The DOI matches its Crossref record; 184 of the 185 references it cites were found in a registry or an index.
Apoptosis and necroptosis in the liver: a matter of life and death
Open accessAbstract
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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“A key feature of MASH is hepatocyte apoptosis, which correlates with the clinically most important feature of the disease, liver fibrosis (6, 7).”
From Impaired TIM4-mediated efferocytosis by liver macrophages contributes to fibrosis in metabolic dysfunction–associated steatohepatitis (2025) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“The current study amends this fibrocentric concept by demonstrating fibrosis-independent roles for HSCs through RSPO3, regulating critical parameters that affect CLD progression and outcomes, including metabolic hepatocyte functions, liver regeneration and hepatocyte death2,49,50.”
From Hepatic stellate cells control liver zonation, size and functions via R-spondin 3 (2025) · cites this paper as [50]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Hepatocyte apoptosis is a key feature of metabolic dysfunction–associated steatohepatitis (MASH)”
From Impaired TIM4-mediated efferocytosis by liver macrophages contributes to fibrosis in metabolic dysfunction–associated steatohepatitis (2025) · cites this paper as [6]
In the citing paper
“In NASH, hepatocytes undergo apoptosis, necroptosis or pyroptosis (a newly described caspase 1-dependent apoptosis observed in NASH),33 thereby initiating inflammation in several ways.”
From Understanding the cellular interactome of non-alcoholic fatty liver disease (2022) · cites this paper as [33]
In the citing paper
“Whilst this process has anti-inflammatory potential, as it removes intracellular content which could otherwise act as DAMPs, efferocytosis also triggers macrophages to release transforming growth factor (TGF)β.”
From Understanding the cellular interactome of non-alcoholic fatty liver disease (2022) · cites this paper as [33]
In the citing paper
“This signalling pathway positively and negatively modulates inflammation in a number of ways, including via the activation of HSCs, a key source of scar-producing myofibroblasts.33,41”
From Understanding the cellular interactome of non-alcoholic fatty liver disease (2022) · cites this paper as [33]
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Citations
Cites
1 retracted
Apoptosis and Molecular Targeting Therapy in Cancer
Hassan, M. K., Watari, H., Abu-Almaaty, A. H., Ohba, Y., & Sakuragi, N. (2014) · BioMed Research International · doi:10.1155/2014/150845 · Cited by 1,155
RetractedFerroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695
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Gout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326
Steatohepatitis: A tale of two “hits”?
Day, C. P., & James, O. F. W. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70599-2 · Cited by 4,285
Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
Scaffidi, P., Misteli, T., & Bianchi, M. E. (2002) · Nature · doi:10.1038/nature00858 · Cited by 4,221
The Danger Model: A Renewed Sense of Self
Matzinger, P. (2002) · Science · doi:10.1126/science.1071059 · Cited by 4,205
Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
Friedmann Angeli, J. P., Schneider, M., Proneth, B., Tyurina, Y. Y., Tyurin, V. A., Hammond, V. J., Herbach, N., Aichler, M., Walch, A., Eggenhofer, E., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3064 · Cited by 3,732
Apoptosis, oncosis, and necrosis. An overview of cell death.
Majno, G., & Joris, I. (1995) · PubMed · Cited by 3,328
Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis
Sanyal, A. J., Chalasani, N., Kowdley, K. V., McCullough, A., Diehl, A. M., Bass, N. M., Neuschwander-Tetri, B. A., Lavine, J. E., Tonascia, J., Unalp, A., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0907929 · Cited by 3,327
Cited by
Sorted by citations
Microbiota in health and diseases
Hou, K., Wu, Z.-X., Chen, X.-Y., Wang, J.-Q., Zhang, D., Xiao, C., Zhu, D., Koya, J. B., Wei, L., Li, J., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00974-4 · Cited by 3,171
Mechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002
Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives
Roehlen, N., Crouchet, E., & Baumert, T. F. (2020) · Cells · doi:10.3390/cells9040875 · Cited by 1,237
The multifaceted role of ferroptosis in liver disease
Chen, J., Li, X., Ge, C., Min, J., & Wang, F. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-00941-0 · Cited by 683
Mechanisms of Fibrosis Development in Nonalcoholic Steatohepatitis
Schwabe, R. F., Tabas, I., & Pajvani, U. B. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.311 · Cited by 671
Self-citation
Metadata
- Authors
- Schwabe, R. F., & Luedde, T.
- Affiliations
- Columbia University Irving Medical Center (US)
- Universitätsklinikum Aachen (DE)
- Corresponding author
- Schwabe, Robert F.
- Luedde, Tom
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2018-09-24
- Volume
- 15
- Issue
- 12
- Pages
- 738-752
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- 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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