Novel MRI assessment of treatment response in HIV-associated NAFLD: a randomized trial of an SCD1 inhibitor (ARRIVE Trial)
Aramchol, an oral stearoyl-coenzyme-A-desaturase-1 (SCD1) inhibitor, has been shown to reduce hepatic-fat content in patients with primary nonalcoholic-fatty-liver-disease (NAFLD), however, its effect in patients with HIV-associated NAFLD is unknown. The 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 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 co-localized regions-of-interest. Secondary endpoints included changes in liver-stiffness using MR-elastography (MRE) and vibration-controlled-transient-elastography (VCTE) and exploratory endpoints included changes in total body fat and muscle depots on DXA, whole-body and cardiac MRI. The mean (±SD) of age and BMI were 48.2±10.3 years and 30.7±4.6kg/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% vs end-of-treatment MRI-PDFF:14.4%, p=0.24) versus placebo at -1.4% (baseline-MRI-PDFF:13.3% vs end-of-treatment MRI-PDFF:11.9%, p=0.26), respectively. There was no difference in the relative decline in mean MRI-PDFF between aramchol group and placebo (6.8% versus 1.1%, p=0.68). There were no differences in MRE 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 utilizing novel MRI-based assessment in patients with HIV-associated NAFLD.
Ajmera VH1,2, Cachay E3, Ramers C4, Vodkin I2, Bassirian S1, Singh S1, Mangla N1, Bettencourt R1, Aldous JL5, Park D5, Lee D3, Blanchard J3, Mamidipalli A6, Boehringer A6, Aslam S7, Leinhard OD8,9, Richards L1, Sirlin C6, Loomba R1,2,10. Hepatology. 2019 Apr 23. doi: 10.1002/hep.30674. [Epub ahead of print]
1. NAFLD Research Center, Department of Medicine, La Jolla, California.
2. Division of Gastroenterology, Department of Medicine, La Jolla, California.
3. Division of Infectious Diseases, Owen Clinic, University of California San Diego, San Diego, California.
4. Family Health Center, San Diego, California.
5. San Ysidro Health, San Diego, California.
6. Liver Imaging Group, University of California, San Diego, La Jolla, California.
7. Division of Infectious Diseases and Global Public Health, University of California, San Diego, San Diego, California.
8. AMRA Medical AB, Linkoping, Sweden.
9. Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
10. Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, California.