Clinical Predictors of Liver Fibrosis Presence and Progression in HIV-Associated NAFLD.

BACKGROUND: Nonalcoholic fatty disease (NAFLD) affects over one-third of people living with HIV. Nonetheless, the natural history of HIV-associated NAFLD is poorly understood, including which patients are most likely to have a progressive disease course. METHODS: We leveraged a randomized trial of the growth hormone-releasing hormone analogue tesamorelin to treat NAFLD in HIV. Sixty-one participants with HIV-associated NAFLD were randomized to tesamorelin or placebo for 12 months. Participants underwent liver biopsy at baseline and 12 months with histologic evaluation performed by an expert pathologist blinded to treatment. RESULTS: In all participants with baseline biopsies (n=58), 43% had hepatic fibrosis. Individuals with fibrosis had higher NAFLD Activity Score (NAS) (3.6+/-2.0 vs. 2.0+/-0.8, P<0.0001) and visceral fat content (284+/-91 cm2 vs. 212+/-95 cm2, P=0.005), but no difference in hepatic fat or BMI. Among placebo-treated participants with paired biopsies (n=24), 38% had hepatic fibrosis progression over 12 months. For each 25 cm2 higher visceral fat at baseline, the odds of fibrosis progression increased by 37% (OR 1.37, 95% CI 1.03, 2.07). There was no difference in baseline NAS score between fibrosis progressors and non-progressors, though NAS score rose over time in the progressor group (1.1+/-0.8 vs. -0.5+/-0.6, P<0.0001). CONCLUSIONS: In this longitudinal study of HIV-associated NAFLD, high rates of hepatic fibrosis and progression were observed. Visceral adiposity was identified as a novel clinical predictor of worsening fibrosis. In contrast, baseline histologic characteristics were not found to relate to fibrosis changes over time. Further studies are needed to identify additional biomarkers of accelerated disease.