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Cell death markers in cirrhotic patients with acute decompensation

Macdonald, S; Andreola, F; Bachtiger, P; Amoros, A; Pavesi, M; Mookerjee, R; Zheng, YB; ... Jalan, R; + view all (2018) Cell death markers in cirrhotic patients with acute decompensation. Hepatology , 67 (3) pp. 989-1002. 10.1002/hep.29581. Green open access

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Abstract

The aims of this study were to determine the role of cell death in cirrhotic patients with acute decompensation (AD) and acute on chronic liver failure (ACLF) using plasma-based biomarkers. The patients studied were part of the CANONIC study (N=337; AD: 258; ACLF: 79); additional cohorts included healthy volunteers, stable cirrhotic patients 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 the plasma by ELISA. 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 amino transferase and bilirubin but not with markers of extra hepatic organ injury. TUNEL 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). CONCLUSION: Cell death, likely hepatic, is an important feature of AD and ACLF and its magnitude correlates with clinical severity. Non-apoptotic 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 the type of organ failure. This article is protected by copyright. All rights reserved.

Type: Article
Title: Cell death markers in cirrhotic patients with acute decompensation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/hep.29581
Publisher version: http://dx.doi.org/10.1002/hep.29581
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Acute decompensation of cirrhosis, Acute on chronic liver failure, cell death, inflammation, organ failure
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
URI: http://discovery.ucl.ac.uk/id/eprint/10026179
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