Clinical Information

Individuals with hepatitis C virus (HCV) genotype 1 infections have variable responses to treatment with pegylated-interferon and ribavirin combination therapy. Some individuals will respond to treatment with sustained viral response, while other patients have poor response and fail to achieve sustained viral clearance.

Response to pegylated-interferon and ribavirin combination therapy in HCV genotype 1-infected individuals has been found to be closely associated with a single-nucleotide variant (SNV), designated rs12979860, located 3 kilobases upstream from the interleukin 28B gene locus (IL28B, also known as IFNL3) present on human chromosome 19.

HCV genotype 1-infected individuals with the CC genotype, as compared to either the CT or TT genotypes, of this SNP in IL28B have approximately 2- to 3-fold greater rates of sustained viral response to combined pegylated-interferon and ribavirin therapy.(1) Similar increases in sustained viral response rates were observed across various racial groups, including European Americans (95% CI, 1.8- to 2.3-fold), African Americans (95% CI, 1.9- to 4.7-fold), and Hispanics (95% CI, 1.4- to 3.2-fold).(1) The CC genotype has also been associated with a 3-fold increase in rate of spontaneous clearance of HCV.(2,4) The SNV in IL28B is only one of many factors that can influence response rates to pegylated-interferon and ribavirin combination therapy in HCV genotype 1 infection, and the SNV genotype result should be interpreted in the context of other clinical factors present in a given patient.

Frequency of the rs12979860 C allele varies across different racial and ethnic groups. The rs12979860 C variant is most frequently present in individuals from East Asia (allele frequency >0.9) and least common in individuals of African origin (allele frequency 0.2-0.5).(2) In a recent US-based study, the favorable CC genotype was observed in 37% of whites, 29% Hispanics, and 14% of African Americans tested.

The mechanism by which the IL28B genotype mediates response to pegylated-interferon and ribavirin combination therapy among HCV genotype 1-infected individuals is not yet understood and is the subject of intense ongoing research. The impact of the IL28B-related alteration on response rates in patients infected with HCV genotypes other than genotype 1 is still being investigated.