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IL-28B polymorphisms and treatment response in hepatitis C virus patients with persistently normal alanine aminotransferase.

ABSTRACT: AIM:To examine the association between the interleukin 28B (IL-28B) genotype and treatment response in hepatitis C virus (HCV)-infected patients with persistently normal alanine aminotransferase (PNALT). METHODS:We compared the treatment response of HCV-infected patients with PNALT to that of patients with non-PNALT. Between February 2010 and April 2013, 278 patients infected with HCV were enrolled in this study. All of the patients were treated with peginterferon-alpha 2a or 2b plus ribavirin. In addition, 180 ?g of peginterferon alpha-2a or 1.5 ?g/kg peginterferon alpha-2b per week plus weight-based ribavirin (600-1000 mg/d) were typically administered for 24 wk to HCV genotype 2-infected patients or for 48-72 wk to HCV genotype 1-infected patients. In all of the patients, the IL-28B rs8099917 genotype was determined using a TaqMan single-nucleotide polymorphism assay. HCV RNA was measured using the COBAS TaqMan HCV test. RESULTS:Female patients were dominant in the PNALT group (P < 0.0001). Among 72 HCV genotype 1-infected patients with PNALT, the early virologic response (EVR) rates (P < 0.01) and the sustained virologic response (SVR) rates (P < 0.01) were higher in patients with the IL-28B TT genotype than in those with the IL-28B TG/GG genotype. In HCV genotype 1-infected patients with PNALT, multivariate logistic-regression analysis showed that SVR was independently predicted by the IL-28B rs8099917 TT type (P < 0.05) and having an EVR (P < 0.01). The IL-28B rs8099917 TT genotype strongly correlated with treatment response in HCV genotype 1-infected Asian patients with PNALT. CONCLUSION:The IL-28B genotype may be useful for selecting HCV genotype 1-infected patients with PNALT who should receive interferon-based treatment.

SUBMITTER: Miyamura T

PROVIDER: S-EPMC3847947 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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IL-28B polymorphisms and treatment response in hepatitis C virus patients with persistently normal alanine aminotransferase.

Miyamura Tatsuo T Kanda Tatsuo T Nakamura Masato M Jiang Xia X Wu Shuang S Nakamoto Shingo S Mikami Shigeru S Takada Nobuo N Imazeki Fumio F Yokosuka Osamu O

World journal of hepatology 20131101 11

<h4>Aim</h4>To examine the association between the interleukin 28B (IL-28B) genotype and treatment response in hepatitis C virus (HCV)-infected patients with persistently normal alanine aminotransferase (PNALT).<h4>Methods</h4>We compared the treatment response of HCV-infected patients with PNALT to that of patients with non-PNALT. Between February 2010 and April 2013, 278 patients infected with HCV were enrolled in this study. All of the patients were treated with peginterferon-alpha 2a or 2b p ...[more]

PMID: 24303092

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Project description:BACKGROUND:Cytokines play an important role in the regulation of the immune response. In hepatitis C virus (HCV) infection, cytokine levels may influence the outcome of acute HCV infection. Polymorphisms in cytokine genes have been associated to different expression levels in response to infection. This study was carried out to investigate the association of several cytokine gene polymorphisms with disease outcome in HCV-infected patients. FINDINGS:Patients with chronic or spontaneously resolved HCV infection were included in a cross-sectional study. A comparative analysis was performed between the groups regarding frequency distribution of the following cytokines' gene polymorphisms: IL-10 (-1082 A/G; -819?T/C; -592 A/C), IL-4 (+33C/T), IFN-? (+874?T/A), TNF-? (-238?G/A and -308?G/A) and IL-28B (rs12979860 C/T and rs8099917 T/G). RESULTS:Eighteen patients with spontaneous viral clearance and 161 with chronic HCV infection were included. In the comparative analysis, the GG genotype of the IL-10 polymorphism -1082A/G was more frequent in patients with spontaneous viral clearance when compared to patients with chronic HCV (41.2% vs 6.2%; p = 0.001). This association was also found for the CC genotype of the IL-4 polymorphism +33C/T (72.2% vs 36.7%; p = 0.017) and the CC and TT genotypes of the IL-28B polymorphisms rs 12979860 and rs 8099917 (88.9% vs 30.3%; p?<?0.001 and 88.9% vs 49.6%; p = 0.002). The IL10 (A-1082?G) and IL-28B (Crs12979860T) gene polymorphisms showed odds ratios of 12.848 and 11.077, respectively, and thus may have a greater influence on HCV spontaneous viral clearance. The IFN-? (+874?T/A), TNF-? (-238?G/A and -308?G/A) polymorphisms did not show significant association with spontaneous viral clearance or chronicity. CONCLUSION:The G allele for IL-10 (-1082 A/G), the C allele for IL-4 (+3 C/T) and the C and T alleles for IL-28B (rs12979860 and rs8099917, respectively) are associated with spontaneous viral clearance in hepatitis C infection.

Dataset Information

IL-28B polymorphisms and treatment response in hepatitis C virus patients with persistently normal alanine aminotransferase.

Publications

IL-28B polymorphisms and treatment response in hepatitis C virus patients with persistently normal alanine aminotransferase.

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