A randomized, controlled, crossover pilot study of losartan for pediatric nonalcoholic fatty liver disease.

• Type of Material: Article
• Authors: Miriam Benedicta Vos, Emory University; Ran Jin, Emory University; Juna V. Konomi, Emory University; Rebecca Cleeton, Emory University; Jessica Cruz, Emory University; Saul Karpen, Emory University; Dellys M. Soler Rodriguez, Emory University; Jennifer Frediani, Emory University; Courtney McCracken, Emory University; Jean A. Welsh, Emory University
• Language: English
• Date: 2018
• Publisher: BMC (part of Springer Nature)
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s). 2018
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s40814-018-0306-4
• Title of Journal or Parent Work: Pilot and Feasibility Studies
• ISSN: 2055-5784
• Volume: 4
• Issue: 1
• Start Page: 109
• End Page: 109
• Grant/Funding Information: The study was funded, in part, from grants from the National Institutes of NIH R03 DK096157 (Vos) and NIH K23 DK080953-05 (Vos) and the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454.
• Keywords: Insulin resistance; Treatment; Fatty liver disease; Children; Plasminogen activator inhibitor-1; Pilot
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Nutrition

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children, and currently, there are no FDA-approved therapies. Plasminogen activator inhibitor-1 (PAI-1) is elevated in children with NAFLD and associated with increased disease severity. Losartan potassium (losartan) is an angiotensin II receptor blocker (ARB) that reduces PAI-1 production and improves insulin sensitivity that has been proposed as a treatment for pediatric NAFLD but has not previously been tested. Methods: This was an 8-week randomized, double-blind, placebo-controlled, phase 2a, crossover study (with a 6-week washout between conditions) for safety and preliminary efficacy of losartan 50 mg a day taken orally in 12 normotensive children with biopsy proven nonalcoholic steatohepatitis (NASH). Results: Twelve children enrolled in the study, and nine completed all visits. No changes in blood pressure or serious adverse events occurred during the study. Trends in improvement in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and homeostatic model assessment insulin resistance (HOMA-IR) were seen with losartan treatment compared to the placebo time-period. More participants decreased ALT on losartan as compared to placebo (89% [8 out 9] vs. 56% [5 out of 9], respectively). Conclusions: This data provides preliminary evidence that losartan treatment is safe over 8 weeks in children with NAFLD and supports consideration of larger studies to test its efficacy. Trial registration: URL and trial identification number: https://clinicaltrials.gov/show/NCT01913470, NCT01913470.Date registered: August 1, 2013.