The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease
Abstract
Nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) are the leading causes of chronic liver disease worldwide. NAFLD and ALD share pathophysiological, histological and genetic features and both alcohol and metabolic dysfunction coexist as aetiological factors in many patients with hepatic steatosis. A diagnosis of NAFLD requires the exclusion of significant alcohol consumption and other causes of liver disease. However, data suggest that significant alcohol consumption is often under-reported in patients classified as having NAFLD and that alcohol and metabolic factors interact to exacerbate the progression of liver disease. In this Review, we analyse existing data on the interaction between alcohol consumption and metabolic syndrome as well as the overlapping features and differences in the pathogenesis of ALD and NAFLD. We also discuss the clinical implications of the coexistence of alcohol consumption, of any degree, in patients with evidence of metabolic derangement as well as the use of alcohol biomarkers to detect alcohol intake. Finally, we summarize the evolving nomenclature of fatty liver disease and describe a recent proposal to classify patients at the intersection of NAFLD and ALD. We propose that, regardless of the presumed aetiology, patients with fatty liver disease should be evaluated for both metabolic syndrome and alcohol consumption to enable better prognostication and a personalized medicine approach.
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Factors beyond alcohol consumption contribute to the rising prevalence of ALD and primary liver cancer.
“Our findings suggest that factors beyond alcohol consumption contribute to the rising prevalence of ALD and primary liver cancer [25,26].”
From Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000–2021 (2025) · cites this paper as [25]
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A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis
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Extracellular Vesicles in NAFLD/ALD: From Pathobiology to Therapy
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Self-citationThe times they are a-changin' (for NAFLD as well)
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Mechanisms of enterohepatic fibroblast growth factor 15/19 signaling in health and disease
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Biomarkers for monitoring alcohol use
Cabezas, J., Lucey, M. R., & Bataller, R. A. (2016) · Clinical Liver Disease · doi:10.1002/cld.571 · Cited by 59 · see citing works
Self-citationAmerican Association for the Study of Liver Disease
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Treating inflammation to combat non-alcoholic fatty liver disease
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Liver Bid suppression for treatment of fibrosis associated with non-alcoholic steatohepatitis
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Burden of liver disease progression in hospitalized patients with type 2 diabetes mellitus
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Alcohol-associated liver disease
Mackowiak, B., Fu, Y., Maccioni, L., & Gao, B. (2024) · Journal of Clinical Investigation · doi:10.1172/jci176345 · Cited by 359 · see citing works
Hepatocellular carcinoma: updates on epidemiology, surveillance, diagnosis and treatment
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Metabolic dysfunction-associated steatotic liver disease in adults
Huang, D. Q., Wong, V. W., Rinella, M. E., Boursier, J., Lazarus, J. V., Yki‐Järvinen, H., & Loomba, R. S. (2025) · Nature Reviews Disease Primers · doi:10.1038/s41572-025-00599-1 · Cited by 336 · see citing works
Arab, J. P., Díaz, L. A., Rehm, J. T., Im, G. Y., Arrese, M. A., Kamath, P. S., Lucey, M. R., Mellinger, J. L., Thiele, M. S., Thursz, M. R., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.11.028 · Cited by 186 · see citing works
Self-citationIsraelsen, M., Torp, N., Johansen, S., Hansen, C. D., Hansen, E. D., Thorhauge, K., Hansen, J. K., Villesen, I., Bech, K., Wernberg, C., et al. (2024) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(23)00443-0 · Cited by 174 · see citing works
From NAFLD to MASLD: implications of the new nomenclature for preclinical and clinical research
Hsu, C. L., & Loomba, R. S. (2024) · Nature Metabolism · doi:10.1038/s42255-024-00985-1 · Cited by 123 · see citing works
Díaz, L. A., Fuentes–López, E., Idalsoaga, F. J., Ayares, G., Corsi, Ó., Arnold, J., Cannistra, M., Vio, D., Márquez‐Lomas, A., Ramírez, C., et al. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.11.006 · Cited by 107 · see citing works
Self-citationGenetics of Metabolic Dysfunction-associated Steatotic Liver Disease: The State of the Art Update
Sookoian, S. C., Rotman, Y., & Valenti, L. V. C. (2024) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2024.05.052 · Cited by 82 · see citing works
Danpanichkul, P., Díaz, L. A., Suparan, K., Tothanarungroj, P., Sirimangklanurak, S., Auttapracha, T., Blaney, H. L., Sukphutanan, B., Pang, Y., Kongarin, S., et al. (2025) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2024.0835 · Cited by 85 · see citing works
Self-citationFan, J., Xu, X., Yang, R.-X., Nan, Y., Wei, L., Jia, J., Zhuang, H., Shi, J., Li, X., Cm, S., et al. (2024) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2024.00311 · Cited by 85 · see citing works
Schneider, C. V., Schneider, K. M., Raptis, A. A., Huang, H. Y. R., Trautwein, C., & Loomba, R. S. (2024) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.17958 · Cited by 69 · see citing works
Tamaki, N., Kimura, T., Wakabayashi, S., Umemura, T., Kurosaki, M., Loomba, R. S., & Izumi, N. (2024) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.18015 · Cited by 69 · see citing works
Endogenous ethanol production in health and disease
Meijnikman, A. S., Nieuwdorp, M., & Schnabl, B. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00937-w · Cited by 69 · see citing works
Food inequity and insecurity and MASLD: burden, challenges, and interventions
Zelber‐Sagi, S., Carrieri, P., Pericàs, J. M., Wajcman, D. I., Younossi, Z. M., & Lazarus, J. V. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00959-4 · Cited by 62 · see citing works
Díaz, L. A., Arab, J. P., Idalsoaga, F. J., Perelli, J., Vega, J. A., Dirchwolf, M., Carreño, J., Samith, B., Valério, C. M., Moreira, R. O., et al. (2025) · Annals of Hepatology · doi:10.1016/j.aohep.2025.101903 · Cited by 66 · see citing works
Self-citationAlcohol-related liver disease: A global perspective
Castro‐Narro, G., Díaz, L. A., Ortega, E. K., Garín, M. F. B., Reyes, E. C., Delfin, P. S. M., Arab, J. P., & Bataller, R. A. (2024) · Annals of Hepatology · doi:10.1016/j.aohep.2024.101499 · Cited by 58 · see citing works
Self-citationDíaz, L. A., Lazarus, J. V., Fuentes–López, E., Idalsoaga, F. J., Ayares, G., Desaleng, H., Danpanichkul, P., Cotter, T. G., Dunn, W., Francisco Barrera, M., et al. (2024) · Communications Medicine · doi:10.1038/s43856-024-00649-x · Cited by 55 · see citing works
Self-citationMASLD treatment—a shift in the paradigm is imminent
Machado, M. V. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1316284 · Cited by 51 · see citing works
Israelsen, M. E., Thorhauge, K. H., Andersen, P., Johansen, S., Schnefeld, H. L., Bech, K., Hansen, J. K., Torp, N., Jensen, E. L., Hansen, E. D., et al. (2025) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2025.02.007 · Cited by 49 · see citing works
Díaz, L. A., Winder, G. S., Leggio, L., Bajaj, J. S., Bataller, R. A., & Arab, J. P. (2023) · Hepatology · doi:10.1097/hep.0000000000000645 · Cited by 46 · see citing works
Self-citationThe Rising Global Burden of MASLD and Other Metabolic Diseases (2000–2021)
Danpanichkul, P., Suparan, K., Díaz, L. A., Fallon, M. B., Chen, V. L., Namsathimaphorn, K., Rakwong, K., Inkongngam, T., Kaeosri, C., Kalligeros, M., et al. (2025) · United European Gastroenterology Journal · doi:10.1002/ueg2.70072 · Cited by 43 · see citing works
Self-citationOchoa‐Allemant, P., Serper, M., Wang, R. X., Tang, H., Ghandour, B., Khan, S., & Mahmud, N. (2024) · Hepatology · doi:10.1097/hep.0000000000000914 · Cited by 42 · see citing works
Metabolic and alcohol-associated liver disease (MetALD): a representation of duality
Leal-Lassalle, H., Estévez‐Vázquez, O., Cubero, F. J., & Nevzorova, Y. A. (2025) · npj gut and liver. · doi:10.1038/s44355-024-00014-8 · Cited by 41 · see citing works
High inherited risk predicts age-associated increases in fibrosis in patients with MASLD
Díaz, L. A., Alazawi, W., Agrawal, S., Arab, J. P., Arrese, M. A., Idalsoaga, F. J., Barreyro, F. J., Gadano, A. C., Marciano, S., Morales, J. M., et al. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.04.035 · Cited by 43 · see citing works
Self-citationBai, H.-X., Gao, Y., Wang, S., Ma, G.-Y., Zhao, W., Li, X., Wang, Y., Nong, Q.-N., Wang, Y., Tan, J. H., et al. (2024) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2024.123153 · Cited by 40 · see citing works
Wu, H., Chen, J., Guo, S., Deng, J., Zhou, Z., Zhang, X., Qi, T., Yu, F., & Yang, Q. L. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2500099 · Cited by 41 · see citing works
Ionizable polymeric micelles (IPMs) for efficient siRNA delivery
Zhou, Z., Yu, F., Jiang, M., Yao, Z., Wang, J., Pan, F., Feng, R., Zhao, C., Ma, Y., Zhou, J., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55721-w · Cited by 39 · see citing works
The burden of liver disease in Latin America
Díaz, L. A., Villota‐Rivas, M., Francisco Barrera, M., Lazarus, J. V., & Arrese, M. A. (2023) · Annals of Hepatology · doi:10.1016/j.aohep.2023.101175 · Cited by 37 · see citing works
Self-citationMetALD: Does it require a different therapeutic option?
Marek, G. W., & Malhi, H. (2024) · Hepatology · doi:10.1097/hep.0000000000000935 · Cited by 37 · see citing works
Danpanichkul, P., Suparan, K., Ng, C. H., Dejvajara, D., Kongarin, S., Panpradist, N., Chaiyakunapruk, N., Muthiah, M. D., Chen, V. L., Huang, D. Q., et al. (2024) · JHEP Reports · doi:10.1016/j.jhepr.2024.101020 · Cited by 37 · see citing works
Self-citationThe Janus of a disease: Diabetes and metabolic dysfunction-associated fatty liver disease
Francisco Barrera, M., Uribe, J., Olvares, N., Huerta, P., Cabrera, D., & Romero‐Gómez, M. (2024) · Annals of Hepatology · doi:10.1016/j.aohep.2024.101501 · Cited by 36 · see citing works
Metabolic dysfunction and alcohol-associated liver disease (MetALD)
Gao, B., Arab, J. P., Liangpunsakul, S., Ding, W., Szabó, G., Mehal, W. Z., Wang, H., He, Y., Stärkel, P., Llorente, C., et al. (2025) · eGastroenterology · doi:10.1136/egastro-2025-100319 · Cited by 42 · see citing works
Self-citationMetALD : New Perspectives on an Old Overlooked Disease
Ayares, G., Díaz, L. A., Idalsoaga, F. J., Alkhouri, N., Noureddin, M., Bataller, R. A., Loomba, R. S., Arab, J. P., & Arrese, M. A. (2025) · Liver International · doi:10.1111/liv.70017 · Cited by 34 · see citing works
Self-citationClinical trial design, biomarkers and end points in metabolic and alcohol-related liver disease
Díaz, L. A., Thiele, M. S., Louvet, A., Lee, B. P., Ajmera, V. H., Tavaglione, F., Hsu, C. L., Huang, D. Q., Pose, E., Bataller, R. A., et al. (2025) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-025-01120-5 · Cited by 31 · see citing works
Self-citationInnate-like T cells in liver disease.
Yang, A. Y.-P., Wistuba-Hamprecht, K., Greten, T., & Ruf, B. (2024) · Trends in immunology · doi:10.1016/j.it.2024.05.008 · Cited by 30 · see citing works
Canivet, C. M., Boursier, J., & Loomba, R. S. (2024) · Seminars in Liver Disease · doi:10.1055/s-0044-1785196 · Cited by 29 · see citing works
Recent advances of lipid droplet-targeted AIE-active materials for imaging, diagnosis and therapy
Yuan, S., & Zhao, E. (2024) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2024.116802 · Cited by 29 · see citing works
Magyar, C. T. J., O'Kane, G. M., Aceituno, L., Li, Z., Vogel, A., Bruix, J., Mazzaferro, V., & Sapisochín, G. (2024) · Journal of Clinical Oncology · doi:10.1200/jco.24.00857 · Cited by 27 · see citing works
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Self-citationSaczuk, K., Dudek, M., Matczyszyn, K., & Deiana, M. (2024) · Nanoscale Horizons · doi:10.1039/d4nh00186a · Cited by 26 · see citing works
Ktenopoulos, N., Sagris, Μ., Gerogianni, M., Pamporis, K., Apostolos, A., Balampanis, K., Tsioufis, K. P., Toutouzas, K. P., & Tousoulis, D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910595 · Cited by 27 · see citing works
Babuta, M., Nagesh, P. T., Datta, A. A., Remotti, V., Zhuang, Y., Mehta, J., Lami, F., Wang, Y., & Szabó, G. (2024) · Cells · doi:10.3390/cells13110960 · Cited by 25 · see citing works
Hepatic mitochondrial reductive stress in the pathogenesis and treatment of steatotic liver disease
Jokinen, M. J., & Luukkonen, P. K. (2024) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2024.02.003 · Cited by 24 · see citing works
Moving diagnosis of liver fibrosis into the community
Pose, E., Piano, S. S., Thiele, M. S., Fabrellas, N., Tsochatzis, E. A., & Ginès, P. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.01.026 · Cited by 24 · see citing works
Cho, Y. E., Kim, Y. S., Kim, S.-J., Lee, H., & Hwang, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242015489 · Cited by 23 · see citing works
Beneficial Effects of the Ketogenic Diet on Nonalcoholic Fatty Liver Disease (NAFLD/MAFLD)
Dyńka, D., Rodzeń, Ł., Rodzeń, M., Łojko, D., Kraszewski, S., Ibrahim, A., Hussey, M., Deptuła, A., Grzywacz, Ż., Ternianov, A., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13164857 · Cited by 23 · see citing works
Shen, X., Yang, H., Yang, Y., Zhu, X., & Sun, Q. (2024) · MedComm · doi:10.1002/mco2.664 · Cited by 20 · see citing works
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Alcohol-Metabolizing Enzymes, Liver Diseases and Cancer
Liu, T., Zhang, F., Feng, Y., Han, P., & Gao, Y. (2025) · Seminars in Liver Disease · doi:10.1055/a-2551-3320 · Cited by 19 · see citing works
Díaz, L. A., Tavaglione, F., Mittal, N., Bettencourt, R., Amangurbanova, M., Johnson, A., Aguado, D. M., Tincopa, M. A., Loomba, R. K., Khan-Riches, A., et al. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000718 · Cited by 19 · see citing works
Self-citationLiu, C., Seto, W., & Yu, M. (2024) · Hepatology International · doi:10.1007/s12072-024-10699-x · Cited by 18 · see citing works
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Self-citationUnveiling the Cancer Risk Nexus of the Steatotic Liver
Kim, J., & Seki, E. (2024) · Trends in endocrinology and metabolism · doi:10.1016/j.tem.2024.02.017 · Cited by 15 · see citing works
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Perspective on alcohol-induced organ damage via autophagy-dependent cellular changes
Bakheet, A., Anbazhagan, M., Barve, S. S., Dasarathy, S., Dickinson, J. J., Ding, W., Donohue, T. M., Gopal, T., Gukovskaya, A. S., Kharbanda, K. K., et al. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103879 · Cited by 16 · see citing works
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MicroRNAs in metabolic dysfunction‐associated diseases: Pathogenesis and therapeutic opportunities
Ma, N., Tan, J., Chen, Y., Liu, Y., Li, M., & He, Y. (2024) · The FASEB Journal · doi:10.1096/fj.202401464r · Cited by 20 · see citing works
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Self-citationPromoting In Vivo NIR-II Fluorescent Imaging for Lipid in Lipid Metabolism Diseases Diagnosis
Wang, K., Wen, X., Chen, X.-Y., Yue, Y., Yang, Y., Zhu, H., Wang, M., & Jiang, H. (2024) · Analytical Chemistry · doi:10.1021/acs.analchem.3c05676 · Cited by 14 · see citing works
Gut Bacteria in Alcohol-Associated Liver Disease
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- Authors
- Díaz, L. A., Arab, J. P., Louvet, A., Bataller, R., & Arrese, M.
- Affiliations
- Pontificia Universidad Católica de Chile (CL)
- Western University (CA)
- Inserm (FR)
- Corresponding author
- Arrese, Marco
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2023-08-15
- Volume
- 20
- Issue
- 12
- Pages
- 764-783
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- OpenAlex
- W4385851156
- Semantic Scholar
- f457122280dbd0b72d6e068cbffa2b2fe281bb04
- Cited by
- 207
- References
- 252
- Citations by year
- 2026: 58 · 2025: 75 · 2024: 63 · 2023: 11
- FWCI
- 8.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Reviews Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (U01AA021908, U01AA020821)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- non-alcoholic fatty liver disease, alcoholic liver disease, metabolic syndrome, hepatic steatosis, alcohol consumption, alcohol biomarkers, disease classification, pathogenesis, chronic liver disease
- MeSH terms
- Alcohol Drinking, Ethanol, Humans, Biomarkers, Metabolic Syndrome, Non-alcoholic Fatty Liver Disease
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