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Title: Cell death markers in patients with cirrhosis and acute decompensation
Author: Macdonald, Stewart
Andreola, Fausto
Bachtiger, Patrik
Amoros, Alex
Pavesi, Marco
Mookerjee, Rajeshwar
Zheng, Yu Bao
Grønbaek, Henning
Gerbes, Alexander L.
Solà, Elsa
Caraceni, Paolo
Moreau, Richard
Ginès i Gibert, Pere
Arroyo, Vicente
Jalan, Rajiv
Keywords: Cirrosi hepàtica
Cèl·lules hepàtiques
Marcadors bioquímics
Malalties del fetge
Insuficiència hepàtica
Hepatic cirrhosis
Liver cells
Biochemical markers
Liver diseases
Liver failure
Issue Date: 1-Mar-2018
Publisher: Wiley
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). Conclusion: Cell 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.
Note: Versió postprint del document publicat a:
It is part of: Hepatology, 2018, vol. 67, num. 3, p. 989-1002
Related resource:
ISSN: 0270-9139
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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