4. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999;116:1413-1419.
8. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, TorresGonzalez A, Gra-Oramas B, Gonzalez-Fabian L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 2015;149:367-378.e5 quiz e14-5.
10. Wong VW, Wong GL, Chan RS, Shu SS, Cheung BH, Li LS, et al. Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease. J Hepatol 2018;69:1349-1356.
11. Franz MJ, VanWormer JJ, Crain AL, Boucher JL, Histon T, Caplan W, et al. Weight-loss outcomes: a systematic review and metaanalysis of weight-loss clinical trials with a minimum 1-year follow-up. J Am Diet Assoc 2007;107:1755-1767.
17. Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, et al. American association of clinical endocrinology clinical practice guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings: co-sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract 2022;28:528-562.
19. Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006;355:2297-2307.
20. Aithal GP, Thomas JA, Kaye PV, Lawson A, Ryder SD, Spendlove I, et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 2008;135:1176-1184.
21. Cusi K, Orsak B, Bril F, Lomonaco R, Hecht J, Ortiz-Lopez C, et al. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial. Ann Intern Med 2016;165:305-315.
24. Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, et al.; NN9931-4296 Investigators. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med 2021;384:1113-1124.
28. Claudel T, Staels B, Kuipers F. The Farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism. Arterioscler Thromb Vasc Biol 2005;25:2020-2030.
29. Fiorucci S, Antonelli E, Rizzo G, Renga B, Mencarelli A, Riccardi L, et al. The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liver fibrosis. Gastroenterology 2004;127:1497-1512.
30. Wang YD, Chen WD, Wang M, Yu D, Forman BM, Huang W. Farnesoid X receptor antagonizes nuclear factor kappaB in hepatic inflammatory response. Hepatology 2008;48:1632-1643.
31. Younossi ZM, Ratziu V, Loomba R, Rinella M, Anstee QM, Goodman Z, et al.; REGENERATE Study Investigators. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 2020;394:2184-2196 Erratum in: Lancet 2020;396:312. Erratum in: Lancet 2021;397:2336.
35. Lefere S, Puengel T, Hundertmark J, Penners C, Frank AK, Guillot A, et al. Differential effects of selective- and pan-PPAR agonists on experimental steatohepatitis and hepatic macrophages. J Hepatol 2020;73:757-770.
36. Francque SM, Bedossa P, Ratziu V, Anstee QM, Bugianesi E, Sanyal AJ, et al.; NATIVE Study Group. A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH. N Engl J Med 2021;385:1547-1558.
37. National Library of Medicine. Phase 3 study to evaluate the efficacy and safety of elafibranor versus placebo in patients with nonalcoholic steatohepatitis (NASH) (RESOLVE-IT). National Library of Medicine web site, <
https://clinicaltrials.gov/ct2/show/NCT02704403>. Accessed 1 Dec 2022.
38. Reinehr T. Obesity and thyroid function. Mol Cell Endocrinol 2010;316:165-171.
39. Sinha RA, Bruinstroop E, Singh BK, Yen PM. Nonalcoholic fatty liver disease and hypercholesterolemia: roles of thyroid hormones, metabolites, and agonists. Thyroid 2019;29:1173-1191.
40. Harrison SA, Bashir MR, Guy CD, Zhou R, Moylan CA, Frias JP, et al. Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 2019;394:2012-2024.
41. Harrison S, Taub R, Neff G, Moussa S, Alkhouri N, Bashir MJJoH. Primary data analyses of MAESTRO-NAFLD-1 a 52 week doubleblind placebo-controlled phase 3 clinical trial of resmetirom in patients with NAFLD. J Hepatol 2022;77:S14.
42. Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, et al. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science 1997;275:90-94.
45. Harrison SA, Wong VW, Okanoue T, Bzowej N, Vuppalanchi R, Younes Z, et al.; STELLAR-3 and STELLAR-4 Investigators. Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: Results from randomized phase III STELLAR trials. J Hepatol 2020;73:26-39.