Viral, host and interferon-related factors modulating the effect of interferon therapy for hepatitis C virus infection

The estimated prevalence of hepatitis C virus infection in the US is approx imately 1.8%. Although interferon monotherapy and combination therapy of in terferon with ribavirin represent mainstay for treating HCV infection, the rate of sustained virologic response remains suboptimal. The growing eviden ce suggested that the clinical sequence and treatment response of chronic h epatitis C are determined by a dynamic, complex tripartite relationship amo ng HCV infection, the host immune response, and the effect of different int erferon regimens. The treatment response is associated with various viral f actors including the pretreatment viral level, dynamic change of viral leve l during treatment, viral genotype quasispecies and nucleotide mutation in nonstructural protein 5A of hepatitis C virus. Host factors that may affect treatment response include age, gender, race, HLA alleles and the host imm une responses. Interferon regimens, including type, dose, frequency and dur ation of treatment and combination of interferon with other anti-HCV agents also alter the therapeutic response. Understanding these complicated inter action may provide better insights into the mechanism(s) of interferon resp onse, leading to more effective clinical application of interferon therapy.