Microbial translocation and liver disease progression in women coinfected with HIV and hepatitis C virus

Background. Microbial translocation has been implicated in the pathogenesis of liver fibrosis and cirrhosis. We sought to determine whether markers of microbial translocation are associated with liver disease progression during coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Methods. We measured serial plasma lipopolysaccharide (LPS), endotoxin core antibody, intestinal fatty acid-binding protein (I-FABP), soluble CD14 (sCD14), interleukin 6 (IL-6), interleukin 10, and tumor necrosis factor α (TNF-α) levels over a 5-year period in 44 HIV/HCV-coinfected women, 21 of whom experienced liver disease progression and 23 were nonprogressors. Results. While LPS levels did not differ significantly over time between progressors and nonprogressors (P =. 60), progressors had significantly higher plasma levels of sCD14, a marker of monocyte activation by LPS, at the first time point measured (P =. 03) and throughout the study period (P =. 001); progressors also had higher IL-6 and I-FABP levels over the 5-year study period (P =. 02 and. 03, respectively). The associations between progression and sCD14, I-FABP, and IL-6 levels were unchanged in models controlling for HIV RNA and CD4⁺ T-cell count. Conclusions. Although LPS levels did not differ between liver disease progressors and nonprogressors, the association of sCD14, I-FABP, and IL-6 levels with liver disease progression suggests that impairment of gut epithelial integrity and consequent microbial translocation may play a role in the complex interaction of HIV and HCV pathogenesis.