高效价乙型肝炎表面抗体对使用利妥昔单抗的乙型肝炎康复者出现乙型肝炎病毒再激活的预防作用  

Preventive effect of high titer of hepatitis B surface antibody on hepatitis B virus reactivation after rituximab treatment in hepatitis B virus infection resolvers

作　　者：刘亚旭 刘晓清[2] 周宝桐[2] 张路[3] 张炎[3] 杨辰[3] 秦岩[4] Liu Yaxu;Liu Xiaoqing;Zhou Baotong;Zhang Lu;Zhang Yan;Yang Chen;Qin Yan(Department of International Medical Service,Chinese Academy of Medical Science,Peking Union Medical College Hospital,Beijing 100730,China;Department of Infectious Diseases,Chinese Academy of Medical Science,Peking Union Medical College Hospital,Beijing 100730,China;Department of Hematology,Chinese Academy of Medical Science,Peking Union Medical College Hospital,Beijing 100730,China;Department of Nephrology,Chinese Academy of Medical Science,Peking Union Medical College Hospital,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医院国际医疗部,100730 [2]中国医学科学院北京协和医院感染内科,100730 [3]中国医学科学院北京协和医院血液内科,100730 [4]中国医学科学院北京协和医院肾内科,100730

出　　处：《中华传染病杂志》2021年第5期266-270,共5页Chinese Journal of Infectious Diseases

摘　　要：目的探究高效价乙型肝炎表面抗体(hepatitis B surface antibody,抗-HBs)的乙型肝炎康复者在接受利妥昔单抗治疗时是否需要进行预防性抗病毒治疗。方法本研究为前瞻性队列研究,纳入2017年6月至2018年6月于中国医学科学院北京协和医院接受利妥昔单抗治疗的乙型肝炎表面抗原阴性、乙型肝炎核心抗体阳性、抗-HBs阳性患者9例。根据基线抗-HBs水平分为2组,抗-HBs≥100 mIU/mL的患者在充分知情同意后未进行预防性抗病毒治疗,抗-HBs<100 mIU/mL的患者在化学治疗前接受恩替卡韦预防性抗病毒治疗。开始利妥昔单抗治疗后每个月进行随访,检测肝功能、乙型肝炎病毒(hepatitis B virus,HBV)DNA和HBV血清学指标。采用描述性统计方法。结果9例患者中6例为弥漫大B细胞淋巴瘤,1例为华氏巨球蛋白血症,1例为惰性B细胞淋巴瘤,1例为膜性肾病。7例患者抗-HBs≥100 mIU/mL,未接受预防性抗HBV治疗;2例抗-HBs<100 mIU/mL的患者予恩替卡韦(0.5 mg/d)预防性治疗。1例惰性B细胞淋巴瘤患者于第3程利妥昔单抗治疗时抗-HBs效价由基线的21.27 mIU/mL降至6.33 mIU/mL;1例弥漫大B细胞淋巴瘤患者在第4程治疗后抗-HBs效价由172.25 mIU/mL下降至57.76 mIU/mL;1例膜性肾病患者随访1年复查抗-HBs效价由141.47 mIU/mL上升至328.98 mIU/mL;其余患者的抗-HBs水平无明显变化。所有患者在随访过程中均未出现HBV再激活,HBV DNA均为阴性。结论乙型肝炎康复者接受利妥昔单抗治疗后,可能出现抗-HBs效价下降。高效价抗-HBs对乙型肝炎康复者HBV再激活可能有保护作用,此类患者可能不需要进行预防性抗病毒治疗。Objective To explore whether prophylactic anti-viral therapy is needed for hepatitis B virus(HBV)infection resolvers with high titer of hepatitis B surface antibody(anti-HBs)receiving rituximab treatment.Methods This study was a prospective cohort study.Nine patients with hepatitis B surface antigen(HBsAg)negative/hepatitis B core antibody(anti-HBc)positive/anti-HBs positive receiving rituximab treatment in Chinese Academy of Medical Science,Peking Union Medical College Hospital from June 2017 to June 2018 were enrolled.Patients were divided into two groups according to baseline anti-HBs titers.Patients with anti-HBs≥100 mIU/mL did not receive prophylactic treatment after informed consent.Patients with anti-HBs<100 mIU/mL were prescribed with entecavir before the treatment of rituximab.All patients were followed up every month after the first use of rituximab.Liver function,HBV DNA and HBV serology markers were tested.Descriptive statistical analysis was used.Results Of the nine patients,six patients were diagnosed with diffuse large B cell lymphoma(DLBCL),one with Waldenstrom′s macroglobulinemia,one with indolent B-cell lymphoma,and one with membranous nephropathy.There were seven patients with anti-HBs≥100 mIU/mL who did not receive prophylactic anti-HBV therapy,and two patients with anti-HBs<100 mIU/mL who received entecavir(0.5 mg/d)prophylactic treatment before chemotherapy.The anti-HBs titer of the patient with indolent B cell lymphoma decreased from 21.27 mIU/mL to 6.33 mIU/mL during the third course of rituximab treatment.After the fourth course of treatment,the anti-HBs titer of one patient with DLBCL decreased from 172.25 mIU/mL to 57.76 mIU/mL.One patient with membranous nephropathy was followed up for one year and the anti-HBs titer increased from 141.47 mIU/mL to 328.98 mIU/mL.No significant changes of anti-HBs titer were observed in other patients.No HBV reactivation occurred in all patients and HBV DNA remained negative during the follow-up.Conclusions The anti-HBs titer may drop after rituxi

关 键 词：肝炎 乙型 慢性 乙型肝炎康复 乙型肝炎再激活 乙型肝炎表面抗体 利妥昔单抗 

分 类 号：R512.6+2[医药卫生—内科学]