Association of IPS1 polymorphisms with peginterferon efficacy in chronic hepatitis B with HBeAg-positive in the Chinese population

• 212 HBeAg-positive CHB patients treated with PEG-IFN were enrolled in this study.
• The rs2464 CC genotype in IPS1 was independently associated with virological response.
• Three IPS1 genotypes were independently associated with HBeAg seroconversion at the end of treatment.

AimsTo investigate whether IPS1 polymorphisms affect peginterferon alpha (PEG-IFN) efficacy in chronic hepatitis B (CHB) patients using a tag- single nucleotide polymorphism (SNP) approach.MethodsA total of 212 hepatitis B e antigen (HBeAg)-positive patients treated with a 48 weeks of PEG-IFN monotherapy were enrolled initially and 127 patients were followed for 48 weeks posttreatment. Genotype analysis was performed for 10 tag-SNPs in IPS1.ResultsThe 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 1500 IU/mL at 12 weeks 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).ConclusionsPolymorphisms in IPS1 are independently associated with treatment response to PEG-IFN among Chinese HBeAg-positive CHB patients.