Virological Factors Associated With the Occurrence of Hepatitis B Virus (HBV) Reactivation in Patients With Resolved HBV Infection Analyzed Through Ultradeep Sequencing

Background. Hepatitis B virus reactivation (HBVr) is an important complication of immunosuppressive drug therapy. It can occur via both virological and host factors; however, the underlying mechanisms remain largely unknown. Methods. We examined serum samples derived from patients with HBVr and those with acute hepatitis B (AHB). The targeted nucleic acid molecule in hepatitis B virus deoxyribonucleic acid was amplified and analyzed by next-generation sequencing. Results. The percentage of patients infected with genotype Bj among the HBVr patients was significantly higher than that in the AHB patients. The frequency of mutation sites in the whole HBV genome, especially in the envelope region, in the HBVr was significantly higher than that in the AHB. The prevalence of the S3N amino acid substitution in the envelope protein and mutations at positions G1896A and G1899A in the precore region were significantly higher in the HBVr compared with AHB. The population of S3N amino acid substitution and nucleotide G1896A and G1899A mutations in each individual showed a similar percentage of occurrence. Conclusions. We identified specific virological factors in patients with HBVr through ultradeep sequencing. Our findings could be beneficial for the elucidation of mechanisms underlying HBVr development and for disease control.