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Prospective long-term study of hepatitis B virus reactivation in patients with hematologic malignancy
Akihiro Tamori1, Masayuki Hino, Etsushi Kawamura
1Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Background And Aim:
To elucidate the clinical characteristics of hepatitis B virus reactivation (HBV-R), we performed a prospective long-term study of patients with hematologic malignancy, including both hepatitis B virus (HBV) carriers and those with resolved HBV infection.
Methods:
Twenty-one patients with hematopoietic stem-cell transplants (HSCT) and 36 patients given rituximab-based chemotherapy were enrolled. Entecavir was administered prophylactically to eight patients with HBV surface antigen (HBsAg). HBV-DNA was measured every month in 49 patients with resolved HBV infection, and preemptive therapy was given to eight patients with HBV-R.
Results:
HBV-R developed in five (26%) of 19 patients with HSCT and three (10%) of 30 patients given rituximab-based chemotherapy. HBV-R occurred a median of 3 months (range: 2-10) after the end of rituximab-based chemotherapy and 22 months (range: 9-36) after HSCT. HBV-R did not develop in patients with an antibodies against HBsAg (anti-HBs) titer exceeding 200 mIU/mL at baseline. Mutations in the "a" determinant region with amino acid replacement were detected in four of the eight patients with HBV-R. Preemptive therapy prevented severe hepatitis related to HBV-R. Entecavir treatment was stopped in four patients with HBV-R. Since the withdrawal of entecavir, HBV-DNA has not been detected in two patients persistently positive for anti-HBs. No patient had fatal hepatitis.
Conclusions:
Proper management of patients with HBsAg or resolved HBV infection prevented fatal hepatitis related to HBV-R in patients who received immunosuppressive or cytotoxic therapy. Entecavir could be safely discontinued in patients with HBV-R who had acquired anti-HBs.
