Determinants of Treatment Outcomes for Hepatitis C Infection and the Path to Personalized Medicine

Hepatitis C virus (HCV) has emerged as a major viral pandemic over the past two decades, infecting 170 million individuals worldwide. Egypt has the highest prevalence of hepatitis C in the world with prevalence rates of 13%- 15% of the population. Hepatitis C is characterized with its high tendency to induce chronic progressive liver damage in the form of hepatic fibrosis, cirrhosis or liver cancer. There is no vaccine against HCV infection because our understanding of the early interactions between the virus and the host immune system is still limited. The current standard of care for patients with chronic hepatitis C, pegylated interferon alpha and ribavirin combination therapy, has improved the rate of resolution of chronic hepatitis C infection. However, many patients still do not respond to therapy or develop adverse events. Moreover, the prohibitive cost of interferon-based regimen makes them inaccessible for many patients particularly in developing countries. Understanding the host and viral factors associated with viral clearance is necessary for individualizing therapy to maximize sustained virologic response rates, prevent progression to liver disease, and increase the overall benefits of therapy with respect to its costs. Host genetic diversity seems to contribute to the outcome of each phase of the clinical spectrum of HCV infection. Genome wide studies have recently showed significant associations between a set of polymorphisms in the region of the interleukin-28B (IL28B) gene and clearance of HCV in natural infection or after pegylated interferon-alfa and ribavirin treatment. This paper synthesizes the advances in pharmacogenetics of HCV infection, including the lessons learned in Egypt to date.