The Prevalence Of Cancer Related Mutations 1762T/1764A And Pres Deletions In Hepatitis B Virus(HBV)Isolated From HBV/HIV Co-infected Compared To HBV-mono-infected Adults-A Matched Case-control Study

Object To determine the prevalence of cancer related mutations1762T/1764 A and PreS deletions in hepatitis B virus(HBV)isolated from HBV/HIV co-infected compared to HBV-mono-infected adults.Methods According to matched case-control study,serum samples were collected through the Guilin Center for Disease Prevention and Control,the Hechi Center for Disease Prevention and Control,the First Affiliated Hospital of Guangxi University of Chinese Medicine,the Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control,the Cangwu county Center for Disease Prevention and Control and the Sanjiang county Center for Disease Prevention and control from HBV/HIV co-infected individuals and HBV mono-infected individuals,who were HBV and HIV drug-na?ve.Sera were tested for HBV serological markers and viral loads.HBV DNA was extracted using phenol-chloroform.The surface gene and basal core promoter(BCP)geneof HBV was amplified by nested PCR and the amplicons were direct sequenced by Bio Corporation.Phylogenetic analysis was carried out using Mega 5.0 and Bioedit 7.0.Data were analysis by using the Statistical Package for the Social Sciences(SPSSversion17.0).Results The study subjects consisted of sixty-one pairs.The mean age of both groups was 44.9 ± 12.1 years.Three HBV genotypes,including genotype B,C and I,were isolated in this study.Genotype B was the major genotype in both HBV/HIV co-infected(63.4%,39/61)and HBV mono-infected individuals(50.8%,31/61).The prevalence of HBV isolates with1762T/1764 A and/or preS deletion mutations was 37.7%(95% CI: 29.1–46.3).The result of analysis of variance perform that The prevalence of these mutations in HBV/HIV co-infected group(52.5%,95% CI: 40.0–65.0)was significantly higher than in the HBV mono-infected group(23.0%,95% CI: 12.4–33.6)(?2= 11.307,P <0.05).Individually BCP mutations(44.3% 95% CI: 31.9–56.8)occurred more frequently in isolates from co-infected compared to mono-infected individuals(?2 = 7.290,P < 0.05),the preS deletions mutations occurred more frequently in isolates from co-infected(23% 95%CI: 12.4–33.6)compared to mono-infected individuals(?2= 8.270,P < 0.05).The prevalence of BCP double mutations and pre-S deletion of HBV genotype C and I in the case group was higher than that of the control group(?2= 5.074 P<0.05).The prevalence of HBV isolates with BCP double mutations and/or pre S deletion mutations was higher in genotype B than in genotypes C and I and there was no statistical significance.HBV/HIV co-infection was associated with higher viral loads but these higher viral loads were not associated with the higher prevalence of HCC-related HBV mutations.The prevalence of cancer related mutations did not vary withCD4 cell counts.Multivariate analysis revealed that co-infection with HIV was associated with the development of both 1762T/1764A(RR:2.932(1.325–6.488))and preS deletions(RR: 5.759(1.562–21.235)).Conclusion Co-infection with HIV was associated with increased prevalence of HCC-related mutations in HBV isolates from Chinese patients.