Losartan: Not Effective for Pediatric NAFLD

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M Vos et al. Hepatology 2022; https://doi.org/10.1002/hep.32403. Open Access: Randomized placebo-controlled trial of losartan for pediatric NAFLD (Thanks to Jeff Schwimmer’s twitter feed for this link)

Rationale for study: “A number of studies suggest the utility of losartan in NAFLD.[11–17] In adults, two meta-analyses have found that angiotensin receptor blockers (ARBs) improve insulin sensitivity and reduce the incidence of type 2 diabetes.[18, 19] A large retrospective review of hypertensive patients treated with angiotensin-converting enzyme inhibitors and/or ARBs demonstrated a significant association of renin-angiotensin system (RAS) antagonists with reduced odds of advanced hepatic fibrosis on biopsy.[20] “

Design: 83 participants (81% male, 80% Hispanic) with histologically proven NAFLD were randomized to losartan (100 mg daily) (n = 43) or placebo (n = 40). ALT was chosen as a primary endpoint, because “reduction of elevated serum ALT … has been shown to significantly correlate with improvement in histology in children, including fibrosis”

Key findings:

  • The 24-week change in ALT did not differ significantly between losartan versus placebo groups (adjusted mean difference: 1.1 U/l; p = 0.95), although alkaline phosphatase decreased significantly in the losartan group (adjusted mean difference: −23.4 U/l; p = 0.01).
  • The authors “found no benefit of losartan on markers of insulin sensitivity, despite an improvement in systolic blood pressure”

My take: This study shows a very low likelihood that Losartan could be beneficial in NAFLD. I would recommend a book (a quick read) to my colleagues: “How I Killed Pluto and Why It Had It Coming.” In this book, the author, Michael Brown, describes years of seemingly-Sisyphean efforts to locate planetoids in our distant solar system; his work ultimately yielded important discoveries.

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