IL28B Polymorphisms as a Predictor of Response to Therapy in Genotype 1 Chronic Hepatitis C Infections

Hepatitis C virus (HCV) is the most common cause of chronic liver disease in the United States. There are more than 170 million cases worldwide, and about 70% of patients will have persistence of the virus resulting in a chronic infection [1]. These patients are at risk of developing significant complications: 20% will develop cirrhosis, and the incidence of hepatocellular carcinoma is 2% per year in infected patients [2, 3]. Spontaneous remission of the disease is uncommon, and chronic hepatitis C remains the most common cause for liver transplantation in Europe and the United States [4]. The goal of combination therapy with pegylated interferon- ل and ribavirin is to eradicate the virus and prevent longterm complications of hepatitis C. Combination therapy is administered for 24 weeks for HCV genotype 2 or 3 and 48 weeks for HCV genotypes 1 and 4 [5]. A sustained virologic response (SVR) is attained in 80% of patients with genotype 2 and 3 infections [6]. However, in patients infected with genotype 1 virus—the most common virus in the United States and Europe—the overall response rate to therapy is only between 40% and 50%, and this number has remained largely unchanged for the past 10 years [7]. Therefore, the manner in which different people respond to HCVinfection varies considerably, and the viral genotype has the greatest bearing on response to therapy. However, even after controlling for clinical characteristics, disease severity, and medication regimens, African Americans and Hispanics with genotype 1 HCV have lower rates of remission compared to their European-American counterparts [8, 9]. It therefore follows that host genetics also plays a large role in the response to hepatitis C infection. The genome-wide association study (GWAS) by Ge et al. was the first one to convincingly identify host genetic factors that determine the response to treatment with pegylated interferon-ل and ribavirin.