Aims: To investigate whether IPS1 polymorphisms affect peginterferon alpha (PEG-IFN) efficacy in chronic hepatitis B (CHB) patients using a tag- single nucleotide polymorphism (SNP) approach.
Methods: A total of 212 hepatitis B e antigen (HBeAg)-positive patients treated with a 48weeks of PEG-IFN monotherapy were enrolled initially and 127 patients were followed for 48weeks posttreatment. Genotype analysis was performed for 10 tag-SNPs in IPS1.
Results: The end of virological response (EVR) rate was 45.8% (97/212) and the sustained virological response (SVR) rate was 45.7% (58/127). Meanwhile, 35.4% (75/212) achieved HBeAg seroconversion at the end of treatment. In a multivariate analysis, the rs2464 CC genotype was independently associated with EVR (OR 2.21, 95% CI 1.23-3.98, P=0.008) and SVR (OR 2.34, 95% CI 1.05-5.20, P=0.037) after adjustment for sex, age, HBV genotype, baseline levels of HBV DNA and ALT. Meanwhile, rs2464 CC genotype were also independently associated with decline of HBsAg levels below 1500IU/mL at 12weeks of treatment (OR 2.52, 95% CI 1.01-6.29, P=0.047). Furthermore, three SNPs were found to be independently associated with HBeAg seroconversion at the end of treatment. (1) The rs2326369 CC genotype was independently associated with no HBeAg seroconversion (OR 0.52, 95% CI 0.29-0.95, P=0.034); (2) The rs6515831 TT genotype was independently associated with HBeAg seroconversion (OR 2.11, 95% CI 1.14-3.90, P=0.017); (3) The rs2464 CC genotype was independently associated with HBeAg seroconversion (OR 2.36, 95% CI 1.26-4.42, P=0.007).
Conclusions: Polymorphisms in IPS1 are independently associated with treatment response to PEG-IFN among Chinese HBeAg-positive CHB patients.
Keywords: Chronic hepatitis B; IPS1; Interferon therapy; Single nucleotide polymorphism.
Copyright © 2015 Elsevier B.V. All rights reserved.