Association of IL28B polymorphisms with peginterferon treatment response in Chinese Han patients with HBeAg-positive chronic hepatitis B

Abstract

Aims: To investigate whether IL28B polymorphisms could affect the treatment response to peginterferon alpha (PEG-IFN) in chronic hepatitis B (CHB) patients in the Chinese Han population.

Methods: A total of 212 hepatitis B e antigen (HBeAg)-positive patients treated with PEG-IFN monotherapy were enrolled in this study. Genotype analysis was performed for IL28B rs12980275, rs12979860 and rs8099917 using the MassArray system. Response was defined as cases showing normal aminotransferase (ALT) levels, HBV DNA level < 200 IU/ml and HBeAg seroconversion after 48 weeks of PEG-IFN therapy.

Results: The patients were infected with hepatitis B virus (HBV) genotype B (44.8%) and C (55.2%) with a total response rate of 34.9%. For the three SNPs, there were significant differences between the response (R) and non-response (NR) groups both in allele frequencies and genotype distributions. IL28B genotype was independently associated with R for AA vs. N-AA (OR 2.70, 95% CL 1.21-6.01; P = 0.015) at rs12980275 after adjustment for sex, age, HBV genotype, baseline levels of HBV DNA and ALT. There were similar results for rs12979860 CC vs. N-CC (OR 2.56, 95% CL 1.15-5.67; P = 0.021) and rs8099917 TT vs. N-TT (OR 2.80, 95% CL 1.23-6.39; P = 0.015) respectively. Furthermore, one block formed by rs12980275 and rs12979860 was identified in this study. In multivariate analyses, the most common haplotype A-C was independently associated with high rates of R (OR 2.53, 95% CL 1.20-5.34; P = 0.015).

Conclusions: Our study suggested that genetic variations in IL28B may play a critical role in PEG-IFN efficacy in HBeAg-positive CHB patients in Han Chinese.

Keywords: IL28B; chronic hepatitis B; peginterferon; single nucleotide polymorphism; treatment response.