Spontaneous reactivation of hepatitis B virus with multiple novel mutations in an elderly patient with resolved hepatitis B virus infection

Tokio Sasaki; Keisuke Kakisaka; Akio Miyasaka; Masao Nishiya; Naoki Yanagawa; Hidekatsu Kuroda; Takayuki Matsumoto; Masaharu Takahashi; Hiroaki Okamoto

doi:10.1007/s12328-024-01984-1

Spontaneous reactivation of hepatitis B virus with multiple novel mutations in an elderly patient with resolved hepatitis B virus infection

Clin J Gastroenterol. 2024 May 15. doi: 10.1007/s12328-024-01984-1. Online ahead of print.

Authors

Tokio Sasaki¹, Keisuke Kakisaka², Akio Miyasaka², Masao Nishiya³, Naoki Yanagawa³, Hidekatsu Kuroda², Takayuki Matsumoto², Masaharu Takahashi⁴, Hiroaki Okamoto⁴

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Iwate, 028-3694, Japan. sasakito@iwate-med.ac.jp.
² Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Iwate, 028-3694, Japan.
³ Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Iwate, 028-3694, Japan.
⁴ Division of Virology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.

PMID: 38748198
DOI: 10.1007/s12328-024-01984-1

Abstract

Spontaneous reactivation of the Hepatitis B virus (HBV) is rare in individuals with previously resolved infections. This report presents the case of a 71 year-old Japanese woman who experienced HBV reactivation without any prior immunosuppressive therapy or chemotherapy. Before the onset of liver injury, the patient was negative for hepatitis B surface antigen (HBsAg) but positive for hepatitis B surface antibody. She subsequently developed liver injury, with the reappearance of HBsAg and HBV DNA. The patient was successfully treated with tenofovir alafenamide, and prednisolone. Full-genome sequencing of HBV revealed subgenotype B1 without hepatitis B e-negative mutations in the precore and core promoter regions and 12 amino acid alterations in the pre-S1/S, P, and X genes. Notably, the S gene mutations D144A and K160N, which alter the antigenicity of HBsAg and potentially contribute to its reactivation, were identified. This case emphasizes the importance of vigilance for spontaneous reactivation of resolved HBV, highlighting the need for comprehensive genomic analysis to understand the associated virological intricacies.

Keywords: Hepatitis B virus; S gene mutation; Spontaneous reactivation.