Utilizing genomic polymorphisms to personalize hepatitis C therapies

Abstract

The need for liver transplant due to the progression of hepatitis C virus (HCV) infection necessitates the consideration of antiviral treatment. Host genomic variations affect response to HCV treatment and predict the rates of adverse effects. Recently, multiple genomic polymorphisms were found to be critical in predicting treatment response as well as the rate of neuropsychiatric adverse effects in patients infected with HCV who are receiving antiviral treatments. The use of antiviral treatments (pegylated IFN-alpha and ribavirin) to clear HCV infection is associated with poor response in HCV genotype 1 and with the development of depression. Polymorphisms in the promoter region of the IFN-alpha/beta receptor 1 (IFNAR1) can influence the risk of developing depression. Similar polymorphisms in the IL28B gene encoding for IFN-λ-3 are associated with a two- to three-fold improvement in response to treatment. In patients with HCV infection receiving antiviral treatments, genomic variations in two genes can help predict the increased risk of developing depression and the likelihood of achieving virus clearance. This can identify patients who are at an increased likelihood of virus clearance and who should be targeted to receive prophylactic approaches (antidepressants, psychotropics) to prevent the development of depression during HCV antiviral treatment.