The relationship between IL-28B polymorphisms and the response to peginterferon alfa-2a monotherapy in anti-HBe-positive patients with chronic HBV infection.

Abstract

The impact of interleukin 28B (IL-28B) on the results of interferon (IFN)-based therapy in patients chronically infected with hepatitis B virus (HBV) is poorly understood. The aim of this study was to evaluate the relationship between IL-28B markers and the response to IFN monotherapy in Polish patients with anti-hepatitis B e (HBe)-positive chronic hepatitis B (CHB). We determined three single-nucleotide polymorphisms (SNPs) of IL-28B (rs12979860, rs12980275, and rs8099917) in 86 patients who were treated with pegylated interferon (PEG-IFN) for 48 weeks. The effectiveness of the therapy was evaluated based on the virological and biochemical response. The primary efficacy parameters were the HBV DNA viral load below 400 IU/ml and 2,000 IU/ml in combination with alanine aminotransferase (ALT) normalization (<40 IU/l), measured 24 weeks after the treatment. Viral load below 400 IU/ml or 2,000 IU/ml with ALT normalization was achieved by 37 % and 46 % of patients, respectively. It has been shown that the distribution of IL-28B genotypes in the dominant genetic model in patients with different therapeutic success differ significantly only for rs12979860. The IL-28B rs12979860 CC genotype was associated with lower treatment success [odds ratio (OR), 0.31; p = 0.025 and OR, 0.37; p = 0.044 for <400 IU/ml HBV DNA with <40 IU/l ALT, and <2,000 IU/ml HBV DNA with <40 IU/l ALT, respectively]. However, in the conditional logistic regression analysis adjusted by factors associated with combined response, rs12979860 was significantly associated only with <400 IU/ml HBV DNA with <40 IU/l ALT (OR, 0.24; p = 0.026). IL-28B polymorphisms have prognostic significance in assessing the treatment effectiveness based on the virological and biochemical response of patients with anti-HBe-positive CHB.