Antigen-specific immune responses and liver histology in HIV and hepatitis C coinfection

Objective: To test the hypothesis that antigen-specific interferon (IFN)gamma responses are correlated with milder liver disease in subjects coinfected with HIV-1 and hepatitis C virus (HCV). Design: Cellular immune responses were studied in a cohort with HIV/HCV coinfection (n = 107) who underwent liver biopsy. Methods: We measured HCV-specific and recall responses in peripheral blood mononuclear cells using IFN gamma and interleukin (IL)-10 ELISpots, and correlated these immune responses with liver histology. The relationship of immunologic, virologic and clinical variables to inflammation and fibrosis was modeled using recursive partitioning. Results: There were significant negative correlations between inflammatory scores and IFN gamma production in response to the HCV proteins core, NS5 and summed HCV responses. Lower fibrosis scores were also correlated with higher IFN gamma production in response to NS5 and summed HCV proteins. Higher IFN gamma production in response to Candida was significantly associated with lower inflammatory and fibrosis scores. In multivariable models, factors associated with severe fibrosis were lower IFN gamma responses to Candida and summed HCV proteins. Factors associated with severe inflammation were detectable HIV viral load and lower HCV viral load, while predictors of mild inflammation included undetectable HIV viral load and higher IFN gamma response to Candida. Conclusions: In this cohort of subjects coinfected with HIV and HCV, antigen-specific IFN gamma responses are correlated with milder inflammation and fibrosis. Immunological responses best predicted severity of fibrosis, while clinical variables and recall antigen responses best predicted severity of inflammation. (c) 2005 Lippincott Williams & Wilkins