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Original article

Serum interleukin (IL)-10 and IL-12 levels and IL28B gene polymorphisms: pretreatment prediction of treatment failure in chronic hepatitis C

Takeji Umemura, Satoru Joshita, Suguru Yoneda, Yoshihiko Katsuyama, Tetsuya Ichijo, Akihiro Matsumoto, Kaname Yoshizawa, Masao Ota, Eiji Tanaka

Corresponding author name: Takeji Umemura
Corresponding author e-mail: tumemura@shinshu-u.ac.jp

Citation: Antiviral Therapy 2011; 16:1073-1080
doi: 10.3851/IMP1869

Date accepted: 21 February 2011
Date published online: 29 July 2011

Abstract

Background: Both IL28B gene polymorphisms and serum levels of interleukin (IL)-10, IL-12p40 and IL-18 have been reported to affect the outcome of natural and pegylated interferon and ribavirin-treated HCV infection.

Methods: To clarify their association and predictive value in treatment outcome of genotype 1 HCV-infected patients, we measured pretreatment serum IL-10, IL-12p40 and IL-18 levels using multiplex assays and determined IL28B gene polymorphisms (rs 8099917) in 52 cases with chronic hepatitis C.

Results: High baseline levels of IL-10 (P<0.001) and low levels of IL-12p40 (P<0.001) were significantly associated with a non-virological response (NVR) in our cohort. The IL28B polymorphism was tested and TT, TG or GG genotypes were found in 60%, 38% and 2% of patients, respectively, with corresponding NVR rates of 10%, 60% and 100% (P<0.001). Serum cytokine levels were significantly correlated with IL28B gene polymorphisms. When serum IL-10 levels were stratified at 5.0 pg/ml, NVR rates were 50% versus 0% (P=0.004) for the TT genotype and 87% versus 0% (P=0.001) for the TG or GG genotypes. Similarly, low IL-12p40 levels were associated with an NVR in patients with TG or GG genotypes (P=0.006). In multivariate analysis, high IL-10, low IL-12p40 and IL28B TG or GG genotypes were independently associated with an NVR.

Conclusions: Serum IL-10 and IL-12p40 levels in combination with IL28B genotype, especially G-allele carriage, are strong predictive markers of an NVR to HCV treatment with pegylated interferon and ribavirin.

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