ArticleHepatology (Baltimore, Md.)2018
Cell death markers in patients with cirrhosis and acute decompensation.
Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Serum Cytokeratin-18 levels as a prognostic biomarker in advanced liver disease: a comprehensive meta-analysis.Clinical and experimental medicine · 2024Pooled it
- Trial
- Long-term hepatic safety of lomitapide in homozygous familial hypercholesterolaemia.Liver international : official journal of the International Association for the Study of the Liver · 2023Trial
- Acute-on-chronic liver failure: pathophysiological mechanisms and clinical management.Nature reviews. Gastroenterology & hepatology · 2026Review
- Interaction of inflammation and portal hypertension in cirrhosis progression.Nature reviews. Gastroenterology & hepatology · 2025Review
- Unravelling the reversion mechanisms of activated hepatic stellate cell properties by extracellular vesicles from mesenchymal stem cells.World journal of stem cells · 2025Review
- Clinical differences between HBV and alcohol related ACLF in a WGO classification multicenter study.Scientific reports · 2025Article
- Recompensation of Liver Cirrhosis by TIPS Reduces Epithelial Cell Death Markers, Translating Into Improved Clinical Outcome.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Potential therapies for acute-on-chronic liver failure.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- The LIVERAID (LIVER And Infectious Diseases)-ICU score predicts in-hospital mortality in liver cirrhosis patients with infections in the intensive care unit.BMJ open gastroenterology · 2024Article
- Review
- Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression.Biomolecules · 2024Review
- sTREM-1 as promising prognostic biomarker for acute-on-chronic liver failure and mortality in patients with acute decompensation of cirrhosis.World journal of gastroenterology · 2024Article
- Navigating the Labyrinth: Intensive Care Challenges for Patients with Acute-on-Chronic Liver Failure.Journal of clinical medicine · 2024Review
- SEMA6B induces macrophage-mediated inflammation and hepatocyte apoptosis in hepatitis B virus-related acute-on-chronic liver failure.Theranostics · 2024Article
- Novel Therapeutic Approaches in Treatment of Acute-on-Chronic Liver Failure.Seminars in liver disease · 2023Review
- Roles of systemic inflammatory and metabolic responses in the pathophysiology of acute-on-chronic liver failure.JHEP reports : innovation in hepatology · 2023Review
- Potential of circulating receptor-interacting protein kinase 3 levels as a marker of acute liver injury.Scientific reports · 2023Article
- Serum keratin 18-M65 levels detect progressive forms of alcohol-associated liver disease in early noncirrhotic stages.Alcohol, clinical & experimental research · 2023Article
- Serum keratin-18 detects hepatic inflammation and predicts progression in compensated alcohol-associated liver disease.Hepatology communications · 2022Article
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Authors and funding
15 authors at 8 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aims of this study were to determine the role of cell death in patients with cirrhosis and acute decompensation (AD) and acute on chronic liver failure (ACLF) using plasma-based biomarkers. The patients studied were part of the CANONIC (CLIF Acute-on-Chronic Liver Failure in Cirrhosis) study (N = 337; AD, 258; ACLF, 79); additional cohorts included healthy volunteers, stable patients with cirrhosis, and a group of 16 AD patients for histological studies. Caspase-cleaved keratin 18 (cK18) and keratin 18 (K18), which reflect apoptotic and total cell death, respectively, and cK18:K18 ratio (apoptotic index) were measured in plasma by enzyme-linked immunosorbent assay. The concentrations of cK18 and K18 increased and the cK18:K18 ratio decreased with increasing severity of AD and ACLF (P < 0.001, respectively). Alcohol etiology, no previous decompensation, and alcohol abuse were associated with increased cell death markers whereas underlying infection was not. Close correlation was observed between the cell death markers and, markers of systemic inflammation, hepatic failure, alanine aminotransferase, and bilirubin, but not with markers of extrahepatic organ injury. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining confirmed evidence of greater hepatic cell death in patients with ACLF as opposed to AD. Inclusion of cK18 and K18 improved the performance of the CLIF-C AD score in prediction of progression from AD to ACLF (P < 0.05).
conclusionCell death, likely hepatic, is an important feature of AD and ACLF and its magnitude correlates with clinical severity. Nonapoptotic forms of cell death predominate with increasing severity of AD and ACLF. The data suggests that ACLF is a heterogeneous entity and shows that the importance of cell death in its pathophysiology is dependent on predisposing factors, precipitating illness, response to injury, and type of organ failure. (Hepatology 2018;67:989-1002).
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