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Immunopathogenesis of Hepatitis C Virus Infection. Despite advances in therapy, hepatitis C virus infection remains a major global health issue with 3 to 4 million incident cases and 170 million prevalent chronic infections. Complex, partially understood, host-virus interactions determine whether an acute infection with hepatitis C resolves, as occurs in approximately 30% of cases, or generates a persistent hepatic infection, as occurs in the remainder. Once chronic infection is established, the velocity of hepatocyte injury and resultant fibrosis is significantly modulated by immunologic as well as environmental factors. Immunomodulation has been the backbone of antiviral therapy despite poor understanding of its mechanism of action.