A 67-year-old woman underwent PBSCT for therapy-related acute myeloid leukaemia and received azacitidine, busulfan and fludarabine therapy. Before PBSCT, she had been diagnosed with resolved HBV infection; HBsAg, negative; hepatitis B core antibody (HBcAb), positive (180.6 C.O.I.); and hepatitis B surface antibody (HBsAb), positive (36.9 mIU/mL). She had no history of HBV vaccination, but she experienced acute hepatitis B caused by blood transfusion for her child birth before PBSCT. Changes in HBsAb and HBcrAg during the course are presented in Fig. 1, as well as other liver function and viral status, alanine aminotransferase (ALT), HBsAg, HBcAb, HBeAg, hepatitis B e antibody (HBeAb) and HBV-DNA levels. Serum HBcrAg levels were determined via chemiluminescent enzyme immunoassay (LUMIPULSE®, Fujirebio Inc., Tokyo, Japan).

Changes in biochemical and virological parameters in the course of HBsAg seroconversion. The detection limits of HBV-DNA (H) before and after the HBV reactivation were 1.3 and 1.0 LogIU/mL, respectively. *: HBcrAg level was 7.0 LogU/mL (above the detection upper limit). ALT (A), alanine aminotransferase; HBsAg (B), hepatitis B surface antigen; HBsAb (C), hepatitis B surface antibody; HBcrAg (D), hepatitis B core-related antigen; HBcAb (E), hepatitis B core antibody; HBeAg (F), hepatitis B e antigen; HBeAb (G), hepatitis B e antibody

She received rituximab for post-transplant lymphoproliferative disorder 26 months after PBSCT, her HBsAb decreased (8.6 mIU/mL) and HBV-DNA increased slightly to detectable though the levels of < 1.3 logIU/mL. Since she tested positive for HBV-DNA (1.4 logIU/mL) 103 days after the first rituximab therapy (day 0, Fig. 1H), the scheduled rituximab administration was skipped and the first entecavir treatment was started according to the Japanese guideline for HBV reactivation [2]. Immediately after the first entecavir treatment, the HBV-DNA test became negative (day 63, Fig. 1H). Since her liver function (ALT levels) had been normal (Fig. 1A) and both HBsAg and HBV-DNA remained negative during NA treatment (Fig. 1B and H), entecavir was terminated on day 376. According to the retrospective measurements, HBcrAg remained positive (3.6–3.9 logU/mL) while the HBV-DNA level was undetectable under the first entecavir treatment (day 63–455, Fig. 1D). One hundred forty-one days after entecavir cessation, the HBV-DNA test turned positive again (1.8 logIU/mL), suggesting HBV rebound (day 517). Her HBV-DNA level reached 5.2 logIU/mL (day 601, Fig. 1H), her liver function deteriorated and HBV infection worsened; ALT, HBsAg, HBcrAg, HBcAb and HBeAg were elevated to high levels at 280 U/L, 1101.8 IU/mL, 7.0 logU/mL (above the detection range), 727.3 C.O.I. and 1060 S/CO, respectively (day 658, Fig. 1A, B, D, E and F), even though entecavir treatment was resumed on day 615. The HBsAb level, which had been negative before the HBV rebound, further decreased (0.3 mIU/mL) when the HBV rebound was detected (Fig. 1C). ALT peaked at 455 U/L on day 685 when the levels for HBsAg, HBcrAg, HBeAg and HBV-DNA peaked out and declined (Fig. 1A, B, D, F and H). On the contrary, HBsAb and HBeAb levels increased to 292.8–1631.6 mIU/mL and 99.2–99.5%, respectively (Fig. 1C and G), after the rebound, resulting in HBsAg seroconversion with HBcrAg and HBV-DNA levels undetectable. The second entecavir treatment was terminated on day 986. HBV reactivation has not been detected 392 days after the second entecavir cessation, and both HBcrAg and HBV-DNA levels remained undetectable. No difference in medication adherence and renal function was observed between first and second entecavir treatment. Daily dose of entecavir was 0.5 mg for both first and second treatment.