October 12, 2010

IL28B Genomic-Based Treatment Paradigms for Patients With Chronic Hepatitis C Infection: The Future of Personalized HCV Therapies

Am J Gastroenterol advance online publication 5 October 2010; doi: 10.1038/ajg.2010.370

Paul J Clark MD 1, Alex J Thompson MD, PhD 1 and John G McHutchison MD 1

1 Duke Clinical Research Institute and Division of Gastroenterology, Duke University Medical Center, School of Medicine, Duke University, Durham, North Carolina, USA

Correspondence: Paul J. Clark, MD, Division of Gastroenterology, Duke Clinical Research Institute, Duke University Medical Center, PO Box 17969, Durham, North Carolina 27715, USA. E-mail: paul.clark@duke.edu

Received 5 April 2010; Accepted 16 August 2010; Published online 5 October 2010.


Genome-wide association studies (GWAS) have recently identified host genetic variation to be critical for predicting treatment response and spontaneous clearance in patients infected with hepatitis C virus (HCV). These important new studies are reviewed and their future clinical implications discussed. Single-nucleotide polymorphisms in the region of the IL28B gene on chromosome 19, coding for the interferon (IFN)-λ-3 or IL28B gene, are strongly associated with treatment response to pegylated IFN and ribavirin in patients infected with genotype 1 HCV. The good response variant is associated with a twofold increase in the rate of cure. Allele frequencies differ between ethnic groups, largely explaining the observed differences in response rates between Caucasians, African Americans and Asians. IL28B polymorphism is also strongly associated with spontaneous clearance of HCV. The biological mechanisms responsible for these genetic associations remain unknown and are the focus of ongoing research. Knowledge of a patient's IL28B 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 IL28B type.


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