REFERENCES
1. Rinella ME, Lazarus JV, Ratziu V, et al.; NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023;79:1542-56.
2. Dunn N, Al-Khouri N, Abdellatif I, et al. Metabolic dysfunction and alcohol-associated liver disease: a narrative review. Clin Transl Gastroenterol. 2025;16:e00828.
3. Kalligeros M, Vassilopoulos A, Vassilopoulos S, Victor DW, Mylonakis E, Noureddin M. Prevalence of steatotic liver disease (MASLD, MetALD, and ALD) in the United States: NHANES 2017-2020. Clin Gastroenterol Hepatol. 2024;22:1330-2.e4.
4. Lee BP, Dodge JL, Terrault NA. National prevalence estimates for steatotic liver disease and subclassifications using consensus nomenclature. Hepatology. 2024;79:666-73.
5. Dunn N, Zhang W, Blaney HL, et al. Physical activity and advanced fibrosis in MASLD, MetALD, and ALD in a nationally representative cohort: NHANES 2017-2020. Hepatol Commun. 2025;9:e0797.
6. Kwak M, Kim HS, Jiang ZG, et al. MASLD/MetALD and mortality in individuals with any cardio-metabolic risk factor: a population-based study with 26.7 years of follow-up. Hepatology. 2025;81:228-37.
7. Elmustafa F, Tyagi M, Kaur H, et al. Met-ALD and ALD- does differentiating these impact management and clinical outcomes? Curr Hepatol Rep. 2025;24:10.1007/s11901-025.
8. Hagström H, Hegmar H, Moreno C. Interactions between the metabolic syndrome and alcohol consumption increases the risk of liver disease. United European Gastroenterol J. 2024;12:168-76.
9. Singal AK, Mathurin P. Diagnosis and treatment of alcohol-associated liver disease: a review. JAMA. 2021;326:165-76.
10. Francque SM, van der Graaff D, Kwanten WJ. Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications. J Hepatol. 2016;65:425-43.
11. Åberg F, Färkkilä M. Drinking and obesity: alcoholic liver disease/nonalcoholic fatty liver disease interactions. Semin Liver Dis. 2020;40:154-62.
12. Wong VW, Chan RS, Wong GL, et al. Community-based lifestyle modification programme for non-alcoholic fatty liver disease: a randomized controlled trial. J Hepatol. 2013;59:536-42.
13. Keating SE, Chawla Y, De A, George ES. Lifestyle intervention for metabolic dysfunction-associated fatty liver disease: a 24-h integrated behavior perspective. Hepatol Int. 2024;18:959-76.
14. Bernardino M, Tiribelli C, Rosso N. The impact of the mediterranean diet, physical activity, and nutrition education on pediatric metabolic dysfunction-associated steatotic liver disease (MASLD): a review. Nutrients. 2025;18:28.
15. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77:1797-835.
16. Yeoh A, Wong R, Singal AK. The role bariatric surgery and endobariatric therapies in nonalcoholic steatohepatitis. Clin Liver Dis. 2023;27:413-27.
17. Hwang J, Hwang H, Shin H, et al. Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: a systematic review and meta-analysis. Clin Mol Hepatol. 2024;30:561-76.
18. Abdallah M, Brown L, Provenza J, Tariq R, Gowda S, Singal AK. Safety and efficacy of dyslipidemia treatment in NAFLD patients: a meta-analysis of randomized controlled trials. Ann Hepatol. 2022;27:100738.
19. Harrison SA, Bedossa P, Guy CD, et al.; MAESTRO-NASH investigators. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 2024;390:497-509.
20. Sanyal AJ, Newsome PN, Kliers I, et al.; ESSENCE Study Group. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis. N Engl J Med. 2025;392:2089-99.
21. Singal AK, Wong RJ, Dasarathy S, et al. ACG clinical guideline: malnutrition and nutritional recommendations in liver disease. Am J Gastroenterol. 2025;120:950-72.
22. Gratacós-Ginès J, Ariño S, Sancho-Bru P, Bataller R, Pose E. MetALD: clinical aspects, pathophysiology and treatment. JHEP Rep. 2025;7:101250.
23. Patel S, Blaney H, Nassar S, Singal AK. GLP-1 receptor agonists and alcohol use disorder: a systematic review. Alcohol Alcohol. 2025;61:agaf069.
24. Tanguturi Yella SS, Kota Sesha Brahma Sree KS, Mahato SK. The role of glucagon-like peptide-1 receptor agonists in the treatment of alcohol use disorder: current evidence and future directions. J Clin Psychopharmacol. 2025;45:372-5.
25. van Bloemendaal L, Veltman DJ, Ten Kulve JS, et al. Brain reward-system activation in response to anticipation and consumption of palatable food is altered by glucagon-like peptide-1 receptor activation in humans. Diabetes Obes Metab. 2015;17:878-86.
26. Loomba R, Hartman ML, Lawitz EJ, et al.; SYNERGY-NASH Investigators. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis. N Engl J Med. 2024;391:299-310.
27. Newsome PN, Sanyal AJ, Engebretsen KA, et al. Semaglutide 2.4 mg in participants with metabolic dysfunction-associated steatohepatitis: baseline characteristics and design of the phase 3 ESSENCE trial. Aliment Pharmacol Ther. 2024;60:1525-33.
28. Newsome PN, Ambery P. Incretins (GLP-1 receptor agonists and dual/triple agonists) and the liver. J Hepatol. 2023;79:1557-65.
29. Fisher FM, Maratos-Flier E. Understanding the physiology of FGF21. Annu Rev Physiol. 2016;78:223-41.
30. Meroni M, Dongiovanni P, Tiano F, Piciotti R, Alisi A, Panera N. β-Klotho as novel therapeutic target in metabolic dysfunction-associated steatotic liver disease (MASLD): a narrative review. Biomed Pharmacother. 2024;180:117608.
31. Harrison SA, Rolph T, Knott M, Dubourg J. FGF21 agonists: an emerging therapeutic for metabolic dysfunction-associated steatohepatitis and beyond. J Hepatol. 2024;81:562-76.
32. Rose JP, Morgan DA, Sullivan AI, et al. FGF21 reverses MASH through coordinated actions on the CNS and liver. Cell Metab. 2025;37:1515-29.e6.
33. Harrison SA, Ruane PJ, Freilich B, et al. A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis. JHEP Rep. 2023;5:100563.
34. Jeong C, Han N, Jeon N, et al. Efficacy and safety of fibroblast growth factor-21 analogs for the treatment of metabolic dysfunction-associated steatohepatitis: a systematic review and meta-analysis. Clin Pharmacol Ther. 2024;116:72-81.
35. Staels B, Butruille L, Francque S. Treating NASH by targeting peroxisome proliferator-activated receptors. J Hepatol. 2023;79:1302-16.
36. Results from the 52-week phase 2b VOYAGE trial of VK2809 in patients with biopsy-confirmed non-alcoholic steatohepatitis and fibrosis: a randomized, placebo-controlled trial. Gastroenterol Hepatol. 2024;20:13-4.
37. Kamata S, Honda A, Ishii I. Current clinical trial status and future prospects of PPAR-targeted drugs for treating nonalcoholic fatty liver disease. Biomolecules. 2023;13:1264.
38. Goyal O, Nohria S, Goyal P, et al. Saroglitazar in patients with non-alcoholic fatty liver disease and diabetic dyslipidemia: a prospective, observational, real world study. Sci Rep. 2020;10:21117.
39. Siddiqui MS, Parmar D, Sheikh F, et al. Saroglitazar, a dual PPAR α/γ agonist, improves atherogenic dyslipidemia in patients with non-cirrhotic nonalcoholic fatty liver disease: a pooled analysis. Clin Gastroenterol Hepatol. 2023;21:2597-605.e2.
40. Takahashi H, Kessoku T, Kawanaka M, et al. Ipragliflozin improves the hepatic outcomes of patients with diabetes with NAFLD. Hepatol Commun. 2022;6:120-32.
41. Jin Z, Yuan Y, Zheng C, Liu S, Weng H. Effects of sodium-glucose co-transporter 2 inhibitors on liver fibrosis in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: an updated meta-analysis of randomized controlled trials. J Diabetes Complications. 2023;37:108558.
43. Venetsanaki V, Karabouta Z, Polyzos SA. Farnesoid X nuclear receptor agonists for the treatment of nonalcoholic steatohepatitis. Eur J Pharmacol. 2019;863:172661.
44. Loomba R, Noureddin M, Kowdley KV, et al.; for the ATLAS Investigators. Combination therapies including cilofexor and firsocostat for bridging fibrosis and cirrhosis attributable to NASH. Hepatology. 2021;73:625-43.
45. Sanyal AJ, Lopez P, Lawitz EJ, et al. Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a/b trial. Nat Med. 2023;29:392-400.
46. Ratziu V, Harrison SA, Loustaud-Ratti V, et al. Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH. J Hepatol. 2023;78:479-92.
47. Esler WP, Cohen DE. Pharmacologic inhibition of lipogenesis for the treatment of NAFLD. J Hepatol. 2024;80:362-77.
48. Loomba R, Bedossa P, Grimmer K, et al. Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol. 2024;9:1090-100.
49. Calle RA, Amin NB, Carvajal-Gonzalez S, et al. ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials. Nat Med. 2021;27:1836-48.
50. Vujkovic M, Ramdas S, Lorenz KM, et al.; Regeneron Genetics Center, Geisinger-Regeneron DiscovEHR Collaboration, EPoS Consortium, VA Million Veteran Program. A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation. Nat Genet. 2022;54:761-71.
51. Stickel F, Lutz P, Buch S, et al. Genetic variation in HSD17B13 reduces the risk of developing cirrhosis and hepatocellular carcinoma in alcohol misusers. Hepatology. 2020;72:88-102.
52. Schwantes-An TH, Darlay R, Mathurin P, et al.; GenomALC Consortium. Genome-wide association study and meta-analysis on alcohol-associated liver cirrhosis identifies genetic risk factors. Hepatology. 2021;73:1920-31.
53. Francque SM, Bedossa P, Ratziu V, et al.; NATIVE Study Group. A randomized, controlled trial of the Pan-PPAR agonist lanifibranor in NASH. N Engl J Med. 2021;385:1547-58.
54. Sanyal AJ, Bedossa P, Fraessdorf M, et al.; 1404-0043 Trial Investigators. A phase 2 randomized trial of survodutide in MASH and fibrosis. N Engl J Med. 2024;391:311-9.
55. Groenewegen B, Ruissen MM, Crossette E, et al. Consecutive fecal microbiota transplantation for metabolic dysfunction-associated steatotic liver disease: a randomized controlled trial. Gut Microbes. 2025;17:2541035.
56. Bajaj JS. Alcohol, liver disease and the gut microbiota. Nat Rev Gastroenterol Hepatol. 2019;16:235-46.
57. Witkiewitz K, Litten RZ, Leggio L. Advances in the science and treatment of alcohol use disorder. Sci Adv. 2019;5:eaax4043.
58. Anton RF, O’Malley SS, Ciraulo DA, et al.; COMBINE Study Research Group. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006;295:2003-17.
59. Marek GW, Malhi H. MetALD: does it require a different therapeutic option? Hepatology. 2024;80:1424-40.
60. Kranzler HR, Soyka M. Diagnosis and pharmacotherapy of alcohol use disorder: a review. JAMA. 2018;320:815-24.
61. McPheeters M, O’Connor EA, Riley S, et al. Pharmacotherapy for alcohol use disorder: a systematic review and meta-analysis. JAMA. 2023;330:1653-65.
62. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. J Hepatol. 2018;69:154-81.
63. Wu T, Mousa OY, Kulai T, et al. Safety of acamprosate in patients with alcohol-associated liver disease: a single-arm phase 2 trial. Mayo Clin Proc. 2025;100:954-61.
64. Leggio L, Hendershot CS, Farokhnia M, et al. GLP-1 receptor agonists are promising but unproven treatments for alcohol and substance use disorders. Nat Med. 2023;29:2993-5.
65. Wang W, Volkow ND, Berger NA, Davis PB, Kaelber DC, Xu R. Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population. Nat Commun. 2024;15:4548.
66. Quddos F, Hubshman Z, Tegge A, et al. Semaglutide and tirzepatide reduce alcohol consumption in individuals with obesity. Sci Rep. 2023;13:20998.
67. Nasrollahizadeh A, Kheiri G, Javankiani S, et al. Repurposing GLP-1 receptor agonists for alcohol use disorder: a systematic review and meta-analysis. Diabetol Metab Syndr. 2026;18:29.
68. Cooley BJ, Occelli Hanbury-Brown CV, Choi EA, et al. FGF21 analogue PF-05231023 on alcohol consumption and neuronal activity in the nucleus accumbens. Neuropsychopharmacology. 2026;51:519-29.
69. Desai BN, Singhal G, Watanabe M, et al. Fibroblast growth factor 21 (FGF21) is robustly induced by ethanol and has a protective role in ethanol associated liver injury. Mol Metab. 2017;6:1395-406.
70. Flippo KH, Trammell SAJ, Gillum MP, et al. FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit. Cell Metab. 2022;34:317-28.e6.
71. Cronjé HT, Hu S, Gurrell R, et al. Robust human genetic evidence supporting causal effects of FGF21 on reducing alcohol consuming behaviours. medRxiv 2025;2025.11.15.25340305v1. Available from: https://www.medrxiv.org/content/10.1101/2025.11.15.25340305v1.full. [Last accessed on 12 Jun 2026].
72. Shahi A, Yadav A, Rajak S, et al. Liver-specific thyroid hormone receptor-β agonism alleviates alcoholic steatohepatitis (ASH) in mice. Biochem Biophys Res Commun. 2024;734:150742.
73. Matheson J, Le Foll B. Therapeutic potential of peroxisome proliferator-activated receptor (PPAR) agonists in substance use disorders: a synthesis of preclinical and human evidence. Cells. 2020;9:1196.
74. Ferguson LB, Most D, Blednov YA, Harris RA. PPAR agonists regulate brain gene expression: relationship to their effects on ethanol consumption. Neuropharmacology. 2014;86:397-407.
75. Schwandt ML, Diazgranados N, Umhau JC, Kwako LE, George DT, Heilig M. PPARγ activation by pioglitazone does not suppress cravings for alcohol, and is associated with a risk of myopathy in treatment seeking alcohol dependent patients: a randomized controlled proof of principle study. Psychopharmacology. 2020;237:2367-80.
76. Karahanian E, Quintanilla ME, Fernandez K, Israel Y. Fenofibrate--a lipid-lowering drug--reduces voluntary alcohol drinking in rats. Alcohol. 2014;48:665-70.
77. Blednov YA, Benavidez JM, Black M, et al. Peroxisome proliferator-activated receptors α and γ are linked with alcohol consumption in mice and withdrawal and dependence in humans. Alcohol Clin Exp Res. 2015;39:136-45.
78. Rivera-Meza M, Muñoz D, Jerez E, et al. Fenofibrate administration reduces alcohol and saccharin intake in rats: possible effects at peripheral and central levels. Front Behav Neurosci. 2017;11:133.
79. Mutlu EA, Gillevet PM, Rangwala H, et al. Colonic microbiome is altered in alcoholism. Am J Physiol Gastrointest Liver Physiol. 2012;302:G966-78.
80. Wang SC, Chen YC, Chen SJ, Lee CH, Cheng CM. Alcohol addiction, gut microbiota, and alcoholism treatment: a review. Int J Mol Sci. 2020;21:6413.
81. Vatsalya V, Feng W, Kong M, et al. The beneficial effects of Lactobacillus GG therapy on liver and drinking assessments in patients with moderate alcohol-associated hepatitis. Am J Gastroenterol. 2023;118:1457-60.
82. Bajaj JS, Gavis EA, Fagan A, et al. A randomized clinical trial of fecal microbiota transplant for alcohol use disorder. Hepatology. 2021;73:1688-700.
83. Yu L, Wang L, Yi H, Wu X. Beneficial effects of LRP6-CRISPR on prevention of alcohol-related liver injury surpassed fecal microbiota transplant in a rat model. Gut Microbes. 2020;11:1015-29.
84. Arab JP, Díaz LA, Rehm J, et al. Metabolic dysfunction and alcohol-related liver disease (MetALD): position statement by an expert panel on alcohol-related liver disease. J Hepatol. 2025;82:744-56.
85. Gao B, Arab JP, Liangpunsakul S, et al. Metabolic dysfunction and alcohol-associated liver disease (MetALD). eGastroenterology. 2025;3:e100319.
86. Tampaki M, Tsochatzis E, Lekakis V, Cholongitas E. Prevalence, characteristics and outcomes of patients with metabolic and alcohol related/associated liver disease (MetALD): a systematic review and meta-analysis. Metabolism. 2025;163:156101.
87. Liu H, Lefere S, Guillot A, Zheng MH, Tacke F. Bariatric surgery for metabolic dysfunction-associated steatotic liver disease (MASLD): current knowledge of mechanisms. Hepatology. 2025;Epub ahead of print.
88. Singal AK, Leggio L, DiMartini A. Alcohol use disorder in alcohol-associated liver disease: two sides of the same coin. Liver Transpl. 2024;30:200-12.
89. Rady ED, Cotter TG. Integrating phosphatidylethanol to enhance alcohol quantification in steatotic liver disease and clinical trials. Liver Int. 2026;46:e70489.
90. Harrison SA, Schattenberg JM, Taub R, Labriola D. SAT-263 resmetirom treatment of a subgroup of patients with possible MetALD enrolled in MAESTRO-NASH, a phase 3 NASH/MASH serial liver biopsy study. J Hepatol. 2024;80:S141-2.
91. Sodhi M, Rezaeianzadeh R, Kezouh A, Etminan M. Risk of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists for weight loss. JAMA. 2023;330:1795-7.
92. Heymsfield SB, Aronne LJ, Montgomery P, et al. Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial. Nat Med. 2026;32:869-82.
93. Neokosmidis G, Cholongitas E, Tziomalos K. Acetyl-CoA carboxylase inhibitors in non-alcoholic steatohepatitis: is there a benefit? World J Gastroenterol. 2021;27:6522-6.
94. Niu C, Zhang J, Idoate-Domench DJ, et al. Evaluating the long-term benefits of medications for alcohol use disorder in alcohol-associated cirrhosis. Liver Int. 2025;45:e70424.
