Tamori Akihiro, Hino Masayuki, Kawamura Etsushi, Fujii Hideki, Uchida-Kobayashi Sawako, Morikawa Hiroyasu, Nakamae Hirohisa, Enomoto Masaru, Murakami Yoshiki, Kawada Norifumi
Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.
J Gastroenterol Hepatol. 2014 Sep;29(9):1715-21. doi: 10.1111/jgh.12604.
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.
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.
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.
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.
为阐明乙型肝炎病毒再激活（HBV-R）的临床特征，我们对血液系统恶性肿瘤患者进行了一项前瞻性长期研究，这些患者包括乙型肝炎病毒（HBV）携带者和已治愈HBV感染的患者。
纳入21例接受造血干细胞移植（HSCT）的患者和36例接受基于利妥昔单抗化疗的患者。对8例乙型肝炎表面抗原（HBsAg）阳性患者预防性给予恩替卡韦。对49例已治愈HBV感染的患者每月检测HBV-DNA，并对8例发生HBV-R的患者进行抢先治疗。
19例接受HSCT的患者中有5例（26%）发生HBV-R，30例接受基于利妥昔单抗化疗的患者中有3例（10%）发生HBV-R。HBV-R发生于基于利妥昔单抗化疗结束后中位3个月（范围：2 - 10个月）以及HSCT后22个月（范围：9 - 36个月）。基线时乙型肝炎表面抗体（抗-HBs）滴度超过200 mIU/mL的患者未发生HBV-R。8例发生HBV-R的患者中有4例检测到“a”决定簇区域氨基酸置换突变。抢先治疗预防了与HBV-R相关的严重肝炎。4例发生HBV-R的患者停用了恩替卡韦。自停用恩替卡韦以来，2例抗-HBs持续阳性患者未检测到HBV-DNA。无患者发生致命性肝炎。
对HBsAg阳性或已治愈HBV感染的患者进行适当管理可预防接受免疫抑制或细胞毒性治疗患者中与HBV-R相关的致命性肝炎。对于已获得抗-HBs的HBV-R患者，恩替卡韦可安全停用。
