IL28B polymorphisms predict reduction of HCV RNA from the first day of therapy in chronic hepatitis C

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J Hepatol. 2011 Feb 24. [Epub ahead of print]

IL28B polymorphisms predict reduction of HCV RNA from the first day of therapy

in chronic hepatitis C.

Bochud PY, Bibert S, Negro F, Haagmans B, Soulier A, Ferrari C, Missale G,

Zeuzem S, Pawlotsky JM, Schalm S, Hellstrand K, Neumann AU, Lagging M; the

DITTO-HCV study group.

Service of Infectious Diseases, Department of Medicine, University Hospital and

University of Lausanne, Switzerland.

Abstract

BACKGROUND: Single nucleotide polymorphisms (SNPs) associated with IL28B

influence the outcome of peginterferon-α/ribavirin therapy of chronic hepatitis

C virus (HCV) infection. We analyzed the kinetics of HCV RNA during therapy as a

function of IL28B SNPs.

METHODS: IL28B SNPs rs8099917, rs12979860, and rs12980275 were genotyped in 242

HCV treatment-naïve Caucasian patients (67% genotype 1, 28% genotype 2 or 3)

receiving peginterferon-α2a (180 μg weekly) and ribavirin (1000-1200 mg daily)

with serial HCV-RNA quantifications. Associations between IL28B polymorphisms

and early viral kinetics were assessed, accounting for relevant covariates.

RESULTS: In the multivariate analyses for genotype 1 patients, the T allele of

rs12979860 (T(rs12979860)) was an independent risk factor for a less pronounced

first phase HCV RNA decline (log(10) 0.89 IU/ml among T carriers vs. 2.06 among

others, adjusted P<0.001) and lower rapid (15% vs. 38%, adjusted P=0.007) and

sustained viral response rates (48% versus 66%, adjusted P<0.001). In univariate

analyses, T(rs12979860) was also associated with a reduced second phase decline

(P=0.002), but this association was no longer significant after adjustment for

the first phase decline (adjusted P=0.8). In genotype 2/3 patients,

T(rs12979860) was associated with a reduced first phase decline (adjusted

P=0.04), but not with second phase decline.

CONCLUSION: Polymorphisms in IL28B are strongly associated with the first phase

viral decline during peginterferon-α/ribavirin therapy of chronic HCV

infection, irrespective of HCV genotype.

Copyright © 2011. Published by Elsevier B.V.

PMID: 21354446 [PubMed - as supplied by publisher]

[Guest guest]

J Hepatol. 2011 Feb 24. [Epub ahead of print]

IL28B polymorphisms predict reduction of HCV RNA from the first day of therapy

in chronic hepatitis C.

Bochud PY, Bibert S, Negro F, Haagmans B, Soulier A, Ferrari C, Missale G,

Zeuzem S, Pawlotsky JM, Schalm S, Hellstrand K, Neumann AU, Lagging M; the

DITTO-HCV study group.

Service of Infectious Diseases, Department of Medicine, University Hospital and

University of Lausanne, Switzerland.

Abstract

BACKGROUND: Single nucleotide polymorphisms (SNPs) associated with IL28B

influence the outcome of peginterferon-α/ribavirin therapy of chronic hepatitis

C virus (HCV) infection. We analyzed the kinetics of HCV RNA during therapy as a

function of IL28B SNPs.

METHODS: IL28B SNPs rs8099917, rs12979860, and rs12980275 were genotyped in 242

HCV treatment-naïve Caucasian patients (67% genotype 1, 28% genotype 2 or 3)

receiving peginterferon-α2a (180 μg weekly) and ribavirin (1000-1200 mg daily)

with serial HCV-RNA quantifications. Associations between IL28B polymorphisms

and early viral kinetics were assessed, accounting for relevant covariates.

RESULTS: In the multivariate analyses for genotype 1 patients, the T allele of

rs12979860 (T(rs12979860)) was an independent risk factor for a less pronounced

first phase HCV RNA decline (log(10) 0.89 IU/ml among T carriers vs. 2.06 among

others, adjusted P<0.001) and lower rapid (15% vs. 38%, adjusted P=0.007) and

sustained viral response rates (48% versus 66%, adjusted P<0.001). In univariate

analyses, T(rs12979860) was also associated with a reduced second phase decline

(P=0.002), but this association was no longer significant after adjustment for

the first phase decline (adjusted P=0.8). In genotype 2/3 patients,

T(rs12979860) was associated with a reduced first phase decline (adjusted

P=0.04), but not with second phase decline.

CONCLUSION: Polymorphisms in IL28B are strongly associated with the first phase

viral decline during peginterferon-α/ribavirin therapy of chronic HCV

infection, irrespective of HCV genotype.

Copyright © 2011. Published by Elsevier B.V.

PMID: 21354446 [PubMed - as supplied by publisher]