Cellular and molecular interactions in coinfection with hepatitis C virus and human immunodeficiency virus

Abstract

Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is associated with increased HCV replication and a more rapid progression to severe liver disease, including the development of cirrhosis and hepatocellular carcinoma. In this review, we discuss the current understanding of the pathogenesis of HCV/HIV coinfection and the cellular and molecular mechanisms associated with the accelerated course of liver disease. The strength and breadth of HCV-specific T-cell responses are reduced in HCV/HIV-coinfected patients compared with those infected with HCV alone, suggesting that the immunosuppression induced by HIV compromises immune responses to HCV. HCV is not directly cytopathic, but many of the pathological changes observed in the liver of infected patients are a direct result of the intrahepatic antiviral immune responses. Apoptosis also has a role in HCV-mediated liver damage through the induction of apoptotic pathways involving the host immune response and HCV viral proteins. This review summarises the evidence correlating the role of cell-mediated immune responses and apoptosis with liver disease progression in HCV/HIV-coinfected patients.