Potential role for interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection

Jason Grebely, Kathy Petoumenos, Margaret Hellard, Gail V Matthews, Vijayaprakash Suppiah, Tanya Applegate, Barbara Yeung, Phillipa Marks, William Rawlinson, Andrew R. Lloyd, David Booth, John Martin Kaldor, Jacob George, Gregory J Dore, Pip Marks, Paul S. Haber, Rose Ffrench, Peter White, Carolyn Day, Ingrid van BeekGeoff McCaughan, Annie Madden, Kate Dolan, Geoff C Farrell, Nick Crofts, William Sievert, David Baker, Brian Acraman, Janaki Amin, Anna Doab, Therese Carroll, Oanh Nguyen, Sally von Bibra, Suzy Teutsch, Hui Li, Alieen Oon, Barbara Cameron, Brendan Jacka, Yong Pan, Jacqueline Flynn, Kylie Goy, David Shaw, Joe Sasadeusz, Darrell Crawford, Nghi Phung, Mark T Bloch, Brian M Hughes, Lindsay Mollison, Stuart Roberts, Paul Desmond, ATAHC Study Group

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    81 Citations (Scopus)

    Abstract

    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 virologicresponse 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 treatmentinduced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes.

    Original languageEnglish
    Pages (from-to)1216-1224
    Number of pages9
    JournalHepatology
    Volume52
    Issue number4
    DOIs
    Publication statusPublished - 22 Nov 2010

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