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Interleukin 28B Polymorphisms and Hepatitis C-Translating the Association into Clinical Decision Making.

ABSTRACT: Host genetic factors have long been suspected to play a role in predicting outcome and treatment response in hepatitis C virus (HCV) infection. This was confirmed recently by three landmark genome-wide association studies (GWAS) published in 2009, which identified single nucleotide polymorphisms near the interleukin (IL) 28B region that were more common in responders to treatment. There has subsequently been rapidly increasing data regarding the significance of the IL28B polymorphism not only in response to therapy but also in spontaneous clearance of acute HCV infection. This clinical association of Il28B genotype with HCV may lead to personalized HCV therapy, where the clinician may tailor the duration and type of therapy for an individual patient. This review summarizes the available data on the impact of IL28B polymorphisms on HCV infection and discusses the possible approach to translate this association into clinical decision making for the treatment of HCV infection.

SUBMITTER: Puri CP

PROVIDER: S-EPMC3940297 | biostudies-other | 2011 Jun

REPOSITORIES: biostudies-other

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Interleukin 28B Polymorphisms and Hepatitis C-Translating the Association into Clinical Decision Making.

Puri Col Pankaj CP

Journal of clinical and experimental hepatology 20110601 1

Host genetic factors have long been suspected to play a role in predicting outcome and treatment response in hepatitis C virus (HCV) infection. This was confirmed recently by three landmark genome-wide association studies (GWAS) published in 2009, which identified single nucleotide polymorphisms near the interleukin (IL) 28B region that were more common in responders to treatment. There has subsequently been rapidly increasing data regarding the significance of the IL28B polymorphism not only in ...[more]

PMID: 25755307

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Project description:UNLABELLED:Polymorphisms in the IL28B (interleukin-28B) gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of IL28B in spontaneous and treatment-induced clearance following recent HCV infection. The Australian Trial in Acute Hepatitis C (ATAHC) was a study of the natural history and treatment of recent HCV, as defined by positive anti-HCV antibody, preceded by either acute clinical HCV infection within the prior 12 months or seroconversion within the prior 24 months. Factors associated with spontaneous and treatment-induced HCV clearance, including variations in IL28B, were assessed. Among 163 participants, 132 were untreated (n = 52) or had persistent infection (infection duration ?26 weeks) at treatment initiation (n = 80). Spontaneous clearance was observed in 23% (30 of 132 participants). In Cox proportional hazards analysis (without IL28B), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (adjusted hazards ratio = 2.86; 95% confidence interval = 1.24, 6.59; P = 0.014). Among participants with IL28B genotyping (n = 102 of 163 overall and 79 of 132 for the spontaneous clearance population), rs8099917 TT homozygosity (versus GT/GG) was the only factor independently predicting time to spontaneous clearance (adjusted hazard ratio = 3.78; 95% confidence interval = 1.04, 13.76; P = 0.044). Participants with seroconversion illness with jaundice were more frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%, P = 0.047). Among participants adherent to treatment and who had IL28B genotyping (n = 54), sustained virologic response was similar among TT homozygotes (18 of 29 participants, 62%) and those with GG/GT genotype (16 of 25, 64%, P = 0.884). CONCLUSION:During recent HCV infection, genetic variations in IL28B region were associated with spontaneous but not treatment-induced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes.

Dataset Information

Interleukin 28B Polymorphisms and Hepatitis C-Translating the Association into Clinical Decision Making.

Publications

Interleukin 28B Polymorphisms and Hepatitis C-Translating the Association into Clinical Decision Making.

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