Interferon Stimulated Genes and Hepatitis C Virus Infection

Abstract

Hepatitis C Virus (HCV) is a major cause of chronic liver disease worldwide. In addition to viral and environmental behavioral factors, host genetic diversity is believed to contribute to the spectrum of the disease. The sequencing of the human genome, together with the development of high-throughput technologies that measure the function of the genome, have afforded unique opportunities to develop profiles that can distinguish and classify discrete subsets of a disease and predict a response to therapy. In 2011, 2 directly acting antivirals (DAAs) have been approved for chronic HCV genotype 1 infection, Telaprevir and Boceprevir, and open a new area for HCV therapy. These 2 NS3/4 protease inhibitors are given in combination with pegylated interferon and ribavirin. Several DAAs are in development. Since a significant number of patients will fail to respond to treatment, or will have significant side effects, it is of major interest to predict a response to treatment as early as possible. Several studies are ongoing to identify biomarkers that could predict treatment outcome in patients with hepatitis C before treatment. Many of the genes upregulated in the liver between nonresponders and responders codes molecules secreted in the serum and can constitute a logical functional approach for the development of serum markers predictors of response to treatment. In the next future, further studies have several challenges to fight. First, large prospective cohorts with well phenotyped patients and appropriate tissue controls are needed. For response to treatment, the appropriate definition of sustained response and the same treatment regimen have to be addressed. Furthermore, improved technology and analytical procedures and the use of large numbers of patients for validation are needed.