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.
Competing Interests: Declarations. Conflict of interest: Satoshi MOCHIDA has received speaking fees or honoraria from Abbvie GK, Gilead Sciences Inc., Ohtsuka Pharmaceutical Co. Ltd., Torey Medical Co. Ltd, Eisai Co., Ltd. Asuka Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co., Ltd., has received research grants from Abbvie GK, Eisai Co., Ltd. Sumitomo Pharma Co., Ltd. intellim Corporation. Human rights: All the procedures were performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. Informed consent: Informed consent was obtained from the patient to publish the clinical and virological findings.
(© 2024. Japanese Society of Gastroenterology.)