BASIC—LIVER, PANCREAS, AND BILIARY TRACT Human Immunodeficiency Virus-Related Microbial Translocation and Progression of Hepatitis C

Background & Aims: Human immunodeficiency virus (HIV)-1 infection has been associated with enhanced microbial translocation, and microbial translocation is a mechanism through which alcohol and some enteric conditions cause liver disease. We hypothesized that HIV promotes liver disease by enhancing microbial translocation. Methods: We studied human cohorts in which hepatitis C virus (HCV) and HIV outcomes were carefully characterized. Results: HIV-related CD4 lymphocyte depletion was strongly associated with microbial translocation as indicated by elevated levels of circulating lipopolysaccharide (LPS), LPS-binding protein, soluble CD14, and fucose-binding lectin (AAL) reactive to immunoglobulin G specific for the -galactose epitope and suppressed levels of endotoxin core antibodies (EndoCAb IgM) in HIV-infected subjects compared with the same persons before they had HIV infection and compared with HIV-uninfected subjects. The same measures of microbial translocation were strongly associated with HCV-related liver disease progression (cirrhosis), eg, LPS, odds ratio, 19.0 (P .002); AAL, odds ratio, 27.8 (P < .0001); in addition, levels of LPS were elevated prior to recognition of cirrhosis. Conclusions: Microbial translocation may be a fundamental mechanism through which HIV accelerates progression of chronic liver disease.