Higher 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 Chinese adults

Abstract

In the era of combination therapy for human immunodeficiency virus (HIV), liver disease including hepatocellular carcinoma (HCC), are the major causes of death for patients co-infected with hepatitis B virus (HBV) and HIV. However, the mechanisms remain obscure. We aimed to determine whether HCC-related HBV mutations including 1762T/1764A double mutation and pre-S deletions occur more frequently in HBV/HIV co-infected individuals compared to HBV mono-infected individuals. In this study, the basic core promoter (BCP) and the preS/S regions of HBV isolated from 61 pairs of HBV/HIV co-infected and HBV mono-infected participants were analyzed. We found that the prevalence of HBV isolates with 1762T/1764A and/or preS deletion mutations was 37.7% (95% CI: 29.1–46.3). 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) (X2=11.307, P<0.05). 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. Individually 1762T1764A (44.3%) or preS deletions (23%) occurred more frequently in isolates from co-infected compared to mono-infected individuals (21.3%, 4.9%, respectively) (X2=7.290, P<0.05; X2=8.270, P<0.05). Moreover, 1762T/1764A and preS deletions occurred more frequently in genotypes C and I compared to genotype B (p<0.05). 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)). These results demonstrate that co-infection with HIV was associated with increased prevalence of HCC-related mutations in HBV isolates from Chinese patients.