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目的:探讨拉米夫定预防非霍奇金淋巴瘤(NHL)免疫化学治疗后HBV感染再激活失败的可能原因。方法:收集5例曾使用拉米夫定预防性抗病毒治疗,经利妥昔单抗联合化学治疗后发生HBV感染再激活NHL患者的临床资料,分析其诊治经过及治疗失败的可能原因。结果:5例患者均为弥漫性大B细胞淋巴瘤。其中1例患者化学治疗及利妥昔单抗治疗前HBVDNA超过108copies/L;2例患者在化学治疗期间反复出现ALT升高2～4倍;2例患者化学治疗结束后停用拉米夫定,但仍使用利妥昔单抗或行放射治疗。2例患者发生病毒突破,并且均未在ALT升高前及时更换抗病毒治疗药物,其中1例伴酪氨酸-蛋氨酸-天门冬氨酸-天门冬氨酸变异。经治疗后3例患者获得持续病毒应答,未再发生肝炎活动。余2例患者由于合并肝性脑病及凝血功能障碍,治疗无效,分别于HBV感染再激活的1～3周死亡。结论:化学治疗前HBV DNA定量高,过早停用拉米夫定,前C区变异,病毒突破,化学治疗期间氨基转移酶反复升高等可能为拉米夫定预防免疫化学治疗后HBV感染再激活失败的危险因素。
Objective: To investigate the possible reasons for the failure of lamivudine in preventing the reactivation of HBV infection after non-Hodgkin’s lymphoma (NHL) immunochemotherapy. Methods: The clinical data of 5 patients who had been treated with lamivudine prophylactic antiviral therapy and HBV infection reactivated after rituximab combined with chemotherapy were collected and analyzed. The possible causes of diagnosis and treatment failure were analyzed. Results: All 5 patients were diffuse large B cell lymphoma. HBVDNA more than 108copies / L before chemotherapy and rituximab in 1 patient; ALT increased 2 to 4 times repeatedly in 2 patients during chemotherapy; 2 patients stopped using lamivudine after chemotherapy , But still using rituximab or line radiotherapy. Two patients had a viral breakthrough and none of them changed their antiviral medication immediately before ALT was elevated. One patient had a tyrosine-methionine-aspartate-aspartate mutation. After treatment, 3 patients received a sustained virus response, no recurrence of hepatitis activity. The remaining 2 patients died of hepatic encephalopathy and coagulation dysfunction due to the combination of hepatic encephalopathy and treatment failure, respectively, in 1 to 3 weeks after reactivation of HBV infection. Conclusions: High quantitative HBV DNA before chemotherapy, lamivudine discontinuation prematurely, mutation in precore region, breakthrough of virus and repeated increase of aminotransferase during chemotherapy may be the result of lamivudine in preventing HBV infection after immunochemotherapy The risk of failure to activate.