Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta‐analysis
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Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage–specific risk of all‐cause and liver‐related mortality in NAFLD. Through a systematic review and meta‐analysis, we identified five adult NAFLD cohort studies reporting fibrosis stage–specific mortality (0‐4). Using fibrosis stage 0 as a reference population, fibrosis stage–specific mortality rate ratios (MRRs) with 95% confidence intervals (CIs) for all‐cause and liver‐related mortality were estimated. The study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. Included were 1,495 NAFLD patients with 17,452 patient years of follow‐up. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all‐cause mortality, and this risk increased with increases in the stage of fibrosis: stage 1, MRR = 1.58 (95% CI 1.19‐2.11); stage 2, MRR = 2.52 (95% CI 1.85‐3.42); stage 3, MRR = 3.48 (95% CI 2.51‐4.83); and stage 4, MRR = 6.40 (95% CI 4.11‐9.95). The results were more pronounced as the risk of liver‐related mortality increased exponentially with each increase in the stage of fibrosis: stage 1, MRR = 1.41 (95% CI 0.17‐11.95); stage 2, MRR = 9.57 (95% CI 1.67‐54.93); stage 3, MRR = 16.69 (95% CI 2.92‐95.36); and stage 4, MRR = 42.30 (95% CI 3.51‐510.34). Limitations of the study include an inability to adjust for comorbid conditions or demographics known to impact fibrosis progression in NAFLD and the inclusion of patients with simple steatosis and nonalcoholic steatohepatitis without fibrosis in the reference comparison group. Conclusion: The risk of liver‐related mortality increases exponentially with increase in fibrosis stage; these data have important implications in assessing the utility of each stage and benefits of regression of fibrosis from one stage to another. (H epatology 2017;65:1557‐1565).
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The degree of liver fibrosis is the most robust histological predictor of liver-related morbidity and mortality in MASLD patients.
“The degree of liver fibrosis remains the most robust histological predictor of liver-related morbidity and mortality in patients with MASLD (Dulai et al. 2017).”
From The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion (2026) · cites this paper as Dulai et al. 2017
The Introduction calls fibrosis progression among the most important predictors of disease outcomes in NAFLD, and the Discussion (Main findings) reports that liver-related mortality rises with fibrosis stage. The meta-analysis does not assess liver-related morbidity or directly compare fibrosis with other histological predictors, so it does not establish the full claim that fibrosis is the most robust predictor of both outcomes. Page numbers are not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPrognosis in NAFLD is mostly influenced by the grade of fibrosis rather than the presence or absence of NASH.
“prognosis is mostly influenced by the grade of fibrosis rather than presence/absence of NASH [9, 10].”
From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [10]
The Introduction says fibrosis development and progression are the most important predictors of outcomes in NAFLD, and the Discussion (Main findings) reports increasing mortality with higher fibrosis stage. The paper does not establish the specific comparison with the presence or absence of NASH; its Limitations note that the reference group included both simple steatosis and NASH without fibrosis. No page numbers are available in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredOnce NASH and/or advanced fibrosis (fibrosis stage 3 or cirrhosis) and/or portal hypertension is confirmed, patients are at increased risk for liver-related complications (hepatic decompensation and hepatocellular carcinoma) and liver-related mortality.
“once a diagnosis of NASH and/or advanced fibrosis (i.e. fibrosis stage 3 or cirrhosis) and/or portal hypertension is confirmed patients are at an increased risk for liver‐related complications (i.e. hepatic decompensation and hepatocellular carcinoma) and liver‐related mortality [9, 10, 25].”
From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [10]
The Discussion (Main findings; page not provided) reports substantially higher liver-related mortality at fibrosis stages 3 and 4, supporting that part of the claim. The Discussion (Strengths and limitations; page not provided) says the analysis could not distinguish NASH from simple steatosis or quantify specific causes of liver-related death. It does not establish increased risk from NASH or portal hypertension alone, or assess hepatic decompensation and hepatocellular carcinoma as separate complications. (LLM, conf=0.87)
Experimental — accuracy not yet measuredProgression to NASH involves hepatocyte damage and liver inflammation, and development of liver fibrosis is the key determinant of patient outcomes.
“The progression to NASH involves hepatocyte damage and liver inflammation, with the development of liver fibrosis being the key determinant of patient outcomes 3-9 .”
From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [6]
The Introduction (page not provided) calls fibrosis development and progression the most important predictors of outcomes in NAFLD, and the Discussion’s Main findings report increasing mortality with fibrosis stage. The paper does not describe progression to NASH in terms of hepatocyte damage and liver inflammation, so that part of the sentence is not supported by this source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn patients with MASLD, liver fibrosis represents the primary determinant of mortality.
“In patients with MASLD, liver fibrosis represents the primary determinant of mortality [258–261].”
From Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells (2025) · cites this paper as [259]
The amount of fibrosis is the strongest predictor of death in MASH patients and is therefore the main target of drug development.
“Among these features, the extent of fibrosis is the strongest predictor of patient mortality, and is therefore the focus of drug development efforts (13-16).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [16]
Fibrosis is the most significant predictor of patient mortality in MASH.
“Such clinical observations, coupled with the knowledge that fibrosis is the most significant predictor of patient mortality in MASH, focus renewed attention on mechanisms of both spontaneous and pharmacologic-induced fibrosis regression (13-16), as more research is needed to develop clinical interventions that halt progression or reverse the disease.”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [16]
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Cites
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & for the PRISMA Group (2009) · BMJ · doi:10.1136/bmj.b2535 · Cited by 83,823 · see citing works
Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & the PRISMA Group* (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-151-4-200908180-00135 · Cited by 37,554 · see citing works
Stang, A. (2010) · European Journal of Epidemiology · doi:10.1007/s10654-010-9491-z · Cited by 17,396 · see citing works
Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016) · Hepatology · doi:10.1002/hep.28431 · Cited by 10,781 · see citing works
Self-citationChalasani, N., Younossi, Z. M., Lavine, J. E., Diehl, A. M., Brunt, E. M., Cusi, K. J., Charlton, M., & Sanyal, A. J. (2012) · Hepatology · doi:10.1002/hep.25762 · Cited by 3,798 · see citing works
Self-citationNonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.
MATTEONI, C., YOUNOSSI, Z., GRAMLICH, T., BOPARAI, N., LIU, Y., & MCCULLOUGH, A. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70506-8 · Cited by 3,345 · see citing works
Self-citationAngulo, P., Kleiner, D. E., Dam-Larsen, S., Adams, L. A., Bjornsson, E. S., Charatcharoenwitthaya, P., Mills, P. R., Keach, J. C., Lafferty, H. D., Stahler, A., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.04.043 · Cited by 2,987 · see citing works
The Natural History of Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study
Adams, L. A., Lymp, J. F., St. Sauver, J., Sanderson, S. O., Lindor, K. D., Feldstein, A., & Angulo, P. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.04.014 · Cited by 2,890 · see citing works
Nonalcoholic Fatty Liver Disease
Rinella, M. E. (2015) · JAMA · doi:10.1001/jama.2015.5370 · Cited by 2,289 · see citing works
Ekstedt, M., Hagström, H., Nasr, P., Fredrikson, M., Stål, P., Kechagias, S., & Hultcrantz, R. (2015) · Hepatology · doi:10.1002/hep.27368 · Cited by 2,287 · see citing works
Self-citationSingh, S., Allen, A. M., Wang, Z., Prokop, L. J., Murad, M. H., & Loomba, R. (2015) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2014.04.014 · Cited by 1,748 · see citing works
Self-citationNon-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis
Targher, G., Byrne, C. D., Lonardo, A., Zoppini, G., & Barbui, C. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.05.013 · Cited by 1,429 · see citing works
Younossi, Z. M., Stepanova, M., Rafiq, N., Makhlouf, H. R., Younoszai, Z., Agrawal, R., & Goodman, Z. D. (2011) · Hepatology · doi:10.1002/hep.24268 · Cited by 636 · see citing works
Self-citationPiscaglia, F., Svegliati‐Baroni, G., Barchetti, A., Pecorelli, A., Marinelli, S., Tiribelli, C., Bellentani, S., & on behalf of the HCC‐NAFLD Italian Study Group (2016) · Hepatology · doi:10.1002/hep.28368 · Cited by 604 · see citing works
Dulai, P. S., Sirlin, C. B., & Loomba, R. S. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.06.005 · Cited by 357 · see citing works
Self-citationHistological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients
Leung, J. C., Loong, T. C., Wei, J. L., Wong, G. L., Chan, A. W. H., Choi, P. C., Shu, S. S., Chim, A. M., Chan, H. L., & Wong, V. W. (2016) · Hepatology · doi:10.1002/hep.28697 · Cited by 348 · see citing works
Self-citationNonalcoholic fatty liver disease and aging: Epidemiology to management
Bertolotti, M. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i39.14185 · Cited by 309 · see citing works
Non‐invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE
Doycheva, I., Cui, J. Y., Nguyen, P., Costa, E. A., Hooker, J. C., Hofflich, H., Bettencourt, R., Brouha, S. S., Sirlin, C. B., & Loomba, R. S. (2015) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13405 · Cited by 209 · see citing works
Self-citationDirect and Indirect Economic Burden of Chronic Liver Disease in the United States
Stepanova, M., de Avila, L., Afendy, M., Younossi, I. M., Phạm, T. T. H., Cable, R., & Younossi, Z. M. (2016) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2016.07.020 · Cited by 179 · see citing works
Self-citationSebastiani, G., Alshaalan, R., Wong, P. Y. N., Rubino, M., Salman, A., Metrakos, P. P., Deschênes, M., & Ghali, P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128774 · Cited by 99 · see citing works
Self-citationTapper, E. B., Hunink, M. G. M., Afdhal, N. H., Lai, M., & Sengupta, N. (2016) · PLoS ONE · doi:10.1371/journal.pone.0147237 · Cited by 68 · see citing works
Goossens, N., Hoshida, Y., Song, W., Jung, M. K., Morel, P., Nakagawa, S., Zhang, B., Frossard, J., Spahr, L., Friedman, S. L., et al. (2015) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2015.10.010 · Cited by 61 · see citing works
Review article: emerging anti‐fibrotic therapies in the treatment of non‐alcoholic steatohepatitis
Noureddin, M., Anstee, Q. M., & Loomba, R. S. (2016) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13620 · Cited by 50 · see citing works
Self-citation
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- [19]Sutton AJ Methods for meta-analysis in medical research Chichester; New York J. Wiley 2000
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Rinella, M. E., Neuschwander-Tetri, B. A., Siddiqui, M. S., Abdelmalek, M. F., Caldwell, S., Barb, D., Kleiner, D. E., & Loomba, R. (2023) · Hepatology · doi:10.1097/hep.0000000000000323 · Cited by 2,667 · see citing works
Self-citationYounossi, Z. M., Golabi, P., de Avila, L., Paik, J. M., Srishord, M., Fukui, N., Qiu, Y., Burns, L., Afendy, A., & Nader, F. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.06.021 · Cited by 2,235 · see citing works
Self-citationA phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis
Harrison, S. A., Bedossa, P., Guy, C. D., Schattenberg, J. M., Loomba, R., Taub, R., Labriola, D., Moussa, S. E., Neff, G. W., Rinella, M. E., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2309000 · Cited by 2,084 · see citing works
Self-citationMechanisms 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 · see citing works
Self-citationEstes, C., Anstee, Q. M., Arias, M., Bantel, H., Bellentani, S., Caballería, J., Colombo, M., Craxı̀, A., Crespo, J., Day, C. P., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.05.036 · Cited by 1,986 · see citing works
Self-citationBerzigotti, A., Tsochatzis, E., Boursier, J., Castera, L., Cazzagon, N., Friedrich-Rust, M., Petta, S., & Thiele, M. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.05.025 · Cited by 1,925 · see citing works
Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Younossi, Z., Tacke, F., Arrese, M., Chander Sharma, B., Mostafa, I., Bugianesi, E., Wai‐Sun Wong, V., Yilmaz, Y., George, J., Fan, J., et al. (2019) · Hepatology · doi:10.1002/hep.30251 · Cited by 1,858 · see citing works
Self-citationNoninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease
Castera, L., Friedrich-Rust, M., & Loomba, R. (2019) · Gastroenterology · doi:10.1053/j.gastro.2018.12.036 · Cited by 1,494 · see citing works
Self-citationEddowes, P. J., Sasso, M., Allison, M., Tsochatzis, E. A., Anstee, Q. M., Sheridan, D. A., Guha, I. N., Cobbold, J., Deeks, J. J., Paradis, V., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.01.042 · Cited by 1,425 · see citing works
From NASH to HCC: current concepts and future challenges
Anstee, Q. M., Reeves, H. L., Kotsiliti, E., Govaere, O., & Heikenwalder, M. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0145-7 · Cited by 1,392 · see citing works
Younossi, Z. M., Ratziu, V., Loomba, R., Rinella, M., Anstee, Q. M., Goodman, Z., Bedossa, P., Geier, A., Beckebaum, S., Newsome, P. N., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)33041-7 · Cited by 1,277 · see citing works
Self-citationNonalcoholic Fatty Liver Disease 2020: The State of the Disease
Cotter, T. G., & Rinella, M. E. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.01.052 · Cited by 1,205 · see citing works
Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease
Sanyal, A. J., Van Natta, M. L., Clark, J., Neuschwander-Tetri, B. A., Diehl, A., Dasarathy, S., Loomba, R., Chalasani, N., Kowdley, K., Hameed, B., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2029349 · Cited by 1,146 · see citing works
Self-citationLoomba, R., Seguritan, V., Li, W., Long, T., Klitgord, N., Bhatt, A., Dulai, P. S., Caussy, C., Bettencourt, R., Highlander, S. K., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.001 · Cited by 1,123 · see citing works
Self-citationTaylor, R. S., Taylor, R. J., Bayliss, S., Hagström, H., Nasr, P., Schattenberg, J. M., Ishigami, M., Toyoda, H., Wai-Sun Wong, V., Peleg, N., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.01.043 · Cited by 1,069 · see citing works
Self-citationHagström, H., Nasr, P., Ekstedt, M., Hammar, U., Stål, P., Hultcrantz, R., & Kechagias, S. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.07.027 · Cited by 1,067 · see citing works
Self-citationEpidemiology of metabolic dysfunction-associated steatotic liver disease
Younossi, Z. M., Kalligeros, M., & Henry, L. (2025) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2024.0431 · Cited by 960 · see citing works
Self-citationLipotoxicity and the gut-liver axis in NASH pathogenesis
Marra, F., & Svegliati-Baroni, G. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.11.014 · Cited by 847 · see citing works
Stefan, N., Häring, H., & Cusi, K. J. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30154-2 · Cited by 848 · see citing works
Eslam, M., Sarin, S. K., Wong, V. W., Fan, J.-G., Kawaguchi, T., Ahn, S. H., Zheng, M., Shiha, G. E.-S., Yilmaz, Y. N., Gani, R. A., et al. (2020) · Hepatology International · doi:10.1007/s12072-020-10094-2 · Cited by 837 · see citing works
Self-citationNewsome, P. N., Sasso, M., Deeks, J. J., Paredes, A. H., Boursier, J., Chan, W., Yilmaz, Y. N., Czernichow, S., Zheng, M., Wong, V. W., et al. (2020) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(19)30383-8 · Cited by 823 · see citing works
Self-citationVilar-Gomez, E., Calzadilla-Bertot, L., Wai-Sun Wong, V., Castellanos, M., Aller-de la Fuente, R., Metwally, M., Eslam, M., Gonzalez-Fabian, L., Alvarez-Quiñones Sanz, M., Conde-Martin, A. F., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.04.034 · Cited by 806 · see citing works
Self-citationHarrison, S. A., Bashir, M. R., Guy, C. D., Zhou, R., Moylan, C. A., Frias, J. P., Alkhouri, N., Bansal, M. B., Baum, S., Neuschwander-Tetri, B. A., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)32517-6 · Cited by 802 · see citing works
A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH
Francque, S. M., Bedossa, P., Ratziu, V., Anstee, Q. M., Bugianesi, E., Sanyal, A. J., Loomba, R., Harrison, S. A., Balabanska, R., Mateva, L., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2036205 · Cited by 801 · see citing works
Self-citationMetabolic dysfunction-associated steatotic liver disease (MASLD): a state-of-the-art review
Chan, W.-K., Chuah, K.-H., Rajaram, R. B., Lim, L.-L., Ratnasingam, J., & Vethakkan, S. R. (2023) · Journal of Obesity & Metabolic Syndrome · doi:10.7570/jomes23052 · Cited by 776 · see citing works
Changing epidemiology, global trends and implications for outcomes of NAFLD
Wong, V. W.-S., Ekstedt, M., Wong, G. L.-H., & Hagström, H. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.04.036 · Cited by 765 · see citing works
Self-citationMortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort
Simon, T. G., Roelstraete, B., Khalili, H., Hagström, H., & Ludvigsson, J. F. (2021) · Gut · doi:10.1136/gutjnl-2020-322786 · Cited by 673 · see citing works
Current and future pharmacological therapies for NAFLD/NASH
Sumida, Y., & Yoneda, M. (2017) · Journal of Gastroenterology · doi:10.1007/s00535-017-1415-1 · Cited by 670 · see citing works
NAFLD and cardiovascular diseases: a clinical review
Kasper, P., Martin, A., Lang, S., Kütting, F., Goeser, T., Demir, M., & Steffen, H. (2020) · Clinical Research in Cardiology · doi:10.1007/s00392-020-01709-7 · Cited by 670 · see citing works
Kanwal, F., Shubrook, J. H., Adams, L. A., Pfotenhauer, K., Wai-Sun Wong, V., Wright, E., Abdelmalek, M. F., Harrison, S. A., Loomba, R., Mantzoros, C. S., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.07.049 · Cited by 618 · see citing works
Self-citationNoninvasive biomarkers in NAFLD and NASH — current progress and future promise
Wong, V. W., Adams, L. A., de Lédinghen, V., Wong, G. L., & Sookoian, S. C. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0014-9 · Cited by 617 · see citing works
Self-citationZaharia, O. P., Strassburger, K., Strom, A., Bönhof, G. J., Karusheva, Y., Antoniou, S., Bódis, K., Markgraf, D. F., Burkart, V., Müssig, K., et al. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30187-1 · Cited by 600 · see citing works
Peiseler, M., Schwabe, R., Hampe, J., Kubes, P., Heikenwälder, M., & Tacke, F. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.06.012 · Cited by 564 · see citing works
Krenkel, O., Puengel, T., Govaere, O., Abdallah, A. T., Mossanen, J. C., Kohlhepp, M., Liepelt, A., Lefebvre, E., Luedde, T., Hellerbrand, C., et al. (2018) · Hepatology · doi:10.1002/hep.29544 · Cited by 557 · see citing works
Epidemiology of chronic liver diseases in the USA in the past three decades
Younossi, Z. M., Stepanova, M., Younossi, Y., Golabi, P., Mishra, A., Rafiq, N., & Henry, L. L. (2019) · Gut · doi:10.1136/gutjnl-2019-318813 · Cited by 550 · see citing works
Self-citationLoomba, R., Lawitz, E., Mantry, P. S., Jayakumar, S., Caldwell, S. H., Arnold, H., Diehl, A. M., Djedjos, C. S., Han, L., Myers, R. P., et al. (2018) · Hepatology · doi:10.1002/hep.29514 · Cited by 549 · see citing works
Self-citationOrgan and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications
Weiskirchen, R., Weiskirchen, S., & Tacke, F. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.06.003 · Cited by 546 · see citing works
Oxidative Stress in Liver Pathophysiology and Disease
Allameh, A., Niayesh‐Mehr, R., Aliarab, A., Sebastiani, G., & Pantopoulos, K. (2023) · Antioxidants · doi:10.3390/antiox12091653 · Cited by 565 · see citing works
Self-citationPast, present and future perspectives in nonalcoholic fatty liver disease
Sanyal, A. J. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0144-8 · Cited by 522 · see citing works
Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH
Loomba, R., Sanyal, A. J., Kowdley, K. V., Bhatt, D. L., Alkhouri, N., Frias, J. P., Bedossa, P., Harrison, S. A., Lazas, D., Barish, R., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2304286 · Cited by 522 · see citing works
Self-citationAnstee, Q. M., Darlay, R., Cockell, S., Meroni, M., Govaere, O., Tiniakos, D., Burt, A. D., Bedossa, P., Palmer, J., Liu, Y.-L., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.04.003 · Cited by 499 · see citing works
Self-citationHarrison, S. A., Wong, V. W.-S., Okanoue, T., Bzowej, N., Vuppalanchi, R., Younes, Z., Kohli, A., Sarin, S., Caldwell, S. H., Alkhouri, N., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.02.027 · Cited by 497 · see citing works
Self-citationDeterminants of Fibrosis Progression and Regression in NASH
Schuppan, D., Surabattula, R., & Wang, X. Y. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.11.012 · Cited by 479 · see citing works
Pierantonelli, I., & Svegliati‐Baroni, G. (2018) · Transplantation · doi:10.1097/tp.0000000000002480 · Cited by 459 · see citing works
Srivastava, A., Gailer, R., Tanwar, S., Trembling, P. M., Parkes, J., Rodger, A. J., Suri, D., Thorburn, D., Sennett, K., Morgan, S., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.03.033 · Cited by 449 · see citing works
Younossi, Z. M., Loomba, R. S., Anstee, Q. M., Rinella, M. E., Bugianesi, E., Marchesini, G., Neuschwander‐Tetri, B. A., Serfaty, L., Negro, F., Caldwell, S. H., et al. (2017) · Hepatology · doi:10.1002/hep.29721 · Cited by 431 · see citing works
Self-citationYounossi, Z. M., Golabi, P., Price, J. K., Owrangi, S., Gundu-Rao, N., Satchi, R., & Paik, J. M. (2024) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2024.03.006 · Cited by 416 · see citing works
Self-citationHsu, C. L., Caussy, C., Imajo, K., Chen, J., Singh, S., Kaulback, K., Le, M., Hooker, J. C., Tu, X. M., Bettencourt, R., et al. (2018) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.05.059 · Cited by 422 · see citing works
Self-citationRho, H., Terry, A. R., Chronis, C., & Hay, N. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.06.013 · Cited by 421 · see citing works
Younossi, Z. M., Marchesini, G., Cortez‐Pinto, H., & Petta, S. (2018) · Transplantation · doi:10.1097/tp.0000000000002484 · Cited by 405 · see citing works
Self-citationNAFLD: Mechanisms, Treatments, and Biomarkers
Nassir, F. (2022) · Biomolecules · doi:10.3390/biom12060824 · Cited by 422 · see citing works
Malehmir, M., Pfister, D., Gallage, S., Szydlowska, M., Inverso, D., Kotsiliti, E., Leone, V., Peiseler, M., Surewaard, B. G. J., Rath, D., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0379-5 · Cited by 398 · see citing works
Sanyal, A. J., Harrison, S. A., Ratziu, V., Abdelmalek, M. F., Diehl, A. M., Caldwell, S., Shiffman, M. L., Aguilar Schall, R., Jia, C., McColgan, B., et al. (2019) · Hepatology · doi:10.1002/hep.30664 · Cited by 390 · see citing works
Self-citationHarrison, S. A., Abdelmalek, M. F., Caldwell, S., Shiffman, M. L., Diehl, A. M., Ghalib, R., Lawitz, E. J., Rockey, D. C., Schall, R. A., Jia, C., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.07.006 · Cited by 384 · see citing works
Self-citationRatziu, V., Sanyal, A., Harrison, S. A., Wong, V. W., Francque, S., Goodman, Z., Aithal, G. P., Kowdley, K. V., Seyedkazemi, S., Fischer, L., et al. (2020) · Hepatology · doi:10.1002/hep.31108 · Cited by 378 · see citing works
Self-citationSelvaraj, E. A., Mózes, F. E., Jayaswal, A. N. A., Zafarmand, M. H., Vali, Y., Lee, J. A., Levick, C. K., Young, L. A. J., Palaniyappan, N., Liu, C.-H., et al. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.04.044 · Cited by 376 · see citing works
Self-citationNon-alcoholic fatty liver disease
Maurice, J. B., & Manousou, P. (2018) · Clinical Medicine · doi:10.7861/clinmedicine.18-3-245 · Cited by 367 · see citing works
Younossi, Z. M., Loomba, R. S., Rinella, M. E., Bugianesi, E., Marchesini, G., Neuschwander‐Tetri, B. A., Serfaty, L., Negro, F., Caldwell, S. H., Ratziu, V., et al. (2017) · Hepatology · doi:10.1002/hep.29724 · Cited by 382 · see citing works
Self-citationLoomba, R. S., Lim, J. K., Patton, H. M., & El‐Serag, H. B. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.12.053 · Cited by 360 · see citing works
Self-citationIsraelsen, M. E., Francque, S., Tsochatzis, E. A., & Krag, A. A. (2024) · The Lancet · doi:10.1016/s0140-6736(24)01811-7 · Cited by 370 · see citing works
Cusi, K. J., Abdelmalek, M. F., Apovian, C. M., Balapattabi, K., Bannuru, R. R., Barb, D., Bardsley, J. K., Beverly, E. A., Corbin, K. D., ElSayed, N. A., et al. (2025) · Diabetes Care · doi:10.2337/dci24-0094 · Cited by 396 · see citing works
Self-citationChallenges and opportunities in NASH drug development
Harrison, S. A., Allen, A. M., Dubourg, J., Noureddin, M., & Alkhouri, N. (2023) · Nature Medicine · doi:10.1038/s41591-023-02242-6 · Cited by 353 · see citing works
Hartman, M. L., Sanyal, A. J., Loomba, R., Wilson, J. M., Nikooienejad, A., Bray, R., Karanikas, C. A., Duffin, K. L., Robins, D. A., & Haupt, A. (2020) · Diabetes Care · doi:10.2337/dc19-1892 · Cited by 351 · see citing works
Self-citationMuzurović, E. M., Mikhailidis, D. P., & Mantzoros, C. S. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154770 · Cited by 339 · see citing works
A Gut Microbiome Signature for Cirrhosis Due to Nonalcoholic Fatty Liver Disease
Caussy, C., Tripathi, A., Humphrey, G., Bassirian, S., Singh, S., Faulkner, C., Bettencourt, R., Rizo, E., Richards, L., Xu, Z. Z., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09455-9 · Cited by 338 · see citing works
Self-citationFibrosis and alcohol-related liver disease
Lackner, C., & TINIAKOS, D. G. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2018.12.003 · Cited by 326 · see citing works
Simon, T. G., Roelstraete, B., Hagström, H., Sundström, J., & Ludvigsson, J. F. (2021) · Gut · doi:10.1136/gutjnl-2021-325724 · Cited by 331 · see citing works
Metabolic Syndrome and Sarcopenia
Nishikawa, H., Asai, A., Fukunishi, S., Nishiguchi, S., & Higuchi, K. (2021) · Nutrients · doi:10.3390/nu13103519 · Cited by 333 · see citing works
An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH
Tacke, F., Puengel, T., Loomba, R., & Friedman, S. L. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.03.038 · Cited by 321 · see citing works
Self-citationNonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors
Francque, S., Szabo, G., Abdelmalek, M. F., Byrne, C. D., Cusi, K., Dufour, J.-F., Roden, M., Sacks, F., & Tacke, F. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00366-5 · Cited by 316 · see citing works
Farrell, G., Schattenberg, J. M., Leclercq, I., Yeh, M. M., Goldin, R., Teoh, N., & Schuppan, D. (2019) · Hepatology · doi:10.1002/hep.30333 · Cited by 313 · see citing works
Haldar, D., Kern, B., Hodson, J., Armstrong, M. J., Adam, R., Berlakovich, G., Fritz, J., Feurstein, B., Popp, W., Karam, V., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.04.011 · Cited by 313 · see citing works
Natural history and progression of metabolic dysfunction-associated steatotic liver disease
Hagström, H., Shang, Y., Hegmar, H., & Nasr, P. (2024) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(24)00193-6 · Cited by 310 · see citing works
Self-citationCurrent treatment of non‐alcoholic fatty liver disease
Paternostro, R., & Trauner, M. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13531 · Cited by 305 · see citing works
Vali, Y., Lee, J., Boursier, J., Spijker, R., Löffler, J., Verheij, J., Brosnan, M. J., Böcskei, Z., Anstee, Q. M., Bossuyt, P. M., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.03.036 · Cited by 302 · see citing works
Diabetes mellitus—Progress and opportunities in the evolving epidemic
Abel, E. D., Gloyn, A. L., Evans‐Molina, C., Joseph, J. J., Misra, S., Pajvani, U. B., Simcox, J., Suszták, K., & Drucker, D. J. (2024) · Cell · doi:10.1016/j.cell.2024.06.029 · Cited by 330 · see citing works
Lifestyle interventions in nonalcoholic fatty liver disease
Younossi, Z. M., Zelber-Sagi, S., Henry, L., & Gerber, L. H. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00800-4 · Cited by 281 · see citing works
Self-citationHarrison, S. A., Neff, G., Guy, C. D., Bashir, M. R., Paredes, A. H., Frias, J. P., Younes, Z., Trotter, J. F., Gunn, N. T., Moussa, S. E., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.08.004 · Cited by 280 · see citing works
Therapeutic pipeline in nonalcoholic steatohepatitis
Vuppalanchi, R., Noureddin, M., Alkhouri, N., & Sanyal, A. J. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00408-y · Cited by 278 · see citing works
Anstee, Q. M., Lawitz, E. J., Alkhouri, N., Wong, V. W., Romero‐Gomez, M., Okanoue, T., Trauner, M., Kersey, K., Li, G., Han, L., et al. (2019) · Hepatology · doi:10.1002/hep.30842 · Cited by 277 · see citing works
Self-citationCaballería, L., Pera, G., Arteaga, Í., Rodríguez, L., Alumà, A., Morillas, R. M., de la Ossa, N., Díaz, A., Expósito, C., Miranda, D., et al. (2018) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2017.12.048 · Cited by 276 · see citing works
Boland, M. L., Laker, R. C., Mather, K., Nawrocki, A., Oldham, S., Boland, B. B., Lewis, H., Conway, J., Naylor, J., Guionaud, S., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0209-6 · Cited by 270 · see citing works
Tokushige, K., Ikejima, K., Ono, M., Eguchi, Y., Kamada, Y., Itoh, Y., Akuta, N., Yoneda, M., Iwasa, M., Yoneda, M., et al. (2021) · Journal of Gastroenterology · doi:10.1007/s00535-021-01796-x · Cited by 276 · see citing works
KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease
Kang, S. H., Lee, H. W., Yoo, J., Cho, Y., Kim, S. U., Lee, T. H., Jang, B. K., Ahn, S. B., Ahn, S. B., Kim, H., et al. (2021) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2021.0178 · Cited by 271 · see citing works
Macrophage MerTK Promotes Liver Fibrosis in Nonalcoholic Steatohepatitis
Cai, B., Dongiovanni, P., Corey, K. E., Wang, X., Shmarakov, I. O., Zheng, Z., Kasikara, C., Davra, V., Meroni, M., Chung, R. T., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.013 · Cited by 266 · see citing works
Non-alcoholic fatty liver disease: A patient guideline
Francque, S. M., Marchesini, G., Kautz, A., Walmsley, M., Dorner, R., Lazarus, J. V., Zelber-Sagi, S., Hallsworth, K., Busetto, L., Frühbeck, G., et al. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100322 · Cited by 264 · see citing works
Obstructive Sleep Apnea, Hypoxia, and Nonalcoholic Fatty Liver Disease
Mesarwi, O. A., Loomba, R. S., & Malhotra, A. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201806-1109tr · Cited by 265 · see citing works
Self-citationHarrison, S. A., Rossi, S. J., Paredes, A. H., Trotter, J. F., Bashir, M. R., Guy, C. D., Banerjee, R., Jaros, M. J., Owers, S., Baxter, B. A., et al. (2020) · Hepatology · doi:10.1002/hep.30590 · Cited by 262 · see citing works
Liver fibrosis: Pathophysiology and clinical implications
Berumen, J. A., Baglieri, J., Kisseleva, T., & Mekeel, K. L. (2020) · WIREs Mechanisms of Disease · doi:10.1002/wsbm.1499 · Cited by 262 · see citing works
Golabi, P., Paik, J. M., Alqahtani, S. A., Younossi, Y., Tuncer, G., & Younossi, Z. M. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.05.022 · Cited by 261 · see citing works
Self-citationNon-invasive methods for imaging hepatic steatosis and their clinical importance in NAFLD
Tamaki, N., Ajmera, V. H., & Loomba, R. S. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00584-0 · Cited by 254 · see citing works
Self-citationLe, P., Tatar, M., Dasarathy, S., Alkhouri, N., Herman, W. H., Taksler, G. B., Deshpande, A., Ye, W., Adekunle, O. A., McCullough, A. J., et al. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.54707 · Cited by 261 · see citing works
Baratta, F., Pastori, D., Angelico, F., Balla, A., Paganini, A. M., Cocomello, N., Ferro, D., Violi, F., Sanyal, A. J., & Ben, M. D. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2019.12.026 · Cited by 252 · see citing works
Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis
Zhu, C., Kim, K., Wang, X., Bartolome, A., Salomao, M., Dongiovanni, P., Meroni, M., Graham, M. J., Yates, K. P., Diehl, A. M., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat0344 · Cited by 250 · see citing works
Zou, B., Yeo, Y. H., Nguyen, V. H., Cheung, R. C., Ingelsson, E., & Nguyen, M. H. (2020) · Journal of Internal Medicine · doi:10.1111/joim.13069 · Cited by 250 · see citing works
Lipidomic biomarkers and mechanisms of lipotoxicity in non-alcoholic fatty liver disease
Svegliati‐Baroni, G., Pierantonelli, I., Torquato, P., Marinelli, R., Ferreri, C., Chatgilialoglu, C., Bartolini, D., & Galli, F. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.05.029 · Cited by 250 · see citing works
Lim, G. E. H., Tang, A. S. P., Ng, C. H., Chin, Y. H., Lim, W. H., Tan, D. J. H., Yong, J. N., Xiao, J., Lee, C. W.-M., Chan, M. Y., et al. (2021) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2021.11.038 · Cited by 248 · see citing works
Krenkel, O., Hundertmark, J., Ritz, T., Weiskirchen, R., & Tacke, F. (2019) · Cells · doi:10.3390/cells8050503 · Cited by 241 · see citing works
Heyens, L. J. M., Busschots, D., Koek, G. H., Robaeys, G., & Francque, S. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.615978 · Cited by 243 · see citing works
Wattacheril, J. J., Abdelmalek, M. F., Lim, J. K., & Sanyal, A. J. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.06.013 · Cited by 236 · see citing works
- Authors
- Dulai, P. S., Singh, S., Patel, J., Soni, M., Prokop, L. J., Younossi, Z., Sebastiani, G., Ekstedt, M., Hagstrom, H., Nasr, P., Stal, P., Wong, V. W., Kechagias, S., Hultcrantz, R., & Loomba, R.
- Affiliations
- University of California San Diego (US)
- Mayo Clinic (US)
- Inova Fairfax Hospital (US)
- McGill University Health Centre (CA)
- Linköping University (SE)
- Department of Gastroenterology and Hepatology,Karolinska University Hospital, Karolinska Institutet,Stockholm,Sweden
- Karolinska University Hospital (SE)
- Chinese University of Hong Kong (HK)
- Corresponding author
- Loomba, Rohit
- ORCID
- Venue
- Hepatology
- Published
- 2017-03-31
- Volume
- 65
- Issue
- 5
- Pages
- 1557-1565
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC5397356
- OpenAlex
- W2580009538
- Cited by
- 1,965
- References
- 23
- Citations by year
- 2026: 199 · 2025: 193 · 2024: 227 · 2023: 263 · 2022: 240 · 2021: 272 · 2020: 249 · 2019: 163 · 2018: 101 · 2017: 48 · 2015: 1 · 2013: 1
- FWCI
- 20.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Bristol-Myers Squibb
- Gilead Sciences
- American Gastroenterological Association (R01‐DK106419, K23DK090303, 5T32DK007202)
- National Institutes of Health
- Fonds de Recherche du Québec - Santé
- National Institute of Diabetes and Digestive and Kidney Diseases (DK090303, R01DK106419, T32DK007202, K23DK090303)
- National Institute of Environmental Health Sciences (P42ES010337)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- non-alcoholic fatty liver disease, liver fibrosis, fibrosis stage, mortality risk, all-cause mortality, liver-related mortality, NAFLD progression, simple steatosis, nonalcoholic steatohepatitis, comorbidities, mortality prediction model, liver cancer, liver cirrhosis
- MeSH terms
- Fibrosis, Humans, Liver, Non-alcoholic Fatty Liver Disease
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