免疫检查点抑制剂治疗致乙型肝炎病毒再激活肿瘤患者临床特征及危险因素分析  

Clinical characteristics and risk factors of HBV reactivation in cancer patientsreceiving immune checkpoints inhibitors

作　　者：雷定佳 罗华婷 曾玥影 罗海英 王睿[1] 唐瑶[1] 秦波[1] LEI Dingjia;LUO Huating;ZENG Yueying;LUO Haiying;WANG Rui;TANG Yao;QIN Bo(Department of Infectious Diseases,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学附属第一医院感染科,重庆400016

出　　处：《中国感染与化疗杂志》2023年第3期306-312,共7页Chinese Journal of Infection and Chemotherapy

基　　金：重庆市自然科学基金面上项目(cstc2020jcyj-msxmX0221)。

摘　　要：目的研究乙型肝炎病毒(HBV)相关感染(HBsAg阳性或HBcAb阳性)肿瘤患者接受免疫检查点抑制剂(ICI)治疗后HBV再激活发生事件及临床特征,探索HBV再激活危险因素。方法收集127例HBsAg阳性或HBcAb阳性肿瘤患者的临床资料,包括基线资料、生化指标、免疫相关不良事件等,研究终点为HBV再激活发生事件,采用SPSS 26.0统计软件分析其临床特征及危险因素。结果127例患者中7例(5.5%)发生HBV再激活,包括6例发生HBV再激活相关肝炎。研究分析显示未预防抗病毒治疗是HBV再激活危险因素(P=0.026);预防性与未预防性抗病毒治疗组间HBV再激活发生率(OR 0.492,95%CI 0.410~0.590,P=0.026)、HBV再激活相关肝炎发生率(OR 0.496,95%CI 0.414~0.593,P=0.046),差异具有统计学意义。7例HBV再激活患者包括5例HBsAg阳性,2例HBsAg阴性、HBcAb阳性。7例患者治疗前HBV DNA均处于较低检测水平,其中4例基线HBV DNA阴性(<100 IU/mL),再激活时中位HBV DNA水平4400 IU/mL(1310~141000 IU/mL),6例患者因HBV再激活延缓抗肿瘤治疗,无因HBV再激活相关肝炎死亡患者。结论建议在使用ICI的高危人群中,应尽可能进行HBV血清学的普遍筛查。若使用ICI的肿瘤患者存在HBsAg阳性、HBcAb阳性等高危因素,建议不考虑基线HBV DNA水平即开始预防性抗病毒治疗。Objective To study HBV reactivation(HBVr)events and clinical features of HBV-related(HBsAg-positive or HBcAb-positive)tumor patients receiving immune checkpoint inhibitors(ICIs),and examine the risk factors of HBV reactivation.Methods The clinical data of 127 HBsAg-positive or HBcAb-positive cancer patients were collected,including baseline,biochemical data,and immune-related adverse events(iRAEs).The primary outcome was the occurrence of HBV reactivation.All data were analyzed with SPSS 26.0 software package.Results HBV reactivation was identified in 7 patients(5.5%),including HBV reactivation-related hepatitis in 6(4.7%)patients.The results indicated that lacking antiviral prophylaxis was the only significant risk factor causing HBV reactivation(P=0.026).Without antiviral prophylaxis,the incidence of HBV reactivation(OR=0.492,95%CI:0.410-0.590,P=0.026)and HBV reactivation-related hepatitis(OR=0.496,95%CI:0.414-0.593,P=0.046)was significantly higher.HBsAg was positive in 5 of the 7 patients,while HBsAg-negative and HBcAb-positive in 2 of the 7 patients.HBV DNA level was at low level before treatment with immune checkpoint inhibitors in all of the 7 patients,including baseline HBV DNA negative(<100 IU/mL)in 4 patients.The median HBV DNA level was 4400 IU/mL(1310-141000 IU/mL)at HBV reactivation.Anti-tumor therapy was delayed due to HBVr-related hepatitis in 6 patients.None of the 7 patients died of HBVr-related hepatitis.Conclusions Regular serological screening for HBV should be carried out in the high risk population receiving ICIs.Pre-emptive antiviral therapy is recommended if tumor patients are HBsAg-positive or HBcAb-positive under ICI treatment,regardless of the baseline HBV DNA level.

关 键 词：恶性肿瘤 免疫检查点抑制剂 抗病毒治疗 乙型肝炎病毒 再激活 

分 类 号：R512.62[医药卫生—内科学]