{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:22:22Z","timestamp":1787772142104,"version":"build-2784847793"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common cause of chronic hepatitis in adult and pediatric patients. Adolescents with severe MASLD can demonstrate a more aggressive disease phenotype as they more commonly develop liver fibrosis than BMI matched adults. Therefore, MASLD is the fastest growing indication for liver transplants in young adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Pioglitazone has been shown to improve liver histology in adult patients with MASLD, and in some studies, it attenuated liver fibrosis. Despite its perceived efficacy, pioglitazone is not widely used, likely due to its side effect profile, specifically increased weight gain. Topiramate lowers body weight in adolescents and in combination with phentermine, is one of the few FDA-approved medications for the management of obesity in children over 12 years of age. We performed a retrospective review of the outcomes in pediatric patients with severe MASLD, treated with the combined pioglitazone and topiramate therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Here, we report a case series of seven adolescents with severe MASLD and \u2265F2 liver fibrosis treated with the combined pioglitazone and topiramate therapy. The combined therapy improved mean serum ALT from 165 \u00b1 80 U\/L to 89 \u00b1 62 U\/L after 12 months mean duration of treatment. One patient who completed 24 months of the combined therapy demonstrated a decrease in liver stiffness from 8.9 kPa to 5.6 kPa, as assessed by FibroScan elastography. There was a significant increase in body weight during this time, however, body mass index as a percentage of the 95\n                      <jats:sup>th<\/jats:sup>\n                      percentile adjusted for age and gender did not increase significantly, 151 \u00b1 29% vs. 152 \u00b1 28%. Moreover, waist circumference, mid-upper arm circumference, percent body fat, and muscle mass were not significantly different before and after treatment. Serum lipid levels and hemoglobin A1c also did not change with the treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>In summary, this case series provides encouraging results about the efficacy of the combined pioglitazone and topiramate therapy for the management of adolescents with severe MASLD, which should be further explored in clinical studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/sjg.sjg_428_23","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T07:00:46Z","timestamp":1715324446000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["The combined pioglitazone and topiramate therapy for management of pediatric patients with severe MASLD"],"prefix":"10.4103","author":[{"given":"Callen","family":"Conroy","sequence":"first","affiliation":[{"name":"University of Kentucky College of Medicine, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelia","family":"Radulescu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Kentucky College of Medicine and Kentucky Children\u2019s Hospital, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanna L.","family":"Attia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Gastroenterology, University of Kentucky College of Medicine and Kentucky Children\u2019s Hospital, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Shelman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T.","family":"Lee","sequence":"additional","affiliation":[{"name":"Abdominal and Emergency Radiology Divisions, Department of Radiology, University of Kentucky, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto Galuppo","family":"Monticelli","sequence":"additional","affiliation":[{"name":"Department of Radiology-Division of Vascular and Interventional Radiology, University of Kentucky, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Kentucky HealthCare, Lexington, KY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Kohli","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Children\u2019s Hospital Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Softic","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Gastroenterology, University of Kentucky College of Medicine and Kentucky Children\u2019s Hospital, Lexington, Kentucky, USA"},{"name":"Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"key":"R1-20240829","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"R2-20240829","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1002\/hep.27368","article-title":"Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up","volume":"61","author":"Ekstedt","year":"2015","journal-title":"Hepatology"},{"key":"R3-20240829","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1038\/s41395-018-0088-6","article-title":"NASH leading cause of liver transplant in women:Updated analysis of indications for liver transplant and ethnic and gender variances","volume":"113","author":"Noureddin","year":"2018","journal-title":"Am J Gastroenterol"},{"key":"R4-20240829","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.cld.2004.04.010","article-title":"Nonalcoholic fatty liver disease in the pediatric population","volume":"8","author":"Lavine","year":"2004","journal-title":"Clin Liver Dis"},{"key":"R5-20240829","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1136\/gut.2008.171280","article-title":"The natural history of non-alcoholic fatty liver disease in children:A follow-up study for up to 20 years","volume":"58","author":"Feldstein","year":"2009","journal-title":"Gut"},{"key":"R6-20240829","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/tri.12694","article-title":"Liver transplantation for nonalcoholic steatohepatitis in young patients","volume":"29","author":"Alkhouri","year":"2016","journal-title":"Transpl Int"},{"key":"R7-20240829","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1053\/j.gastro.2020.07.034","article-title":"Progression of fatty liver disease in children receiving standard of care lifestyle advice","volume":"159","author":"Xanthakos","year":"2020","journal-title":"Gastroenterology"},{"key":"R8-20240829","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/oby.20174","article-title":"Nonalcoholic fatty liver disease in severely obese adolescent and adult patients","volume":"21","author":"Holterman","year":"2013","journal-title":"Obesity (Silver Spring)"},{"key":"R9-20240829","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1097\/MPG.0b013e3181a9387b","article-title":"Rapid progression of NASH in childhood","volume":"50","author":"Kohli","year":"2010","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"R10-20240829","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1111\/j.1572-0241.2002.06003.x","article-title":"Obese children with steatohepatitis can develop cirrhosis in childhood","volume":"97","author":"Molleston","year":"2002","journal-title":"Am J Gastroenterol"},{"key":"R11-20240829","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1097\/MCG.0000000000000925","article-title":"Nonalcoholic steatohepatitis is the most rapidly increasing indication for liver transplantation in young adults in the United States","volume":"52","author":"Doycheva","year":"2018","journal-title":"J Clin Gastroenterol"},{"key":"R12-20240829","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1001\/jama.2011.520","article-title":"Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents:The TONIC randomized controlled trial","volume":"305","author":"Lavine","year":"2011","journal-title":"JAMA"},{"key":"R13-20240829","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1089\/ars.2018.7704","article-title":"The antioxidant effects of hydroxytyrosol and vitamin E on pediatric nonalcoholic fatty liver disease, in a clinical trial:A new treatment?","volume":"31","author":"Nobili","year":"2019","journal-title":"Antioxid Redox Signal"},{"key":"R14-20240829","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1139\/apnm-2016-0689","article-title":"Efficacy of docosahexaenoic acid-choline-vitamin E in paediatric NASH:A randomized controlled clinical trial","volume":"42","author":"Zohrer","year":"2017","journal-title":"Appl Physiol Nutr Metab"},{"key":"R15-20240829","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/hep.22336","article-title":"Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease:A randomized, controlled trial","volume":"48","author":"Nobili","year":"2008","journal-title":"Hepatology"},{"key":"R16-20240829","doi-asserted-by":"crossref","first-page":"e0168216","DOI":"10.1371\/journal.pone.0168216","article-title":"Docosahexanoic acid plus vitamin D treatment improves features of NAFLD in children with serum vitamin D deficiency:Results from a single centre trial","volume":"11","author":"Della Corte","year":"2016","journal-title":"PLoS One"},{"key":"R17-20240829","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s00431-021-04243-4","article-title":"Vitamin D and nonalcoholic fatty liver disease in children:A randomized controlled clinical trial","volume":"181","author":"El Amrousy","year":"2022","journal-title":"Eur J Pediatr"},{"key":"R18-20240829","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1053\/j.gastro.2016.08.027","article-title":"In children with nonalcoholic fatty liver disease, cysteamine bitartrate delayed release improves liver enzymes but does not reduce disease activity scores","volume":"151","author":"Schwimmer","year":"2016","journal-title":"Gastroenterology"},{"key":"R19-20240829","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/hep.32403","article-title":"Randomized placebo-controlled trial of losartan for pediatric nonalcoholic fatty liver disease","volume":"76","author":"Vos","year":"2022","journal-title":"Hepatology"},{"key":"R20-20240829","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/hep.32322","article-title":"Pediatric NASH therapies:A speedbump on the road to success","volume":"76","author":"Softic","year":"2022","journal-title":"Hepatology"},{"key":"R21-20240829","doi-asserted-by":"crossref","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":"R22-20240829","doi-asserted-by":"crossref","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":"R23-20240829","doi-asserted-by":"crossref","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":"R24-20240829","doi-asserted-by":"crossref","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":"R25-20240829","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1517\/14740331003623218","article-title":"Pioglitazone:Side effect and safety profile","volume":"9","author":"Shah","year":"2010","journal-title":"Expert Opin Drug Saf"},{"key":"R26-20240829","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jpag.2013.09.015","article-title":"Effects of the insulin sensitizer pioglitazone on menstrual irregularity, insulin resistance and hyperandrogenism in young women with polycystic ovary syndrome","volume":"27","author":"Stabile","year":"2014","journal-title":"J Pediatr Adolesc Gynecol"},{"key":"R27-20240829","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1742-2094-4-3","article-title":"Effect of pioglitazone treatment on behavioral symptoms in autistic children","volume":"4","author":"Boris","year":"2007","journal-title":"J Neuroinflammation"},{"key":"R28-20240829","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.jpeds.2006.08.049","article-title":"Pioglitazone as adjunctive therapy in adolescents with type 1 diabetes","volume":"149","author":"Zdravkovic","year":"2006","journal-title":"J Pediatr"},{"key":"R29-20240829","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13229-018-0241-5","article-title":"A pilot dose finding study of pioglitazone in autistic children","volume":"9","author":"Capano","year":"2018","journal-title":"Mol Autism"},{"key":"R30-20240829","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1016\/j.jaci.2016.01.033","article-title":"Pioglitazone as a novel therapeutic approach in chronic granulomatous disease","volume":"137","author":"Migliavacca","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"R31-20240829","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1056\/NEJMoa1109333","article-title":"A clinical trial to maintain glycemic control in youth with type 2 diabetes","volume":"366","author":"Group","year":"2012","journal-title":"N Engl J Med"},{"key":"R32-20240829","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.3390\/nu14071500","article-title":"Dietary counseling aimed at reducing sugar intake yields the greatest improvement in management of weight and metabolic dysfunction in children with obesity","volume":"14","author":"Radulescu","year":"2022","journal-title":"Nutrients"},{"key":"R33-20240829","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jpeds.2013.07.050","article-title":"Use of magnetic resonance elastography to assess hepatic fibrosis in children with chronic liver disease","volume":"164","author":"Xanthakos","year":"2014","journal-title":"J Pediatr"},{"key":"R34-20240829","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"R35-20240829","doi-asserted-by":"crossref","first-page":"e12862","DOI":"10.1111\/ijpo.12862","article-title":"Stratification by obesity class, rather than age, can identify a higher percent of children at risk for non-alcoholic fatty liver disease and metabolic dysfunction","volume":"17","author":"Radulescu","year":"2021","journal-title":"Pediatr Obes"},{"key":"R36-20240829","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1097\/MPG.0b013e3182722aee","article-title":"Serum retinol-binding protein 4 is independently associated with pediatric NAFLD and fasting triglyceride level","volume":"56","author":"Huang","year":"2013","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"R37-20240829","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1177\/0009922814542481","article-title":"Topiramate for weight reduction in adolescents with severe obesity","volume":"54","author":"Fox","year":"2015","journal-title":"Clin Pediatr (Phila)"},{"key":"R38-20240829","first-page":"297","article-title":"The effect of topiramate on weight loss in patients with type 2 diabetes","volume":"18","author":"Moradi","year":"2013","journal-title":"J Res Med Sci"},{"key":"R39-20240829","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00228-006-0220-1","article-title":"The effect of topiramate on energy balance in obese men:A 6-month double-blind randomized placebo-controlled study with a 6-month open-label extension","volume":"63","author":"Tremblay","year":"2007","journal-title":"Eur J Clin Pharmacol"},{"key":"R40-20240829","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1016\/j.eplepsyres.2014.08.013","article-title":"Pharmacokinetic interactions between topiramate and pioglitazone and metformin","volume":"108","author":"Manitpisitkul","year":"2014","journal-title":"Epilepsy Res"},{"key":"R41-20240829","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1056\/NEJMoa2208601","article-title":"Investigators ST:Once-Weekly Semaglutide in Adolescents with Obesity","volume":"387","author":"Weghuber","year":"2022","journal-title":"N Engl J Med"},{"key":"R42-20240829","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1056\/NEJMoa2028395","article-title":"Investigators NN:A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis","volume":"384","author":"Newsome","year":"2021","journal-title":"N Engl J Med"},{"key":"R43-20240829","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jhep.2023.02.010","article-title":"Ketohexokinase-C regulates global protein acetylation to decrease carnitine palmitoyltransferase 1a-mediated fatty acid oxidation","volume":"79","author":"Helsley","year":"2023","journal-title":"J Hepatol"}],"container-title":["Saudi Journal of Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/sjg.sjg_428_23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:30:56Z","timestamp":1787769056000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/sjg.sjg_428_23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,10]]},"references-count":43,"URL":"https:\/\/doi.org\/10.4103\/sjg.sjg_428_23","relation":{},"ISSN":["1319-3767","1998-4049"],"issn-type":[{"value":"1319-3767","type":"print"},{"value":"1998-4049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,10]]},"assertion":[{"value":"2023-12-23","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-14","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}