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Hepatol Res. 2012 Sep;42(9):841-53. doi: 10.1111/j.1872-034X.2012.01002.x. Epub 2012 Apr 23.

Impact of interleukin-28B genotype on in vitro and in vivo systems of hepatitis C virus replication.

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Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences Liver Research Project Center, Hiroshima University Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan.


Identification of the relationship between the interleukin (IL)-28B genotype and the effect of peginterferon plus ribavirin treatment has had a great impact on the study of antiviral therapy for patients with chronic hepatitis C virus (HCV) infection. Differential expression levels of interferon-stimulated genes (ISG) in the liver and white blood cells based on the IL-28B genotype, which may in turn lead to differences in outcome of therapy, indicate that previous studies should be re-evaluated taking the effect of the IL-28B single nucleotide polymorphism (SNP) into consideration, although the exact mechanism of how variation in IL-28B SNPs affect HCV eradication remains unknown. These results suggest that the genotypes of multiple cell types, including liver and immune cells, contribute to the efficacy of therapy. Studies using human hepatocyte chimeric mice, in which effector cells of the human adaptive immune response are absent, showed that viral load, ISG expression levels and reduction of HCV RNA by interferon are affected by the IL-28B genotype. Genetic differences among hepatocytes may, therefore, contribute to differences in baseline viral loads and response to interferon therapy. Further studies should be done to clarify the mechanism of action of IL-28B SNP on viral load and effect of interferon treatment. Advances in cell culture systems and human hepatocyte chimeric mice, as well as upcoming in vitro and in vivo experimental systems, provide an effective platform to examine the effects of host and viral genetic variation on infection and response to interferon.

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