[Truncated abstract] Hepatitis C is one of the most common infections worldwide affecting around 170 million individuals1. Approximately 30% of individuals that are infected with the Hepatitis C virus (HCV) will naturally resolve the infection but most develop chronic infection that often leads to liver cirrhosis and hepatocellular carcinoma1 2. Current standard of care for HCV infection involves the use of interferon alpha (pegIFN-α), an immunomodulatory molecule, and ribavirin (RBV). However, this treatment regime is only effective in about 50% of individuals. Treatment outcome is associated with HCV genotype, viral load decline during the initial phase of treatment and host genetic factors such as IL28B3-6. IL28B encodes for interferon lambda 3 and is involved in the host’s innate anti-viral response to viruses. To date, there is limited information regarding how IL28B affects viral evolution and in-turn clinical outcomes7. IFN is likely to have a role in other diseases in which the host’s innate immune response is important. In this study we examine the association between IL28B variation and HCV diversity and how this interaction may affect treatment outcome as well as the role of IL28B in allergic disease. IL28B typing and HCV sequencing was performed on three well-characterised HCV cohorts. Sixty eight samples were obtained from a cohort of chronic HCV-infected subjects in Western Australia and the Swiss HIV cohort study. These subjects were all treatment naïve at the time of sampling and had existing HCV sequence in the HCV NS5 region. DNA samples from the two cohorts were typed for the tagging SNP rs12979860 three kilobases upstream of IL28B. Ninety five samples were from a cohort of chronic genotype 1-infected subjects from Duke University, US...
|Unpublished - 2011