长、短疗程口服抗病毒药预防急性髓系白血病患者乙型肝炎病毒再激活的观察研究  

Observational studies on prophylaxis of hepatitis B virus reactivation with long or short course oral antiviral agents among patients with acute myeloid leukemia

作　　者：庄衍[1] 唐勇[1] 俞夜花[1] 杭海芳[1] 叶为德[1] 刘隽[1] 

机构地区：[1]上海交通大学医学院附属第九人民医院血液内科,上海200011

出　　处：《中国癌症杂志》2017年第12期964-969,共6页China Oncology

基　　金：上海交通大学医学院附属第九人民医院科室融合基金(九院融合2017)

摘　　要：背景与目的:乙型肝炎病毒(hepatitis B virus,HBV)再激活是急性髓系白血病(acute myeloid leukemia,AML)合并HBV感染的患者接受诱导和巩固化疗期间严重并发症之一,核苷类抗HBV药物(包括拉米夫定和恩替卡韦等)已成为预防和抢先治疗HBV再激活主要抗病毒药物。该研究观察并探究AML合并HBV感染患者化疗前后长疗程和短疗程口服核苷类抗HBV药物预防病毒再激活的临床疗效和安全性。方法:回顾性分析29例AML合并HBV感染并接受至少4个疗程化疗患者的临床资料。根据患者口服核苷类抗HBV药物预防治疗前HBV表面抗原(hepatitis B surface antigen,HBs Ag)含量以及抗HBV药物持续服用时间分为4个亚组,系统分析和比较不同亚组患者HBV再激活情况和药物不良反应。结果:长疗程预防(long course prophylaxis group,LCP)组,即口服抗HBV药物持续至化疗结束后6个月以上,该组患者的HBV再激活率和HBV相关性肝炎发生率分别为5.56%(1/18)和0%(0/18),明显低于短疗程预防(short course prophylaxis group,SCP)组患者(即口服抗HBV药物持续至化疗结束后1个月以内)的45.45%(5/11)和36.36%(4/11),差异有统计学意义(P=0.018和P=0.014),而LCP和SCP组患者的HBV原发耐药率分别为11.11%(2/18)和9.09%(1/11),差异无统计学意义(P>0.05)。进一步亚组分析显示,预防治疗前HBs Ag阳性患者(HBs Ag大于等于0.05 IU/m L)经长疗程预防,其HBV再激活率和HBV相关性肝炎发生率分别为8.33%(1/12)和0%(0/12),明显低于SCP组,66.67%(4/6)和66.67%(4/6),差异有统计学意义(P=0.022和P=0.005);同时,LCP和SCP组中HBs Ag(+)患者的HBV原发耐药率分别为8.33%(1/12)和16.67%(1/6),差异无统计学意义(P>0.05)。此外,LCP组中HBs Ag阴性患者(HBs Ag小于0.05 IU/m L)的HBV再激活率、肝炎发生率和原发耐药率与SCP组中HBs Ag(-)患者比较,差异无统计学意义(P>0.05)。LCP和SCP组患者均未发生3级以上药物毒性反应。结论:长疗程口服核苷类抗HBV�Background and purpose： Hepatitis B virus （HBV） reactivation is one of the serious complications among patients with acute myeloid leukemia （AML） following cytotoxic induction and consolidation chemotherapy. Nucleoside analogs including lamivudine and entecavir have been widely used as prophylactic or preemptive treatment for HBV reactivation. This study was to investigate clinical efficacy and safety of long or short course oral anti- HBV agents for preventing HBV reactivation in AML patients with HBV infection during chemotherapy. Methods： The medical records of 29 AML patients with HBV infection receiving at least 4 courses of chemotherapy were retrospectively identified and systematically analyzed. These patients were further divided into four groups according to their hepatitis B surface antigen （HBsAg） status prior to initiation of chemotherapy and duration of prophylactic therapy. Reactivation of HBV and toxicity profiles of oral antiviral agents were systematically analyzed and compared among different groups. Results： HBV reactivation and documented HBV-related hepatitis were significantly lower in AML patients under long course antiviral prophylaxis （i.e. continuing oral antiviral therapy for at least 6 months after cessation of chemotherapy, LCP group） than in the patients with short course antiviral prophylaxis （i.e. continuing oral antiviral therapy for one month after cessation of chemotherapy, SCP group）, which was 5.56% （1/18） and 0% （0/18） compared with 45.45% （5/11） and 36.36% （4/11） （P=0.018 and P=-0.014）. There was little difference in the incidence of antiviral resistance between LCP and SCP groups [ 11.11% （2/18） vs 9.09% （1/11）, P〉0.05 ] . Furthermore, the rates of HBV reactivation and HBV-related hepatitis were significantly lower in AML patients with positive HBsAg （HBsAg ≥ 0.05 IU/mL） under long course antiviral prophylaxis than in HBsAg positive patients who received short course antiviral agents E 8.33% （1/12） and 0% （

关 键 词：急性髓系白血病 乙型肝炎病毒再激活 预防性抗病毒治疗 

分 类 号：R733.7[医药卫生—肿瘤]