Clinical implication and viral mutation in basal core promoter/pre-core of hepatitis B virus C/D recombinant.

Background And Aim: Hepatitis B virus (HBV) C/D recombinant is predominant in Tibet in Western China. Although the geographical and ethnic distributions of the C/D recombinant have been described, the clinical implication and the characteristics of viral mutation in the basal core promoter (BCP)/pre-core (PC) region remain unclear.

Methods: A total of 174 chronic HBV carriers, including 115 with chronic hepatitis B, 45 with liver cirrhosis, and 14 with hepatocellular carcinoma, were enrolled. Using next-generation sequencing, the S and BCP/PC genes were determined and analyzed.

Results: Genotypes B, C2, D, and C/D recombinant were detected in 1.1% (2/174), 19.5% (34/174), 0.6% (1/174) and 78.7% (137/174) of the patients, respectively. The clinical parameters and viral mutation frequency in the BCP/PC region were compared between C2- and C/D recombinant-infected patients. The distribution of C2 and C/D did not differ by disease status or liver function. Significantly higher levels of HBV DNA (6.7 ± 1.6 vs. 5.9 ± 1.5, p = 0.014), HBeAg (263.5 vs. 20.0, p = 0.013) and A1762T/G1764A double-mutations (81.0 vs. 61.8%, p = 0.018), but a lower frequency of G1896A stop mutation (33.6 vs. 76.5%, p < 0.001) was observed in patients with the C/D recombinant than in patients with genotype C2. The clonal frequencies of A1762T, G1764A, G1896A and A1846T were lower in patients with C/D than C2.

Conclusion: The C/D recombinant has different mutation pattern in the BCP/PC region compared with genotype C2. The lower clonal frequencies of BCP/PC mutations may explain the higher levels of HBV DNA and HBeAg in C/D-infected patients.