Cited by 589Cell death mechanisms and regulationLiver physiology and pathologyLiver Disease Diagnosis and Treatment

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Apoptosis and necroptosis in the liver: a matter of life and death

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Schwabe, Robert F., Luedde, Tom·2018·Nature Reviews Gastroenterology & Hepatology

DOI 10.1038/s41575-018-0065-yPMC PMC6490680

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Abstract

Cell death represents a basic biological paradigm that governs outcomes and long-term sequelae in almost every hepatic disease condition. Acute liver failure is characterized by massive loss of parenchymal cells but is usually followed by restitution ad integrum. By contrast, cell death in chronic liver diseases often occurs at a lesser extent but leads to long-term alterations in organ architecture and function, contributing to chronic hepatocyte turnover, the recruitment of immune cells and activation of hepatic stellate cells. These chronic cell death responses contribute to the development of liver fibrosis, cirrhosis and cancer. It has become evident that, besides apoptosis, necroptosis is a highly relevant form of programmed cell death in the liver. Differential activation of specific forms of programmed cell death might not only affect outcomes in liver diseases but also offer novel opportunities for therapeutic intervention. Here, we summarize the underlying molecular mechanisms and open questions about disease-specific activation and roles of programmed cell death forms, their contribution to response signatures and their detection. We focus on the role of apoptosis and necroptosis in acute liver injury, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and liver cancer, and possible translations into clinical applications.

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Authors: Schwabe, R. F., & Luedde, T.
Affiliations: Columbia University Irving Medical Center (US)
Universitätsklinikum Aachen (DE)
Corresponding author: Schwabe, Robert F.
Luedde, Tom
ORCID: Schwabe, Robert F.
Luedde, Tom
Venue: Nature Reviews Gastroenterology & Hepatology
Publisher: Springer Science and Business Media LLC
Published: 2018-09-24
Volume: 15
Issue: 12
Pages: 738-752
ISSN: 1759-5045 (ISSN-L)
1759-5053
DOI: 10.1038/s41575-018-0065-y
PMC: PMC6490680
OpenAlex: W2890337997
Cited by: 582
References: 185
Citations by year: 2026: 51 · 2025: 82 · 2024: 93 · 2023: 91 · 2022: 94 · 2021: 78 · 2020: 59 · 2019: 33
FWCI: 4.17
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Gastroenterology & Hepatology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Alcohol Abuse and Alcoholism (U01AA021912)
National Cancer Institute (R01CA190844, R01CA200597)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116620)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Keywords: apoptosis, necroptosis, programmed cell death, liver injury, acute liver failure, chronic liver disease, liver fibrosis, liver cirrhosis, liver cancer, non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, hepatic stellate cells, hepatocyte turnover, cell death detection
MeSH terms: Animals, Humans, Liver, Liver Diseases, Necrosis, Cell Death, Apoptosis

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Apoptosis and necroptosis in the liver: a matter of life and death

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