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Discovery of critical host factor, IL‐28B, associated with response to hepatitis C virus treatment
Author(s) -
Mizokami Masashi
Publication year - 2012
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2011.07054.x
Subject(s) - interleukin 28b , ribavirin , medicine , pegylated interferon , hepatitis c virus , hepatitis c , genome wide association study , liver transplantation , genotype , immunology , population , viral load , interferon , virology , transplantation , virus , single nucleotide polymorphism , gene , biology , genetics , environmental health
Chronic hepatitis C affects 2.2–3.0% of the world population (130 million–170 million). Pegylated interferon‐α (PEG‐IFN‐α) in combination with ribavirin (RBV), the approved and standard therapy, leads to viral eradication in about 50% of treated patients. In 2009, genome‐wide association studies (GWAS) identified host genetic variation to be critical for predicting treatment response and spontaneous clearance in patients infected with hepatitis C virus (HCV). A correlated set of polymorphisms in the region of the interleukin‐28B (IL‐28B) gene on chromosome 19, coding for interferon (IFN)‐λ3 were associated with clearance of genotype 1 hepatitis C virus (HCV) in patients treated with PEG‐IFN‐α and RBV. The same polymorphisms were subsequently associated with spontaneous clearance of HCV in untreated patients. In addition, prediction of viral response to PEG‐IFN‐α and RBV therapy of patients with recurrent HCV infection after orthotopic liver transplantation depends on the IL‐28B genotype of both recipient and donor tissues. Diagnosis of a patient's IL‐28B genotype is likely to aid in clinical decision making with standard‐of‐care regimens. Future studies will investigate the possibility of individualizing treatment duration and novel regimens according to IL‐28B genotype. As GWAS yield unexpected data, this approach could lead to the development of novel drug therapy, such as already appears promising with IFN‐λ. In this Okuda lecture, I present the current understanding in regard to the relationship between host variations and clinical outcome of hepatitis C.