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Gastroenterology. 2014 Oct;147(4):765-783.e4. doi: 10.1053/j.gastro.2014.07.018. Epub 2014 Jul 18.

Cell death and cell death responses in liver disease: mechanisms and clinical relevance.

Author information

1
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany. Electronic address: tluedde@ukaachen.de.
2
Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California.
3
Department of Medicine, Columbia University, New York, New York; Institute of Human Nutrition, Columbia University, New York, New York. Electronic address: rfs2102@cumc.columbia.edu.

Abstract

Hepatocellular death is present in almost all types of human liver disease and is used as a sensitive parameter for the detection of acute and chronic liver disease of viral, toxic, metabolic, or autoimmune origin. Clinical data and animal models suggest that hepatocyte death is the key trigger of liver disease progression, manifested by the subsequent development of inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Modes of hepatocellular death differ substantially between liver diseases. Different modes of cell death such as apoptosis, necrosis, and necroptosis trigger specific cell death responses and promote progression of liver disease through distinct mechanisms. In this review, we first discuss molecular mechanisms by which different modes of cell death, damage-associated molecular patterns, and specific cell death responses contribute to the development of liver disease. We then review the clinical relevance of cell death, focusing on biomarkers; the contribution of cell death to drug-induced, viral, and fatty liver disease and liver cancer; and evidence for cell death pathways as therapeutic targets.

KEYWORDS:

Alcoholic Liver Disease; Apoptosis; Caspases; Clinical Trial; DAMP; DILI; Hepatocellular Carcinoma; NASH; Necroptosis; Necrosis; Necrosome; RIP Kinases; RIP3; Viral Hepatitis

PMID:
25046161
PMCID:
PMC4531834
DOI:
10.1053/j.gastro.2014.07.018
[Indexed for MEDLINE]
Free PMC Article

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