HBV gene mutations in six multidrug-resistant chronic hepatitis B patients in China

The application of many nucleoside analogs has produced multidrug-resistant mutant strains of hepatitis B virus (HBV). This study aimed to analyze the association between HBV gene mutations in chronic hepatitis B patients and antiviral multidrug resistance. The whole HBV genome in serum samples of six cases of clinical multidrug-resistant patients was amplified using polymerase chain reaction (PCR), then purified and cloned into the pMD18T plasmid to construct 19 clones of recombinant pMD18T-HBV plasmids for whole genome sequencing. The mutations in the P region and other regions in the HBV genome were analyzed. We found that the 19 clones of HBV from these six cases were all of the C genotype. The major common mutation site in the P region was rtM204V/I, and the accompanied common sites were rtQ333K, rtH337N, and rtD392S. The common mutations in the S region of the 19 clones were T56N, K57Q, D62A, and V157A. The common mutation sites in the X region were A41S, G85A, and L92V. There was no common mutation site discovered in the C region. In conclusion, the detection of mutation sites in HBV will help reveal the mechanism underlying the multidrug-resistance of HBV and improve clinical antiviral therapy in chronic hepatitis B patients.