Kim Jin Seok, Hahn Jee Sook, Park Sun Young, Kim Yuri, Park In Hae, Lee Chun Kyon, Cheong June-Won, Lee Seung Tae, Min Yoo Hong
Department of Internal Medicine, Yonsei University College of Medicine, 134, Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea.
Yonsei Med J. 2007 Feb 28;48(1):78-89. doi: 10.3349/ymj.2007.48.1.78.
Hepatitis B virus (HBV) reactivation is the frequent complication after cytotoxic chemotherapy in HBsAg-positive non-Hodgkin's lymphoma (NHL) patients. Pre-chemotherapy viral load may be a risk factor and HBeAg-positive status is associated with increased viral load. The aim of this study was to investigate the long-term treatment outcome of lamivudine in preventing HBV reactivation and its associated morbidity according to HBeAg status. Twenty-four adult HBsAg-positive NHL patients were taken 100 mg of lamivudine daily before the initiation of chemotherapy. The median duration of lamivudine therapy was 11.5 months (range: 1-54 months) and the median number of chemotherapy cycles was 6 (range: 1-16 cycles). The steroid containing chemotherapy regimens were used in 18 patients (75%), and the anti-CD20 monoclonal antibody containing chemotherapy regimen was used in 6 patients (25%). Four patients received autologous peripheral blood stem cell transplantation without resultant HBV reactivation. Hepatitis related to HBV reactivation was developed in 1 patient among 14 HBeAg-positive patients and no one among 10 HBeAg-negative. One patient developed HBV reactivation after lamivudine withdrawal, and 4 patients developed the YMDD (tyrosine-methionine-aspartate-aspartate) mutation during lamivudine therapy. There were no statistical differences in HBV reactivation rate during chemotherapy according to the HBeAg status. Our results demonstrate that lamivudine should be considered preemptively before the chemotherapy for all HBsAg-positive NHL patients to prevent HBV reactivation, regardless of pre-chemotherapy HBeAg status. Finally, compared with the chronic hepatitis B patients, similar rate of HBV reactivation after lamivudine withdrawal and development of YMDD mutation was observed in NHL patients.
乙肝病毒(HBV)再激活是HBsAg阳性的非霍奇金淋巴瘤(NHL)患者接受细胞毒性化疗后常见的并发症。化疗前的病毒载量可能是一个危险因素,HBeAg阳性状态与病毒载量增加有关。本研究的目的是根据HBeAg状态,探讨拉米夫定预防HBV再激活及其相关发病率的长期治疗效果。24例成年HBsAg阳性的NHL患者在化疗开始前每天服用100mg拉米夫定。拉米夫定治疗的中位持续时间为11.5个月(范围:1 - 54个月),化疗周期的中位数为6个(范围:1 - 16个周期)。18例患者(75%)使用了含类固醇的化疗方案,6例患者(25%)使用了含抗CD20单克隆抗体的化疗方案。4例患者接受了自体外周血干细胞移植,未发生HBV再激活。14例HBeAg阳性患者中有1例发生了与HBV再激活相关的肝炎,10例HBeAg阴性患者中无人发生。1例患者在停用拉米夫定后发生HBV再激活,4例患者在拉米夫定治疗期间发生了YMDD(酪氨酸 - 甲硫氨酸 - 天冬氨酸 - 天冬氨酸)突变。根据HBeAg状态,化疗期间HBV再激活率无统计学差异。我们的结果表明,对于所有HBsAg阳性的NHL患者,无论化疗前HBeAg状态如何,在化疗前都应预防性使用拉米夫定以预防HBV再激活。最后,与慢性乙型肝炎患者相比,NHL患者停用拉米夫定后HBV再激活率及YMDD突变发生率相似。