{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:48:37Z","timestamp":1778600917375,"version":"3.51.4"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the effects of vitamin E, pioglitazone, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with non-alcoholic fatty liver disease (NAFLD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>A network meta-analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Data Sources<\/jats:title><jats:p>PubMed, Embase, Cochrane Library, and Web of Science databases from their inception until September 1, 2021.<\/jats:p><\/jats:sec><jats:sec><jats:title>Eligibility Criteria for Selecting Studies<\/jats:title><jats:p>Randomized controlled trials (RCTs) comparing the effects of four different drugs in patients with NAFLD were included. All superiority, non-inferiority, phase II and III, non-blinded, single-blinded, and double-blinded trials were included. Interventions of interest included vitamin E (\u03b1-tocopherol and \u03b4-tocotrienol), pioglitazone, three kinds of GLP-1 receptor agonists (liraglutide, semaglutide, and dulaglutide), four SGLT2 inhibitors (dapagliflozin, empagliflozin, ipragliflozin, and tofogliflozin), and comparisons of these different drugs, and placebos.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measures<\/jats:title><jats:p>The outcome measures included changes in non-invasive tests [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), controlled attenuation parameter (CAP), enhanced liver fibrosis (ELF) score, liver fat content (LFC), and keratin-18 (K-18)] and invasive tests [fibrosis score and resolution of non-alcoholic steatohepatitis (NASH)].<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty-seven trials including 3,416 patients were eligible for inclusion in the study. Results refer to vitamin E, pioglitazone, GLP-1 receptor agonists, and SGLT2 inhibitors. First, placebos were used as a reference. \u03b4-Tocotrienol was superior to placebo in decreasing the GGT level. Semaglutide, ipragliflozin, and pioglitazone induced a significantly higher decrease in the ALT level than a placebo. Semaglutide, pioglitazone, and dapagliflozin were superior to placebo in decreasing the AST level. Tofogliflozin and pioglitazone induced a significantly higher decrease in the K-18 level than a placebo. Liraglutide was superior to placebo in decreasing CAP. Liraglutide, pioglitazone, and vitamin E induced a significantly higher increase in resolution of NASH than a placebo. As for pairwise comparisons, semaglutide and pioglitazone were superior to liraglutide in decreasing the ALT level. Semaglutide induced a significantly higher decrease in the ALT level than dulaglutide. Semaglutide was obviously superior to empagliflozin, liraglutide, dulaglutide, and tofogliflozin in decreasing the AST level. Pioglitazone induced a significantly higher decrease in the GGT level than ipragliflozin. \u03b4-Tocotrienol was superior to liraglutide in decreasing the GGT level. Tofogliflozin and pioglitazone induced a significantly higher decrease in the K-18 level than dulaglutide. Pioglitazone was superior to vitamin E in increasing the resolution of NASH. Furthermore, liraglutide treatment had the highest SUCRA ranking in decreasing CAP and ELF scores and increasing the resolution of NASH. Pioglitazone treatment had the highest SUCRA ranking in decreasing LFC and fibrosis scores. Tofogliflozin treatment had the highest SUCRA ranking in decreasing K-18, while dapagliflozin treatment had the highest SUCRA ranking in decreasing the GGT level. Semaglutide treatment had the highest SUCRA ranking in decreasing the levels of ALT and AST.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The network meta-analysis provided evidence for the efficacy of vitamin E, pioglitazone, SGLT2 inhibitors, and GLP-1 receptor agonists in treating patients with NAFLD. To find the best guide-level drugs, it is necessary to include more RCTs with these off-label drugs, so that patients and clinicians can make optimal decisions together.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic Review Registration<\/jats:title><jats:p><jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero<\/jats:ext-link>, identifier: CRD42021283129.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2022.793203","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T09:58:24Z","timestamp":1645783104000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Efficacy of Off-Label Therapy for Non-alcoholic Fatty Liver Disease in Improving Non-invasive and Invasive Biomarkers: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.3389","volume":"9","author":[{"given":"Qian","family":"Luo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruojun","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzi","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qihan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuning","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei Jing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1016\/j.jhep.2015.11.004","article-title":"EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease","volume":"64","year":"2016","journal-title":"J Hepatol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/nrneph.2016.170","article-title":"Renal, metabolic and cardiovascular considerations of SGLT2 inhibition","volume":"13","author":"DeFronzo","year":"2017","journal-title":"Nat Rev Nephrol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.metabol.2018.11.014","article-title":"Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics","volume":"92","author":"Polyzos","year":"2019","journal-title":"Metabolism."},{"key":"B4","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.jhep.2019.06.021","article-title":"The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis","volume":"71","author":"Younossi","year":"2019","journal-title":"J Hepatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/nrgastro.2013.197","article-title":"NAFLD-the next global epidemic","volume":"10","author":"Ray","year":"2013","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1001\/jama.2015.5370","article-title":"Nonalcoholic fatty liver disease: a systematic review","volume":"313","author":"Rinella","year":"2015","journal-title":"JAMA."},{"key":"B7","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1111\/apt.12352","article-title":"Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis","volume":"38","author":"Hoofnagle","year":"2013","journal-title":"Aliment Pharmacol Ther."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1002\/hep.30782","article-title":"Report on the AASLD\/EASL Joint Workshop on Clinical Trial Endpoints in NAFLD","volume":"70","author":"Rinella","year":"2019","journal-title":"Hepatology."},{"key":"B9","doi-asserted-by":"publisher","first-page":"8936865","DOI":"10.1155\/2021\/8936865","article-title":"GLP-1 Receptor agonist effects on lipid and liver profiles in patients with nonalcoholic fatty liver disease: systematic review and meta-analysis","volume":"2021","author":"Rezaei","year":"2021","journal-title":"Can J Gastroenterol Hepatol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1111\/jdi.13237","article-title":"Effects of sodium-glucose cotransporter 2 inhibitors on non-alcoholic fatty liver disease in patients with type 2 diabetes: A meta-analysis of randomized controlled trials","volume":"11","author":"Xing","year":"2020","journal-title":"J Diabetes Investig."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-alcoholic fatty liver disease","volume":"397","author":"Powell","year":"2021","journal-title":"Lancet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"615409","DOI":"10.3389\/fendo.2021.615409","article-title":"Pioglitazone for NAFLD patients with prediabetes or type 2 diabetes mellitus: a meta-analysis","volume":"12","author":"Lian","year":"2021","journal-title":"Front Endocrinol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/jgh.15221","article-title":"Systematic review with meta-analysis: the effect of vitamin E supplementation in adult patients with non-alcoholic fatty liver disease","volume":"36","author":"Vadarlis","year":"2021","journal-title":"J Gastroenterol Hepatol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes","volume":"373","author":"Zinman","year":"2015","journal-title":"N Engl J Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1056\/NEJMoa1607141","article-title":"Semaglutide and cardiovascular outcomes in patients with type 2 diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N Engl J Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1056\/NEJMoa1603827","article-title":"Liraglutide and cardiovascular outcomes in type 2 diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N Engl J Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1056\/NEJMoa060326","article-title":"A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis","volume":"355","author":"Belfort","year":"2006","journal-title":"N Engl J Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.2337\/dc19-0167","article-title":"Role of vitamin e for nonalcoholic steatohepatitis in patients with type 2 diabetes: a randomized controlled trial","volume":"42","author":"Bril","year":"2019","journal-title":"Diabetes Care."},{"key":"B19","doi-asserted-by":"publisher","first-page":"278","DOI":"10.17179\/excli2016-846","article-title":"Effects of symbiotic and vitamin E supplementation on blood pressure, nitric oxide and inflammatory factors in non-alcoholic fatty liver disease","volume":"16","author":"Ekhlasi","year":"2017","journal-title":"EXCLI J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2659","DOI":"10.1111\/liv.15005","article-title":"PPAR-\u03b3-induced changes in visceral fat and adiponectin levels are associated with improvement of steatohepatitis in patients with NASH","volume":"41","author":"Gastaldelli","year":"2021","journal-title":"Liver Int."},{"key":"B21","doi-asserted-by":"publisher","first-page":"i4428","DOI":"10.1136\/bmj.i4428","article-title":"Non-alcoholic fatty liver disease (NAFLD): summary of NICE guidance","volume":"354","author":"Glen","year":"2016","journal-title":"BMJ."},{"key":"B22","doi-asserted-by":"publisher","first-page":"105020","DOI":"10.1016\/j.phrs.2020.105020","article-title":"Efficacy and safety of HIF prolyl-hydroxylase inhibitor vs epoetin and darbepoetin for anemia in chronic kidney disease patients not undergoing dialysis: a network meta-analysis","volume":"159","author":"Zheng","year":"2020","journal-title":"Pharmacol Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1002\/hep4.1680","article-title":"Relationship of ELF and PIIINP with liver histology and response to vitamin e or pioglitazone in the PIVENS trial","volume":"5","author":"Gawrieh","year":"2021","journal-title":"Hepatol Commun."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.21203\/rs.3.rs-596467\/v1","article-title":"First-in-Asian double-blind randomized trial to assess the efficacy and safety of insulin sensitizer in nonalcoholic steatohepatitis patients","volume":"15","author":"Huang","year":"2021","journal-title":"Hepatol Int."},{"key":"B25","doi-asserted-by":"publisher","first-page":"102494","DOI":"10.1016\/j.ctim.2020.102494","article-title":"Delta-tocotrienol supplementation improves biochemical markers of hepatocellular injury and steatosis in patients with nonalcoholic fatty liver disease: a randomized, placebo-controlled trial","volume":"52","author":"Pervez","year":"2020","journal-title":"Complement Ther Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1053\/j.gastro.2008.06.047","article-title":"Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis","volume":"135","author":"Aithal","year":"2008","journal-title":"Gastroenterology."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3213","DOI":"10.3390\/jcm9103213","article-title":"One year's treatment with the glucagon-like peptide 1 receptor agonist liraglutide decreases hepatic fat content in women with nonalcoholic fatty liver disease and prior gestational diabetes mellitus in a randomized, placebo-controlled trial","volume":"9","author":"Vedtofte","year":"2020","journal-title":"J Clin Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1111\/jdi.13457","article-title":"Favorable effect of sodium-glucose cotransporter 2 inhibitor, dapagliflozin, on non-alcoholic fatty liver disease compared with pioglitazone","volume":"12","author":"Cho","year":"2021","journal-title":"J Diabetes Investig."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1056\/NEJMoa0907929","article-title":"Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis","volume":"362","author":"Sanyal","year":"2010","journal-title":"N Engl J Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1056\/NEJMoa2028395","article-title":"A Placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis","volume":"384","author":"Newsome","year":"2021","journal-title":"N Engl J Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1007\/s00125-018-4675-2","article-title":"Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study","volume":"61","author":"Eriksson","year":"2018","journal-title":"Diabetologia."},{"key":"B32","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1007\/s13300-021-01011-3","article-title":"Empagliflozin improves liver steatosis and fibrosis in patients with non-alcoholic fatty liver disease and type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial","volume":"12","author":"Chehrehgosha","year":"2021","journal-title":"Diabetes Ther."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.2337\/dc17-0518","article-title":"Comparison of ipragliflozin and pioglitazone effects on nonalcoholic fatty liver disease in patients with type 2 diabetes: a randomized, 24-week, open-label, active-controlled trial","volume":"40","author":"Ito","year":"2017","journal-title":"Diabetes Care."},{"key":"B34","doi-asserted-by":"publisher","first-page":"298","DOI":"10.2337\/dc19-0641","article-title":"Empagliflozin effectively lowers liver fat content in well-controlled type 2 diabetes: a randomized, double-blind, phase 4, placebo-controlled trial","volume":"43","author":"Kahl","year":"2020","journal-title":"Diabetes Care."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.2337\/dc19-1892","article-title":"Effects of novel dual GIP and GLP-1 receptor agonist tirzepatide on biomarkers of nonalcoholic steatohepatitis in patients with type 2 diabetes","volume":"43","author":"Hartman","year":"2020","journal-title":"Diabetes Care."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1111\/jdi.13279","article-title":"Comparison of the effects of three kinds of glucose-lowering drugs on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, open-label, three-arm, active control study","volume":"11","author":"Kinoshita","year":"2020","journal-title":"J Diabetes Investig."},{"key":"B37","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1111\/jgh.15131","article-title":"Use of metabolic syndrome severity to assess treatment with vitamin E and pioglitazone for non-alcoholic steatohepatitis","volume":"36","author":"Gurka","year":"2021","journal-title":"J Gastroenterol Hepatol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"305","DOI":"10.7326\/M15-1774","article-title":"Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial","volume":"165","author":"Cusi","year":"2016","journal-title":"Ann Intern Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2952","DOI":"10.1111\/jgh.15580","article-title":"The effects of dapagliflozin on hepatic and visceral fat in type 2 diabetes patients with non-alcoholic fatty liver disease","volume":"36","author":"Phrueksotsai","year":"2021","journal-title":"J Gastroenterol Hepatol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2588","DOI":"10.1007\/s00125-016-4100-7","article-title":"Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: a randomised placebo-controlled trial","volume":"59","author":"Smits","year":"2016","journal-title":"Diabetologia."},{"key":"B41","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s00125-019-05021-6","article-title":"Placebo-controlled randomised trial with liraglutide on magnetic resonance endpoints in individuals with type 2 diabetes: a pre-specified secondary study on ectopic fat accumulation","volume":"63","author":"Bizino","year":"2020","journal-title":"Diabetologia."},{"key":"B42","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/S0140-6736(15)00803-X","article-title":"Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study","volume":"387","author":"Armstrong","year":"2016","journal-title":"Lancet."},{"key":"B43","doi-asserted-by":"publisher","first-page":"4697","DOI":"10.1007\/s12325-020-01498-5","article-title":"Effect of empagliflozin on liver steatosis and fibrosis in patients with non-alcoholic fatty liver disease without diabetes: a randomized, double-blind, placebo-controlled trial","volume":"37","author":"Taheri","year":"2020","journal-title":"Adv Ther."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e001990","DOI":"10.1136\/bmjdrc-2020-001990","article-title":"Comparing the effects of tofogliflozin and pioglitazone in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus (ToPiND study): a randomized prospective open-label controlled trial","volume":"9","author":"Yoneda","year":"2021","journal-title":"BMJ Open Diabetes Res Care."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2762","DOI":"10.1007\/s11695-021-05412-y","article-title":"Gastric bypass compared with sleeve gastrectomy for nonalcoholic fatty liver disease: a systematic review and meta-analysis","volume":"31","author":"de Brito","year":"2021","journal-title":"Obes Surg."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e31394","DOI":"10.1371\/journal.pone.0031394","article-title":"Exendin-4 improves steatohepatitis by increasing Sirt1 expression in high-fat diet-induced obese C57BL\/6J mice","volume":"7","author":"Lee","year":"2012","journal-title":"PLoS ONE."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2318","DOI":"10.1002\/hep.30670","article-title":"Incretin-based therapies for the management of nonalcoholic fatty liver disease in patients with type 2 diabetes","volume":"69","author":"Cusi","year":"2019","journal-title":"Hepatology."},{"key":"B48","doi-asserted-by":"publisher","first-page":"609135","DOI":"10.3389\/fendo.2020.609135","article-title":"Sodium-glucose co-transporter 2 inhibitors for non-alcoholic fatty liver disease in asian patients with type 2 diabetes: a meta-analysis","volume":"11","author":"Wong","year":"2021","journal-title":"Front Endocrinol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1002\/hep.21006","article-title":"Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob\/ob mice","volume":"43","author":"Ding","year":"2006","journal-title":"Hepatology."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1016\/j.jhep.2010.09.032","article-title":"Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase","volume":"54","author":"Ben-Shlomo","year":"2011","journal-title":"J Hepatol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1002\/hep.23569","article-title":"Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway","volume":"51","author":"Gupta","year":"2010","journal-title":"Hepatology."},{"key":"B52","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1038\/nrgastro.2016.3","article-title":"Management of NAFLD: a stage-based approach","volume":"13","author":"Rinella","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1056\/NEJMc1412427","article-title":"Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease","volume":"371","author":"Shulman","year":"2014","journal-title":"N Engl J Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.nut.2012.07.003","article-title":"Obesity, systemic inflammation, and increased risk for cardiovascular disease and diabetes among adolescents: a need for screening tools to target interventions","volume":"29","author":"DeBoer","year":"2013","journal-title":"Nutrition."},{"key":"B55","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1136\/gut.2006.091967","article-title":"new silybin-vitamin E-phospholipid complex improves insulin resistance and liver damage in patients with non-alcoholic fatty liver disease: preliminary observations","volume":"55","author":"Federico","year":"2006","journal-title":"Gut."},{"key":"B56","doi-asserted-by":"publisher","first-page":"734847","DOI":"10.3389\/fmed.2021.734847","article-title":"PNPLA3, TM6SF2, and MBOAT7 influence on nutraceutical therapy response for non-alcoholic fatty liver disease: a randomized controlled trial","volume":"8","author":"Dallio","year":"2021","journal-title":"Front Med."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.793203\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T09:58:29Z","timestamp":1645783109000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.793203\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,25]]},"references-count":56,"alternative-id":["10.3389\/fmed.2022.793203"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.793203","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,25]]},"article-number":"793203"}}