https://pubmed.ncbi.nlm.nih.gov/35133671/ NAFLD
Hepatology. 2022 Feb 8.
doi: 10.1002/hep.32403. Online ahead of print.
Randomized Placebo-Controlled Trial of Losartan for Pediatric Nonalcoholic Fatty Liver Disease
Miriam B Vos 1, Mark L Van Natta 2, Niviann M Blondet 3, Srinivasan Dasarathy 4, Mark Fishbein 5, Paula Hertel 6, Ajay K Jain 7, Saul J Karpen 1, Joel E Lavine 8, Saeed Mohammad 5, Laura A Miriel 2, Jean P Molleston 9, Marialena Mouzaki 10, Arun Sanyal 11, Emily P Sharkey 2, Jeffrey B Schwimmer 12, James Tonascia 2, Laura A Wilson 2, Stavra A Xanthakos 10, NASH Clinical Research Network
Abstract
Background & aims: To date, no pharmacotherapy exists for pediatric nonalcoholic fatty liver disease (NAFLD). Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its anti-fibrotic effects.
Approach & results: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically-confirmed NAFLD at 10 sites (September 2018- April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥3, and serum alanine aminotransferase (ALT) ≥50 U/L. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT levels from baseline to 24 weeks and the pre-set sample size was n=110. Treatment effects were assessed using linear regression of change in treatment group adjusted for baseline value. 83 participants (81% male, 80% Hispanic) were randomized to losartan (n=43) or placebo (n=40). During an enrollment pause, necessitated by the COVID-19 pandemic, an unplanned interim analysis showed low probability (7%) of significant group difference. The Data and Safety Monitoring Board recommended early study termination. Baseline characteristics were similar between groups. The 24-week change in ALT did not differ significantly between losartan vs. placebo groups (adjusted mean difference: 1.1 U/L; 95% CI=-30.6, 32.7; p=0.95), although alkaline phosphatase decreased significantly in the losartan group (adjusted mean difference: -23.4 U/L; 95% CI=-41.5, -5.3; p=0.01). Systolic blood pressure decreased in the losartan group but increased in placebo (adjusted mean difference: -7.5 mmHg; 95% CI=-12.2, -2.8; p=0.002). Compliance by pill counts and numbers and types of adverse events did not differ by group.
Conclusion: Losartan did not significantly reduce ALT in children with NAFLD when compared to placebo.