Microbial Translocation and Gut-Damage is Associated with Elevated Fast Score in Women Living with and without HIV

Abstract

Steatohepatitis is common in persons living with HIV (PLWH) and may be associated with gut microbial translocation (MT). However, few have evaluated the gut-liver axis in PLWH. We examined associations of HIV and circulating biomarkers linked to MT and gut-damage with the FibroScan-AST (FAST) score, a non-invasive surrogate for steatohepatitis with advanced fibrosis, in the Women’s Interagency HIV Study. Among 883 women with HIV (WWH) and 354 without HIV, we used multivariable regression to examine the associations of HIV and serum biomarkers linked to MT and gut-damage (KT ratio, I-FABP, sCD14, and sCD163) with log-transformed FAST score after adjusting for key covariates. We used a path analysis and mediation models to determine the mediating effect of each biomarker on the association of HIV with FAST. HIV infection was associated with a 49% higher FAST score. MT biomarker levels were higher in WWH than women without HIV (p<0.001 for each). MT biomarker MT mediated 13-32% of the association of HIV and FAST score. Biomarkers linked to MT and gut-damage are associated with higher FAST score and mediate the association of HIV with higher FAST. Our findings suggest that MT may be an important mechanism by which HIV increases the risk of steatohepatitis with advanced fibrosis.