Nonalcoholic fatty liver disease (NAFLD) – ranging from steatosis to steatohepatitis to fibrosis – is a major cause of liver disease in HIV. While simple steatosis is regarded as relatively benign, hepatic fibrosis has been linked to all-cause and liver-specific mortality. The natural history of NAFLD in HIV, including which patients are likely to develop clinically overt disease, is not well known. In the current study, we leverage liver biopsy samples from a clinical trial of HIV-associated NAFLD to identify predictors of fibrosis presence and progression.
We recently completed a randomized trial of the growth hormone-releasing hormone analogue tesamorelin to treat NAFLD in HIV. In this study, we found that tesamorelin reduced liver fat and prevented fibrosis progression. Sixty-one participants with HIV and NAFLD were randomized to tesamorelin or placebo for 12 months. NAFLD was defined as hepatic fat fraction (HFF) ≥ 5% by magnetic resonance spectroscopy in the absence of active hepatitis B or C or excess alcohol consumption. Individuals with cirrhosis were excluded. Participants underwent liver biopsy at baseline and 12 months; histologic evaluation was performed by a single expert pathologist blinded to treatment and biopsy order.
Among 58 participants with baseline biopsies, 43% had hepatic fibrosis (stage 1, 36%; stage 2, 40%; stage 3, 24%). Fibrosis was associated with greater visceral fat content at baseline (284 ± 91 cm2 vs. 212 ± 95 cm2, P = 0.005), but not subcutaneous fat or BMI. While HFF did not differ between groups, individuals with fibrosis had higher NAFLD Activity Score (3.6 ± 2.0 vs. 2.0 ± 0.8, P < 0.0001), ALT (41 ± 30 U/L vs. 23 ± 8 U/L, P = 0.002), and AST (44 ± 27 U/L vs. 24 ± 10 U/L, P = 0.0003). Among 24 participants randomized to placebo with paired liver biopsies, 38% had progression of fibrosis over 12 months. Higher visceral fat content at baseline (306 ± 119 cm2 vs. 212 ± 89 cm2, P = 0.04) was the only clinical predictor of fibrosis progression, which remained significant upon adjusting for BMI, HFF, and NAS Score. Age, sex, race, duration of HIV, and CD4 count did not relate to fibrosis presence or progression.
High rates of liver fibrosis presence and progression were observed in a cohort with HIV and NAFLD. Individuals with greater visceral fat content at baseline were more likely to have baseline fibrosis and progression of fibrosis, suggesting that these patients should be closely monitored and targeted for intervention.