Comprehensive genome analysis of hepatitis B virus using nanopore sequencing technology in patients with previously resolved infection and spontaneous reactivation without drug exposure.

A 75-year-old Japanese woman experienced persistent fatigue and progressive jaundice for 6 weeks, and was subsequently diagnosed with acute liver failure. She had not received any immunosuppressive therapies and/or antineoplastic chemotherapy. Blood tests revealed elevated levels of HBsAg, HBV-DNA, and anti-HBc IgG, while anti-HBc IgM was negative. She had undergone hepatitis virus testing 48 weeks earlier, during which HBsAg was negative, indicating that HBV reactivation occurred in a patient with a previously resolved infection, without any drug therapies as triggers, ultimately leading to acute liver failure. Despite receiving multidisciplinary intensive treatment, her condition worsened, resulting in death. Full-length genomic analysis of the HBV strain, performed using nanopore sequencing technology, identified an I126S substitution in HBsAg, known as a vaccine escape mutation, along with a quasispecies consisting primarily of two HBV clone variants: one full-length and the other with a deletion in the nt2,448-nt488 region (sp1 spliced variant). These genetic factors may have contributed to the spontaneous HBV reactivation.