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
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
How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease?
Geng, Y., Faber, K. N., de Meijer, V. E., Blokzijl, H., & Moshage, H. J. (2021) · Hepatology International · doi:10.1007/s12072-020-10121-2 · Cited by 465
Oxidative stress and regulated cell death in Parkinson’s disease
Dionísio, P. A., Amaral, J. D., & Rodrigues, C. M. P. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101263 · Cited by 443
Self-citationXu, X., Poulsen, K. L., Wu, L., Liu, S., Miyata, T., Song, Q., Wei, Q., Zhao, C., Lin, C., & Yang, J. B. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01119-3 · Cited by 387
“Multiple types of cell death, including apoptosis, necroptosis, pyroptosis, and ferroptosis, as well as autophagy, are associated with the development of NAFL/ NASH.(72,293,294) Among targeting different formats of cell death, inhibition of apoptosis has achieved promising results, here we focus on anti-apoptosis agen…”
BackgroundInfluentialFerroptosis in Liver Diseases: An Overview
Capelletti, M. M., Manceau, H., Puy, H., & Peoc’h, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144908 · Cited by 369
“New studies focused on the molecular basis of ferroptosis could help in deciphering the existing connections between the single components of the metabolic pathway.”
BackgroundInfluentialLiu, Z., Wang, M., Wang, X., Bu, Q., Wang, Q., Su, W., Li, L., Zhou, H., & Lü, L. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102305 · Cited by 363
“Increased hepatocyte pyroptosis contributes to the pathology of acute and chronic liver diseases [35,36].”
BackgroundUpdated mechanisms of MASLD pathogenesis
Li, Y., Yang, P., Ye, J., Xu, Q., Wu, J., & Wang, Y. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02108-x · Cited by 354
“In terms of cellular morphology, ferroptosis is characterized by smaller mitochondrial volume, increased membrane density, and a lower number of cristae, along with insignificant changes in the nucleus [93].”
BackgroundCell Death in Liver Diseases: A Review
Shojaie, L., Iorga, A., & Dara, L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249682 · Cited by 309
“Further research using GSDMD KO models with other dietary models is needed to study the role of pyroptosis in NAFLD/NASH [47,89,136].”
MethodInfluentialTNF in the liver: targeting a central player in inflammation
Tiegs, G., & Horst, A. K. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00910-2 · Cited by 231
Insights into N6-methyladenosine and programmed cell death in cancer
Liu, L., Li, H., Hu, D., Wang, Y., Shao, W., Zhong, J., Yang, S., Liu, J., & Zhang, J. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01508-w · Cited by 241
Immunological mechanisms and therapeutic targets of fatty liver diseases
Wang, H., Mehal, W. Z., Nagy, L. E., & Rotman, Y. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00579-3 · Cited by 234
The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease
Díaz, L. A., Arab, J. P., Louvet, A., Bataller, R., & Arrese, M. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00822-y · Cited by 207
“Both metabolic dysfunction and chronic alcohol exposure induce multiple forms of cellular stress that lead to cell injury and death, which are key drivers of disease progression 97 .”
BackgroundLuci, C., Bourinet, M., Leclère, P. S., Anty, R., & Gual, P. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.597648 · Cited by 195
“Targeting the Liver Injury (Hepatocyte Death) As previously described, different types of hepatocyte death have been associated with NAFLD progression and drive hepatic inflammation (40).”
BackgroundYang, Y. M., Cho, Y. E., & Hwang, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020774 · Cited by 207
“In the liver, ferroptosis generates ROS and depletes glutathione levels [78,79].”
BackgroundRoles of RIPK3 in necroptosis, cell signaling, and disease
Morgan, M. J., & Kim, Y. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00868-z · Cited by 197
Tillman, E. J., & Rolph, T. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.601290 · Cited by 214
Lan, T., Yu, Y., Zhang, J., Li, H.-N., Weng, Q., Jiang, S., Tian, S., Xu, T., Hu, S., Yang, G., et al. (2021) · Hepatology · doi:10.1002/hep.31749 · Cited by 176
“Lipotoxicity eventually leads to hepatocyte injury or even death (24); thus, serum ALT and AST levels were measured.”
BackgroundXiao, Y., Zhao, C., Tai, Y., Li, B., Lan, T., Lai, E., Dai, W., Guo, Y., Gan, C., Kostallari, E., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102691 · Cited by 182
Liu, J., Zhou, J., Luan, Y., Li, X., Meng, X., Liao, W., Tang, J., & Wang, Z. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01466-w · Cited by 175
“GSDMD-mediated hepatocyte pyroptosis contributes to accelerated pathogenesis in acute and chronic liver disease [156–159].”
BackgroundNon-alcoholic Fatty Liver Disease and Alcohol-Related Liver Disease: Two Intertwined Entities
Idalsoaga, F., Kulkarni, A. V., Mousa, O. Y., Arrese, M., & Arab, J. P. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00448 · Cited by 136
Vachliotis, I. D., & Polyzos, S. (2023) · Current Obesity Reports · doi:10.1007/s13679-023-00519-y · Cited by 115
The role of bile acids in cholestatic liver injury
Cai, S., & Boyer, J. L. (2021) · Annals of Translational Medicine · doi:10.21037/atm-20-5110 · Cited by 129
“Necroptosis is a form of regulated necrotic cell death (59,60).”
BackgroundROS/RNS as molecular signatures of chronic liver diseases
Che, Z., Zhou, Z., Li, S.-Q., Gao, L., Xiao, J., & Wong, N.-K. (2023) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2023.08.001 · Cited by 110
Xu, S.-X., Chen, Y.-E., Miao, J., Li, Y.-H., Liu, J., Zhang, J., Liang, J., Chen, S.-X., & Hou, S.-Z. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155465 · Cited by 101
Nuclear receptors linking metabolism, inflammation, and fibrosis in nonalcoholic fatty liver disease
Puengel, T., Liu, H., Guillot, A., Heymann, F., Tacke, F., & Peiseler, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052668 · Cited by 95
“In recent years, a better understanding of cell death mechanisms has expanded the number of known processes involved in metabolic liver diseases, from apoptosis to mitochondrial permeability transition (MPT)-driven necrosis, and necroptosis, autophagic apoptosis, and pyroptosis [38].”
BackgroundGuo, T., Yan, W., Cui, X., Liu, N., Wei, X., Sun, Y., Fan, K.-X., Liu, J., Zhu, Y.-Y., Wang, Z., et al. (2023) · Molecular Medicine · doi:10.1186/s10020-023-00721-7 · Cited by 93
“In recent years, accumulating evidence indicates that ferroptosis is involved in the progression of NAFLD (Gautheron et al. 2020; Wang et al. 2022b).”
BackgroundSalvianolic acid B attenuates liver fibrosis by targeting Ecm1 and inhibiting hepatocyte ferroptosis
Fu, Y., Zhou, X., Wang, L., Fan, W., Gao, S., Zhang, D., Ling, Z., Zhang, Y., Ma, L., Bai, F., et al. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103029 · Cited by 93
“In recent years, increasing research has focused on the contribution of hepatocytes and extracellular matrix to the progression of liver fibrosis [7 – 9].”
BackgroundZhuge, A., Li, S., Han, S., Yuan, Y., Shen, J., Wu, W., Wang, K., Xia, J., Wang, Q., Gu, Y., et al. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.10.010 · Cited by 97
Why Do So Many Nonalcoholic Steatohepatitis Trials Fail?
Ratziu, V., & Friedman, S. L. (2023) · Gastroenterology · doi:10.1053/j.gastro.2020.05.046 · Cited by 88
Shi, H., Wang, X., Li, F., Gerlach, B. D., Yurdagul, A., Moore, M. P., Zeldin, S., Zhang, H., Cai, B., Zheng, Z., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abp8309 · Cited by 85
“One theory holds that molecules leaking from uncleared dead cells, such as damage-associated molecular patterns, might activate hepatic macrophages and hepatic stellate cells (HSCs), triggering hepatic inflammation and fibrosis (11, 12).”
BackgroundIron, Oxidative Stress, and Metabolic Dysfunction—Associated Steatotic Liver Disease
Gensluckner, S., Wernly, B., Datz, C., & Aigner, E. S. (2024) · Antioxidants · doi:10.3390/antiox13020208 · Cited by 82
“In MASLD, different cell death mechanisms like necroptosis, pyroptosis, and ferroptosis contribute to disease progression [49].”
BackgroundHepatic Stellate Cell-Immune Interactions in NASH
Carter, J. K., & Friedman, S. L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.867940 · Cited by 79
“These pathways involve rapid membrane permeabilization and release of cytoplasmic contents, triggering a stronger immune response than apoptosis (12).”
BackgroundPeleman, C., Francque, S., & Berghe, T. V. (2024) · EBioMedicine · doi:10.1016/j.ebiom.2024.105088 · Cited by 89
Ferroptosis and metabolic dysfunction‐associated fatty liver disease: Is there a link?
Feng, G., Byrne, C. D., Targher, G., Wang, F.-D., & Zheng, M. (2022) · Liver international (Print) · doi:10.1111/liv.15163 · Cited by 77
Wang, Y., Zhao, Y., Wang, Z., Sun, R., Zou, B., Li, R., Liu, D., Lin, M., Zhou, J., Ning, S., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.652782 · Cited by 82
“Pyroptosis is a newly identified type of programmed cell death (PCD) characterized by pore formation in the plasma membrane, swelling, cell rupture, and proinflammatory factor release (11, 12).”
BackgroundChen, C., Liu, J., Lin, X., Xiang, A., Ye, Q., Guo, J., Tao, R., Xu, J., & Hu, S. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-01958-9 · Cited by 71
“Unlikeapoptotic cell death, lytic forms of cell death, such as pyroptosis and ferroptosis, lead to membrane permeabilization and cell lysis and the subsequent release of intracellular components and in fl ammatory cytokines [155, 156].”
BackgroundChen, T.-X., Meng, Y., Zhou, Z.-H., Li, H., Wan, L.-F., Kang, A., Guo, W., Ren, K., Song, X., Chen, Y., et al. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01183-4 · Cited by 66
“Pyroptosis may be activated by lipid toxicity, inflammation, and oxidative stress during NAFLD development [20, 21].”
BackgroundPyroptosis: Mechanisms and Links with Fibrosis
Song, Z., Gong, Q., & Guo, J. (2021) · Cells · doi:10.3390/cells10123509 · Cited by 68
“A large number of studies have shown that pyroptosis plays an important role in the process of liver fibrosis [29,48].”
BackgroundTargeting cell death in NAFLD: mechanisms and targeted therapies
Xu, H., Wan, S., An, Y., Wu, Q., Xing, Y.-H., Deng, C.-H., Zhang, P., Long, Y., Xu, B.-T., & Jiang, Z. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02168-z · Cited by 72
“Based on accumulating evidence, RCD is closely related to the initiation and progression of NAFLD [6, 7].”
BackgroundXue, M., Tian, Y., Sui, Y., Zhao, H. J., Gao, H., Liang, H., Qiu, X., Sun, Z., Zhang, Y., & Qin, Y. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113402 · Cited by 66
Inflammatory signaling in NASH driven by hepatocyte mitochondrial dysfunctions
Myint, M., Oppedisano, F., De Giorgi, V., Kim, B.-M., Marincola, F. M., Alter, H. J., & Nesci, S. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04627-0 · Cited by 61
“Hepatocyte RCD, including apoptosis and lytic forms of hepatocellular death, such as necrosis, necroptosis, pyroptosis and ferroptosis [85], drives activation of Kupffer cells and other non-parenchymal cells, such as HSCs.”
BackgroundInaba, Y., Hashiuchi, E., Watanabe, H., Kimura, K., Oshima, Y., Tsuchiya, K., Murai, S., Takahashi, C., Matsumoto, M., Kitajima, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-35804-w · Cited by 65
Liu, B., Yi, W., Mao, X., Yang, L., & Rao, C. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00614.2020 · Cited by 63
Cell Death in Hepatocellular Carcinoma: Pathogenesis and Therapeutic Opportunities
García‐Pras, E., Fernández‐Iglesias, A., Gracia‐Sancho, J., & Pérez‐del‐Pulgar, S. (2021) · Cancers · doi:10.3390/cancers14010048 · Cited by 62
“Pyroptosis is a highly proinflammatory cell death mode, predominantly dependent on caspase-1 and caspase 4/5/11 [15,46].”
BackgroundTumor necrosis factor-α signaling in nonalcoholic steatohepatitis and targeted therapies
Lü, S., Wang, Y., & Liu, J. (2021) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2021.09.009 · Cited by 79
Regulation of Ferroptosis Pathway by Ubiquitination
Wang, X., Wang, Y., Li, Z., Qin, J., & Wang, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.699304 · Cited by 54
Peleman, C., Hellemans, S., Veeckmans, G., Arras, W., Zheng, H., Koeken, I., San, E. V., Hassannia, B., Walravens, M., Kayirangwa, E., et al. (2024) · Cell Death and Differentiation · doi:10.1038/s41418-024-01348-9 · Cited by 60
“Log-rank test, two-way ANOVA with post-hoc test. importance is dif fi cult to study [6, 7].”
MethodThe liver as a central "hub" of the immune system: pathophysiological implications
Ronca, V., Gerussi, A., Collins, P., Parente, A., Oo, Y. H., & Invernizzi, P. (2025) · Physiological Reviews · doi:10.1152/physrev.00004.2023 · Cited by 59
Bekric, D., Ocker, M., Mayr, C., Stintzing, S., Ritter, M., Kiesslich, T., & Neureiter, D. (2022) · Cancers · doi:10.3390/cancers14071826 · Cited by 58
Zhao, Q., Chen, D., Chen, H., Wang, Y., Shi, W. L., Lu, Y., Ren, Y.-Z., Wu, Y., Pang, Y., Deng, H. X., et al. (2024) · Hepatology · doi:10.1097/hep.0000000000000868 · Cited by 54
“Hepatocyte injury and death are known to initiate ACLF [1 – 5, 35 ] ; however , whether and how cell death occurs and affects HBV-related ACLF progression remain unclear.”
Jiang, X., Deng, W.-Z., Tao, S., Tang, Z., Chen, Y.-H., Tian, M.-X., Wang, T., Tao, C., Li, Y.-Z., Fang, Y., et al. (2023) · Cell Discovery · doi:10.1038/s41421-022-00504-0 · Cited by 50
Zhuge, A., Li, S., Yuan, Y., Han, S., Xia, J., Wang, Q., Wang, S., Lou, P., Li, B., & Li, L. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102582 · Cited by 48
“Primarily, regulated cell death (RCD) in metabolic liver disease is comprised of apoptosis, necroptosis, pyroptosis and ferroptosis [20,21].”
BackgroundZhang, J., Xie, H.-N., Yao, J., Jin, W., Pan, H., Pan, Z.-Q., Xie, D.-Y., & Xie, D.-H. (2022) · Human Cell · doi:10.1007/s13577-022-00820-3 · Cited by 50
“A previous study indicated that ferroptosis played a critical role for the development NAFLD [41].”
BackgroundRIPK3 dampens mitochondrial bioenergetics and lipid droplet dynamics in metabolic liver disease
Afonso, M. B., Islam, T., Magusto, J., Amorim, R., Lenoir, V., Simões, R. F., Teixeira, J., Silva, L. C., Wendum, D., Jéru, I., et al. (2022) · Hepatology · doi:10.1002/hep.32756 · Cited by 56
Self-citationHa, Y., Jeong, I., & Kim, T. H. (2022) · Biomedicines · doi:10.3390/biomedicines10102530 · Cited by 47
Ferroptosis in non-alcoholic liver disease: Molecular mechanisms and therapeutic implications
Cheng, Z., Chu, H., Zhu, Q., & Yang, L. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1090338 · Cited by 45
“It is commonly accepted that ferroptosis, as a modality of cell death, is usually concomitant with compromised cellular membrane and the release of cellular constituents, which can recruit a number of immune cells, further eliciting strong inflammatory responses (8).”
BackgroundInfluentialMiyata, T., Wu, X., Fan, X., Huang, E., Sanz‐García, C., Ross, C. K. C., Roychowdhury, S., Bellar, A., McMullen, M. R., Dasarathy, J., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.140180 · Cited by 45
“Discussion Multiple pathways of regulated cell death are implicated in the progression of metabolic liver diseases; however, the contributions of individual pathways of regulated cell death to specific liver diseases are not well understood (31).”
MetALD: Clinical aspects, pathophysiology and treatment
Gratacós‐Ginès, J., Ariño, S., Sancho‐Bru, P., Bataller, R. A., & Pose, E. (2024) · JHEP Reports · doi:10.1016/j.jhepr.2024.101250 · Cited by 45
“82”
Xu, J., Wu, D., Zhou, S., Hu, H., Li, F., Guan, Z., Zhan, X., Gao, Y., Wang, P., & Rao, Z. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01357-6 · Cited by 48
“Different types of cell death occur simultaneously in various liver diseases, including liver injury, metabolic liver disease, and cancer [3, 4].”
BackgroundWu, C., Bian, Y., Lu, B., Wang, D., Azami, N. L. B., Wei, G., Ma, F., & Sun, M. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03495-4 · Cited by 43
“DAMPs released from injurious hepatocytes produced inflammatory factors by activating Kuffer cells, so as to further promoted and maintained the activation of hepatic stellate cells (HSCs), and finally lead to the continuous secretion of collagen and fibers by HSCs, thus forming hepatic fibrosis and even cirrhosis [45…”
BackgroundZhang, H.-J., Zhou, L., Zhou, Y.-H., Wang, L.-L., Jiang, W.-L., Liu, L., Yue, S., Zheng, P.-D., & Liu, H.-G. (2021) · Life Science · doi:10.1016/j.lfs.2021.119963 · Cited by 41
Oleanolic acid inhibits mercury chloride induced-liver ferroptosis by regulating ROS/iron overload.
Ouyang, C., Ma, X., Zhao, J., Li, S., Liu, C., Tang, Y., Zhou, J., Chen, J., Li, X., & Li, W.-W. (2023) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2023.114973 · Cited by 39
Yuan, Y., Li, Y., Li, L., Liu, H., Pang, Y., & Yan, H. (2022) · Toxicology Letters · doi:10.1016/j.toxlet.2022.08.007 · Cited by 39
Harnessing ferroptosis for precision oncology: challenges and prospects
Fernández-Acosta, R., Vintea, I., Koeken, I., Hassannia, B., & Berghe, T. V. (2025) · BMC Biology · doi:10.1186/s12915-025-02154-6 · Cited by 36
“…injuries and inflammatory diseases [164–166], including rheumatoid arthritis [167], inflammatory bowel disease [168, 169], metabolic dysfunction-associated steatotic liver disease (MASLD) [170], and liver fibrosis [171], driven by advances in biomarker discovery and precision medicine.”
Liver fibrosis is a common pathological change in the liver of dairy cows with fatty liver.
Zhang, C., Shao, Q., Liu, M.-C., Wang, X., Loor, J., Jiang, Q., Cuan, S., Li, X., Wang, J., Li, Y.-X., et al. (2023) · Journal of Dairy Science · doi:10.3168/jds.2022-22021 · Cited by 36
Iron as a therapeutic target in chronic liver disease
Kouroumalis, E., Tsomidis, I., & Voumvouraki, A. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i4.616 · Cited by 42
Physiological Effects of Ferroptosis on Organ Fibrosis
Du, X., Dong, R., Wu, Y., & Ni, B. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/5295434 · Cited by 33
“[44]”
Ferroptosis: Shedding Light on Mechanisms and Therapeutic Opportunities in Liver Diseases
You, H., Wang, L., Bu, F., Meng, H., Huang, C., Fang, G.-Y., & Li, J. (2022) · Cells · doi:10.3390/cells11203301 · Cited by 33
Research mechanisms of and pharmaceutical treatments for ferroptosis in liver diseases
Yu, J. G., & Wang, J. (2020) · Biochimie · doi:10.1016/j.biochi.2020.11.002 · Cited by 39
Pathophysiological Mechanisms in Non-Alcoholic Fatty Liver Disease: From Drivers to Targets
Santos‐Laso, Á., Gutiérrez‐Larrañaga, M., Alonso‐Peña, M., Medina, J. M., Iruzubieta, P., Arias, M., López‐Hoyos, M., & Crespo, J. (2021) · Biomedicines · doi:10.3390/biomedicines10010046 · Cited by 34
“This enzyme might directly cause hepatocyte injury, and activate HSCs, and its deletion in HFD-induced NASH decreases liver inflammation and fibrosis [134,135].”
BackgroundInfluentialEfferocytosis in liver disease
Shi, H., Moore, M. P., Wang, X., & Tabas, I. (2024) · JHEP Reports · doi:10.1016/j.jhepr.2023.100960 · Cited by 30
“Multiple forms of liver cell death, including necrosis, apoptosis, necroptosis, pyroptosis, and ferroptosis, have been reported in various types of liver disease, 5 – 8, 22”
BackgroundThe key players of inflammasomes and pyroptosis in sepsis-induced pathogenesis and organ dysfunction
Zhu, L., Hu, M., Xu, H., Xu, H., Ren, B., Xu, R., Guo, M., Chen, H., Zhang, D., & Fang, H. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1586364 · Cited by 31
Kinases control of regulated cell death revealing druggable targets for Parkinson’s disease
Mansour, H. M., Mohamed, A. F., El-Khatib, A. S., & Khattab, M. M. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101841 · Cited by 44
Elucidating cuproptosis in metabolic dysfunction-associated steatotic liver disease
Li, Y., Qi, P., Song, S., Wang, Y., Wang, H., Cao, P., Liu, Y., & Wang, Y. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116585 · Cited by 28
Tang, S., Zhang, X., Duan, Z., Xu, M., Kong, M., Zheng, S., Bai, L., & Chen, Y. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.109808 · Cited by 30
Recent progress in the effect of ferroptosis of HSCs on the development of liver fibrosis
Tang, R., Luo, J., Zhu, X., Miao, P., Tang, H. Y., Jian, Y., Ruan, S., Ling, F., & Tang, M. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1258870 · Cited by 26
“…iron overload induced ferroptosis, they release ROS and proin fl ammatory factors, transmit risk signals to surrounding cells including in fl ammatory cells and HSCs, and induce chronic in fl ammation and directly or indirectly induce the activation and proliferation of HSCs (Gautheron et al., 2020).”
BackgroundMori fructus aqueous extracts attenuates liver injury by inhibiting ferroptosis via the Nrf2 pathway
Wei, Y., Gao, C., Wang, H.-R., Zhang, Y.-N., Gu, J.-H., Zhang, X.-Y., Gong, X.-H., & Hao, Z.-H. (2023) · Journal of Animal Science and Biotechnology · doi:10.1186/s40104-023-00845-0 · Cited by 27
Cheng, Z., Chu, H., Seki, E., Lin, R., & Yang, L. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1431921 · Cited by 31
“The morphological features of ferroptosis encompass mitochondrial atrophy, decreased or obliterated mitochondrial cristae, as well as cellular membrane rupture (Gautheron et al., 2020).”
BackgroundInfluentialShi, J., Liu, Y., Wang, Y., Gao, R., Wang, Y., & Liu, J. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1194343 · Cited by 26
“In general, previous studies have shown that iron overload is an important factor driving alcohol-induced liver injury (Chu et al., 2019; Gautheron et al., 2020; Chen et al., 2021b).”
BackgroundThe role of MLKL in Hepatic Ischemia-Reperfusion Injury of Alcoholic Steatotic Livers
Chen, H., McKeen, T., Chao, X., Chen, A., Deng, F., Jaeschke, H., Ding, W., & Ni, H. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.67533 · Cited by 29
“While excessive pyroptosis causes various inflammatory diseases like sepsis, pyroptosis also gains more attention in the pathogenesis of ALD and IR injury [52, 53].”
BackgroundRao, Y., Li, C., Hu, Y., Xu, Y., Song, B., Guo, S., Jiang, Z., Zhao, D., Chen, S.-B., Tan, J., et al. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15727 · Cited by 27
“We also identified many novel HSF1-associated transcripts involved in autophagy and ferroptosis, such as ATG10, PARK2 and SFXN1 (Table S1), which have also been reported to be involved in the development of MAFLD/NASH in vivo (Gautheron et al., 2020; Tanaka et al., 2016).”
BackgroundAdvancements in the Alcohol-Associated Liver Disease Model
Zhu, L., Li, H.-D., Xu, J., Li, J., Cheng, M., Meng, X., Huang, C., & Li, J. (2022) · Biomolecules · doi:10.3390/biom12081035 · Cited by 30
“In addition, long-term alcohol consumption increases the serum ferritin concentration and transporter saturation, thereby increasing hepatic iron storage and the production of reactive oxygen species and causing local inflammation [19,40].”
BackgroundQiu, J.-N., Le, Y.-F., Liu, N., Chen, L., Jiang, Y.-W., Wang, Y.-H., Fan, X.-H., Rong, X.-L., Yu, Z., Li, S.-T., et al. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c04929 · Cited by 24
Zhou, X.-Y., Wang, J., & Zhou, S.-F. (2024) · Aging · doi:10.18632/aging.205693 · Cited by 24
“In the process, GSH is consumed, GXP4 activity is inhibited, lipid peroxidation occurs, inducing cell ferroptosis, and exacerbating ALD development [34, 35].”
BackgroundMesenchymal stem cells and ferroptosis: Clinical opportunities and challenges
Cui, M., Chen, F., Shao, L., Wei, C., Zhang, W., Sun, W., & Wang, J. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e25251 · Cited by 22
Zhao, S.-S., Guo, Y., & Yin, X. (2024) · Frontiers in Bioscience · doi:10.31083/j.fbl2901030 · Cited by 24
“These lead to the release of DAMPs, which in turn induce inflammatory responses and consequential secondary injury [ 98].”
BackgroundSitbon, A., Delmotte, P.-R., Pistorio, V., Halter, S., Gallet, J., Gautheron, J., & Monsel, A. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05282-9 · Cited by 24
“Pyroptosis serves as another modality of programmed cell death marked by the expulsion of pro-inflammatory substances, relevant in hepatic inflammation and damage [28].”
BackgroundSelf-citationLe, Y.-F., Guo, J., Liu, Z., Liu, J., Liu, Y., Chen, H., Qiu, J.-N., Wang, C., Dou, X., & Lu, D.-Z. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.117239 · Cited by 22
Yang, Y., Wang, X., Zhang, H., Li, J., Chen, J., Yu, M., Li, G.-X., Zhang, R.-L., & Ge, M. (2022) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2022.110216 · Cited by 21
Unravelling the Role of PANoptosis in Liver Diseases: Mechanisms and Therapeutic Implications
Xiong, W., Li, J., Tian, A., & Mao, X. (2025) · Liver International · doi:10.1111/liv.70000 · Cited by 19
Wang, H.-T., Su, Z.-J., Qian, Y., Shi, B.-J., Li, H., An, W.-B., Xiao, Y., Qiu, C., Guo, Z., Zhong, J., et al. (2024) · Molecular Biomedicine · doi:10.1186/s43556-024-00227-6 · Cited by 20
“Many studies have highlighted the critical role of the ferroptosis of hepatocytes in orchestrating a cascade of immune responses during endotoxemia [8–10].”
Guo, J., Le, Y., Yuan, A., Liu, J., Chen, H., Qiu, J., Wang, C., Dou, X., Yuan, X., & Lu, D. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.118080 · Cited by 23
Contribution of classification based on ferroptosis-related genes to the heterogeneity of MAFLD
Dai, X., Zhang, R., & Wang, B.-M. (2022) · BMC Gastroenterology · doi:10.1186/s12876-022-02137-9 · Cited by 20
“Different types of cell death, such as necroptosis, pyroptosis and ferroptosis, coexist as metabolic liver disease progresses [4].”
BackgroundMa, F., Wang, L., Chi, H., Li, X.-Y., Xu, Y., Chen, K., Zhou, J., Yang, R., Liu, J., Xu, K., et al. (2025) · Cell Proliferation · doi:10.1111/cpr.70018 · Cited by 18
AT1 receptor autoantibodies mediate effects of metabolic syndrome on dopaminergic vulnerability.
Pedrosa, M. A., Labandeira, C., Valenzuela, R., Quijano, A., Sanchez-Andrade, M., Suárez-Quintanilla, J., Lanciego, J., Labandeira-Garcia, J., & Rodriguez-Perez, A. I. (2022) · Brain, behavior, and immunity · doi:10.1016/j.bbi.2022.12.009 · Cited by 18
Lipid Peroxidation in Ferroptosis and Association with Nonalcoholic Fatty Liver Disease
Zhao, S., Yan, G., & Yin, X. (2023) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2812332 · Cited by 18
“Evidence suggests ferroptosis is tightly associated with lipid peroxidation (LPO) in NAFLD and can therefore be an important target for preventing and treating NAFLD [8].”
BackgroundMicroRNAs and Nonalcoholic Steatohepatitis: A Review
Morishita, A., Oura, K., Tadokoro, T., Fujita, K., Tani, J., Kobara, H., Ono, M., Himoto, T., & Masaki, T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914482 · Cited by 19
“…involvement of miRNAs in various pathological conditions and the formation of diseases via post-transcriptional regulation [31]. miRNA– disease relationships have been most studied in the fields of cancer and infectious diseases for which nucleic acid medicine therapies have already been attempted.”
BackgroundExosomal microRNAs and Progression of Nonalcoholic Steatohepatitis (NASH)
Qi, X., & Lai, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113501 · Cited by 14
“Lipotoxicity in hepatocytes has been recognized as the fundamental feature of NASH [1].”
BackgroundRegulated lytic cell death in breast cancer
Liu, M., Wang, L., Xia, X., Wu, Y., Zhu, C., Duan, M., Wei, X., Hu, J., & Lei, L. (2021) · Cell Biology International · doi:10.1002/cbin.11705 · Cited by 19
“Importantly, these new RCD pathways may exist concurrently in pathological conditions, and there are several common overlapped mechanisms that can serve as ‘backup’ death mechanisms to ensure biological homoeostasis when the threshold that causes cell death is reached (Gautheron et al., 2020).”
BackgroundThe role of RIPK3 in liver mitochondria bioenergetics and function
Islam, T., Afonso, M. B., & Rodrigues, C. M. P. (2021) · European Journal of Clinical Investigation · doi:10.1111/eci.13648 · Cited by 16
Self-citation
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
