The Relationship Between The Precore/Basal Core Promoter Mutants Of Hepatitis B Virus And Therapeutic Effect Of Peginterferon Alpha-2b ± Adefovir Dipivoxil And The Changes In Mutants Before And After Treatment

ObjectiveTo investigate the relationship between therapeutic effect of peg-interferon alpha-2b and pre-core(PC)(G1896A)and basal core promoter(BCP)(A1762T/G1764A)mutants of hepatitis B virus.To investigate the changes of G1896 A and A1762 T / G1764 A mutants before and after treatmentMaterials and MethodsEighty-nine treatment-na?ve patients with HBe Ag-positive CHB were treated with Peg-IFNα-2b mono-therapy or combined with adefovir for 48 weeks and followed up for 24 weeks.Serum HBs Ag,HBe Ag,ALT and HBV DNA was quantified for the samples taken at baseline(week 0),during the treatment period(weeks 4,8,12,24,36 and 48),and during follow-up(weeks 60 and 72).Every patient in the regular follow-up were collected 20 m L venous blood and centrifuged to take the serum and stored at-80℃.Serum HBV genomic templates were extracted from each patient at week 0 and week 72.PC and BCP regions were amplified by PCR and sequenced to analyze the mutation status.Results1.Within the total cohort,WT(wild-type)virus was detectable in only 16 patients(18%),and mutants(Non-WT)were detected in 73 patients(82%).Patients with genotype B are more likely to have PC mutations and patients with genotype C are more likely to have BCP mutations.2.The level of HBe Ag in WT group was higher than that in Non-WT group(P <0.05).When patients were divided into four groups based on the overall quartile of HBe Ag levels,it was found that as HBe Ag levels increased,the proportion of WT type gradually increased.3.The genotypes B and C had no significant effect on the therapeutic response(HBe Ag seroconversion,combined response)of Peg-IFNα-2b or Peg-IFNα-2b +ADV.4.Within the total cohort(n = 89),there was no significant difference in HBe Ag seroconversion between the monotherapy and the combination groups at 72 weeks(27% vs 40%,P = 0.204).However,there was a statistically significant difference in combined response rates between monotherapy and combination groups at 72weeks(11% vs 33%,P = 0.013).5.There was no significant difference in HBe Ag seroconversion(P > 0.05)or combined response(P > 0.05)between patients with wild-type virus or mutants(PC type,BCP type and PC+BCP type).6.Patients with HBe Ag seroconversion or combined response and successful sequenced in week 72 found no reversal of Non-WT to WT phenomenon.Conclusion1.PC/BCP mutations have a high prevalence in HBe Ag-positive CHB patients.2.PC/BCP mutations have no significant effect on the efficacy of Peg-IFNα-2b monotherapy or in combination with adefovir.3.Patients with HBe Ag seroconversion or combined response and successful sequenced in week 72 found no reversal of Non-WT to WT phenomenon.4.Peg-IFNα-2b combined with adefovir treatment can improve the combined response rate at the end of follow-up.