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Multicenter Study
. 2010 Oct;52(4):1216-24.
doi: 10.1002/hep.23850.

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

Jason Grebely  1 , Kathy Petoumenos, Margaret Hellard, Gail V Matthews, Vijayaprakash Suppiah, Tanya Applegate, Barbara Yeung, Phillipa Marks, William Rawlinson, Andrew R Lloyd, David Booth, John M Kaldor, Jacob George, Gregory J Dore; ATAHC Study Group
Collaborators, Affiliations
Multicenter Study

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

Jason Grebely et al. Hepatology. 2010 Oct.

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 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.

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Figures

Figure 1
Figure 1
Overview of study population
Figure 2
Figure 2
A. Time to spontaneous HCV clearance among participants with GG/GT and TT genotypes at the SNP rs8099917 in the IL28B gene in the ATAHC study, excluding treated participants with an estimated duration of infection <26 weeks (n=79). B. Time to spontaneous HCV clearance among participants with GG/GA and AA genotypes at the SNP rs12980275 in the IL28B gene in the ATAHC study, excluding treated participants with an estimated duration of infection <26 weeks (n=75).
Figure 2
Figure 2
A. Time to spontaneous HCV clearance among participants with GG/GT and TT genotypes at the SNP rs8099917 in the IL28B gene in the ATAHC study, excluding treated participants with an estimated duration of infection <26 weeks (n=79). B. Time to spontaneous HCV clearance among participants with GG/GA and AA genotypes at the SNP rs12980275 in the IL28B gene in the ATAHC study, excluding treated participants with an estimated duration of infection <26 weeks (n=75).
Figure 3
Figure 3
Proportion with SVR among participants adherent to therapy with rs8099917 and rs12980275 genotyping.
Figure 4
Figure 4
Proposed algorithm for incorporation of IL28B genetic testing into clinical management of acute HCV infection.
See this image and copyright information in PMC

Comment in

References

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