Predictors of response to interferon therapy

An optimal treatment schedule is the first factor that influences sustained responses to interferon (IFN) therapy. There is growing evidence that prolonged IFN therapy (at least 12 months or longer) increases the sustained response rate. A low viremia at baseline favorably affects the long-term response to IFN. High viral replication does not preclude response, but highly viremic patients tend not to sustain their response. Patients with genotypes 2 and 3 (Simmonds classification) have an improved likelihood of responding compared to patients with genotype 1; unfortunately, genotype 1 predominates in Western countries. The “quasispecies” diversity of hepatitis C virus (HCV) may play a role in determining response to IFN, which is more likely in patients with lesser degrees of HCV diversity. However, studying the nucleotide diversity of the hypervariable region 1 of HCV is a very complex and expensive process that cannot be applied to a large number of patients. The sustained response rate is higher in patients with mild disease than in cirrhotic patients. Cirrhotics should be treated with caution, since IFN therapy could induce serious side effects and decompensation. Baseline predictive factors of response are useful to improve the cost-benefit ratio of IFN therapy but cannot be considered inclusion/exclusion criteria. The decision on how to treat should be based upon the individual characteristics of each patient.