MRI Assessment of Treatment Response in HIV-associated NAFLD: A Randomized Trial of a Stearoyl-Coenzyme-A-Desaturase-1 Inhibitor (ARRIVE Trial).

Abstract

Aramchol, an oral stearoyl-coenzyme-A-desaturase-1 inhibitor, has been shown to reduce hepatic fat content in patients with primary nonalcoholic fatty liver disease (NAFLD); however, its effect in patients with human immunodeficiency virus (HIV)-associated NAFLD is unknown. The aramchol for HIV-associated NAFLD and lipodystrophy (ARRIVE) trial was a double-blind, randomized, investigator-initiated, placebo-controlled trial to test the efficacy of 12 weeks of treatment with aramchol versus placebo in HIV-associated NAFLD. Fifty patients with HIV-associated NAFLD, defined by magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) ≥5%, were randomized to receive either aramchol 600 mg daily (n = 25) or placebo (n = 25) for 12 weeks. The primary endpoint was a change in hepatic fat as measured by MRI-PDFF in colocalized regions of interest. Secondary endpoints included changes in liver stiffness using magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE), and exploratory endpoints included changes in total-body fat and muscle depots on dual-energy X-ray absorptiometry (DXA), whole-body MRI, and cardiac MRI. The mean (± standard deviation) of age and body mass index were 48.2 ± 10.3 years and 30.7 ± 4.6 kg/m2 , respectively. There was no difference in the reduction in mean MRI-PDFF between the aramchol group at -1.3% (baseline MRI-PDFF 15.6% versus end-of-treatment MRI-PDFF 14.4%, P = 0.24) and the placebo group at -1.4% (baseline MRI-PDFF 13.3% versus end-of-treatment MRI-PDFF 11.9%, P = 0.26). There was no difference in the relative decline in mean MRI-PDFF between the aramchol and placebo groups (6.8% versus 1.1%, P = 0.68). There were no differences in MRE-derived and VCTE-derived liver stiffness and whole-body (fat and muscle) composition analysis by MRI or DXA. Compared to baseline, end-of-treatment aminotransferases were lower in the aramchol group but not in the placebo arm. There were no significant adverse events. Conclusion: Aramchol, over a 12-week period, did not reduce hepatic fat or change body fat and muscle composition by using MRI-based assessment in patients with HIV-associated NAFLD (clinicaltrials.gov ID:NCT02684591).

• Authors: Veeral H Ajmera, Edward Cachay, Christian Ramers, Irine Vodkin, Shirin Bassirian, Seema Singh, Neeraj Mangla, Richele Bettencourt, Jeannette L Aldous, Daniel Park, Daniel Lee, Jennifer Blanchard, Adrija Mamidipalli, Andrew Boehringer, Saima Aslam, Olof Dahlqvist Leinhard, Lisa Richards, Claude Sirlin, Rohit Loomba
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 70 Issue 5 Pg. 1531-1545 (11 2019) ISSN: 1527-3350 [Electronic] United States
• PMID: 31013363 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 by the American Association for the Study of Liver Diseases.

Chemical References

• Cholic Acids
• aramchol

Topics

• Adult
• Cholic Acids (therapeutic use)
• Double-Blind Method
• Elasticity Imaging Techniques
• Female
• HIV Infections (complications)
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease (diagnostic imaging, drug therapy, etiology)