Potential Role for Interleukin-28B Genotype in Treatment Decision-Making in Recent Hepatitis C Virus Infection

被引：140

作者：

Grebely, Jason ^{[1
]}

Petoumenos, Kathy ^{[1
]}

Hellard, Margaret ^{[2
,3
]}

Matthews, Gail V. ^{[1
,4
]}

Suppiah, Vijayaprakash ^{[5
,6
,7
]}

Applegate, Tanya ^{[1
]}

Yeung, Barbara ^{[1
]}

Marks, Phillipa ^{[1
]}

Rawlinson, William ^{[8
,9
]}

Lloyd, Andrew R. ^{[8
]}

Booth, David ^{[7
]}

Kaldor, John M. ^{[1
]}

George, Jacob ^{[5
,6
]}

Dore, Gregory J. ^{[1
,4
]}

机构：

[1] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res NCHECR, Sydney, NSW, Australia

[2] Burnet Inst, Melbourne, Vic, Australia

[3] Alfred Hosp, Infect Dis Unit, Melbourne, Vic, Australia

[4] St Vincents Hosp, HIV Immunol Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia

[5] Univ Sydney, Westmead Hosp, Sydney, NSW 2006, Australia

[6] Univ Sydney, Westmead Millennium Inst, Storr Liver Unit, Sydney, NSW 2006, Australia

[7] Univ Sydney, Westmead Millennium Inst, Inst Immunol & Allergy Res, Sydney, NSW 2006, Australia

[8] UNSW, Sch Med Sci, Ctr Infect & Inflammat Res, Sydney, NSW, Australia

[9] Prince Wales Hosp, SEALS Microbiol, Div Virol, Sydney, NSW, Australia

来源：

HEPATOLOGY | 2010年 / 52卷 / 04期

关键词：

PEGYLATED INTERFERON-ALPHA; GENETIC-VARIATION; DRUG-USERS; THERAPY; IL28B; CLEARANCE; RIBAVIRIN; COHORT;

D O I：

10.1002/hep.23850

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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 ha7Ard 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 treatmentinduced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes. (HEPATOLOGY 2010;52:1216-1224)

引用

页码：1216 / 1224

页数：9

共 25 条

[1] Potential biases in estimates of hepatitis C RNA clearance in newly acquired hepatitis C infection among a cohort of injecting drug users [J].

Amin, J. ;

Law, M. G. ;

Micallef, J. ;

Jauncey, M. ;

Van Beek, I. ;

Kaldor, J. M. ;

Dore, G. J. .

EPIDEMIOLOGY AND INFECTION, 2007, 135 (01) :144-150

[2] Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[3] Acute hepatitis C virus infection: A chronic problem [J].

Blackard, Jason T. ;

Shata, M. Tarek ;

Shire, Norah J. ;

Sherman, Kenneth E. .

HEPATOLOGY, 2008, 47 (01) :321-331

[4] New insights into the immunopathogenesis of chronic hepatitis C [J].

Diepolder, Helmut. M. .

ANTIVIRAL RESEARCH, 2009, 82 (03) :103-109

[5] Effective Treatment of Injecting Drug Users With Recently Acquired Hepatitis C Virus Infection [J].

Dore, Gregory J. ;

Hellard, Margaret ;

Matthews, Gail V. ;

Grebely, Jason ;

Haber, Paul S. ;

Petoumenos, Kathy ;

Yeung, Barbara ;

Marks, Philippa ;

van Beek, Ingrid ;

McCaughan, Geoffrey ;

White, Peter ;

French, Rosemary ;

Rawlinson, William ;

Lloyd, Andrew R. ;

Kaldor, John M. .

GASTROENTEROLOGY, 2010, 138 (01) :123-135

[6] Mechanism of action of interferon and ribavirin in treatment of hepatitis C [J].

Feld, JJ ;

Hoofnagle, JH .

NATURE, 2005, 436 (7053) :967-972

[7] Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance [J].

Ge, Dongliang ;

Fellay, Jacques ;

Thompson, Alexander J. ;

Simon, Jason S. ;

Shianna, Kevin V. ;

Urban, Thomas J. ;

Heinzen, Erin L. ;

Qiu, Ping ;

Bertelsen, Arthur H. ;

Muir, Andrew J. ;

Sulkowski, Mark ;

McHutchison, John G. ;

Goldstein, David B. .

NATURE, 2009, 461 (7262) :399-401

[8] Spontaneous clearance and the beneficial impact of treatment on clearance during recent hepatitis C virus infection [J].

Grebely, J. ;

Matthews, G. V. ;

Petoumenos, K. ;

Dore, G. J. .

JOURNAL OF VIRAL HEPATITIS, 2010, 17 (12) :896-896

[9] Treatment of acute hepatitis C with interferon alfa-2b [J].

Jaeckel, E ;

Cornberg, M ;

Wedemeyer, H ;

Santantonio, T ;

Mayer, J ;

Zankel, M ;

Pastore, G ;

Dietrich, M ;

Trautwein, C ;

Manns, MP .

NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (20) :1452-1457

[10] Duration of peginterferon therapy in acute hepatitis C: A randomized trial [J].

Kamal, SM ;

Moustafa, KN ;

Chen, J ;

Fehr, J ;

Moneim, AA ;

Khalifa, KE ;

El Gohary, LA ;

Ramy, AH ;

Madwar, MA ;

Rasenack, J ;

Afdhal, NH .

HEPATOLOGY, 2006, 43 (05) :923-931

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