Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
3293190 | Gastroenterology | 2014 | 23 Pages |
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
MLKLBcl-2MIRALTK18MPTHMGB1DAMPNACPCDXIAPRIP3Jnkidiosyncratic drug-induced liver injuryTNFHSCNF-κBNAFLDc-Jun N-terminal kinaseHCCN-acetylcysteineROSALDAdenosine TriphosphateATPASTAspartate aminotransferaseDrug-induced liver injuryAlanine aminotransferasenonalcoholic steatohepatitisdamage-associated molecular patternmitochondrial permeability transitionalcoholic liver diseaseNonalcoholic fatty liver diseasehigh-mobility group box 1ApoptosisDILIHepatic stellate cellendoplasmic reticulumtumor necrosis factornuclear factor κBTRAILB-cell lymphoma 2Programmed cell deathMicroRNANecroptosisNash NecrosisHBVHCVHepatitis C virusViral hepatitishepatitis B virusRIPX-linked Inhibitor of Apoptosis Proteinmixed lineage kinase domain-like proteinReceptor-interacting proteinClinical trialHepatocellular carcinomaCaspaseskeratin 18Reactive oxygen species
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Authors
Tom Luedde, Neil Kaplowitz, Robert F. Schwabe,