TY - JOUR
T1 - Potential role for interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection
AU - Grebely, Jason
AU - Petoumenos, Kathy
AU - Hellard, Margaret
AU - Matthews, Gail V.
AU - Suppiah, Vijayaprakash
AU - Applegate, Tanya
AU - Yeung, Barbara
AU - Marks, Phillipa
AU - Rawlinson, William
AU - Lloyd, Andrew R.
AU - Booth, David
AU - Kaldor, John M.
AU - George, Jacob
AU - Dore, Gregory J.
AU - Marks, Pip
AU - Haber, Paul
AU - Ffrench, Rose
AU - White, Peter
AU - Day, Carolyn
AU - van Beek, Ingrid
AU - McCaughan, Geoff
AU - Madden, Annie
AU - Dolan, Kate
AU - Farrell, Geoff
AU - Crofts, Nick
AU - Sievert, William
AU - Baker, David
AU - Acraman, Brian
AU - Amin, Janaki
AU - Doab, Anna
AU - Carroll, Therese
AU - Nguyen, Oanh
AU - von Bibra, Sally
AU - Teutsch, Suzy
AU - Li, Hui
AU - Oon, Alieen
AU - Cameron, Barbara
AU - Jacka, Brendan
AU - Pan, Yong
AU - Flynn, Jacqueline
AU - Goy, Kylie
AU - Shaw, David
AU - Sasadeusz, Joe
AU - Crawford, Darrell
AU - Phung, Nghi
AU - Bloch, Mark
AU - Hughes, Brian
AU - Mollison, Lindsay
AU - Roberts, Stuart
AU - Desmond, Paul
N1 - Publisher Copyright:
© 2010 by the American Association for the Study of Liver Diseases.
PY - 2010/11/22
Y1 - 2010/11/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77957965687&partnerID=8YFLogxK
U2 - 10.1002/hep.23850
DO - 10.1002/hep.23850
M3 - Article
SN - 0270-9139
VL - 52
SP - 1216
EP - 1224
JO - Hepatology
JF - Hepatology
IS - 4
ER -