Fatty Liver Disease in HIV: Predictors and Response to Statin Therapy

BACKGROUND: Liver disease has emerged as a leading cause of mortality and morbidity in HIV. Much of the current challenge in liver disease is related to nonalcoholic fatty liver disease (NAFLD). In HIV-uninfected populations, statin therapy has been suggested as potential intervention, but no such data is available in HIV. The aims of this study are to investigate the effect of rosuvastatin on hepatic steatosis in HIV infection, measured by Liver Fat Score (LFS) and to assess the natural history and predictors of changes in hepatic steatosis over 96 weeks. METHODS: This is a secondary analysis of the SATURN-HIV trial, in which HIV+ adults on stable ART with HIV-1 RNA < 1,000 copies/mL and LDL-cholesterol < 130mg/dL were randomized to 10mg daily rosuvastatin or placebo. Changes in LFS and in markers of systemic inflammation and monocyte activation were assessed from entry through week 96. Spearman correlations, multivariable linear regression and logistic regression were used to study relationships among variables. RESULTS: Overall, 147 patients were randomized (n = 72 to rosuvastatin n = 75 to placebo); 78% were male, 68% African Americans, 8% had chronic hepatitis C and mean age and BMI were 46 years and 29kg/mm(2). A significant increase in LFS over 96 weeks was seen in both the placebo and statin arms (p = 0.01 and p < 0.01 respectively, p = 0.49 between groups). Furthermore, the progression from no-steatosis (LFS ≤ -0.64) at baseline to steatosis (LFS > -0.64) at week 96 was higher in rosuvastatin arm (OR = 4.3, p = 0.03), and remained statistically significant after adjusting for demographics, HOMA (baseline and change over 96 weeks), hepatitis C, heavy alcohol use and HIV parameters. Baseline LFS was independently associated with IP-10 (β = 0.82, p = 0.03) and sCD163 (β = 0.43, p = 0.005), and the increase in LFS over 96 weeks was independently associated with IP-10 (β = 2.85, p = 0.02). CONCLUSION: In HIV+ subjects on ART, hepatic steatosis increased over time, regardless of statin treatment, and was independently associated with markers of immune activation. The progression from non-steatosis to hepatic steatosis was greater on statin. Despite its effective role in reducing cardiovascular disease risk and inflammation, statin therapy does not appear effective in hepatic steatosis. DISCLOSURES: C. O. Hileman, Gilead: Medical Advisory Board, Research support; G. Mccomsey, Gilead: Consultant, Consulting fee and Research support; BMS: Consultant, Consulting fee and Research support; GSK/ViiV: Consultant, Consulting fee and Research support; ICON: Consultant, Consulting fee; Merck: Investigator, Research support