The DOI matches its Crossref record; 147 of the 148 references it cites were found in a registry or an index.
Lytic cell death in metabolic liver disease
Open accessAbstract
Regulated cell death is intrinsically associated with inflammatory liver disease and is pivotal in governing outcomes of metabolic liver disease. Different types of cell death may coexist as metabolic liver disease progresses to inflammation, fibrosis, and ultimately cirrhosis. In addition to apoptosis, lytic forms of hepatocellular death, such as necroptosis, pyroptosis and ferroptosis elicit strong inflammatory responses due to cell membrane permeabilisation and release of cellular components, contributing to the recruitment of immune cells and activation of hepatic stellate cells. The control of liver cell death is of fundamental importance and presents novel opportunities for potential therapeutic intervention. This review summarises the underlying mechanism of distinct lytic cell death modes and their commonalities, discusses their relevance to metabolic liver diseases of different aetiologies, and acknowledges the limitations of current knowledge in the field. We focus on the role of hepatocyte necroptosis, pyroptosis and ferroptosis in non-alcoholic fatty liver disease, alcohol-associated liver disease and other metabolic liver disorders, as well as potential therapeutic implications.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Damaged and dying hepatocytes release damage-associated molecular patterns (DAMPs); potent activators of the innate immune system (209).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [209]
In the citing paper
“These pathways involve rapid membrane permeabilization and release of cytoplasmic contents, triggering a stronger immune response than apoptosis (12).”
From Hepatic Stellate Cell-Immune Interactions in NASH (2022) · cites this paper as [12]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Shulga, N., & Pastorino, J. G. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.580175 · Cited by 14 · cited 1×
“Pyroptosis triggered by gut-derived PAMPS and by metabolic-derived DAMPs (ATP and uric acid) resulted in release of inflammasome-dependent cytokines from immune cells in ALD patients and in cells exposed to ethanol [120, 122].”
BackgroundRetractedFerroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691 · cited 5×
“Ferroptosis can be induced either in a canonical way by a direct or indirect inactivation of the glutathione peroxidase 4 (GPX4), the major protective mechanism of biological membranes against peroxidation damage, or in a non-canonical manner by increasing the labile iron pool [48].”
BackgroundInfluentialRegulation of Ferroptotic Cancer Cell Death by GPX4
Yang, W. S., SriRamaratnam, R., Welsch, M. E., Shimada, K., Skouta, R., Viswanathan, V. S., Cheah, J. H., Clemons, P. A., Shamji, A. F., Clish, C. B., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.010 · Cited by 7,713 · cited 1×
“By indirectly blocking the Xc− transporter, erastin inhibits GSH synthesis, which is used by GPX4 to eliminate the production of phospholipid hydroperoxides (PL-OOH), the major mediator of chain reactions in lipoxygenases [53].”
BackgroundGalluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Self-citationCleavage of GSDMD by inflammatory caspases determines pyroptotic cell death
Shi, J., Zhao, Y., Wang, K., Shi, X., Wang, Y., Huang, H., Zhuang, Y., Cai, T., Wang, F., & Shao, F. (2015) · Nature · doi:10.1038/nature15514 · Cited by 6,659 · cited 4×
“Caspases-1 and -11 cleave GSDMD into a 31-kDa N-terminal GSDMDNT fragment, which exhibits intrinsic pore-forming activity, and a 22-kDa C-terminal GSDMDCT fragment that binds to GSDMDNT to maintain the protein in an inhibitory state [40, 41].”
BackgroundInfluentialMechanisms of NAFLD development and therapeutic strategies
Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M., & Sanyal, A. J. (2018) · Nature Medicine · doi:10.1038/s41591-018-0104-9 · Cited by 4,354 · cited 1×
“Although metabolic alterations caused by free fatty acid overload is considered a major cause for hepatocyte damage, the mechanisms driving disease progression from simple steatosis to NASH remain incompletely understood [72].”
BackgroundACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition
Doll, S., Proneth, B., Tyurina, Y. Y., Panzilius, E., Kobayashi, S., Ingold, I., Irmler, M., Beckers, J., Aichler, M., Walch, A., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2239 · Cited by 4,293
Ferroptosis: process and function
Xie, Y., Hou, W., Song, X., Yu, Y., Huang, J., Sun, X., Kang, R., & Tang, D. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2015.158 · Cited by 3,727
The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis
Bersuker, K., Hendricks, J. M., Li, Z., Magtanong, L., Ford, B., Tang, P. H., Roberts, M. A., Tong, B., Maimone, T. J., Zoncu, R., et al. (2019) · Nature · doi:10.1038/s41586-019-1705-2 · Cited by 3,703 · cited 1×
“Recently, the ferroptosis suppressor protein 1 (FSP1), previously known as apoptosis-inducing factor mitochondrial 2 (AIFM2), was identified as a key component of a non-mitochondrial CoQ10 (ubiquinone) antioxidant system that acts in parallel to the GPX4 canonical pathway to halt the progression of lipid peroxides [58…”
BackgroundCaspase-11 cleaves gasdermin D for non-canonical inflammasome signalling
Kayagaki, N., Stowe, I. B., Lee, B. L., O’Rourke, K., Anderson, K., Warming, S., Cuellar, T., Haley, B., Roose-Girma, M., Phung, Q. T., et al. (2015) · Nature · doi:10.1038/nature15541 · Cited by 3,686 · cited 2×
“Caspases-1 and -11 cleave GSDMD into a 31-kDa N-terminal GSDMDNT fragment, which exhibits intrinsic pore-forming activity, and a 22-kDa C-terminal GSDMDCT fragment that binds to GSDMDNT to maintain the protein in an inhibitory state [40, 41].”
Background
Research works printed but not linked: 1
- Orning, 2019, Gasdermins and their role in immunity and inflammation, J Exp Med, 216, 2453, 10.1084/jem.20190545 · DOI
Cited by
Sorted by citations
Items 201–213 of 213
Intravital Imaging as a Tool to Uncover Roles of Immune Cells in Chronic Liver Diseases
Rashid, M., Lee, W., & Kubes, P. (2026) · JHEP Reports · doi:10.1016/j.jhepr.2026.102030
Yao, C., Sheng, J.-H., Zheng, W., Kang, M.-J., Duan, L., & Yuan, X. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1856946
“The goal is twofold: to inhibit ferroptosis in hepatocytes for alleviating inflammation and injury, and to selectively induce ferroptosis in hepatic stellate cells for eliminating activated cells and reversing fibrosis (Gautheron et al., 2020; Horn and Tacke, 2024).”
Wang, Y., Hao, D., Fan, X.-Y., Pan, L.-M., Duan, H., Yan, J., Yao, Y., Zha, M., Sarun, P., Du, Y.-J., et al. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.179251
Yu, W., Yin, K., Liu, C., Ding, J., & Shi, Y. (2026) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s626893
Tang, D., Wu, Y.-N., Ding, L., Ding, X.-L., Chen, J., Sun, Y.-T., Guo, J.-J., Lu, L.-J., & Wang, R.-Y. (2026) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2026.08.006
Li, C., Wang, X., He, A., Bao, T., Zhuang, W., He, C., & Yang, Y. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18070887
Wang, Z., Zhang, F., Cao, S., Xue, X., Li, H., Liu, Q., Wang, D., & Wu, Y. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1797182
“Necrosulfonamide, as an MLKL inhibitor, prevents MLKL membrane translocation and pore formation (180), thereby directly inhibiting this inflammatory cell death program.”
Ginsenosides in Liver Fibrosis: Pharmacological Actions and Therapeutic Potential.
Li, N., Ye, F.-H., Yu, F., Hao, L.-Y., Li, S.-H., Peng, Q., Deng, J.-L., Zhang, J., & Hu, X.-Y. (2026) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x26500436
Tan, X., Zou, H., Huang, X.-J., Guo, M., Yu, R., Liu, X., Peng, T., Yang, X., & Qin, C.-S. (2026) · BMJ Open · doi:10.1136/bmjopen-2024-094809
“38 Alcohol, a key factor in the nomenclature updates, promotes hepatic steatosis by impairing mitochondrial function, 39 inducing hepatocellular injury and death, 40 and increasing intestinal permeability.”
Apigenin-5-O-glucoside alleviates hepatic fibrosis through NOX4-mediated ferroptosis in zebrafish.
Li, M., Deng, K.-L., Cheng, J., Shi, H.-C., Li, Y.-Y., Wang, Y., Wen, J.-J., Lv, Z.-P., & Huang, S. (2026) · Phytomedicine · doi:10.1016/j.phymed.2026.157956
Chen, R., & Wang, W. (2025) · Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · doi:10.11817/j.issn.1672-7347.2025.250040
Editorial: Secreted proteins as novel biomarkers and therapeutic targets in NAFLD
Xiong, X. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1277101
Wang, B., Yang, L.-Y., Liu, T., Sun, Z., Jiang, A., & Li, Z. (2026) · Sensors and actuators. B, Chemical · doi:10.1016/j.snb.2026.140287
Metadata
- Authors
- Gautheron, J., Gores, G. J., & Rodrigues, C. M. P.
- Affiliations
- Inserm (FR)
- Mayo Clinic (US)
- University of Lisbon (PT)
- Corresponding author
- Rodrigues, Cecília M.P.
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 73
- Issue
- 2
- Pages
- 394-408
- ISSN
- 0168-8278 (ISSN-L)
- PMC
- PMC7371520
- OpenAlex
- W3016394009
- Cited by
- 225
- References
- 148
- Citations by year
- 2026: 31 · 2025: 32 · 2024: 49 · 2023: 40 · 2022: 42 · 2021: 23 · 2020: 8
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Fondation pour la Recherche Médicale
- Fundação para a Ciência e a Tecnologia
- National Institutes of Health
- H2020 Marie Skłodowska-Curie Actions
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- lytic cell death, metabolic liver disease, pyroptosis, ferroptosis, apoptosis, liver inflammation, liver fibrosis, liver cirrhosis, hepatic stellate cells, non-alcoholic fatty liver disease, alcoholic liver disease, therapeutic target
- MeSH terms
- Pyroptosis, Necroptosis, Ferroptosis, Regulated Cell Death, Humans, Liver Diseases, Drug Discovery
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
