Tadashi Inuzuka, Atsushi Takai, Masayuki Ueno, Masako Mishima, Haruhiko Takeda, Ken Takahashi, Takahisa Kayahara, Hiroyuki Takabatake, Hirokazu Mouri, Hiroshi Seno
Hepatitis B virus (HBV) reactivation is a major complication of immunosuppressive therapy or chemotherapy in patients with resolved HBV infection, yet the clinical significance of low-level HBV DNA reappearance remains unclear. We retrospectively analyzed 69 patients with resolved HBV infection who developed HBV DNA reappearance under immunosuppression. Among them, 38 patients were initially managed without immediate nucleos(t)ide analogue therapy, allowing assessment of HBV DNA kinetics. True reactivation was defined as HBV DNA ≥ 3.3 log IU/mL after initial detection. Of the 38 monitored patients, 7 (18%) progressed to true reactivation, 18 (47%) achieved spontaneous viral clearance, and 13 initiated antiviral therapy before meeting either definition. Distinct risk patterns emerged: all patients with an initial HBV DNA level ≥ 2.0 log IU/mL progressed to true reactivation, whereas only 2 of 20 with lower levels did so. Hematologic malignancy was also strongly associated with clinically significant reactivation, with true reactivation occurring in 6 of 12 patients compared with 1 of 13 patients with other diseases. These findings suggest that low-level HBV DNA reappearance under immunosuppression represents transient viremia rather than progressive reactivation. Risk stratification based on initial viral load and underlying disease may enable individualized management, reducing unnecessary antiviral therapy while maintaining patient safety.