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 Beek; Geoff 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

doi:10.1002/hep.23850

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

Research output: Contribution to journal › Article › Research › peer-review

156 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 language	English
Pages (from-to)	1216-1224
Number of pages	9
Journal	Hepatology
Volume	52
Issue number	4
DOIs	https://doi.org/10.1002/hep.23850
Publication status	Published - 22 Nov 2010

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10.1002/hep.23850

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Grebely, J., Petoumenos, K., Hellard, M., Matthews, G. V., Suppiah, V., Applegate, T., Yeung, B., Marks, P., Rawlinson, W., Lloyd, A. R., Booth, D., Kaldor, J. M., George, J., Dore, G. J., Marks, P., Haber, P. S., Ffrench, R., White, P., Day, C., ... ATAHC Study Group (2010). Potential role for interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection. Hepatology, 52(4), 1216-1224. https://doi.org/10.1002/hep.23850

@article{35a29d4b9a304b6fb3bdcfefbd7e2439,

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

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.",

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

year = "2010",

month = nov,

day = "22",

doi = "10.1002/hep.23850",

language = "English",

volume = "52",

pages = "1216--1224",

journal = "Hepatology",

issn = "0270-9139",

publisher = "John Wiley & Sons",

number = "4",

}

Grebely, J, Petoumenos, K, Hellard, M, Matthews, GV, Suppiah, V, Applegate, T, Yeung, B, Marks, P, Rawlinson, W, Lloyd, AR, Booth, D, Kaldor, JM, George, J, Dore, GJ, Marks, P, Haber, PS, Ffrench, R, White, P, Day, C, van Beek, I, McCaughan, G, Madden, A, Dolan, K, Farrell, GC, Crofts, N, Sievert, W, Baker, D, Acraman, B, Amin, J, Doab, A, Carroll, T, Nguyen, O, von Bibra, S, Teutsch, S, Li, H, Oon, A, Cameron, B, Jacka, B, Pan, Y, Flynn, J, Goy, K, Shaw, D, Sasadeusz, J, Crawford, D, Phung, N, Bloch, MT, Hughes, BM, Mollison, L, Roberts, S, Desmond, P & ATAHC Study Group 2010, 'Potential role for interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection', Hepatology, vol. 52, no. 4, pp. 1216-1224. https://doi.org/10.1002/hep.23850

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 Martin

AU - George, Jacob

AU - Dore, Gregory J

AU - Marks, Pip

AU - Haber, Paul S.

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 C

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 T

AU - Hughes, Brian M

AU - Mollison, Lindsay

AU - Roberts, Stuart

AU - Desmond, Paul

AU - ATAHC Study Group

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

C2 - 20803561

AN - SCOPUS:77957965687

SN - 0270-9139

VL - 52

SP - 1216

EP - 1224

JO - Hepatology

JF - Hepatology

IS - 4

ER -

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

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