pedro Póvoa
- NOVA Medical School, CHRC, NOVA University of Lisbon, Lisbon, Portugal; Intensive Care Unit 4, Department of Intensive Care, São Francisco Xavier Hospital, ULSLO, Lisboa, Portugal; Center for Clinical Epidemiology and Research Unit of Clinical Epidemiology, OUH Odense University Hospital, Denmark
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Wejnaruemarn S, Susantitaphong P, Komolmit P, Treeprasertsuk S, Thanapirom K. Procalcitonin and presepsin for detecting bacterial infection and spontaneous bacterial peritonitis in cirrhosis: A systematic review and meta-analysis. World J Gastroenterol 2025; 31:99506. [PMID: 39958447 PMCID: PMC11752710 DOI: 10.3748/wjg.v31.i6.99506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 11/23/2024] [Accepted: 12/23/2024] [Indexed: 01/10/2025] Open
Abstract
BACKGROUND Diagnosing bacterial infections (BI) in patients with cirrhosis can be challenging because of unclear symptoms, low diagnostic accuracy, and lengthy culture testing times. Various biomarkers have been studied, including serum procalcitonin (PCT) and presepsin. However, the diagnostic performance of these markers remains unclear, requiring further informative studies to ascertain their diagnostic value. AIM To evaluate the pooled diagnostic performance of PCT and presepsin in detecting BI among patients with cirrhosis. METHODS We performed a systematic search of the MEDLINE, EMBASE, and Scopus databases for studies that evaluated the diagnostic role of PCT and presepsin from inception to June 2024. Sensitivity and specificity values were pooled using a random effects model. BI was diagnosed based on clinical manifestations, physical examination, laboratory data, and radiological findings. RESULTS Of the 6639 articles retrieved, 28 met the inclusion criteria and included 4287 patients with 1789 cases of BI (41.7%). The bivariate pooled sensitivity and specificity estimates of PCT for BI diagnosis were 0.73 [95% confidence interval (CI): 0.64-0.81] and 0.83 (95%CI: 0.79-0.87), respectively. The diagnostic odds ratio (DOR) of PCT was 17.21 (95%CI: 9.57-30.95). Presepsin showed a pooled sensitivity of 0.75 (95%CI: 0.60-0.86), specificity of 0.80 (95%CI: 0.68-0.88), and DOR of 12.33 (95%CI: 5.10-29.83) for diagnosing BI. The pooled sensitivity and specificity of PCT for diagnosing spontaneous bacterial peritonitis (SBP) were 0.76 (95%CI: 0.67-0.84) and 0.87 (95%CI: 0.78-0.92), respectively. The positive likelihood ratio of PCT was 5.57 (95%CI: 3.34-9.29), which was sufficiently indicative of SBP. The DOR of PCT was 29.50 (95%CI: 12.30-70.80). CONCLUSION PCT and presepsin have high sensitivity and specificity for detecting BI in patients with cirrhosis. Furthermore, PCT has good diagnostic value as a rule-in test for SBP diagnosis.
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Affiliation(s)
- Salisa Wejnaruemarn
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Paweena Susantitaphong
- Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
- Center of Excellence for Metabolic Bone Disease in CKD Patients, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Hepatic Fibrosis and Cirrhosis, Chulalongkorn University, Bangkok 10330, Thailand
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Hepatic Fibrosis and Cirrhosis, Chulalongkorn University, Bangkok 10330, Thailand
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
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Hackstein CP. Liver damage and immune responses. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:56-64. [PMID: 39793602 DOI: 10.1055/a-2365-3796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2025]
Abstract
Chronic liver disease (CLD) has massive systemic repercussions including major impacts on the body's immune system. Abnormalities in phenotype, function and numbers of various immune cell subsets have been established by a large number of clinical and pre-clinical studies. The loss of essential immune functions renders CLD-patients exceptionally susceptible to bacterial and viral infections and also impairs the efficacy of vaccination. Consequently, infections represent a major clinical issue causing significant morbidity and mortality in these patients. Mechanistically, the immune dysfunction associated with CLD results from the increased translocation of bacteria and bacterial cues from the intestine. These trigger a signaling axis around the cytokines IFN I and IL-10 in hepatic myeloid cells, which aside from impairing the function of the myeloid cells themselves, also has notable negative impacts on the functionality of other immune cells. T cells in CLD-patients and -models are especially affected by this signaling axis and display a variety of quantitative and qualitative defects. Due to the high clinical relevance, understanding the mechanisms underlaying CED-associated immune dysfunction is of critical importance to discover and develop new therapeutic targets.
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Affiliation(s)
- Carl-Philipp Hackstein
- Institut für Molekulare Immunologie, Technische Universität München, München, Germany
- Zentrum für Infektionsprävention (ZIP), Technische Universität München, Freising, Germany
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Ferguson Toll J, Solà E, Perez MA, Piano S, Cheng A, Subramanian AK, Kim WR. Infections in decompensated cirrhosis: Pathophysiology, management, and research agenda. Hepatol Commun 2024; 8:e0539. [PMID: 39365139 PMCID: PMC11458171 DOI: 10.1097/hc9.0000000000000539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 08/01/2024] [Indexed: 10/05/2024] Open
Abstract
Bacterial infections in patients with cirrhosis lead to a 4-fold increase in mortality. Immune dysfunction in cirrhosis further increases the risk of bacterial infections, in addition to alterations in the gut microbiome, which increase the risk of pathogenic bacteria. High rates of empiric antibiotic use contribute to increased incidence of multidrug-resistant organisms and further increases in mortality. Despite continous advances in the field, major unknowns regarding interactions between the immune system and the gut microbiome and strategies to reduce infection risk and improve mortality deserve further investigation. Here, we highlight the unknowns in these major research areas and make a proposal for a research agenda to move toward improving disease progression and outcomes in patients with cirrhosis and infections.
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Affiliation(s)
- Jessica Ferguson Toll
- Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA
| | | | - Salvatore Piano
- Department of Medicine, University Hospital of Padova, Padova, Italy
| | - Alice Cheng
- Department of Medicine, University of Chicago, Chicago, Illinois, USA
| | - Aruna K. Subramanian
- Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - W. Ray Kim
- Department of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA
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Rodríguez-Negrete EV, Gálvez-Martínez M, Sánchez-Reyes K, Fajardo-Felix CF, Pérez-Reséndiz KE, Madrigal-Santillán EO, Morales-González Á, Morales-González JA. Liver Cirrhosis: The Immunocompromised State. J Clin Med 2024; 13:5582. [PMID: 39337069 PMCID: PMC11432654 DOI: 10.3390/jcm13185582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 09/11/2024] [Accepted: 09/17/2024] [Indexed: 09/30/2024] Open
Abstract
Systemic inflammation and immunodeficiency are important components of cirrhosis-associated immune dysfunction (CAID), the severity of which is dynamic, progressive, and associated with the greater deterioration of liver function. Two inflammation phenotypes have been described: low-grade and high-grade systemic inflammation. Both of these phenotypes are related to liver cirrhosis function; thus, high-grade inflammation is correlated with the severity of hepatic insufficiency, bacterial translocation, and organic insufficiency, with which the risk of infections increases and the prognosis worsens. Bacterial translocation (BT) plays a relevant role in persistent systemic inflammation in patients with cirrhosis, and the prophylactic employment of antibiotics is useful for reducing events of infection and mortality.
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Affiliation(s)
- Elda Victoria Rodríguez-Negrete
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico; (E.V.R.-N.); (M.G.-M.); (C.F.F.-F.); (K.E.P.-R.)
- Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico;
| | - Marisol Gálvez-Martínez
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico; (E.V.R.-N.); (M.G.-M.); (C.F.F.-F.); (K.E.P.-R.)
| | - Karina Sánchez-Reyes
- Servicio de Cirugía General, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico;
| | - Carlos Fernando Fajardo-Felix
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico; (E.V.R.-N.); (M.G.-M.); (C.F.F.-F.); (K.E.P.-R.)
| | - Karla Erika Pérez-Reséndiz
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico; (E.V.R.-N.); (M.G.-M.); (C.F.F.-F.); (K.E.P.-R.)
| | | | - Ángel Morales-González
- Escuela Superior de Cómputo, Instituto Politécnico Nacional, Unidad Profesional “A. López Mateos”, Ciudad de México 07738, Mexico
| | - José Antonio Morales-González
- Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico;
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Incicco S, Angeli P, Piano S. Infectious Complications of Portal Hypertension. Clin Liver Dis 2024; 28:525-539. [PMID: 38945641 DOI: 10.1016/j.cld.2024.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Patients with cirrhosis and clinically significant portal hypertension are at high risk of developing bacterial infections (BIs) that are the most common trigger of acute decompensation and acute-on-chronic liver failure. Furthermore, after decompensation, the risk of developing BIs further increases in an ominous vicious circle. BIs may be subtle, and they should be ruled out in all patients at admission and in case of deterioration. Timely administration of adequate empirical antibiotics is the cornerstone of treatment. Herein, we reviewed current evidences about pathogenesis, clinical implications and management of BIs in patients with cirrhosis and portal hypertension.
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Affiliation(s)
- Simone Incicco
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy.
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Lan NTN, Lieu DQ, Anh TN, Thuong LH, Tuong TTK, Bang MH. Characteristics and Related Factors of Bacterial Infection Among Patients With Cirrhosis. Mater Sociomed 2024; 36:90-96. [PMID: 38590588 PMCID: PMC10999149 DOI: 10.5455/msm.2024.36.90-96] [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: 01/19/2024] [Accepted: 02/25/2024] [Indexed: 04/10/2024] Open
Abstract
Background Infection causes cirrhosis to decompensate, affecting liver function and resulting in several complications, including esophageal variceal hemorrhage, hepatic encephalopathy, and hepatorenal syndrome. Objective: This study aimed to identify the prevalence, essential features, and related factors of bacterial infection among patients with cirrhosis in Vietnam. Methods This retrospective study included 317 patients diagnosed with cirrhosis, who were divided into two groups: group 1 including 125 patients with bacterial infection and group 2 including 192 patients without bacterial infection. Infection was diagnosed on the basis of its localization. Results Spontaneous bacterial peritonitis (SBP; 31.2%) and pneumonia (28.8%) were the most common infections identified. The procalcitonin (PCT) level had a strong diagnostic value with an area under the curve value of 0.868. The most common type of gram-negative bacteria was Escherichia coli, while the gram-positive bacteria seen were Staphylococcus, Enterococcus, and Streptococcus among the patients with infection. In the logistic regression analysis, Child-Pugh class B and C (p<0.001, OR=4.14, CI=1.90-9.03; OR=4.76, CI=2.03-11.16, respectively) and the presence of acute kidney injury (p=0.009, OR=2.57, CI=1.27-5.22) and gastrointestinal hemorrhage (p=0.035, OR=0.39, CI=0.16-0.94) significantly differed between the groups. Conclusion The most prevalent type of bacterial infection in patients with cirrhosis is SBP, with gram-negative bacteria being the most common cause. The PCT level is useful in identifying infection in patients with cirrhosis. Decompensated cirrhosis is linked to a higher risk of infection.
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Affiliation(s)
| | - Dau Quang Lieu
- Department of Internal Medicine, Hanoi Medical University Hospital, Hanoi, Vietnam
| | - Tran Ngoc Anh
- Department of Internal Medicine, Hanoi Medical University Hospital, Hanoi, Vietnam
- Department of Internal Medicine, Hanoi Medical University, Hanoi, Vietnam
| | - Le Hoai Thuong
- Department of Internal Medicine, Hanoi Medical University, Hanoi, Vietnam
| | - Tran-Thi Khanh Tuong
- Department of Internal Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
| | - Mai Hong Bang
- Department of Gastroenterology, 108 Military Central Hospital, Hanoi, Vietnam
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Abstract
Bacterial infections (BIs) are the most common precipitating event of acute-on-chronic liver failure (ACLF) and a frequent complication of ACLF. BIs aggravate the course of the syndrome and are associated with higher mortality rates. For this reason, BIs should be promptly diagnosed and treated in all patients with ACLF. The administration of an appropriate empirical antibiotic therapy improves survival in patients with BIs and ACLF and is the cornerstone of treatment. Due to the spread of antibiotic resistance worldwide, the empirical treatment should cover multi-drug-resistant organisms. Herein we reviewed the current evidence about the management of BIs in ACLF.
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Affiliation(s)
- Simone Incicco
- Department of Medicine (DIMED), Unit of Internal Medicine and Hepatology (UIMH), University Hospital of Padova, Via Giustiniani 2, Padova 35128, Italy
| | - Paolo Angeli
- Department of Medicine (DIMED), Unit of Internal Medicine and Hepatology (UIMH), University Hospital of Padova, Via Giustiniani 2, Padova 35128, Italy
| | - Salvatore Piano
- Department of Medicine (DIMED), Unit of Internal Medicine and Hepatology (UIMH), University Hospital of Padova, Via Giustiniani 2, Padova 35128, Italy.
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Schult D, Rasch S, Schmid RM, Lahmer T, Mayr U. EASIX Is an Accurate and Easily Available Prognostic Score in Critically Ill Patients with Advanced Liver Disease. J Clin Med 2023; 12:jcm12072553. [PMID: 37048641 PMCID: PMC10094870 DOI: 10.3390/jcm12072553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 03/18/2023] [Accepted: 03/22/2023] [Indexed: 03/31/2023] Open
Abstract
Acute-on-chronic liver failure (ACLF) is associated with high mortality. Objective prognostic scores are important for treatment decisions. EASIX (Endothelial Activation and Stress Index) is a simple biomarker consisting of LDH, platelets, and creatinine, reflecting endothelial dysfunction after allogeneic stem cell transplantation. Considering endothelial dysfunction in the pathogenesis of ACLF, this study aimed to test the discriminative ability of EASIX in advanced liver disease. We retrospectively analysed the prognostic potential of EASIX to predict 28-day and 3-month mortality in a total of 188 liver cirrhotic patients requiring treatment at the intensive care unit. We evaluated the ability of EASIX to rule out early infections and predict the need for hemodialysis. EASIX performed moderately better than established scores in predicting 28-day mortality (AUC = 0.771) and was nearly equivalent (AUC = 0.791) to SOFA and APACHE-II in the prediction of 3-month mortality. Importantly, EASIX showed better diagnostic potential in ruling out clinically apparent infections than common proinflammatory markers (AUC = 0.861, p < 0.001) and showed suitable accuracy in predicting the need for hemodialysis (AUC = 0.833). EASIX is an accurate, objective and easily assessable biomarker for predicting mortality and complications in patients with advanced liver disease.
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Jeong JH, Lee SB, Sung A, Shin H, Kim DH. Factors predicting mortality in patients with alcoholic liver cirrhosis visiting the emergency department. Medicine (Baltimore) 2023; 102:e33074. [PMID: 36827072 PMCID: PMC11309678 DOI: 10.1097/md.0000000000033074] [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: 12/20/2022] [Revised: 02/01/2023] [Accepted: 02/02/2023] [Indexed: 02/25/2023] Open
Abstract
Liver cirrhosis (LC) is a major cause of morbidity and mortality worldwide and is becoming a regional and healthcare burden. South Korea is one of the 10 countries with the highest age standardized prevalence of decompensated LC. Moreover, the proportion of patients with alcoholic LC is increasing and there has been no decrease in the incidence of decompensated alcoholic LC. Patients with decompensated LC frequently visit the emergency department (ED). Several studies focused on patients with LC who visited the ED, but the studies about alcoholic LC were limited. This study aimed to identify predicting factors for mortality in alcoholic LC patients visiting the ED. This was a retrospective study of alcoholic LC patients who visited an ED between November 2017 and June 2021. The baseline characteristics, complications of LC, model for end-stage liver disease (MELD) score, and laboratory values including lactate were assessed. The primary outcome was in-hospital mortality. In total, 433 patients with alcoholic LC were included for analysis and the in hospital mortality rate was 15.9% (n = 69). Univariate regression analyses identified that MELD score, lactate, platelet, international normalized ratio, bilirubin, creatinine, albumin, and C-reactive protein (CRP) predicted in-hospital mortality. Multivariate regression analysis showed that MELD score, lactate, albumin, and CRP were significantly associated with in-hospital mortality. MELD score, lactate, albumin, and CRP predicted the mortality in alcoholic LC patients visiting the ED.
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Affiliation(s)
- Jin Hee Jeong
- Department of Emergency Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Republic of Korea
- Gyeongsang Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju-si, Gyeongsangnam-do, Republic of Korea
| | - Sang Bong Lee
- Department of Emergency Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Republic of Korea
| | - Aejin Sung
- Department of Emergency Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Republic of Korea
| | - Hyuntack Shin
- Department of Emergency Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Republic of Korea
| | - Dong Hoon Kim
- Department of Emergency Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Republic of Korea
- Gyeongsang Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju-si, Gyeongsangnam-do, Republic of Korea
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Verma R, Satapathy SK, Bilal M. Procalcitonin and C-reactive protein in the diagnosis of spontaneous bacterial peritonitis. Transl Gastroenterol Hepatol 2022; 7:36. [PMID: 36300145 PMCID: PMC9468983 DOI: 10.21037/tgh-19-297] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 05/12/2021] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a serious complication of cirrhosis and is associated with high morbidity and mortality. Rapid institution of appropriate antibiotics is central to the improved patient outcome. Correctly obtaining ascites fluid for analysis has several technical and logistic limitations resulting in overuse of empiric antibiotics when patients are admitted to the hospital with suspected SBP. Procalcitonin and C-reactive protein (CRP) are non-invasive markers of infection. We conducted a study to illustrate the role of these markers in making the diagnosis of SBP in patients with cirrhosis. METHODS A total of 45 patients were enrolled in this prospective cohort study, 14 (31.1%) of which were found to have SBP. Ascitic fluid neutrophils, serum procalcitonin and CRP levels were measured prior to initiation of antibiotics and these parameters were compared between the two groups. Area under receiver operator characteristic (AUROC) curves were used to assess the diagnostic accuracy of procalcitonin and CRP in this population. We defined neutrocytic SBP group as a combination of patients who had classic SBP (positive ascitic culture and >250 neutrophils/mm3) and culture-negative neutrocytic ascites. RESULTS Serum procalcitonin (2.81±2.59 vs. 0.43±0.48 ng/mL; P=0.0032), serum CRP (60.30±44.48 vs. 22.2±23.28; P=0.0055) and ascitic fluid neutrophil levels (49.23±30.90 vs. 16.7±20.39; P=0.0064) were significantly higher in SBP group than non-SBP group. AUROC for procalcitonin (cut-off >2.0 ng/mL) was 0.75 (95% CI, 0.61-0.88), CRP (cut-off >3.0 mg/L) was 0.55 (95% CI, 0.43-0.68) and for procalcitonin combined with CRP was 0.76 (95% CI, 0.61-0.90) for diagnosing all-cause SBP. In a subgroup analysis of patients with neutrocytic SBP, AUROC for procalcitonin was 0.88 (95% CI, 0.74-1.00), CRP was 0.62 (95% CI, 0.45-0.79) and for procalcitonin combined with CRP was 0.93 (95% CI, 0.81-1.00). Addition of CRP to procalcitonin did not significantly change the AUROC for diagnosis of SBP. CONCLUSIONS Serum procalcitonin could be used as an adjunctive non-invasive biomarker in diagnosing SBP with a high degree of accuracy in cirrhotic patients. Addition of CRP does not seem to significantly increase the diagnostic accuracy of procalcitonin.
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Affiliation(s)
- Rajanshu Verma
- Transplant Hepatology/Gastroenterology fellow, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Sanjaya K. Satapathy
- Department of Transplant Surgery, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
- Medical Director of Liver Transplantation, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases and Liver Transplantation, Northwell Health/North Shore University Hospital, Manhasset, New York, USA
| | - Muhammad Bilal
- Department of Gastroenterology, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
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Zhang S, Ji B, Zhong X, Zhong L, Yang L, Yang C. A Dynamic Nomogram Predicting Portal Vein Thrombosis in Cirrhotic Patients During Primary Prophylaxis for Variceal Hemorrhage. Front Med (Lausanne) 2022; 9:887995. [PMID: 35721053 PMCID: PMC9203843 DOI: 10.3389/fmed.2022.887995] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 05/17/2022] [Indexed: 12/16/2022] Open
Abstract
BackgroundPortal vein thrombosis (PVT) would exert a further increase in resistance to portal blood flow, resulting in worsening portal hypertension and poor outcome. This study aimed to identify risk factors and develop an clinically applicable dynamic nomogram predicting the occurrence of PVT in cirrhotic patients during primary prophylaxis for variveal hemorrhage (VH).MethodsThe multi-center retrospective study enrolled cirrhotic patients with high-risk varices, which were further divided into training and validation cohorts for 3 years follow-up. A dynamic nomogram based on the Cox proportional hazard regression model was developed with the cutoff value calculated by X-title analysis. The performance of the nomogram was evaluated with Harrell’s concordance index (C-index), calibration curve and decision curve analysis.Results91 (34.0%) of the whole cohort were diagnosed with PVT during 3-year follow-up. Variables including carvedilol (P < 0.001), low portal vein velocity (P < 0.001), increased size of esophageal varices (P = 0.005), and high HbA1c (P < 0.001) and procalcitonin (P = 0.015) were identified to be independently associated with PVT, which were further incorporated into the dynamic nomogram with optimal cutoff (8.8 and 14.6) for risk-stratification. The C-indexes (0.894 of internal validation and 0.892 of external validation) and calibration curves demonstrated ideal discrimination and calibration. The thresholds for more reasonable application of the nomogram were 0–0.27, 0–0.66, and 0.04–1.00 at 1, 2, and 3-year, respectively.ConclusionThe dynamic nomogram could be accurately and reliably used for clinical risk-stratification of PVT in cirrhotic patients during primary prophylaxis for VH.
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Affiliation(s)
- Shuo Zhang
- Department of Gastroenterology and Hepatology, School of Medicine, Shanghai Tongji Hospital, Tongji University, Shanghai, China
| | - Bing Ji
- Department of Gastroenterology and Hepatology, School of Medicine, Shanghai Tongji Hospital, Tongji University, Shanghai, China
| | - Xuan Zhong
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lan Zhong
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Li Yang
- Department of Gastroenterology and Hepatology, School of Medicine, Shanghai Tongji Hospital, Tongji University, Shanghai, China
- *Correspondence: Li Yang,
| | - Changqing Yang
- Department of Gastroenterology and Hepatology, School of Medicine, Shanghai Tongji Hospital, Tongji University, Shanghai, China
- Changqing Yang,
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Albillos A, Martin-Mateos R, Van der Merwe S, Wiest R, Jalan R, Álvarez-Mon M. Cirrhosis-associated immune dysfunction. Nat Rev Gastroenterol Hepatol 2022; 19:112-134. [PMID: 34703031 DOI: 10.1038/s41575-021-00520-7] [Citation(s) in RCA: 213] [Impact Index Per Article: 71.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/02/2021] [Indexed: 02/08/2023]
Abstract
The term cirrhosis-associated immune dysfunction (CAID) comprises the distinctive spectrum of immune alterations associated with the course of end-stage liver disease. Systemic inflammation and immune deficiency are the key components of CAID. Their severity is highly dynamic and progressive, paralleling cirrhosis stage. CAID involves two different immune phenotypes: the low-grade systemic inflammatory phenotype and the high-grade systemic inflammatory phenotype. The low-grade systemic inflammatory phenotype can be found in patients with compensated disease or clinical decompensation with no organ failure. In this phenotype, there is an exaggerated immune activation but the effector response is not markedly compromised. The high-grade systemic inflammatory phenotype is present in patients with acute-on-chronic liver failure, a clinical situation characterized by decompensation, organ failure and high short-term mortality. Along with high-grade inflammation, this CAID phenotype includes intense immune paralysis that critically increases the risk of infections and worsens prognosis. The intensity of CAID has important consequences on cirrhosis progression and correlates with the severity of liver insufficiency, bacterial translocation and organ failure. Therapies targeting the modulation of the dysfunctional immune response are currently being evaluated in preclinical and clinical studies.
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Affiliation(s)
- Agustín Albillos
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain. .,Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain. .,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.
| | - Rosa Martin-Mateos
- Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.,Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Schalk Van der Merwe
- Laboratory of Hepatology, Department of Chronic Diseases, Metabolism and Aging (CHROMETA), University of Leuven, Leuven, Belgium.,Department of Gastroenterology and Hepatology, University Hospital Gasthuisberg, Leuven, Belgium
| | - Reiner Wiest
- Department of Visceral Surgery and Medicine, University Inselspital, Bern, Switzerland
| | - Rajiv Jalan
- Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, UK.,European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Melchor Álvarez-Mon
- Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.,Department of Internal Medicine, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
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Tornai D, Vitalis Z, Jonas A, Janka T, Foldi I, Tornai T, Sipeki N, Csillag A, Balogh B, Sumegi A, Foldesi R, Papp M, Antal-Szalmas P. Increased sTREM-1 levels identify cirrhotic patients with bacterial infection and predict their 90-day mortality. Clin Res Hepatol Gastroenterol 2021; 45:101579. [PMID: 33773436 DOI: 10.1016/j.clinre.2020.11.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 10/06/2020] [Accepted: 11/06/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Patients with cirrhosis are susceptible to bacterial infections (BIs) that are major causes of specific complications and mortality. However, the diagnosis of BIs can often be difficult in advanced disease stage since their symptoms may overlap with the ones of acute decompensation (AD). Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from monocytes/macrophages and neutrophils during activation and has been reported to correlate with activity of various inflammatory processes. We investigated its diagnostic and prognostic performance in patients with cirrhosis and BI. METHODS Sera of 269 patients were assayed for sTREM-1 by ELISA (172 outpatients and 97 patients with AD of whom 56 had BI). We investigated capacity of sTREM-1 to identify patients with BI and conducted a 90-day follow-up observational study to assess its possible association with short-term mortality. RESULTS sTREM-1 levels were significantly higher in patients with more severe liver disease, BI, and acute-on-chronic liver failure than in patients without these conditions. sTREM-1 had similar accuracy to CRP identifying BI [sTREM-1: AUROC (95%CI) 0.804 (0.711-0.897), p < 0.0001; CRP: 0.791 (0.702-0.881), p < 0.0001)] among AD patients. The combination of these two molecules and the presence of ascites into a composite score significantly increased their discriminative power (AUROC: 0.878, 95%CI: 0.812-0.944, p < 0.0001). High sTREM-1 level (>660 pg/mL) was an independent predictor of 90-day mortality in patients with BI [HR: 2.941, (95%CI: 1.009-8.573), p = 0.048] in our multivariate model. CONCLUSIONS Use of sTREM-1 could increase the recognition of BIs in cirrhosis and help clinicians in mortality risk assessment of these patients.
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Affiliation(s)
- David Tornai
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary; Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Zsuzsanna Vitalis
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Alexa Jonas
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Tamas Janka
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Ildiko Foldi
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Tamas Tornai
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Nora Sipeki
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Aniko Csillag
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Boglarka Balogh
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Andrea Sumegi
- HAS-UD Vascular Biology and Myocardial Pathophysiology Research Group, Hungarian Academy of Sciences, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Roza Foldesi
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Maria Papp
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Peter Antal-Szalmas
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary.
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Miranda-Zazueta G, León-Garduño LAPD, Aguirre-Valadez J, Torre-Delgadillo A. Bacterial infections in cirrhosis: Current treatment. Ann Hepatol 2021; 19:238-244. [PMID: 32317149 DOI: 10.1016/j.aohep.2019.09.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 08/28/2019] [Accepted: 09/03/2019] [Indexed: 02/08/2023]
Abstract
Bacterial infections frequently cause decompensating events in cirrhotic patients and are also the most common factor identified for the development of acute-on-chronic liver failure (ACLF). The increase in the prevalence of infections caused by multidrug-resistant (MDR) microorganisms has resulted in the reduced effectiveness of empiric antimicrobial treatment. We conducted a PubMed search from the last 20 years using the Keywords cirrhosis; multidrug-resistant; infections; diagnosis; treatment; prophylaxis; monitoring; sepsis; nutrition and antibiotic resistant. We made a review about bacterial infections among cirrhotic patients; we mainly focus on the description of diagnostic tools; biomarkers; clinical scores for diagnosis and prognosis also; we made an analysis concerning the monitoring of cirrhotic patients with sepsis and finally made some recommendations about the treatment; prophylaxis and prevention.
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Affiliation(s)
- Godolfino Miranda-Zazueta
- Hepatology and Liver Transplantation Unit, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico
| | - Luis A Ponce de León-Garduño
- Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico
| | | | - Aldo Torre-Delgadillo
- Hepatology and Liver Transplantation Unit, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico.
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Mayr U, Lukas M, Elnegouly M, Vogt C, Bauer U, Ulrich J, Schmid RM, Huber W, Lahmer T. Ascitic Interleukin 6 Is Associated with Poor Outcome and Spontaneous Bacterial Peritonitis: A Validation in Critically Ill Patients with Decompensated Cirrhosis. J Clin Med 2020; 9:jcm9092865. [PMID: 32899730 PMCID: PMC7564827 DOI: 10.3390/jcm9092865] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 08/27/2020] [Accepted: 09/02/2020] [Indexed: 02/08/2023] Open
Abstract
Decompensated cirrhosis predisposes to infectious diseases and acute-on-chronic liver failure (ACLF) in critically ill patients. Infections like spontaneous bacterial peritonitis (SBP) are frequently associated with multi-organ failure and increased mortality. Consequently, reliable predictors of outcome and early diagnostic markers of infection are needed to improve individualized therapy. This study evaluates the prognostic role of ascitic interleukin 6 in 64 patients with cirrhosis admitted to our intensive care unit (ICU). In addition, we analysed the diagnostic ability of ascitic interleukin 6 in a subgroup of 19 patients with SBP. Baseline ascitic interleukin 6 performed well in predicting 3-month mortality in patients with decompensated cirrhosis (area under curve (AUC) = 0.802), as well as in patients fulfilling ACLF-criteria (AUC = 0.807). Ascitic interleukin 6 showed a moderate prognostic advantage compared with common clinical scores and proinflammatory parameters. Moreover, ascitic interleukin 6 had a sufficient diagnostic ability to detect SBP (AUC = 0.901) and was well correlated with ascitic polymorphonuclear neutrophils in SBP (p = 0.002). Interestingly, ascitic interleukin 6 revealed a high predictive value to rule out apparent infections on admission to ICU (AUC = 0.904) and to identify patients with “culture-positive SBP” (AUC = 0.856). Ascitic interleukin 6 is an easily-applicable proinflammatory biomarker with high prognostic and diagnostic relevance in critically ill patients with liver cirrhosis.
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Affiliation(s)
- Ulrich Mayr
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
- Correspondence: ; Tel.: +49-89-4140-5226; Fax: +49-89-4140-4742
| | - Marina Lukas
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
| | - Mayada Elnegouly
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
| | - Christine Vogt
- Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany;
| | - Ulrike Bauer
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
| | - Joerg Ulrich
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
| | - Roland M. Schmid
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
| | - Wolfgang Huber
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
| | - Tobias Lahmer
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
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NUTRIC and Modified NUTRIC are Accurate Predictors of Outcome in End-Stage Liver Disease: A Validation in Critically Ill Patients with Liver Cirrhosis. Nutrients 2020; 12:nu12072134. [PMID: 32709104 PMCID: PMC7400844 DOI: 10.3390/nu12072134] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 07/10/2020] [Accepted: 07/13/2020] [Indexed: 12/15/2022] Open
Abstract
Malnutrition in critically ill patients with cirrhosis is a frequent but often overlooked complication with high prognostic relevance. The Nutrition Risk in Critically ill (NUTRIC) score and its modified variant (mNUTRIC) were established to assess the nutrition risk of intensive care unit patients. Considering the high mortality of cirrhosis in critically ill patients, this study aims to evaluate the discriminative ability of NUTRIC and mNUTRIC to predict outcome. We performed a retro-prospective evaluation in 150 Caucasian cirrhotic patients admitted to our ICU. Comparative prognostic analyses between NUTRIC and mNUTRIC were assessed in 114 patients. On ICU admission, a large proportion of 65% were classified as high NUTRIC (6-10) and 75% were categorized as high mNUTRIC (5-9). High nutritional risk was linked to disease severity and poor outcome. NUTRIC was moderately superior to mNUTRIC in prediction of 28-day mortality (area under curve 0.806 vs. 0.788) as well as 3-month mortality (area under curve 0.839 vs. 0.819). We found a significant association of NUTRIC and mNUTRIC with MELD, CHILD, renal function, interleukin 6 and albumin, but not with body mass index. NUTRIC and mNUTRIC are characterized by high prognostic accuracy in critically ill patients with cirrhosis. NUTRIC revealed a moderate advantage in prognostic ability compared to mNUTRIC.
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Fluid Biomarkers for Predicting the Prognosis of Liver Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:7170457. [PMID: 32280697 PMCID: PMC7114768 DOI: 10.1155/2020/7170457] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 01/12/2020] [Accepted: 02/04/2020] [Indexed: 12/15/2022]
Abstract
Liver cirrhosis is the terminal stage of most chronic liver conditions, with a high risk of mortality. Careful evaluation of the prognosis of cirrhotic patients and providing precise management are crucial to reduce the risk of mortality. Although the liver biopsy and hepatic venous pressure gradient (HVPG) can efficiently evaluate the prognosis of cirrhotic patients, their application is limited due to the invasion procedures. Child-Pugh score and the model for end-stage liver disease (MELD) score had been widely used in the assessment of cirrhotic prognosis, but the defects of subjective variable application in Child-Pugh score and unsuitability to all phases of liver cirrhosis in MELD score limit their prognostic values. In recent years, continuous efforts have been made to investigate the prognostic value of body fluid biomarkers for cirrhotic patients, and promising results have been reported. Since the collection of fluid specimens is easy, noninvasive, and repeatable, fluid biomarkers can be ideal indicators to predict the prognosis of cirrhosis. Here, we reviewed noninvasive fluid biomarkers in different prognostic functions, including the prediction of survival and complication development.
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Elsadek HM, Elhawari SA, Mokhtar A. A novel serum index for accurate diagnosis of spontaneous bacterial peritonitis in cirrhotic patients without other infections. EGYPTIAN LIVER JOURNAL 2020. [DOI: 10.1186/s43066-020-0021-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Abstract
Background
The accurate non-invasive diagnosis of spontaneous bacterial peritonitis (SBP) in patients with decompensated liver cirrhosis has not been achieved yet. The aim of the study was to obtain an unmistakable diagnosis of SBP using a new simple serum bioscore, made by combined measurement of procalcitonin (PCT), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), which we called the PEC index. This cross-sectional analytic study comprised 178 cirrhotic patients with ascites (60 patients with SBP and 118 patients with sterile ascites), after excluding non-SBP infection, during the period from March 2019 until September 2019. In all participants, serum levels of PCT, ESR, and CRP were measured, and PEC index was calculated [PEC index = PCT × (ESR + CRP)].
Results
Patients with SBP (n = 60) had significantly higher serum PEC index than those with sterile ascites (n = 118) (41.0/31.2–93.0 vs. 9.9/5.9–15.0, P < 0.001). PEC index distinguished culture positive cases significantly (P < 0.001). Using receiver operating characteristic (ROC) statistics, the sensitivity and specificity of PCT, at a cutoff value of 0.590 ng/mL, for SBP diagnosis, were 81.67% and 93.33%, respectively (area under the curve [AUC] = 0.879; 95% confidence interval [CI] 0.809–0.948). The sensitivity and specificity of ESR, at a cutoff value of 27.0 mm/hour, were 73.33% and 61.67%, respectively (AUC = 0.679; 95% CI 0.581–0.776). The sensitivity and specificity of CRP, at a cutoff value of 21.0 mg/L, were 93.33% and 51.67%, respectively (AUC = 0.736; 95% CI 0.639–0.833). While, the sensitivity and specificity of PEC index, at a cutoff value of 20, were highest (98.33% and 96.67%, respectively, AUC = 0.977; 95% CI 0.940–0.996).
Conclusion
Serum PEC index makes an accurate noninvasive diagnosis of SBP, after excluding other infections.
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Engelmann C, Tacke F. Dekompensierte Leberzirrhose und akut-auf-chronisches Leberversagen. DER GASTROENTEROLOGE 2020; 15:22-33. [DOI: 10.1007/s11377-019-00407-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Fischer P, Grigoras C, Bugariu A, Nicoara-Farcau O, Stefanescu H, Benea A, Hadade A, Margarit S, Sparchez Z, Tantau M, Ionescu D, Procopet B. Are presepsin and resistin better markers for bacterial infection in patients with decompensated liver cirrhosis? Dig Liver Dis 2019; 51:1685-1691. [PMID: 31221548 DOI: 10.1016/j.dld.2019.05.025] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 05/17/2019] [Accepted: 05/20/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Bacterial infections impair prognosis in patients with cirrhosis. Presepsin and, more recently, resistin are promising markers of infection and sepsis in patients without cirrhosis. AIMS The aim of our study was to assess the performance of presepsin and resistin as early markers of infection compared with C reactive protein (CRP) and procalcitonin (PCT), and their prognostic relevance in patients with decompensated cirrhosis. METHODS One hundred and fourteen consecutive patients with decompensated cirrhosis were enrolled and followed-up for 28 days. Diagnostic performances of CRP, PCT, presepsin and resistin were assessed. RESULTS Fifty-three (46.5%) patients had bacterial infections of which 30 (56%) had sepsis. Presepsin and resistin had similar performance as CRP and PCT for the diagnosis of infection (best cut-off of 1444 pg/ml and 20 ng/ml, respectively) and sepsis. Presepsin (HR = 5.5; 95%CI: 2.36-13.21, p < 0.0001) and the ≥500 pg/ml increase of presepsin at 48 h (HR = 9.24; 95%CI: 3.66-23.27, p < 0.008) were independently associated with 28-day mortality. CONCLUSIONS Presepsin and resistin have similar diagnostic performances to CRP and PCT for bacterial infection in decompensated cirrhosis. Presepsin and Δ presepsin ≥500 pg/ml have also a prognostic relevance for 28-day mortality.
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Affiliation(s)
- Petra Fischer
- University of Medicine and Pharmacy "Iuliu Hatieganu", 3rd Medical Clinic, Hepatology Department, Cluj-Napoca, Romania
| | - Crina Grigoras
- University of Medicine and Pharmacy "Iuliu Hatieganu", 3rd Medical Clinic, Hepatology Department, Cluj-Napoca, Romania
| | - Anca Bugariu
- University of Medicine and Pharmacy "Iuliu Hatieganu", 3rd Medical Clinic, Hepatology Department, Cluj-Napoca, Romania
| | - Oana Nicoara-Farcau
- University of Medicine and Pharmacy "Iuliu Hatieganu", 3rd Medical Clinic, Hepatology Department, Cluj-Napoca, Romania
| | - Horia Stefanescu
- Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Hepatology Department, Cluj-Napoca, Romania
| | - Andreea Benea
- Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Hepatology Department, Cluj-Napoca, Romania
| | - Adina Hadade
- University of Medicine and Pharmacy "Iuliu Hatieganu", Department of Anesthesia and Intensive Care I, Cluj-Napoca, Romania
| | - Simona Margarit
- University of Medicine and Pharmacy "Iuliu Hatieganu", Department of Anesthesia and Intensive Care I, Cluj-Napoca, Romania
| | - Zeno Sparchez
- University of Medicine and Pharmacy "Iuliu Hatieganu", 3rd Medical Clinic, Hepatology Department, Cluj-Napoca, Romania; Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Hepatology Department, Cluj-Napoca, Romania
| | - Marcel Tantau
- University of Medicine and Pharmacy "Iuliu Hatieganu", 3rd Medical Clinic, Hepatology Department, Cluj-Napoca, Romania; Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Hepatology Department, Cluj-Napoca, Romania
| | - Daniela Ionescu
- University of Medicine and Pharmacy "Iuliu Hatieganu", Department of Anesthesia and Intensive Care I, Cluj-Napoca, Romania; Outcome Research Consortium, Cleveland, USA
| | - Bogdan Procopet
- University of Medicine and Pharmacy "Iuliu Hatieganu", 3rd Medical Clinic, Hepatology Department, Cluj-Napoca, Romania; Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Hepatology Department, Cluj-Napoca, Romania.
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Luo J, Wu X, Zhang Y, Huang W, Jia B. Role of ascitic prostaglandin E2 in diagnosis of spontaneous bacterial peritonitis and prediction of in-hospital mortality in patients with decompensated cirrhosis. Medicine (Baltimore) 2019; 98:e16016. [PMID: 31261505 PMCID: PMC6617449 DOI: 10.1097/md.0000000000016016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Spontaneous bacterial peritonitis (SBP) is one of the most frequent and severe complications in patients with decompensated cirrhosis. Early antibiotic therapy is extremely important for successful treatment and reducing mortality. Prostaglandin E2 (PGE2) is a regulator of the immune response and infection. This study aimed to explore whether ascitic PGE2 could be used as a marker for diagnosing SBP and predicting in-hospital mortality.Patients with cirrhosis and ascites undergoing abdominal paracentesis were enrolled in our study. Demographic, clinical, and laboratory parameters were recorded at the time of paracentesis and ascitic PGE2 levels were determined by ELISA. The correlation between ascitic PGE2 level and SBP as well as in-hospital mortality were analyzed.There were 224 patients enrolled, 29 (13%) patients diagnosed as SBP based on the current guideline criteria. The ascitic PGE2 level of patients with SBP [32.77 (26.5-39.68) pg/mL] was significantly lower than that of patients without SBP [49.72 (37.35-54.72) pg/mL]. In ROC analysis, the AUC of ascitic PGE2 for the diagnosis of SBP was 0.75, and the AUC of ascitic PGE2 combined with WBC and ascitic PGE2 combined with neutrophils were 0.90 and 0.90, respectively, which were significantly higher than that of ascitic PGE2. In multivariate analysis, ascites PGE2≤32.88 pg/mL (OR: 9.39; 95% CI: 1.41-67.44, P = .026), hepatic encephalopathy (OR: 18.39; 95% CI: 3.00-113.13, P = .002) and a higher MELD score (OR: 1.25; 95% CI: 1.05-1.40, P = .009) remained independent predictors of in-hospital mortality.Ascitic PGE2 level is likely to be a valuable marker in prediction of in-hospital mortality in patients with decompensated cirrhosis, and its value in diagnosis of SBP was not superior to other inflammatory indicators.
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23
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Mani I, Alexopoulou A, Vasilieva L, Hadziyannis E, Agiasotelli D, Bei M, Alexopoulos T, Dourakis SP. Human beta-defensin-1 is a highly predictive marker of mortality in patients with acute-on-chronic liver failure. Liver Int 2019; 39:299-306. [PMID: 30261128 DOI: 10.1111/liv.13977] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 08/16/2018] [Accepted: 09/19/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIM Human beta-defensin-1 (hBD-1) is a natural antimicrobial peptide expressed in the epithelia of multiple tissues including the digestive tract. In the current study, hBD-1 levels were determined in different subsets of patients with decompensated cirrhosis including acute-on-chronic liver failure (ACLF). In addition, the association with mortality of hBD-1, C-reactive protein (CRP) and procalcitonin (PCT) was assessed. METHODS A total of 125 patients were divided into three groups: 39 with ACLF (derivation cohort), 46 with acute decompensation without ACLF (AD) and 40 with decompensated cirrhosis without an acute event (DC). The data from 24 different ACLF patients were used for validation and 15 healthy individuals as control group. RESULTS Serum hBD-1, CRP and PCT levels were higher in ACLF compared to both AD and DC groups (P < 0.001). Healthy controls demonstrated similar hBD-1 and PCT values compared to DC group. In ROC curve, the performance of hBD-1 to predict 60-day mortality in ACLF group was similar in derivation and validation cohorts (c-statistic 0.834 and 0.879, respectively). CRP was a poor predictor of mortality. In ACLF group, patients with high hBD-1 (>36.625 ng/mL) had a poor prognosis at 60 days compared to those with lower values (log-rank P = 0.001). In Cox multivariate regression analysis, only hBD-1 (HR 1.020, 95%CI 1.006-1.035, P = 0.006) emerged as an independent predictor of death in ACLF group. In AD group, neither hBD-1 nor PCT or CRP variables were associated with mortality. CONCLUSIONS High hBD-1 was detected at presentation in patients with ACLF who died during follow-up period. hBD-1 is an accurate predictor of short-term mortality in patients with ACLF.
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Affiliation(s)
- Iliana Mani
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexandra Alexopoulou
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Larisa Vasilieva
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Emilia Hadziyannis
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Danai Agiasotelli
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Myrianthi Bei
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Theodoros Alexopoulos
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Spyros P Dourakis
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece
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24
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The Diagnostic and Prognostic Values of C-Reactive Protein and Procalcitonin during Bacterial Infections in Decompensated Cirrhosis. Gastroenterol Res Pract 2018; 2018:5915947. [PMID: 31582968 PMCID: PMC6748174 DOI: 10.1155/2018/5915947] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Accepted: 11/25/2018] [Indexed: 12/30/2022] Open
Abstract
Background Bacterial infection (BI) represents the main cause of decompensation and death in cirrhotic patients. Procalcitonin (PCT) and C-reactive protein (CRP) are two widely used biomarkers that may be helpful for early detection of BI especially in the presence of inflammation. Their accuracy for the diagnosis of BI in patients with chronic liver disease has been a subject of debate. In this study, we aimed to learn whether PCT and CRP would be helpful as early markers of BI in patients with cirrhosis and to evaluate their prognostic value in terms of mortality. Subjects and Methods We retrospectively included 92 adult patients with decompensated cirrhosis. PCT and CRP plasma levels were obtained within the first 24 hours of admission. Their diagnostic and prognostic values were compared using the appropriate statistical analysis. Results Ninety-two patients were included. BI was diagnosed in 60 patients (65%). Mean white blood cell (WBC) count (p = 0.005) and PCT and CRP serum levels (p < 0.001) were higher in the BI group than in the non-BI (NBI) group. The diagnostic accuracy of CRP and PCT for the diagnosis of BI was better than that of WBC. CRP was the most sensitive marker (70%) while PCT was the more specific (96.6%). No one of those biomarkers was predictive of 3-month mortality in patients with BI. Conclusion Regarding BI in patients with decompensated cirrhosis, CRP maintains efficiency slightly higher than that of the PCT without being discriminative. However, no prognostic value has been established for these markers.
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25
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Righi E. Management of bacterial and fungal infections in end stage liver disease and liver transplantation: Current options and future directions. World J Gastroenterol 2018; 24:4311-4329. [PMID: 30344417 PMCID: PMC6189843 DOI: 10.3748/wjg.v24.i38.4311] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2018] [Revised: 09/11/2018] [Accepted: 10/05/2018] [Indexed: 02/06/2023] Open
Abstract
Patients with liver cirrhosis are susceptible to infections due to various mechanisms, including abnormalities of humoral and cell-mediated immunity and occurrence of bacterial translocation from the intestine. Bacterial infections are common and represent a reason for progression to liver failure and increased mortality. Fungal infections, mainly caused by Candida spp., are often associated to delayed diagnosis and high mortality rates. High level of suspicion along with prompt diagnosis and treatment of infections are warranted. Bacterial and fungal infections negatively affect the outcomes of liver transplant candidates and recipients, causing disease progression among patients on the waiting list and increasing mortality, especially in the early post-transplant period. Abdominal, biliary tract, and bloodstream infections caused by Gram-negative bacteria [e.g., Enterobacteriaceae and Pseudomonas aeruginosa (P. aeruginosa)] and Staphylococcus spp. are commonly encountered in liver transplant recipients. Due to frequent exposure to broad-spectrum antibiotics, invasive procedures, and prolonged hospitalizations, these patients are especially at risk of developing infections caused by multidrug resistant bacteria. The increase in antimicrobial resistance hampers the choice of an adequate empiric therapy and warrants the knowledge of the local microbial epidemiology and the implementation of infection control measures. The main characteristics and the management of bacterial and fungal infections in patients with liver cirrhosis and liver transplant recipients are presented.
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Affiliation(s)
- Elda Righi
- Department of Infectious Diseases, Santa Maria della Misericordia University Hospital, Udine 33100, Italy
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26
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Wang H, Li Y, Zhang F, Yang N, Xie N, Mao Y, Li B. Combination of PCT, sNFI and dCHC for the diagnosis of ascites infection in cirrhotic patients. BMC Infect Dis 2018; 18:389. [PMID: 30097024 PMCID: PMC6086035 DOI: 10.1186/s12879-018-3308-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 08/03/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND It is difficult to diagnose ascites infection early in cirrhotic patients. The present study was to create and evaluate a new bioscore combined with PCT, sNFI and dCHC in the diagnosis of ascites infection in cirrhotic patients. METHODS Two hundred and fifty-nine consecutive patients were enrolled; of which 51 patients were culture-positive spontaneous bacterial peritonitis (culture-positive SBP) and 58 patients were culture-negative SBP. The efficacy of procalcitonin(PCT), c-reactive protein (CRP), white blood cell (WBC), mean fluorescence intensity of mature neutrophils(sNFI) and difference in hemoglobin concentration between newly formed and mature red blood cells(dCHC) for diagnosing ascites infection was examined. These parameters were used to create a scoring system. The scoring system was analyzed by logistic regression analysis to determine which parameters were statistically different between ascites infection and non-ascites infection patients. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic ability of bioscore for ascites infection. RESULTS In ROC analysis, the area under the curves (AUC) for PCT was 0.852 (95% CI 0.803-0.921, P < 0.001), dCHC 0.837 (95% CI 0.773-0.923, P < 0.001), CRP 0.669 (95% CI 0.610-0.732, P = 0.0624), sNFI 0.838 (95% CI 0.777-0.903, P < 0.001), and WBC 0.624 (95% CI 0.500-0.722, P = 0.0881). Multivariate analysis revealed PCT, dCHC and sNFI to be statistically significant. The combination of these three parameters in the bioscore had an AUC of 0.937 (95% CI 0.901-0.994, P < 0.001). A bioscore of ≥3.40 was considered to be statistically significant in making a positive diagnosis of ascites infection. In different groups of ascites infection, bioscore also shown a high diagnostic value of AUC was 0.947(95% CI 0.882-0.988, P < 0.001) and 0.929 (95% CI 0.869-0.974, P < 0.001) for culture-positive SBP and culture-negative SBP group respectively. CONCLUSION The composite markers of combining PCT, dCHC and sNFI could be a valuable diagnostic score to early diagnose ascites infection in patients with cirrhosis.
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Affiliation(s)
- Han Wang
- Clinical Diagnostic Centre, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
| | - Yan Li
- Clinical Diagnostic Centre, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
| | - Fangfang Zhang
- Out-patient department, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
| | - Ning Yang
- Clinical Diagnostic Centre, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
| | - Na Xie
- Out-patient department, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
| | - Yuanli Mao
- Clinical Diagnostic Centre, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
| | - Boan Li
- Clinical Diagnostic Centre, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
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Engelmann C, Berg T. Management of Infectious Complications Associated with Acute-on-Chronic Liver Failure. Visc Med 2018; 34:261-268. [PMID: 30345283 DOI: 10.1159/000491107] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Introduction Acute-on-chronic liver failure (ACLF) is associated with a high susceptibility to infections leading to complications and poor prognosis. The sensitized immune system overwhelmingly responds to invading bacteria leading to organ damage. After resolution of infection or prolonged disease duration, the phagocytic system becomes irresponsive with a reduced bacterial clearance capacity promoting secondary infection. Methods This review focuses on the best management strategies for patients with ACLF and infections. Using the following terms, an extensive literature research on the Medline database was performed: 'acute-on-chronic liver failure', 'infection', 'ACLF', 'bacteria', 'multi-resistance'. Results Analysis of the literature confirmed that delayed diagnosis and treatment of infections in patients with ACLF results in a poor prognosis. Patients with ACLF should be considered as having a potential infection and should undergo a complete screening for sepsis. Once biochemical analysis indicates a potential infection, such as abnormal levels of C-reactive protein and procalcitonin, antibiotic treatment should be initiated immediately without microbiological culture results. For community-acquired infections third-generation cephalosporins are still the first choice, whereas in the nosocomial setting antibiotics with broader spectrum, such as piperacillin/combactam or carbapenems ± glycopeptides, are preferred. The patient should be re-assessed 48 h after treatment initiation in order to tailor the treatment. Non-response is suspicious, likely due to bacterial resistance or fungal infection, which should be considered when choosing further treatment strategies. Albumin substitution to prevent hepatorenal syndrome and to improve patients' outcome is mandatory in patients with spontaneous bacterial peritonitis. Prophylactic antibiotic therapy is suitable to prevent infections in high-risk patients. Conclusion The screening for infections and its treatment is an essential part of managing patients with ACLF. In order to improve patients' prognosis, antibiotic treatment should be initiated once an infection is suspected. However, preventive strategies are already established and should be applied according to the guidelines.
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Affiliation(s)
- Cornelius Engelmann
- Section Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - Thomas Berg
- Section Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
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Palyu E, Harsfalvi J, Tornai T, Papp M, Udvardy M, Szekeres-Csiki K, Pataki L, Vanhoorelbeke K, Feys HB, Deckmyn H, Tornai I. Major Changes of von Willebrand Factor Multimer Distribution in Cirrhotic Patients with Stable Disease or Acute Decompensation. Thromb Haemost 2018; 118:1397-1408. [PMID: 29972862 PMCID: PMC6202934 DOI: 10.1055/s-0038-1661393] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Background
There is an unstable balance between pro- and anti-haemostatic processes in patients with cirrhosis. We hypothesized, that in patients with acute decompensation (AD) the major alterations of von Willebrand factor (VWF) could contribute to the pro-thrombotic situation as compared to patients with stable (ST) cirrhosis.
Patients and Methods
We analysed different parameters of VWF, including detailed multimer distribution by densitometry and platelet adhesion, together with
ad
isintegrin-like
a
nd
m
etalloproteinase with
t
hrombo
s
pondin type-1 motifs
13
(ADAMTS13) activity and antigen and C-reactive protein (CRP) levels in patients with ST cirrhosis (
n
= 99), with AD (
n
= 54) and controls (
n
= 92).
Results
VWF antigen, ristocetin co-factor as well as collagen-binding activities were elevated in both cirrhotic groups in a stepwise manner. There was a decrease in high and an increase in low molecular weight multimer ratios in the majority of ST cirrhosis. However, in 24 out of 54 AD patients, ultra-large VWF multimers (ultra-large molecular weight multimers [ULMWM]) were found. ADAMTS13 activity in ST and AD patients without ULMWM was similar to controls (median [interquartile range; IQR]%: 98 [67–132] and 91 [60–110] vs. 106 [88–117], respectively). The presence of ULMWM in AD patients was associated with low ADAMTS13 activity [33 (24–49)%] and high CRP level [23 (7.1–83.6) mg/L]. Adhesion of normal platelets showed a stepwise increase in the presence of cirrhotic plasmas, reaching the highest level in AD patients with ULMWM.
Conclusion
Characteristic changes of VWF parameters are seen in ST cirrhosis. In AD patients, highly increased VWF and reduced ADAMTS13 activity could be found, along with the presence of ULMWM, which are possible markers and contributors of the disease progression.
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Affiliation(s)
- Eszter Palyu
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Jolan Harsfalvi
- Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary
| | - Tamas Tornai
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Maria Papp
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Miklos Udvardy
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Katalin Szekeres-Csiki
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Lajos Pataki
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Karen Vanhoorelbeke
- Laboratory for Thrombosis Research, IRF Life Science, KU Leuven Kulak, Kortrijk, Belgium
| | - Hendrik B Feys
- Transfusion Research Center, Belgian Red Cross-Flanders, Ghent, Belgium.,Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Hans Deckmyn
- Laboratory for Thrombosis Research, IRF Life Science, KU Leuven Kulak, Kortrijk, Belgium
| | - Istvan Tornai
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
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Yamada T, Imai S, Koshizuka Y, Tazawa Y, Kagami K, Tomiyama N, Sugawara R, Yamagami A, Shimamura T, Iseki K. Necessity for a Significant Maintenance Dosage Reduction of Voriconazole in Patients with Severe Liver Cirrhosis (Child–Pugh Class C). Biol Pharm Bull 2018; 41:1112-1118. [DOI: 10.1248/bpb.b18-00164] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
| | - Shungo Imai
- Department of Pharmacy, Hokkaido University Hospital
| | - Yasuyuki Koshizuka
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine
| | - Yuki Tazawa
- Department of Pharmacy, Hokkaido University Hospital
| | | | | | | | | | | | - Ken Iseki
- Department of Pharmacy, Hokkaido University Hospital
- Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Laboratory of Clinical Pharmaceutics and Therapeutics
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Clarifying the role of C-reactive protein as a bacterial infection predictor in decompensated cirrhosis. Eur J Gastroenterol Hepatol 2018; 30:645-651. [PMID: 29384797 DOI: 10.1097/meg.0000000000001081] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Bacterial infections are frequent in cirrhosis and may induce other deleterious complications. Ultrasensitive C-reactive protein (US-CRP), like other acute-phase proteins, is often considered useful in predicting bacterial infection in decompensated cirrhosis. However, US-CRP's reliability remains inconclusive, as inflammation in cirrhosis causes US-CRP synthesis independently of infection. The aim of this study was to clarify US-CRP's role as an infection predictor in decompensated cirrhosis. PATIENTS AND METHODS This was a prospective single-center study with systematic inclusion of cirrhotic patients admitted because of decompensation. RESULTS A total of 118 patients were enrolled, of whom 47 (39.8%) had an overt infection, defined by clinical and laboratory/imaging criteria. Within those, 17 had infection confirmed by culture bacterial identification. Escherichia coli was the most frequent isolated bacteria. Seventeen patients had spontaneous bacterial peritonitis, but only four (23.5%) had positive ascitic fluid cultures. US-CRP levels were significantly higher in cases of overt infection and positive culture groups than the no infection group (median: 4.14 and 6.40 vs. 1.11 mg/dl, P<0.0001 for both). When considering both overt infection and positive culture groups, the US-CRP values of area under the curve as an infection predictor were, respectively, 0.824 and 0.870, P<0.0001 for both, with associated cutoff values of 2.40 and 3.92 mg/dl, and sensitivity and specificity of 78.7/74.6 and 82.4/79.2%, respectively. CONCLUSION The ideal US-CRP infection confirmatory cutoff is probably situated between 2.40 and 3.92 mg/dl. However, as infection is somewhat concealed and hazardous in cirrhotic patients, if not considered with lower US-CRP levels according to specific clinic scenarios, it should be carefully considered, at least, if US-CRP is greater than 2.40 mg/dl (0.5 mg/dl normal upper cutoff).
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Yeoh SF, Lee TJ, Chew KL, Lin S, Yeo D, Setia S. Echinocandins for management of invasive candidiasis in patients with liver disease and liver transplantation. Infect Drug Resist 2018; 11:805-819. [PMID: 29881298 PMCID: PMC5985852 DOI: 10.2147/idr.s165676] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Candida species remains one of the most important causes of opportunistic infections worldwide. Invasive candidiasis (IC) is associated with considerable morbidity and mortality in liver disease (LD) patients if not treated promptly. Echinocandins are often recommended as a first-line empirical treatment for managing IC and can especially play a critical role in managing IC in LD patients. However, advanced LD patients are often immunocompromised and critically ill. Hence altered pharmacokinetics, drug interactions as well as tolerance issues of antifungal treatments are a concern in these patients. This comprehensive review examines the epidemiology, risk factors and diagnosis of IC in patients with LD and evaluates differences between three available echinocandins for treating this group of patients.
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Affiliation(s)
- Siang Fei Yeoh
- Department of Pharmacy, National University Health System, Singapore, Singapore
| | - Tae Jin Lee
- Department of Pharmacy, National University of Singapore, Singapore, Singapore
| | - Ka Lip Chew
- Department of Laboratory Medicine, National University Hospital, Singapore, Singapore
| | - Stephen Lin
- Global Medical Affairs, Asia-Pacific region, Pfizer, Hong Kong, People’s Republic of China
| | - Dennis Yeo
- Medical Affairs, Pfizer Pte. Ltd., Singapore, Singapore
| | - Sajita Setia
- Medical Affairs, Pfizer Pte. Ltd., Singapore, Singapore
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Piano S, Brocca A, Mareso S, Angeli P. Infections complicating cirrhosis. Liver Int 2018; 38 Suppl 1:126-133. [PMID: 29427501 DOI: 10.1111/liv.13645] [Citation(s) in RCA: 114] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Accepted: 11/23/2017] [Indexed: 12/15/2022]
Abstract
Patients with cirrhosis have a high risk of bacterial infections. Bacterial infections induce systemic inflammation that may lead to organ failure and acute-on-chronic liver failure (ACLF) resulting in a high risk of short term mortality. The early diagnosis and treatment of bacterial infections is essential to improve the patient's prognosis. However, in recent years, the spread of multidrug resistant (MDR) bacterial infections has reduced the efficacy of commonly used antibiotics such as third generation cephalosporins. In patients at high risk of MDR bacteria, such as those with nosocomial infections, the early administration of broad spectrum antibiotics has been shown to improve the prognosis. However, early de-escalation of antibiotics is recommended to reduce a further increase in antibiotic resistance. Strategies to prevent acute kidney injury and other organ failures should be implemented. Although prophylaxis of bacterial infections with antibiotics improves the prognosis in selected patients, their use should be limited to patients at high risk of developing infections. In this article, we review the pathogenesis and management of bacterial infections in patients with cirrhosis.
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Affiliation(s)
- Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Alessandra Brocca
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Sara Mareso
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy
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Bacterial Infection and Predictors of Mortality in Patients with Autoimmune Liver Disease-Associated Acute-On-Chronic Liver Failure. Can J Gastroenterol Hepatol 2018; 2018:5108781. [PMID: 29623264 PMCID: PMC5830018 DOI: 10.1155/2018/5108781] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 12/13/2017] [Accepted: 01/11/2018] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE To date, few studies are available on autoimmune liver disease-associated acute-on-chronic liver failure (ACLF). The aim of this study is to investigate bacterial infection and predictors of mortality in these patients. METHODS We retrospectively studied patients with autoimmune liver disease from August 2012 to August 2017. Clinical data of the patients were retrieved for analysis. RESULTS There were 53 ACLF patients and 53 patients without ACLF in this study. The ACLF group had a higher prevalence of complications (P < 0.05). The 28-day and 90-day mortality rates were also obviously high in patients with ACLF (38.3% and 74.5%, resp.) (P < 0.05). No predictor was significantly associated with 28-day and 90-day transplant-free mortality. In 53ACLF patients, 40 (75.5%) patients showed bacterial infection. ACLF patients with bacterial infection showed high Child-Pugh score, MELD score, CLIF-SOFA score, 28-day mortality, and 90-day mortality (P > 0.05). Moreover, C-reactive protein (CRP) using 12.15 mg/L cut-off value proved to be more accurate than procalcitonin in identifying patients with infection. CONCLUSIONS Autoimmune liver disease-associated ACLF showed more complications and high mortality. Bacterial infection patients displayed a more severe condition than those without infection. Elevated CRP is an accurate marker for diagnosing bacterial infection in autoimmune liver disease-associated ACLF patients.
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34
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Deutsch M, Manolakopoulos S, Andreadis I, Giannaris M, Kontos G, Kranidioti H, Pirounaki M, Koskinas J. Bacterial infections in patients with liver cirrhosis: clinical characteristics and the role of C-reactive protein. Ann Gastroenterol 2018; 31:77-83. [PMID: 29333070 PMCID: PMC5759615 DOI: 10.20524/aog.2017.0207] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Accepted: 09/26/2017] [Indexed: 12/13/2022] Open
Abstract
Background The diagnosis of bacterial infection in cirrhotic patients may be difficult, because of the absence of classical signs such as fever and raised white blood cell count. The role of C-reactive protein (CRP) in this context has not been clearly defined. Methods Clinical and laboratory characteristics of 210 consecutive cirrhotic patients with (n=100) or without (n=110) bacterial infection were compared with a control group of non-cirrhotic patients with infection (n=106). Results Significantly fewer patients with cirrhosis had a body temperature ≥37°C when presenting with bacterial infection (56% cirrhotic vs. 85.5% non-cirrhotic patients, P=0.01). Mean leukocyte count was 6.92 × 103/mm3 in patients with cirrhosis and infection, 5.75 × 103/mm3 (P=0.02) in cirrhotic patients without infection, and 11.28 × 103/mm3 in non-cirrhotic patients with infection (P<0.001). Multivariate analysis revealed that CRP level and model for end-stage liver disease score were significantly associated with the presence of infection in patients with cirrhosis. A cutoff level of CRP>10 mg/L indicated the presence of infection with a sensitivity of 68%, a specificity of 84.5% and an area under the receiver operating characteristic curve of 0.8197. CRP cutoff level differed according to the severity of the liver disease: Child-Pugh score (CPS) A: 21.3 mg/L, B: 17 mg/L, and C: 5.78 mg/L. Conclusions CRP at admission could help diagnose infection in cirrhotic patients. Since the severity of liver disease seems to affect the CRP values, lower CRP levels might indicate infection. Clinical suspicion is necessary to avoid delay in diagnosis and initiate antibiotic treatment.
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Affiliation(s)
- Melanie Deutsch
- 2 Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Spilios Manolakopoulos
- 2 Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Ioannis Andreadis
- 2 Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Markos Giannaris
- 2 Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - George Kontos
- 2 Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Hariklia Kranidioti
- 2 Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - Maria Pirounaki
- 2 Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - John Koskinas
- 2 Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
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Predictors of Early Readmission in Patients With Cirrhosis After the Resolution of Bacterial Infections. Am J Gastroenterol 2017; 112:1575-1583. [PMID: 28853729 DOI: 10.1038/ajg.2017.253] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Accepted: 07/13/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVES In patients with cirrhosis, infections represent a frequent trigger for complications, increasing frequency of hospitalizations and mortality rate. This study aimed to identify predictors of early readmission (30 days) and of mid-term mortality (6 months) in patients with liver cirrhosis discharged after a hospitalization for bacterial and/or fungal infection. METHODS A total of 199 patients with cirrhosis discharged after an admission for a bacterial and/or fungal infection were included in the study and followed up for a least 6 months. RESULTS During follow-up, 69 patients (35%) were readmitted within 30 days from discharge. C-reactive protein (CRP) value at discharge (odds ratio (OR)=1.91; P=0.022), diagnosis of acute-on-chronic liver failure during the hospital stay (OR=2.48; P=0.008), and the hospitalization in the last 30 days previous to the admission/inclusion in the study (OR=1.50; P=0.042) were found to be independent predictors of readmission. During the 6-month follow-up, 47 patients (23%) died. Age (hazard ratio (HR)=1.05; P=0.001), model of end-stage liver disease (MELD) score (HR=1.13; P<0.001), CRP (HR=1.85; P=0.001), refractory ascites (HR=2.22; P=0.007), and diabetes (HR=2.41; P=0.010) were found to be independent predictors of 6-month mortality. Patients with a CRP >10 mg/l at discharge had a significantly higher probability of being readmitted within 30 days (44% vs. 24%; P=0.007) and a significantly lower probability of 6-month survival (62% vs. 88%; P<0.001) than those with a CRP ≤10 mg/l. CONCLUSIONS CRP showed to be a strong predictor of early hospital readmission and 6-month mortality in patients with cirrhosis after hospitalization for bacterial and/or fungal infection. CRP values could be used both in the stewardship of antibiotic treatment and to identify fragile patients who deserve a strict surveillance program.
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36
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Nier A, Engstler AJ, Maier IB, Bergheim I. Markers of intestinal permeability are already altered in early stages of non-alcoholic fatty liver disease: Studies in children. PLoS One 2017; 12:e0183282. [PMID: 28880885 PMCID: PMC5589126 DOI: 10.1371/journal.pone.0183282] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 08/01/2017] [Indexed: 02/07/2023] Open
Abstract
Background & aims Recent studies have shown that patients with manifest non-alcoholic fatty liver disease (NAFLD), e.g. steatosis grade 3 or steatohepatitis with or without beginning fibrosis frequently show altered fecal microbiota composition and elevated bacterial endotoxin levels. However, if these alterations are signs of a progressing disease or are already found in initial disease stages has not yet been clarified. Methods Twenty children with simple steatosis (grade 1) diagnosed by ultrasound and 29 normal weight healthy control children (age <10 years) were included in the study (mean age 7.6 ± 1.1 years). Metabolic parameters, markers of intestinal barrier function and inflammation were determined. Results Activity of alanine aminotransferase, concentrations of some markers of inflammation and insulin resistance were significantly higher in plasma of NAFLD children than in controls. When compared to controls, plasma bacterial endotoxin and lipopolysaccharide-binding protein (LBP) levels were significantly higher in NAFLD children (+50% and +24%, respectively), while soluble CD14 serum and D-lactate plasma levels as well as the prevalence of small intestinal bacterial overgrowth did not differ between groups. Plasma endotoxin and LBP levels were positive associated with proinflammatory markers like plasminogen activator inhibitor-1, c-reactive protein, interleukin-6 and leptin while no associations with markers of insulin resistance were found. Conclusions Taken together, our results indicate that even in juvenile patients with early stages of NAFLD e.g. simple steatosis grade 1, plasma endotoxin concentrations are already elevated further suggesting that intestinal barrier dysfunction might be present already in the initial phases of the disease.
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Affiliation(s)
- Anika Nier
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria
- Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Jena, Germany
| | - Anna Janina Engstler
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria
- Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Jena, Germany
| | - Ina Barbara Maier
- Department of Nutritional Medicine, (180), University of Hohenheim, Stuttgart, Germany
| | - Ina Bergheim
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria
- Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Jena, Germany
- * E-mail:
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La Mura V, Salerno F. Reply to the diagnostic conundrum of bacterial infections in cirrhotic patients. Liver Int 2017; 37:1412. [PMID: 28845619 DOI: 10.1111/liv.13474] [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] [Indexed: 02/13/2023]
Affiliation(s)
- Vincenzo La Mura
- Medicina Interna, IRCCS San Donato, Università degli studi di Milano, San Donato Milanese, Milano, Italy
| | - Francesco Salerno
- Medicina Interna, IRCCS San Donato, Università degli studi di Milano, San Donato Milanese, Milano, Italy
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38
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Alexopoulou A, Agiasotelli D, Vasilieva LE, Dourakis SP. Bacterial translocation markers in liver cirrhosis. Ann Gastroenterol 2017; 30:486-497. [PMID: 28845103 PMCID: PMC5566768 DOI: 10.20524/aog.2017.0178] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2017] [Accepted: 06/19/2017] [Indexed: 12/12/2022] Open
Abstract
Bacterial translocation (BT) is an important mechanism in the development of infection in liver cirrhosis. The migration and colonization of bacteria and/or bacterial products from the bowel to mesenteric lymph nodes is a controlled process in healthy persons. Increased intestinal permeability, bacterial overgrowth and defect of gut-associated lymphatic tissue promote impaired BT in cirrhotics. We reviewed the reports on markers used for the evaluation of BT published between 1987 and 2016. We focused on the clinical consequences of BT in cirrhosis, as indicated by the values of the BT markers. Patients with cirrhosis are reported to have elevated levels of surrogate markers associated with BT compared with controls. The most widely used BT parameters are C-reactive protein, procalcitonin, bacterial DNA, endotoxin or lipopolysaccharide, lipopolysaccharide binding protein, calprotectin, and bactericidal/permeability increasing protein. High levels of these factors in serum and/or ascitic fluid in humans may be associated with advanced liver disease, hemodynamic instability, high levels of proinflammatory cytokines, susceptibility to the development of severe or recurrent infections, acute-on-chronic liver failure, hepatic encephalopathy, hepatorenal syndrome and poor prognosis during follow up. In conclusion, high levels of BT markers are associated with a high inflammatory response, increased complications of liver cirrhosis and occasionally high fatality rates.
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Affiliation(s)
- Alexandra Alexopoulou
- 2 Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Hippokration" Hospital, Athens, Greece
| | - Danai Agiasotelli
- 2 Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Hippokration" Hospital, Athens, Greece
| | - Larisa E Vasilieva
- 2 Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Hippokration" Hospital, Athens, Greece
| | - Spyros P Dourakis
- 2 Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Hippokration" Hospital, Athens, Greece
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de Oliveira VM, Moraes RB, Stein AT, Wendland EM. Accuracy of C - Reactive protein as a bacterial infection marker in critically immunosuppressed patients: A systematic review and meta-analysis. J Crit Care 2017; 42:129-137. [PMID: 28735154 DOI: 10.1016/j.jcrc.2017.07.025] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Revised: 07/06/2017] [Accepted: 07/10/2017] [Indexed: 12/29/2022]
Abstract
BACKGROUND There is a need for a better understanding of the role of C-reactive protein (CRP) as a valid marker for the detection of bacterial infections in critically immunosuppressed patients. A high negative predictive value of CRP is also needed to rule out sepsis and bacterial infections in immunocompetent patients. However, few studies have evaluated the performance of CRP in immunocompromised hosts. The aim of the present study was to evaluate the performance of CRP as a marker of infection in critically immunosuppressed patients. METHODS The inclusion criterion was immunosuppression for which CRP was used as a bacterial infection marker. Searches were performed in the Cochrane Register, MEDLINE, EMBASE, SCOPUS, Web OF Science, LILACS and CINAHL databases. We applied the Quality Assessment of Diagnostic Accuracy Studies tool 2 (QUADAS 2) to evaluate the quality of the articles and evaluated the test accuracy parameters using hierarchical summary receiver operating characteristic (HSROC) curves and bivariate random effect models. RESULTS Only 13 of 21 studies produced quantitative results. We analyzed all studies using the random effects method (restricted maximum likelihood) and obtained a joint diagnostic odds ratio (DOR) of 3.04 (95% confidence interval [CI] 1.71-5.40) with heterogeneity (I2=91%, Q=181.48, p<0.001). Therefore, a bivariate model was applied. Analyzing the tuberculosis carrier, steroid user, or presence of opportunistic infection subgroups, as described in the proposal, was not possible due to the lack of information on these topics included in the articles. CONCLUSIONS CRP appears to be a good screening tool for sepsis in critically immunosuppressed patients. Submitted PROSPERO 2015: CRD42015019329.
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Affiliation(s)
- Vanessa Martins de Oliveira
- Intensive Care Unit, Hospital de Clinicas de Porto Alegre, Ramiro Barcelos Street 2350, Porto Alegre, Brazil.
| | - Rafael Barberena Moraes
- Intensive Care Unit, Hospital de Clinicas de Porto Alegre, Ramiro Barcelos Street 2350, Porto Alegre, Brazil.
| | - Airton Tetelbom Stein
- Medical Science, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil.
| | - Eliana Márcia Wendland
- Epidemiology, Public Health Department, Federal University of Health Science of Porto Alegre, Porto Alegre, Brazil.
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40
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Foldi I, Tornai T, Tornai D, Sipeki N, Vitalis Z, Tornai I, Dinya T, Antal-Szalmas P, Papp M. Lectin-complement pathway molecules are decreased in patients with cirrhosis and constitute the risk of bacterial infections. Liver Int 2017; 37:1023-1031. [PMID: 28109038 DOI: 10.1111/liv.13368] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 01/12/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Lectin pathway molecules of the complement system are synthesized by hepatocytes and have pivotal role in innate host defence against infectious organisms. Ficolins (FCNs) act as soluble pattern recognition molecules, while mannan-binding lectin serine proteases(MASPs) do as effector molecules in elimination of pathogens. We aimed to study the significance of low level of these molecules in the development of cirrhosis-associated bacterial infections, which has not been elucidated so far. METHODS Sera of 266 stable outpatients with cirrhosis and 160 healthy subjects were assayed for a panel of lectin molecules (FCN-2, FCN-3 and MASP-2) by ELISA. In cirrhosis, a 5-year follow-up observational study was conducted to assess a possible association between lectin levels and development of clinically significant bacterial infections(CSI). RESULTS FCN-2, FCN-3 and MASP-2 levels were significantly lower in cirrhosis compared to healthy subjects and decreased according to disease severity (P<.001 for all molecules). In Kaplan-Meier analysis, development of CSI was associated with low level of FCN-2 (<427 ng/mL, pLogRank=0.047) and FCN-3 (<4857 ng/mL, pLogRank=0.029), but not with MASP-2 deficiency (<100 ng/mL, pLogRank=0.306). Combined FCN deficiency was associated with increased risk of development of bacterial infections in a step-wise manner. Patients with low level of both FCNs had higher cumulative probability of CSI (63.8%) compared to those with low level of one or normal FCN (52.7% and 45.7%, pLogRank=0.016). Neither FCN serum profile, nor MASP-2 deficiency were associated with infection-related mortality. CONCLUSIONS Low level of FCNs associated with hepatic insufficiency might be considered as an additional constituent of cirrhosis-associated immune dysfunction.
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Affiliation(s)
- Ildiko Foldi
- Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Tamas Tornai
- Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - David Tornai
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Nora Sipeki
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Zsuzsanna Vitalis
- Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Istvan Tornai
- Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Tamas Dinya
- Institute of Surgery, Faculty of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Peter Antal-Szalmas
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Maria Papp
- Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
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Agiasotelli D, Alexopoulou A, Vasilieva L, Hadziyannis E, Goukos D, Daikos GL, Dourakis SP. High serum lipopolysaccharide binding protein is associated with increased mortality in patients with decompensated cirrhosis. Liver Int 2017; 37:576-582. [PMID: 27712029 DOI: 10.1111/liv.13264] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Accepted: 09/29/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Lipopolysaccharide-binding-protein (LBP) is an acute-phase-protein produced by hepatocytes. Changes in LBP are associated with the dynamics of bacterial translocation and intestinal permeability in decompensated cirrhosis (DC). We assessed serum and ascitic-fluid (AF) LBP and examined their association with mortality in patients with DC. METHODS Eighty-eight consecutive patients (73.9% males) underwent thorough diagnostic investigations for infection. LBP (ng/mL) was assessed in serum (N=88) and AF (n=49) by enzyme-linked-immunosorbent-assay and expressed in natural logarithm (ln). RESULTS Serum lnLBP was higher in 18 patients with overt infection compared to those without (P<.001). Serum and AF lnLBP 13.49 and 12.11 displayed a very good-negative-predictive value of 90% and 95.1% to rule out infection and spontaneous-bacterial-peritonitis (SBP), respectively. LBP was higher in serum than in AF (P<.001). Serum and AF LBP levels showed a positive correlation with surrogate markers of inflammation. Patients without overt infection were prospectively followed up. The 90-day-mortality rate was 48% and 24.4% in patients with high (≥13.49) and low (<13.49) lnLBP, respectively, (log rank P=0.045). In univariate Cox regression analysis, neutrophils, LBP, MELD score and CRP were predictive of mortality. However, only high LBP (HR 8.1 95%CI 2.0-31.5, P=0.003) and MELD (HR 1.1 95%CI 1.0-1.2, P=0.002) were predictive of mortality in multivariate analysis. CONCLUSIONS Serum and AF LBP concentrations showed a high negative-predictive-value to exclude infection and SBP, respectively. High serum LBP was detected in patients without infection at presentation who died during the 90-day-follow-up period. Elevated serum LBP is a marker of short-term mortality in patients without overt bacterial infection.
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Affiliation(s)
- Danai Agiasotelli
- 2nd Department of Internal Medicine, Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexandra Alexopoulou
- 2nd Department of Internal Medicine, Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Larisa Vasilieva
- 2nd Department of Internal Medicine, Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Emilia Hadziyannis
- 2nd Department of Internal Medicine, Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitris Goukos
- 1st Department of Propedeutic Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - George L Daikos
- 1st Department of Propedeutic Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Spyros P Dourakis
- 2nd Department of Internal Medicine, Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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Papp M, Tornai T, Vitalis Z, Tornai I, Tornai D, Dinya T, Sumegi A, Antal-Szalmas P. Presepsin teardown - pitfalls of biomarkers in the diagnosis and prognosis of bacterial infection in cirrhosis. World J Gastroenterol 2016; 22:9172-9185. [PMID: 27895404 PMCID: PMC5107598 DOI: 10.3748/wjg.v22.i41.9172] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 08/26/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the diagnostic and prognostic value of presepsin in cirrhosis-associated bacterial infections.
METHODS Two hundred and sixteen patients with cirrhosis were enrolled. At admission, the presence of bacterial infections and level of plasma presepsin, serum C-reactive protein (CRP) and procalcitonin (PCT) were evaluated. Patients were followed for three months to assess the possible association between presepsin level and short-term mortality.
RESULTS Present 34.7 of patients had bacterial infection. Presepsin levels were significantly higher in patients with infection than without (median, 1002 pg/mL vs 477 pg/mL, P < 0.001), increasing with the severity of infection [organ failure (OF): Yes vs No, 2358 pg/mL vs 710 pg/mL, P < 0.001]. Diagnostic accuracy of presepsin for severe infections was similar to PCT and superior to CRP (AUC-ROC: 0.85, 0.85 and 0.66, respectively, P = NS for presepsin vs PCT and P < 0.01 for presepsin vs CRP). At the optimal cut-off value of presepsin > 1206 pg/mL sensitivity, specificity, positive predictive values and negative predictive values were as follows: 87.5%, 74.5%, 61.8% and 92.7%. The accuracy of presepsin, however, decreased in advanced stage of the disease or in the presence of renal failure, most probably because of the significantly elevated presepsin levels in non-infected patients. 28-d mortality rate was higher among patients with > 1277 pg/mL compared to those with ≤ 1277 pg/mL (46.9% vs 11.6%, P < 0.001). In a binary logistic regression analysis, however, only PCT (OR = 1.81, 95%CI: 1.09-3.01, P = 0.022) but neither presepsin nor CRP were independent risk factor for 28-d mortality after adjusting with MELD score and leukocyte count.
CONCLUSION Presepsin is a valuable new biomarker for defining severe infections in cirrhosis, proving same efficacy as PCT. However, it is not a useful marker of short-term mortality.
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Tornai T, Vitalis Z, Sipeki N, Dinya T, Tornai D, Antal-Szalmas P, Karanyi Z, Tornai I, Papp M. Macrophage activation marker, soluble CD163, is an independent predictor of short-term mortality in patients with cirrhosis and bacterial infection. Liver Int 2016; 36:1628-1638. [PMID: 27031405 DOI: 10.1111/liv.13133] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Accepted: 03/29/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Innate immune system dysfunction is common in advanced cirrhosis, with a central role of the monocyte/macrophage system. Monocytes and macrophages express the scavenger receptor CD163, which is regulated by inflammatory mediators. Cleavage of the receptor leads to the formation of soluble (s)CD163 that represents an anti-inflammatory response. We aimed to study the clinical importance of sCD163 in cirrhosis. METHODS Sera of 378 patients were assayed for sCD163 by ELISA [193 outpatients and 185 patients with acute decompensation (AD)]. A 5-year follow-up observational study was conducted to assess the possible association between sCD163 level and poor disease outcomes. RESULTS sCD163 level was associated with disease severity, but not with the presence of varices or prior variceal bleeding. In outpatients, sCD163 level did not predict the development of disease-specific complications or the long-term mortality. In patients with AD episode, sCD163 level was significantly higher compared to outpatients but only in the presence of bacterial infection (INF) (AD-INF:4586, AD-NON-INF:3792 and outpatients: 3538 ng/ml, P < 0.015 and P = 0.001, respectively). sCD163 level gradually increased according to severity of infection. During bacterial infections, high sCD163 level (>7000 ng/ml) was associated with increased mortality rate (42% vs. 17%, P < 0.001) and was identified as an independent predictor of 28-day mortality (hazard ratio:2.96, 95% confidence intervals:1.27-6.95) in multivariate Cox-regression model comprising aetiology, co-morbidity, model for end-stage liver disease score and leucocyte count as covariates. CONCLUSIONS High sCD163 level is useful to identify patients with high-risk of death during an AD episode complicated by bacterial infection. This finding serves as an additional hint towards the significance of anti-inflammatory response during bacterial infection.
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Affiliation(s)
- Tamas Tornai
- Division of Gastroenterology, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary
| | - Zsuzsanna Vitalis
- Division of Gastroenterology, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary
| | - Nora Sipeki
- Division of Gastroenterology, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary
| | - Tamas Dinya
- Institute of Surgery, University of Debrecen, Debrecen, Hungary
| | - David Tornai
- Department of Laboratory Medicine, University of Debrecen, Debrecen, Hungary
| | - Peter Antal-Szalmas
- Department of Laboratory Medicine, University of Debrecen, Debrecen, Hungary
| | - Zsolt Karanyi
- Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Istvan Tornai
- Division of Gastroenterology, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary
| | - Maria Papp
- Division of Gastroenterology, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary.
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Waidmann O, Brunner F, Herrmann E, Zeuzem S, Piiper A, Kronenberger B. Cytokeratin 18-based cell death markers indicate severity of liver disease and prognosis of cirrhotic patients. Liver Int 2016; 36:1464-72. [PMID: 26991828 DOI: 10.1111/liv.13117] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2015] [Accepted: 03/07/2016] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS Hepatocyte death is an important factor in development and progression of cirrhosis. Cytokeratin 18-based serum markers reflecting apoptotic (M30) and overall epithelial cell death (M65 and M65EpiDeath) have been used as prognostic parameters for survival in patients with acute liver failure. However, there has been no trial investigating M30, M65 and M65EpiDeath as survival parameters in patients with cirrhosis and acute-on-chronic liver failure. METHODS Patients with cirrhosis were enrolled and followed until death, liver transplantation or last contact. M30, M65 and M65EpiDeath serum levels were quantified in patient's sera. RESULTS Three hundred and thirty-one patients were screened and 211 patients could be included in this study. The median duration of follow-up was 322 days with a range of 1-1382 days. All three cell death parameters correlated with the extent of the severity of the disease. However, M65EpiDeath was the only of the three parameters which was associated with the severe complications of cirrhosis including ascites, spontaneous bacterial peritonitis and hepatorenal syndrome. Additionally, M65EpiDeath was the only cell death parameter which was independently from liver function and its surrogate parameter such as Child-Pugh score and the model of end-stage liver disease associated with overall survival. CONCLUSIONS Epithelial cell death reflected by M65EpiDeath serum levels is an indicator for the severity of cirrhosis and a prognostic survival parameter in cirrhotic patients.
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Affiliation(s)
- Oliver Waidmann
- Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Universitätsklinikum Frankfurt, Frankfurt/Main, Germany.
| | - Friederike Brunner
- Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Universitätsklinikum Frankfurt, Frankfurt/Main, Germany
| | - Eva Herrmann
- Institut für Biostatistik und Mathematische Modellierung, Universitätsklinikum Frankfurt, Frankfurt/Main, Germany
| | - Stefan Zeuzem
- Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Universitätsklinikum Frankfurt, Frankfurt/Main, Germany
| | - Albrecht Piiper
- Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Universitätsklinikum Frankfurt, Frankfurt/Main, Germany
| | - Bernd Kronenberger
- Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Universitätsklinikum Frankfurt, Frankfurt/Main, Germany
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Bunchorntavakul C, Chamroonkul N, Chavalitdhamrong D. Bacterial infections in cirrhosis: A critical review and practical guidance. World J Hepatol 2016; 8:307-321. [PMID: 26962397 PMCID: PMC4766259 DOI: 10.4254/wjh.v8.i6.307] [Citation(s) in RCA: 148] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Revised: 11/23/2015] [Accepted: 01/29/2016] [Indexed: 02/06/2023] Open
Abstract
Bacterial infection is common and accounts for major morbidity and mortality in cirrhosis. Patients with cirrhosis are immunocompromised and increased susceptibility to develop spontaneous bacterial infections, hospital-acquired infections, and a variety of infections from uncommon pathogens. Once infection develops, the excessive response of pro-inflammatory cytokines on a pre-existing hemodynamic dysfunction in cirrhosis further predispose the development of serious complications such as shock, acute-on-chronic liver failure, renal failure, and death. Spontaneous bacterial peritonitis and bacteremia are common in patients with advanced cirrhosis, and are important prognostic landmarks in the natural history of cirrhosis. Notably, the incidence of infections from resistant bacteria has increased significantly in healthcare-associated settings. Serum biomarkers such as procalcitonin may help to improve the diagnosis of bacterial infection. Preventive measures (e.g., avoidance, antibiotic prophylaxis, and vaccination), early recognition, and proper management are required in order to minimize morbidity and mortality of infections in cirrhosis.
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Bartoletti M, Giannella M, Lewis RE, Viale P. Bloodstream infections in patients with liver cirrhosis. Virulence 2016; 7:309-19. [PMID: 26864729 DOI: 10.1080/21505594.2016.1141162] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Bloodstream infections are a serious complication in patients with liver cirrhosis. Dysregulated intestinal bacterial translocation is the predominant pathophysiological mechanism of infections in this setting. For this reason enteric Gram-negative bacteria are commonly encountered as the first etiological cause of infection. However, through the years, the improvement in the management of cirrhosis, the recourse to invasive procedures and the global spread of multidrug resistant pathogens have importantly changed the current epidemiology. Bloodstream infections in cirrhotic patients are characterized by high mortality rate and complications including metastatic infections, infective endocarditis, and endotipsitis (or transjugular intrahepatic portosystemic shunt-related infection). For this reason early identification of patients at risk for mortality and appropriated therapeutic management is mandatory. Liver cirrhosis can significantly change the pharmacokinetic behavior of antimicrobials. In fact hypoproteinaemia, ascitis and third space expansion and impairment of renal function can be translated in an unpredictable drug exposure.
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Affiliation(s)
- Michele Bartoletti
- a Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola Hospital, University of Bologna , Bologna , Italy
| | - Maddalena Giannella
- a Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola Hospital, University of Bologna , Bologna , Italy
| | - Russell Edward Lewis
- a Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola Hospital, University of Bologna , Bologna , Italy
| | - Pierluigi Viale
- a Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant'Orsola Hospital, University of Bologna , Bologna , Italy
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McPherson S, Dyson J, Austin A, Hudson M. Response to the NCEPOD report: development of a care bundle for patients admitted with decompensated cirrhosis-the first 24 h. Frontline Gastroenterol 2016; 7:16-23. [PMID: 26834955 PMCID: PMC4717433 DOI: 10.1136/flgastro-2014-100491] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Revised: 09/22/2014] [Accepted: 09/28/2014] [Indexed: 02/04/2023] Open
Abstract
Recently, there has been a significant increase in the prevalence of chronic liver disease in the UK, and as a result, hospital admissions and deaths due to liver disease have also increased. The 2013 National Confidential Enquiry into Patient Outcome and Death (NCEPOD) of patients with alcohol-related liver disease (ARLD) found that less than half the number of patients who died from ARLD received 'good care', and avoidable deaths were identified. In order to improve the care of patients admitted with ARLD, the NCEPOD report recommended that a 'toolkit' for the acute management of patients admitted with decompensated ARLD be developed and made widely available. As a result, we have developed a 'care bundle' for patients admitted with decompensated cirrhosis (of all aetiologies) to ensure that effective evidence-based treatments are delivered within the first 24 h. This care bundle provides a checklist to ensure that all appropriate investigations are undertaken when a patient with decompensated cirrhosis presents and provides clinicians with clear guidance on the initial management of alcohol withdrawal, infection, acute kidney injury, gastrointestinal bleeding and encephalopathy. The first 24 h are particularly important, as early intervention can reduce mortality and shorten hospital stay, and specialist gastroenterology/liver advice is not always available during this period. This review will discuss the care bundle and the evidence base behind the treatment recommendations made.
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Affiliation(s)
- Stuart McPherson
- Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Jessica Dyson
- Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Andrew Austin
- Department of Gastroenterology, Derby Hospitals NHS Foundation Trust, Derby, UK
- British Society of Gastroenterology, Liver Section, London, UK
| | - Mark Hudson
- Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
- British Association for the Study of the Liver, London, UK
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Yang Y, Li L, Qu C, Zeng B, Liang S, Luo Z, Wang X, Zhong C. Diagnostic Accuracy of Serum Procalcitonin for Spontaneous Bacterial Peritonitis Due to End-stage Liver Disease: A Meta-analysis. Medicine (Baltimore) 2015; 94:e2077. [PMID: 26656333 PMCID: PMC5008478 DOI: 10.1097/md.0000000000002077] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Early diagnosis and prompt treatment of spontaneous bacterial peritonitis (SBP) due to end-stage liver disease is vital to shorten hospital stays and reduce mortality. Many studies have explored the potential usefulness of serum procalcitonin (PCT) in predicting SBP. The aim of this study is to evaluate the overall diagnostic accuracy of PCT levels for identifying SBP due to end-stage liver disease.After performing a systematic search of the Medline, Embase, and Cochrane databases for studies that evaluated the diagnostic role of PCT for SBP, sensitivity, specificity, and other measures of accuracy of PCT concentrations in serum for SBP diagnosis were pooled using random-effects models. A summary receiver operating characteristic curve was used to summarize overall test performance.Seven publications met the inclusion criteria covering 742 episodes of suspected SBP along with 339 confirmed cases. The summary estimates for serum PCT in the diagnosis of SBP attributable to end-stage liver disease were: sensitivity 0.82 (95% CI 0.79-0.87), specificity 0.86 (95% CI 0.82-0.89), positive likelihood ratio 4.94 (95% CI 2.28-10.70), negative likelihood ratio 0.22 (95% CI 0.10-0.52), and diagnostic OR 22.55 (95% CI 7.01-108.30). The area under the curve was 0.92. There was evidence of significant heterogeneity but no evidence of publication bias.Serum PCT is a relatively sensitive and specific test for the identification of SBP. However, due to the limited high-quality studies available, medical decisions should be carefully made in the context of both PCT test results and other clinical findings.
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Affiliation(s)
- Yongtao Yang
- From the Department of Gastroenterology, The 306th Hospital of PLA, Chaoyang District, Beijing, China
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Conti F, Dall'Agata M, Gramenzi A, Biselli M. Biomarkers for the early diagnosis of bacterial infection and the surveillance of hepatocellular carcinoma in cirrhosis. Biomark Med 2015; 9:1343-51. [PMID: 26580585 DOI: 10.2217/bmm.15.100] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The early detection of bacterial infections and hepatocellular carcinoma (HCC) could ameliorate the prognosis of cirrhosis. C-reactive protein and procalcitonin are under investigation in the setting of cirrhosis as markers of sepsis. In the attempt to discriminate bacterial infection from systemic inflammation, the role of novel biomarkers such as lypopolysaccharide binding-protein, mid-regional fragment of pro-adrenomedullin and delta neutrophil index are currently in development. Concerning HCC, many studies attempted to evaluate biomarkers in the hope of ameliorating the accuracy of the surveillance based on ultrasound. The use of α-fetoprotein (AFP) has been extensively investigated, as well as other biomarkers expressed in the serum of HCC patients like lens culinaris agglutinin-reactive fraction of AFP, des-γ-carboxy prothrombin, glypican-3, α-l-fucosidase and their combined use.
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Affiliation(s)
- Fabio Conti
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
| | - Marco Dall'Agata
- Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Università di Ferrara, Ferrara, Italy
| | - Annagiulia Gramenzi
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
| | - Maurizio Biselli
- Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy
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