REFERENCES

1. Feng G, Targher G, Byrne CD, et al. Global burden of metabolic dysfunction-associated steatotic liver disease, 2010 to 2021. JHEP Rep. 2025;7:101271.

2. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77:1335-47.

3. Rinella ME, Lazarus JV, Ratziu V, et al; NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78:1966-86.

4. Kanwal F, Neuschwander-Tetri BA, Loomba R, Rinella ME. Metabolic dysfunction-associated steatotic liver disease: update and impact of new nomenclature on the American Association for the Study of Liver Diseases practice guidance on nonalcoholic fatty liver disease. Hepatology. 2024;79:1212-9.

5. Hagström H, Adams LA, Allen AM, et al. The future of international classification of diseases coding in steatotic liver disease: an expert panel Delphi consensus statement. Hepatol Commun. 2024;8:e0386.

6. 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.

7. Lee CM, Yoon EL, Kim M, et al. Prevalence, distribution, and hepatic fibrosis burden of the different subtypes of steatotic liver disease in primary care settings. Hepatology. 2024;79:1393-400.

8. Schneider CV, Schneider KM, Raptis A, Huang H, Trautwein C, Loomba R. Prevalence of at-risk MASH, MetALD and alcohol-associated steatotic liver disease in the general population. Aliment Pharmacol Ther. 2024;59:1271-81.

9. 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.

10. Ho GJK, Tan FXN, Sasikumar NA, et al. High global prevalence of steatotic liver disease and associated subtypes: a meta-analysis. Clin Gastroenterol Hepatol. 2025;Epub ahead of print.

11. 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.

12. Wu Y, Dong P, Wu Q, et al. Insights into clinical trials for drugs targeting MASLD: progress, challenges, and future directions. Clin Pharmacol Ther. 2025;117:1614-26.

13. Park Y, Jung J, Han S, Kim GA. Metabolic dysfunction-associated steatotic liver disease and MetALD increases the risk of liver cancer and gastrointestinal cancer: a nationwide cohort study. Aliment Pharmacol Ther. 2024;60:1599-608.

14. Díaz LA, Arab JP, Louvet A, Bataller R, Arrese M. The intersection between alcohol-related liver disease and nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2023;20:764-83.

15. Kim D, Wijarnpreecha K, Cholankeril G, Ahmed A. Steatotic liver disease-associated all-cause/cause-specific mortality in the United States. Aliment Pharmacol Ther. 2024;60:33-42.

16. Li M, Chen W, Deng Y, Xie W. Impacts of cardiometabolic risk factors and alcohol consumption on all-cause mortality among MASLD and its subgroups. Nutr Metab Cardiovasc Dis. 2024;34:2085-94.

17. Diaz LA, Ajmera V, Arab JP, et al. An expert consensus delphi panel in metabolic dysfunction- and alcohol-associated liver disease: opportunities and challenges in clinical practice. Clin Gastroenterol Hepatol. 2025;Epub ahead of print.

18. Sanyal AJ, Van Natta ML, Clark J, et al; NASH Clinical Research Network (CRN). Prospective study of outcomes in adults with nonalcoholic fatty liver disease. N Engl J Med. 2021;385:1559-69.

19. Rumgay H, Shield K, Charvat H, et al. Global burden of cancer in 2020 attributable to alcohol consumption: a population-based study. Lancet Oncol. 2021;22:1071-80.

20. Anderson BO, Berdzuli N, Ilbawi A, et al. Health and cancer risks associated with low levels of alcohol consumption. Lancet Public Health. 2023;8:e6-7.

21. Israelsen M, Torp N, Johansen S, et al; GALAXY consortium. Validation of the new nomenclature of steatotic liver disease in patients with a history of excessive alcohol intake: an analysis of data from a prospective cohort study. Lancet Gastroenterol Hepatol. 2024;9:218-28.

22. 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.

23. Kulkarni AV, Singal AK, Kamath PS. Research priorities and future landscape of clinical trials in alcohol-associated liver disease. Clin Liver Dis. 2024;28:831-51.

24. Ayares G, Diaz LA, Idalsoaga F, et al. MetALD: new perspectives on an old overlooked disease. Liver Int. 2025;45:e70017.

25. Bae JH. Racial and ethnic disparities in metabolic dysfunction-associated steatotic liver disease outcomes: a call for culturally sensitive interventions: editorial on “Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: a longitudinal real-world study”. Clin Mol Hepatol. 2024;30:665-8.

26. Díaz Carnicero J, Saurí-Ferrer I, Redon J, et al. Clinical and economic burden of metabolic dysfunction-associated steatotic liver disease (MASLD) in a Spanish Mediterranean region: a population-based study. J Clin Med. 2025;14:2441.

27. Zhao Y, Bo Y, Zu J, et al. Global burden of chronic liver disease and temporal trends: a population-based analysis from 1990 to 2021 with projections to 2050. Liver Int. 2025;45:e70155.

28. Yamamura S, Nakano D, Hashida R, et al. Patient-reported outcomes in patients with non-alcoholic fatty liver disease: a narrative review of Chronic Liver Disease Questionnaire-non-alcoholic fatty liver disease/non-alcoholic steatohepatitis. J Gastroenterol Hepatol. 2021;36:629-36.

29. Younossi Z, Aggarwal P, Shrestha I, et al. The burden of non-alcoholic steatohepatitis: A systematic review of health-related quality of life and patient-reported outcomes. JHEP Rep. 2022;4:100525.

30. Schomerus G, Leonhard A, Manthey J, et al. The stigma of alcohol-related liver disease and its impact on healthcare. J Hepatol. 2022;77:516-24.

31. Lazarus JV, Miralles-Sanchez JE, Agirre-Garrido L, et al. A call to action to address the steatotic liver disease public health threat in Barcelona. Lancet Reg Health Eur. 2025;52:101272.

32. Kardashian A, Serper M, Terrault N, Nephew LD. Health disparities in chronic liver disease. Hepatology. 2023;77:1382-403.

33. Loomba R, Ratziu V, Harrison SA; NASH Clinical Trial Design International Working Group. Expert panel review to compare FDA and EMA guidance on drug development and endpoints in nonalcoholic steatohepatitis. Gastroenterology. 2022;162:680-8.

34. Code of Federal Regulations. Subpart H -- accelerated approval of new drugs for serious or life-threatening illnesses. Available from: https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-314/subpart-H. [Last accessed on 13 Oct 2025].

35. Harvey BE. How improvements in US FDA regulatory process and procedures led to the drug approval for first ever treatment of a common liver disease. Acta Pharmacol Sin. 2025;46:515-24.

36. Harvey BE. NASH: regulatory considerations for clinical drug development and U.S. FDA approval. Acta Pharmacol Sin. 2022;43:1210-4.

37. Sanyal AJ, Friedman SL, McCullough AJ, Dimick-Santos L; American Association for the Study of Liver Diseases, United States Food and Drug Administration. Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis: findings and recommendations from an American Association for the Study of Liver Diseases-U.S. Food and Drug Administration Joint Workshop. Hepatology. 2015;61:1392-405.

38. Keam SJ. Resmetirom: first approval. Drugs. 2024;84:729-35.

39. Younossi Z, Henry L. Contribution of alcoholic and nonalcoholic fatty liver disease to the burden of liver-related morbidity and mortality. Gastroenterology. 2016;150:1778-85.

40. Chiang DJ, McCullough AJ. The impact of obesity and metabolic syndrome on alcoholic liver disease. Clin Liver Dis. 2014;18:157-63.

41. Vuppalanchi R, Chalasani N. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: selected practical issues in their evaluation and management. Hepatology. 2009;49:306-17.

42. Whitfield JB, Schwantes-An TH, Darlay R, et al; GenomALC Consortium. A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers. J Hepatol. 2022;76:275-82.

43. Ganne-Carrié N, Chaffaut C, Bourcier V, et al; for CIRRAL Group. Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis. J Hepatol. 2018;69:1274-83.

44. De Oliveira E Silva ER, Foster D, McGee Harper M, et al. Alcohol consumption raises HDL cholesterol levels by increasing the transport rate of apolipoproteins A-I and A-II. Circulation. 2000;102:2347-52.

45. Cecchini M, Filippini T, Whelton PK, et al. Alcohol intake and risk of hypertension: a systematic review and dose-response meta-analysis of nonexperimental cohort studies. Hypertension. 2024;81:1701-15.

46. Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the alcohol use disorders identification test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption--II. Addiction. 1993;88:791-804.

47. O’Brien CP. The CAGE questionnaire for detection of alcoholism: a remarkably useful but simple tool. JAMA. 2008;300:2054-6.

48. Jørgenrud BM, Bråthen CC, Steinson Stenehjem J, Kristiansen T, Rosseland LA, Bogstrand ST. Identifying excessive chronic alcohol use with phosphatidylethanol in patients with suspected severe injury-results from the IDART study. Alcohol Alcohol. 2024;59:agae014.

49. Stewart SH, Koch DG, Burgess DM, Willner IR, Reuben A. Sensitivity and specificity of urinary ethyl glucuronide and ethyl sulfate in liver disease patients. Alcohol Clin Exp Res. 2013;37:150-5.

50. McKnight-Eily LR, Okoro CA, Turay K, Acero C, Hungerford D. Screening for alcohol use and brief counseling of adults - 13 states and the district of Columbia, 2017. MMWR Morb Mortal Wkly Rep. 2020;69:265-70.

51. Krag A, Torp N, Younossi ZM, Israelsen M. Reporting discrepancy of alcohol intake affecting estimated prevalence of MetALD and ALD. Lancet Gastroenterol Hepatol. 2025;10:282-4.

52. Staufer K, Huber-Schönauer U, Strebinger G, et al. Ethyl glucuronide in hair detects a high rate of harmful alcohol consumption in presumed non-alcoholic fatty liver disease. J Hepatol. 2022;77:918-30.

53. Livingston M, Callinan S. Underreporting in alcohol surveys: whose drinking is underestimated? J Stud Alcohol Drugs. 2015;76:158-64.

54. Díaz LA, König D, Weber S, et al. Management of alcohol use disorder: a gastroenterology and hepatology-focused perspective. Lancet Gastroenterol Hepatol. 2025;10:475-90.

55. Tevik K, Bergh S, Selbæk G, Johannessen A, Helvik AS. A systematic review of self-report measures used in epidemiological studies to assess alcohol consumption among older adults. PLoS One. 2021;16:e0261292.

56. Bradley KA, DeBenedetti AF, Volk RJ, Williams EC, Frank D, Kivlahan DR. AUDIT-C as a brief screen for alcohol misuse in primary care. Alcohol Clin Exp Res. 2007;31:1208-17.

57. Harris JC, Leggio L, Farokhnia M. Blood biomarkers of alcohol use: a scoping review. Curr Addict Rep. 2021;8:500-8.

58. Aboutara N, Szewczyk A, Jungen H, et al. Phosphatidylethanol in patients with liver diseases of different etiologies: analysis of six homologues and comparison with other alcohol markers. Clin Chim Acta. 2022;524:171-8.

59. Stewart SH, Koch DG, Willner IR, Anton RF, Reuben A. Validation of blood phosphatidylethanol as an alcohol consumption biomarker in patients with chronic liver disease. Alcohol Clin Exp Res. 2014;38:1706-11.

60. Hahn JA, Fatch R, Barnett NP, Marcus GM. Phosphatidylethanol vs transdermal alcohol monitoring for detecting alcohol consumption among adults. JAMA Netw Open. 2023;6:e2333182.

61. Helander A, Hansson T. The alcohol biomarker phosphatidylethanol (PEth) - test performance and experiences from routine analysis and external quality assessment. Scand J Clin Lab Invest. 2023;83:424-31.

62. Finanger T, Melby K, Spigset O, Andreassen TN, Lydersen S, Skråstad RB. Relationship between alcohol intake based on daily smartphone-reported consumption and PEth concentrations in healthy volunteers. Alcohol Alcohol. 2024;59:agae040.

63. Tavaglione F, Amangurbanova M, Yang AH, et al. Head-to-head comparison between phosphatidylethanol versus indirect alcohol biomarkers for diagnosis of MetALD versus MASLD: a prospective study. Aliment Pharmacol Ther. 2025;61:1043-54.

64. Hansen ED, Torp N, Johansen S, et al; GALAXY and MicrobLiver consortia. Quantification of alcohol intake in patients with steatotic liver disease and excessive alcohol intake. JHEP Rep. 2025;7:101200.

65. Vaz J, Nasr P, Helander A, et al. Phosphatidylethanol levels distinguish steatotic liver disease subgroups and are associated with risk of major liver outcomes. J Hepatol. 2025;Epub ahead of print.

66. Skråstad RB, Aamo TO, Andreassen TN, et al. Quantifying alcohol consumption in the general population by analysing phosphatidylethanol concentrations in whole blood: results from 24,574 subjects included in the HUNT4 study. Alcohol Alcohol. 2023;58:258-65.

67. Israelsen M, Thorhauge KH, Andersen P, et al. Steatotic liver disease classification is dynamic, affecting clinical trial eligibility and subclass-specific treatments. Clin Gastroenterol Hepatol. 2025;Epub ahead of print.

68. Allen AM, Therneau TM, Ahmed OT, et al. Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design. J Hepatol. 2022;77:1237-45.

69. Cusi K, Budd J, Johnson E, Shubrook J. Making sense of the nonalcoholic fatty liver disease clinical practice guidelines: what clinicians need to know. Diabetes Spectr. 2024;37:29-38.

70. Lindén D, Romeo S. Therapeutic opportunities for the treatment of NASH with genetically validated targets. J Hepatol. 2023;79:1056-64.

71. Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med. 2001;344:495-500.

72. Middleton MS, Heba ER, Hooker CA, et al; NASH Clinical Research Network. Agreement between magnetic resonance imaging proton density fat fraction measurements and pathologist-assigned steatosis grades of liver biopsies from adults with nonalcoholic steatohepatitis. Gastroenterology. 2017;153:753-61.

73. Qu Y, Li M, Hamilton G, Zhang YN, Song B. Diagnostic accuracy of hepatic proton density fat fraction measured by magnetic resonance imaging for the evaluation of liver steatosis with histology as reference standard: a meta-analysis. Eur Radiol. 2019;29:5180-9.

74. de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C; Baveno VII Faculty. Corrigendum to ‘Baveno VII - Renewing consensus in portal hypertension’ [J Hepatol (2022) 959-974]. J Hepatol. 2022;77:271.

75. Park CC, Nguyen P, Hernandez C, et al. Magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty liver disease. Gastroenterology. 2017;152:598-607.e2.

76. Hudson D, Afzaal T, Bualbanat H, et al. Modernizing metabolic dysfunction-associated steatotic liver disease diagnostics: the progressive shift from liver biopsy to noninvasive techniques. Therap Adv Gastroenterol. 2024;17:17562848241276334.

77. Rinella ME, Tacke F, Sanyal AJ, Anstee QM; participants of the AASLD/EASL Workshop. Report on the AASLD/EASL joint workshop on clinical trial endpoints in NAFLD. Hepatology. 2019;70:1424-36.

78. Ratziu V. A critical review of endpoints for non-cirrhotic NASH therapeutic trials. J Hepatol. 2018;68:353-61.

79. Roth NC, Qin J. Histopathology of alcohol-related liver diseases. Clin Liver Dis. 2019;23:11-23.

80. Gratacós-Ginès J, Ariño S, Sancho-Bru P, Bataller R, Pose E. MetALD: clinical aspects, pathophysiology and treatment. JHEP Rep. 2025;7:101250.

81. Kim WR, Mannalithara A, Heimbach JK, et al. MELD 3.0: the model for end-stage liver disease updated for the modern era. Gastroenterology. 2021;161:1887-95.e4.

82. Newsome PN, Buchholtz K, Cusi K, et al; NN9931-4296 Investigators. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-24.

83. 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.

84. Armstrong MJ, Gaunt P, Aithal GP, et al; LEAN trial team. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet. 2016;387:679-90.

85. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al; SELECT Trial Investigators. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389:2221-32.

86. Marso SP, Bain SC, Consoli A, et al; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834-44.

87. Loomba R, Abdelmalek MF, Armstrong MJ, et al; NN9931-4492 investigators. Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8:511-22.

88. 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.

89. Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024;30:2037-48.

90. Harrison SA, Browne SK, Suschak JJ, et al. Effect of pemvidutide, a GLP-1/glucagon dual receptor agonist, on MASLD: a randomized, double-blind, placebo-controlled study. J Hepatol. 2025;82:7-17.

91. 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.

92. 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.

93. 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.

94. Palzes VA, Farokhnia M, Kline-Simon AH, et al. Effectiveness of spironolactone dispensation in reducing weekly alcohol use: a retrospective high-dimensional propensity score-matched cohort study. Neuropsychopharmacology. 2021;46:2140-7.

95. Geng L, Lam KSL, Xu A. The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic. Nat Rev Endocrinol. 2020;16:654-67.

96. Flippo KH, Trammell SAJ, Gillum MP, et al. FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit. Cell Metab. 2022;34:317-328.e6.

97. Harrison SA, Frias JP, Neff G, et al; HARMONY Study Group. Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol. 2023;8:1080-93.

98. Loomba R, Sanyal AJ, Kowdley KV, et al. Randomized, controlled trial of the FGF21 analogue pegozafermin in NASH. N Engl J Med. 2023;389:998-1008.

99. Loomba R, Sanyal AJ, Nakajima A, et al. Pegbelfermin in patients with nonalcoholic steatohepatitis and stage 3 fibrosis (FALCON 1): a randomized phase 2b study. Clin Gastroenterol Hepatol. 2024;22:102-12.e9.

100. Aghara H, Patel M, Chadha P, Parwani K, Chaturvedi R, Mandal P. Unraveling the gut-liver-brain axis: microbiome, inflammation, and emerging therapeutic approaches. Mediators Inflamm. 2025;2025:6733477.

101. Afzaal M, Saeed F, Shah YA, et al. Human gut microbiota in health and disease: unveiling the relationship. Front Microbiol. 2022;13:999001.

102. Rinninella E, Raoul P, Cintoni M, et al. What is the healthy gut microbiota composition? Microorganisms. 2019;7:14.

103. Yan M, Man S, Sun B, et al. Gut liver brain axis in diseases: the implications for therapeutic interventions. Signal Transduct Target Ther. 2023;8:443.

104. Li X, Chen LM, Kumar G, et al. Therapeutic interventions of gut-brain axis as novel strategies for treatment of alcohol use disorder associated cognitive and mood dysfunction. Front Neurosci. 2022;16:820106.

105. Farokhnia M, Rentsch CT, Chuong V, et al. Spironolactone as a potential new pharmacotherapy for alcohol use disorder: convergent evidence from rodent and human studies. Mol Psychiatry. 2022;27:4642-52.

106. Fu L, Yokus B, Gao B, Pacher P. An update on IL-22 therapies in alcohol-associated liver disease and beyond. Am J Pathol. 2025:S00029440(25)00117.

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