Comprehensive molecular mechanisms and clinical therapy in nonalcoholic steatohepatitis: An overview and current perspectives
Tài liệu tham khảo
Jung, 2020, Circulating lipidomic alterations in obese and non-obese subjects with non-alcoholic fatty liver disease, Aliment Pharmacol Ther, 52, 1603, 10.1111/apt.16066
Younossi, 2019, Non-alcoholic fatty liver disease - a global public health perspective, J Hepatol, 70, 531, 10.1016/j.jhep.2018.10.033
Younossi, 2016, Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes, Hepatology, 64, 73, 10.1002/hep.28431
Rinella, 2015, Nonalcoholic fatty liver disease: a systematic review, JAMA, 313, 2263, 10.1001/jama.2015.5370
Povsic, 2019, A structured literature review of the epidemiology and disease burden of non-alcoholic steatohepatitis (NASH), Adv Ther, 36, 1574, 10.1007/s12325-019-00960-3
Allen, 2018, Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: a 20 year-community study, Hepatology, 67, 1726, 10.1002/hep.29546
Zhang, 2016, Effects of moderate and vigorous exercise on nonalcoholic fatty liver disease: a randomized clinical trial, JAMA Intern Med, 176, 1074, 10.1001/jamainternmed.2016.3202
Goldberg, 2017, Changes in the prevalence of hepatitis C virus infection, nonalcoholic steatohepatitis, and alcoholic liver disease among patients with cirrhosis or liver failure on the waitlist for liver transplantation, Gastroenterology, 152
Zhou, 2019, Unexpected rapid increase in the burden of NAFLD in China from 2008 to 2018: a systematic review and meta-analysis, Hepatology, 70, 1119, 10.1002/hep.30702
Ratziu, 2015, Current efforts and trends in the treatment of NASH, J Hepatol, 62, S65, 10.1016/j.jhep.2015.02.041
Romero, 2020, The race to bash NASH: emerging targets and drug development in a complex liver disease, J Med Chem, 63, 5031, 10.1021/acs.jmedchem.9b01701
Khan, 2019, Modulation of insulin resistance in nonalcoholic fatty liver disease, Hepatology, 70, 711, 10.1002/hep.30429
Ioannou, 2016, The role of cholesterol in the pathogenesis of NASH, Trends Endocrinol Metab, 27, 84, 10.1016/j.tem.2015.11.008
Schuppan, 2018, Determinants of fibrosis progression and regression in NASH, J Hepatol, 68, 238, 10.1016/j.jhep.2017.11.012
Cai, 2019, The role of innate immune cells in nonalcoholic steatohepatitis, Hepatology, 70, 1026, 10.1002/hep.30506
Schuster, 2018, Triggering and resolution of inflammation in NASH, Nat Rev Gastroenterol Hepatol, 15, 349, 10.1038/s41575-018-0009-6
Hirsova, 2020, Hepatocyte apoptosis is tumor promoting in murine nonalcoholic steatohepatitis, Cell Death Dis, 11, 80, 10.1038/s41419-020-2283-9
Younossi, 2019, Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial, Lancet, 394, 2184, 10.1016/S0140-6736(19)33041-7
Harrison, 2018, Simtuzumab is ineffective for patients with bridging fibrosis or compensated cirrhosis caused by nonalcoholic steatohepatitis, Gastroenterology, 155, 1140, 10.1053/j.gastro.2018.07.006
Loomba, 2021, Combination therapies including cilofexor and firsocostat for bridging fibrosis and cirrhosis attributable to NASH, Hepatology, 73, 625, 10.1002/hep.31622
Cicero, 2018, Nutraceutical approach to non-alcoholic fatty liver disease (NAFLD): the available clinical evidence, Nutrients, 10, 1153, 10.3390/nu10091153
Borrelli, 2018, Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver disease to hepatocarcinoma: current and innovative therapeutic approaches, Redox Biol, 15, 467, 10.1016/j.redox.2018.01.009
Bessone, 2019, Molecular pathways of nonalcoholic fatty liver disease development and progression, Cell Mol Life Sci, 76, 99, 10.1007/s00018-018-2947-0
Chalasani, 2018, The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases, Hepatology, 67, 328, 10.1002/hep.29367
Schmitz, 2020, Evaluation of NAFLD and fibrosis in obese patients - a comparison of histological and clinical scoring systems, BMC Gastroenterol, 20, 254, 10.1186/s12876-020-01400-1
Vilar-Gomez, 2018, Non-invasive assessment of non-alcoholic fatty liver disease: clinical prediction rules and blood-based biomarkers, J Hepatol, 68, 305, 10.1016/j.jhep.2017.11.013
Abdelmalek, 2021, Nonalcoholic fatty liver disease: another leap forward, Nat Rev Gastroenterol Hepatol, 18, 85, 10.1038/s41575-020-00406-0
Horn, 2022, Role of cholesterol-associated steatohepatitis in the development of NASH, Hepatol Commun, 6, 12, 10.1002/hep4.1801
Scorletti, 2022, A new perspective on NAFLD: focusing on lipid droplets, J Hepatol, 76, 934, 10.1016/j.jhep.2021.11.009
Liebold, 2021, Apoptotic cell signals and heterogeneity in macrophage function: fine-tuning for a healthy liver, Semin Cell Dev Biol, 119, 72, 10.1016/j.semcdb.2021.06.012
Cariou, 2021, Nonalcoholic fatty liver disease as a metabolic disease in humans: a literature review, Diabetes Obes Metab, 23, 1069, 10.1111/dom.14322
Galicia-Garcia, 2020, Pathophysiology of type 2 diabetes mellitus, Int J Mol Sci, 21, 6275, 10.3390/ijms21176275
Finck, 2018, Targeting metabolism, insulin resistance, and diabetes to treat nonalcoholic steatohepatitis, Diabetes, 67, 2485, 10.2337/dbi18-0024
Loomba, 2009, Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis, Aliment Pharmacol Ther, 29, 172, 10.1111/j.1365-2036.2008.03869.x
Harrison, 2020, Insulin sensitizer MSDC-0602K in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase IIb study, J Hepatol, 72, 613, 10.1016/j.jhep.2019.10.023
Kuhre, 2016, The regulation of function, growth and survival of GLP-1-producing L-cells, Clin Sci (Lond), 130, 79, 10.1042/CS20150154
Sumida, 2020, Antidiabetic therapy in the treatment of nonalcoholic steatohepatitis, Int J Mol Sci, 21, 1907, 10.3390/ijms21061907
Armstrong, 2016, Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis, J Hepatol, 64, 399, 10.1016/j.jhep.2015.08.038
Cegla, 2016, Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomized, placebo-controlled phase 2 study, Ann Clin Biochem, 53, 518, 10.1177/0004563216648250
O'Neil, 2018, Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial, Lancet, 392, 637, 10.1016/S0140-6736(18)31773-2
Newsome, 2021, A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis, N Engl J Med, 384, 1113, 10.1056/NEJMoa2028395
Harrison, 2020, Semaglutide for the treatment of non-alcoholic steatohepatitis: trial design and comparison of non-invasive biomarkers, Contemp Clin Trials, 97, 10.1016/j.cct.2020.106174
Chao, 2019, Homeostasis of glucose and lipid in non-alcoholic fatty liver disease, Int J Mol Sci, 20, 298, 10.3390/ijms20020298
Mirarchi, 2022, SGLT2 inhibitors as the Most promising influencers on the outcome of non-alcoholic fatty liver disease, Int J Mol Sci, 23, 3668, 10.3390/ijms23073668
Gutierrez, 2021, Pharmacologic inhibition of ketohexokinase prevents fructose-induced metabolic dysfunction, Mol Metab, 48, 10.1016/j.molmet.2021.101196
Futatsugi, 2020, Discovery of PF-06835919: a potent inhibitor of ketohexokinase (KHK) for the treatment of metabolic disorders driven by the overconsumption of fructose, J Med Chem, 63, 13546, 10.1021/acs.jmedchem.0c00944
Ishimoto, 2012, Opposing effects of fructokinase C and a isoforms on fructose-induced metabolic syndrome in mice, Proc Natl Acad Sci U S A, 109, 4320, 10.1073/pnas.1119908109
Attia, 2021, Evolving role for pharmacotherapy in NAFLD/NASH, Clin Transl Sci, 14, 11, 10.1111/cts.12839
Ross, 2020, Acetyl-CoA carboxylase inhibition improves multiple dimensions of NASH pathogenesis in model systems, Cell Mol Gastroenterol Hepatol, 10, 829, 10.1016/j.jcmgh.2020.06.001
Cho, 2010, Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK, Biochem Biophys Res Commun, 391, 187, 10.1016/j.bbrc.2009.11.029
Lawitz, 2018, Acetyl-CoA carboxylase inhibitor GS-0976 for 12 weeks reduces hepatic De novo lipogenesis and steatosis in patients with nonalcoholic steatohepatitis, Clin Gastroenterol Hepatol, 16
Loomba, 2018, GS-0976 reduces hepatic steatosis and fibrosis markers in patients with nonalcoholic fatty liver disease, Gastroenterology, 155
Alkhouri, 2020, GS-0976 (Firsocostat): an investigational liver-directed acetyl-CoA carboxylase (ACC) inhibitor for the treatment of non-alcoholic steatohepatitis (NASH), Expert Opin Investig Drugs, 29, 135, 10.1080/13543784.2020.1668374
Calle, 2021, 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, 27, 1836, 10.1038/s41591-021-01489-1
Jones, 2015, Molecular pathways: fatty acid synthase, Clin Cancer Res, 21, 5434, 10.1158/1078-0432.CCR-15-0126
Loomba, 2021, TVB-2640 (FASN Inhibitor) for the treatment of nonalcoholic steatohepatitis: FASCINATE-1, a randomized, placebo-controlled phase 2a trial, Gastroenterology, 161, 1475, 10.1053/j.gastro.2021.07.025
Al, 2017, Insights into stearoyl-CoA Desaturase-1 regulation of systemic metabolism, Trends Endocrinol Metab, 28, 831, 10.1016/j.tem.2017.10.003
Yamada, 2015, Characteristics of hepatic fatty acid compositions in patients with nonalcoholic steatohepatitis, Liver Int, 35, 582, 10.1111/liv.12685
Ratziu, 2021, Aramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial, Nat Med, 27, 1825, 10.1038/s41591-021-01495-3
Alves-Bezerra, 2017, Triglyceride metabolism in the liver, Compr Physiol, 8, 1
Devasthale, 2018, Monoacylglycerol acyltransferase 2 (MGAT2) inhibitors for the treatment of metabolic diseases and nonalcoholic steatohepatitis (NASH), J Med Chem, 61, 9879, 10.1021/acs.jmedchem.8b00864
Amin, 2019, Targeting diacylglycerol acyltransferase 2 for the treatment of nonalcoholic steatohepatitis, Sci Transl Med, 11, 10.1126/scitranslmed.aav9701
Pawlak, 2015, Molecular mechanism of PPARalpha action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease, J Hepatol, 62, 720, 10.1016/j.jhep.2014.10.039
Huang, 2022, Emerging evidence of pathological roles of very-low-density lipoprotein (VLDL), Int J Mol Sci, 23
Harrison, 2021, Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a trial, Nat Med, 27, 1262, 10.1038/s41591-021-01425-3
Verzijl, 2020, Pegbelfermin (BMS-986036): an investigational PEGylated fibroblast growth factor 21 analogue for the treatment of nonalcoholic steatohepatitis, Expert Opin Investig Drugs, 29, 125, 10.1080/13543784.2020.1708898
Sanyal, 2019, Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial, Lancet, 392, 2705, 10.1016/S0140-6736(18)31785-9
Boeckmans, 2019, Anti-NASH drug development hitches a lift on PPAR agonism, Cells, 9, 37, 10.3390/cells9010037
Nakajima, 2021, Randomised clinical trial: pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator (SPPARMalpha), versus placebo in patients with non-alcoholic fatty liver disease, Aliment Pharmacol Ther, 54, 1263, 10.1111/apt.16596
Jones, 2017, Seladelpar (MBX-8025), a selective PPAR-delta agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study, Lancet Gastroenterol Hepatol, 2, 716, 10.1016/S2468-1253(17)30246-7
Belfort, 2006, A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis, N Engl J Med, 355, 2297, 10.1056/NEJMoa060326
Bril, 2018, Response to pioglitazone in patients with nonalcoholic steatohepatitis with vs without type 2 diabetes, Clin Gastroenterol Hepatol, 16
Cusi, 2016, Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial, Ann Intern Med, 165, 305, 10.7326/M15-1774
Ratziu, 2010, Long-term efficacy of rosiglitazone in nonalcoholic steatohepatitis: results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial, Hepatology, 51, 445, 10.1002/hep.23270
Ratziu, 2016, Elafibranor, an agonist of the peroxisome proliferator-activated receptor-alpha and -delta, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening, Gastroenterology, 150
Francque, 2021, A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH, N Engl J Med, 385, 1547, 10.1056/NEJMoa2036205
Schumacher, 2021, Posttranslational regulation of HMG CoA reductase, the rate-limiting enzyme in synthesis of cholesterol, Annu Rev Biochem, 90, 659, 10.1146/annurev-biochem-081820-101010
Mullur, 2014, Thyroid hormone regulation of metabolism, Physiol Rev, 94, 355, 10.1152/physrev.00030.2013
Harrison, 2019, Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, Lancet, 394, 2012, 10.1016/S0140-6736(19)32517-6
Hu, 2021, Structural insights into the mechanism of human NPC1L1-mediated cholesterol uptake, Sci Adv, 7, 10.1126/sciadv.abg3188
Zhang, 2022, Niemann-pick C1-like 1 inhibitors for reducing cholesterol absorption, Eur J Med Chem, 230, 10.1016/j.ejmech.2022.114111
Lin, 2016, Cardiovascular risk assessment in the treatment of nonalcoholic steatohepatitis: a secondary analysis of the MOZART trial, Therap Adv Gastroenterol, 9, 152, 10.1177/1756283X15621232
Chow, 2017, The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, Mol Aspects Med, 56, 34, 10.1016/j.mam.2017.04.004
Chambers, 2019, Polyphenol effects on cholesterol metabolism via bile acid biosynthesis, CYP7A1: a review, Nutrients, 11, 2588, 10.3390/nu11112588
Winston, 2020, Diversification of host bile acids by members of the gut microbiota, Gut Microbes, 11, 158, 10.1080/19490976.2019.1674124
Arab, 2017, Bile acids and nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives, Hepatology, 65, 350, 10.1002/hep.28709
Sciarrillo, 2021, Fibroblast growth factor 19: potential modulation of hepatic metabolism for the treatment of non-alcoholic fatty liver disease, Liver Int, 41, 894, 10.1111/liv.14802
Fiorucci, 2020, Bile acid modulators for the treatment of nonalcoholic steatohepatitis (NASH), Expert Opin Investig Drugs, 29, 623, 10.1080/13543784.2020.1763302
Huang, 2021, A new mechanism of obeticholic acid on NASH treatment by inhibiting NLRP3 inflammasome activation in macrophage, Metabolism, 120, 10.1016/j.metabol.2021.154797
Neuschwander-Tetri, 2015, Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial, Lancet, 385, 956, 10.1016/S0140-6736(14)61933-4
Ratziu, 2022, EDP-305 in patients with NASH: a phase II double-blind placebo-controlled dose-ranging study, J Hepatol, 76, 506, 10.1016/j.jhep.2021.10.018
Patel, 2020, Cilofexor, a nonsteroidal FXR agonist, in patients with noncirrhotic NASH: a phase 2 randomized controlled trial, Hepatology, 72, 58, 10.1002/hep.31205
Talukdar, 2021, FGF19 and FGF21: in NASH we trust, Mol Metab, 46, 10.1016/j.molmet.2020.101152
Harrison, 2018, NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, Lancet, 391, 1174, 10.1016/S0140-6736(18)30474-4
Harrison, 2022, Aldafermin in patients with non-alcoholic steatohepatitis (ALPINE 2/3): a randomised, double-blind, placebo-controlled, phase 2b trial, Lancet Gastroenterol Hepatol, 7, 603, 10.1016/S2468-1253(22)00017-6
Fiorucci, 2015, Bile acid-activated receptors, intestinal microbiota, and the treatment of metabolic disorders, Trends Mol Med, 21, 702, 10.1016/j.molmed.2015.09.001
Al-Dury, 2018, Ileal bile acid transporter inhibition for the treatment of chronic constipation, cholestatic pruritus, and NASH, Front Pharmacol, 9, 931, 10.3389/fphar.2018.00931
Newsome, 2020, Volixibat in adults with non-alcoholic steatohepatitis: 24-week interim analysis from a randomized, phase II study, J Hepatol, 73, 231, 10.1016/j.jhep.2020.03.024
Hirsova, 2015, Death receptor-mediated cell death and proinflammatory signaling in nonalcoholic steatohepatitis, Cell Mol Gastroenterol Hepatol, 1, 17, 10.1016/j.jcmgh.2014.11.005
Tamimi, 2011, An apoptosis panel for nonalcoholic steatohepatitis diagnosis, J Hepatol, 54, 1224, 10.1016/j.jhep.2010.08.023
Brenner, 2013, Decoding cell death signals in liver inflammation, J Hepatol, 59, 583, 10.1016/j.jhep.2013.03.033
Loomba, 2018, The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: a randomized, phase 2 trial, Hepatology, 67, 549, 10.1002/hep.29514
Harrison, 2020, Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: results from randomized phase III STELLAR trials, J Hepatol, 73, 26, 10.1016/j.jhep.2020.02.027
Vilar-Gomez, 2018, Fibrosis severity as a determinant of cause-specific mortality in patients with advanced nonalcoholic fatty liver disease: a multi-National Cohort Study, Gastroenterology, 155
Tacke, 2021, Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH)-related liver fibrosis: mechanisms, treatment and prevention, Ann Transl Med, 9, 729, 10.21037/atm-20-4354
Ratziu, 2020, Cenicriviroc treatment for adults with nonalcoholic steatohepatitis and fibrosis: final analysis of the phase 2b CENTAUR study, Hepatology, 72, 892, 10.1002/hep.31108
Friedman, 2018, A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis, Hepatology, 67, 1754, 10.1002/hep.29477
Lefebvre, 2016, Pharmacokinetics, safety, and CCR2/CCR5 antagonist activity of cenicriviroc in participants with mild or moderate hepatic impairment, Clin Transl Sci, 9, 139, 10.1111/cts.12397
Anstee, 2020, Cenicriviroc for the treatment of liver fibrosis in adults with nonalcoholic steatohepatitis: AURORA phase 3 study design, Contemp Clin Trials, 89, 10.1016/j.cct.2019.105922
Ikenaga, 2017, Selective targeting of lysyl oxidase-like 2 (LOXL2) suppresses hepatic fibrosis progression and accelerates its reversal, Gut, 66, 1697, 10.1136/gutjnl-2016-312473
Harrison, 2018, Utility and variability of three non-invasive liver fibrosis imaging modalities to evaluate efficacy of GR-MD-02 in subjects with NASH and bridging fibrosis during a phase-2 randomized clinical trial, PLoS One, 13, 10.1371/journal.pone.0203054
Chalasani, 2020, Effects of belapectin, an inhibitor of Galectin-3, in patients with nonalcoholic steatohepatitis with cirrhosis and portal hypertension, Gastroenterology, 158
Pizarro, 2015, Beneficial effects of mineralocorticoid receptor blockade in experimental non-alcoholic steatohepatitis, Liver Int, 35, 2129, 10.1111/liv.12794
Takai, 2020, Chymase as a possible therapeutic target for amelioration of non-alcoholic steatohepatitis, Int J Mol Sci, 21, 7543, 10.3390/ijms21207543
Okanoue, 2021, Efficacy and safety of apararenone (MT-3995) in patients with nonalcoholic steatohepatitis: a randomized controlled study, Hepatol Res, 51, 943, 10.1111/hepr.13695
Moreno, 2010, Reduction of advanced liver fibrosis by short-term targeted delivery of an angiotensin receptor blocker to hepatic stellate cells in rats, Hepatology, 51, 942
McPherson, 2017, A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis, PLoS One., 12, 10.1371/journal.pone.0175717
Nati, 2016, The role of immune cells in metabolism-related liver inflammation and development of non-alcoholic steatohepatitis (NASH), Rev Endocr Metab Disord, 17, 29, 10.1007/s11154-016-9339-2
Luci, 2020, Chronic inflammation in non-alcoholic steatohepatitis: molecular mechanisms and therapeutic strategies, Front Endocrinol (Lausanne)., 11, 10.3389/fendo.2020.597648
Kolodziejczyk, 2019, The role of the microbiome in NAFLD and NASH, EMBO Mol Med, 11, 10.15252/emmm.201809302
Mouries, 2019, Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development, J Hepatol, 71, 1216, 10.1016/j.jhep.2019.08.005
Park, 2021, Role of microbiota-derived metabolites in alcoholic and non-alcoholic fatty liver diseases, Int J Mol Sci, 23, 426, 10.3390/ijms23010426
Buzzetti, 2016, The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD), Metabolism, 65, 1038, 10.1016/j.metabol.2015.12.012
Ibrahim, 2018, Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a driver of liver inflammation, Gut, 67, 963, 10.1136/gutjnl-2017-315691
Bomhof, 2019, Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial, Eur J Nutr, 58, 1735, 10.1007/s00394-018-1721-2
Sumida, 2018, Current and future pharmacological therapies for NAFLD/NASH, J Gastroenterol, 53, 362, 10.1007/s00535-017-1415-1
Torok, 2015, Vascular adhesion protein 1 in nonalcoholic steatohepatitis: a novel biomarker?, Hepatology, 62, 1313, 10.1002/hep.27942
Li, 2020, C-mpl and TPO expression in the human central nervous system neurons inhibits neuronal apoptosis, Aging (Albany NY)., 12, 7397, 10.18632/aging.103086
Lee, 2014, The emerging landscape of RORgammat biology, Immunity, 40, 451, 10.1016/j.immuni.2014.04.005
Violi, 2010, Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis, N Engl J Med, 363, 1185, 10.1056/NEJMc1006581
Bril, 2019, Role of vitamin E for nonalcoholic steatohepatitis in patients with type 2 diabetes: a randomized controlled trial, Diabetes Care, 42, 1481, 10.2337/dc19-0167
Argo, 2015, Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial, J Hepatol, 62, 190, 10.1016/j.jhep.2014.08.036
Younossi, 2021, Hepatic fat reduction due to resmetirom in patients with nonalcoholic steatohepatitis is associated with improvement of quality of life, Clin Gastroenterol Hepatol, 20, 1354, 10.1016/j.cgh.2021.07.039
Younossi, 2021, Obeticholic acid impact on quality of life in patients with nonalcoholic steatohepatitis: regenerate 18-month interim analysis, Clin Gastroenterol Hepatol, 19, 00751
Wang, 2021, Safety, pharmacokinetics, pharmacodynamics, and formulation of liver-distributed farnesoid X-receptor agonist TERN-101 in healthy volunteers, Clin Pharmacol Drug Dev, 10, 1198, 10.1002/cpdd.960
Harrison, 2021, Efficacy and safety of aldafermin, an engineered FGF19 analog, in a randomized, double-blind, placebo-controlled trial of patients with nonalcoholic steatohepatitis, Gastroenterology, 160
Siebers, 2018, Absorption, distribution, metabolism, and excretion of [(14)C]-volixibat in healthy men: phase 1 open-label study, Eur J Drug Metab Pharmacokinet, 43, 91, 10.1007/s13318-017-0429-7
Harrison, 2020, A randomized, placebo-controlled trial of emricasan in patients with NASH and F1–F3 fibrosis, J Hepatol, 72, 816, 10.1016/j.jhep.2019.11.024
Garcia-Tsao, 2020, Randomized placebo-controlled trial of emricasan for non-alcoholic steatohepatitis-related cirrhosis with severe portal hypertension, J Hepatol, 72, 885, 10.1016/j.jhep.2019.12.010
Sebastiani, 2020, Vitamin E is an effective treatment for nonalcoholic steatohepatitis in HIV mono-infected patients, AIDS, 34, 237, 10.1097/QAD.0000000000002412
Kitson, 2016, High-dose vitamin D supplementation and liver histology in NASH, Gut, 65, 717, 10.1136/gutjnl-2015-310417
Ebrahimpour-Koujan, 2019, Effects of vitamin D supplementation on liver fibrogenic factors in non-alcoholic fatty liver patients with steatohepatitis: study protocol for a randomized clinical trial, Trials, 20, 153, 10.1186/s13063-019-3241-7
Zein, 2011, Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial, Hepatology, 54, 1610, 10.1002/hep.24544
Van Wagner, 2011, Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial, Ann Hepatol, 10, 277, 10.1016/S1665-2681(19)31539-X
Afdhal, 2012, Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia, N Engl J Med, 367, 716, 10.1056/NEJMoa1110709
Dufour, 2020, Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges, Gut, 69, 1877, 10.1136/gutjnl-2019-319104
Alkhouri, 2022, Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial, J Hepatol, 10.1016/j.jhep.2022.04.003
Pockros, 2019, CONTROL: a randomized phase 2 study of obeticholic acid and atorvastatin on lipoproteins in nonalcoholic steatohepatitis patients, Liver Int, 39, 2082, 10.1111/liv.14209
Culafic, 2020, Pentoxifylline with metformin treatment improves biochemical parameters in patients with nonalcoholic steatohepatitis, J Med Biochem., 39, 290
Oliveira, 2019, N-acetylcysteine and/or ursodeoxycholic acid associated with metformin in non-alcoholic steatohepatitis: an open-label multicenter randomized controlled trial, Arq Gastroenterol, 56, 184, 10.1590/s0004-2803.201900000-36
Zohrer, 2017, Efficacy of docosahexaenoic acid-choline-vitamin E in paediatric NASH: a randomized controlled clinical trial, Appl Physiol Nutr Metab, 42, 948, 10.1139/apnm-2016-0689
Lawitz, 2022, Fenofibrate mitigates hypertriglyceridemia in nonalcoholic steatohepatitis patients treated with cilofexor/firsocostat, Clin Gastroenterol Hepatol
Dehnad, 2020, AGER1 downregulation associates with fibrosis in nonalcoholic steatohepatitis and type 2 diabetes, J Clin Invest, 130, 4320
Liu, 2021, Squalene epoxidase induces nonalcoholic steatohepatitis via binding to carbonic anhydrase III and is a therapeutic target, Gastroenterology, 160
Fondevila, 2021, The L-alpha-Lysophosphatidylinositol/G protein-coupled receptor 55 system induces the development of nonalcoholic steatosis and steatohepatitis, Hepatology, 73, 606, 10.1002/hep.31290
