既往HBV感染的淋巴瘤患者接受利妥昔单抗治疗后HBV再激活和肝损伤的单中心临床分析

Clinical analysis of liver injury and HBV reactivation after treatment with Rituximab in lymphoma patients with past HBV infection in a single-center

目的调查既往乙型肝炎病毒(HBV)感染且基线HBV DNA阴性的B细胞非霍奇金淋巴瘤(BNHL)患者,在接受和未接受预防性抗病毒治疗的条件下应用利妥昔单抗单药或联合化疗药物治疗后肝损伤和HBV再激活情况。方法回顾性分析2014年淋巴瘤住院患者的临床资料,进一步收集接受利妥昔单抗治疗的BNHL合并既往HBV感染者治疗前、治疗期间及治疗结束后1年HBV血清免疫学标志物、HBV DNA、肝功能以及抗病毒药物使用等资料以分析相应患者肝损伤和HBV再激活情况。结果共纳入基线HBV DNA阴性、连续接受利妥昔单抗治疗周期数≥2、每周期治疗前定期检测血清ALT水平的BNHL合并HBV既往感染者98例,其中接受恩替卡韦或拉米夫定预防性抗病毒治疗患者65例,未接受预防性抗病毒治疗患者33例。在治疗期间,2组患者肝功能损伤发生率分别为26.2%(17/65)和18.2%(6/33)(χ^(2)=0.774,P=0.379);2组中定期检测HBV DNA水平且监测间隔≤3个月的患者分别为35例和9例,对应HBV再激活率分别为0%(0/35)和11.1%(1/9)(P=0.205),1例HBV再激活的患者给予恩替卡韦抗病毒治疗;98例患者均未发生HBV相关肝炎。在利妥昔单抗治疗结束后1年,2组中分别有41例和24例患者可在医生工作站查询到包含肝功能在内的就诊记录等资料,对应肝功能损伤发生率分别为7.3%(3/41)和12.5%(3/24)(χ^(2)=0.064,P=0.800);2个亚组中定期检测HBV DNA水平且监测间隔≤6个月的患者分别为24例和5例,对应HBV再激活例数均为0;65例患者均未发生HBV相关肝炎。结论合并HBV既往感染且基线HBV DNA阴性的BNHL患者接受利妥昔单抗治疗后存在HBV再激活的风险,定期监测HBV DNA和肝功能水平非常必要。

Objective To investigate the occurrence of liver injury and hepatitis B virus(HBV)reactivation after treatment with Ritux-imab-containing regimens in B-cell non-Hodgkin′s lymphoma(B-NHL)patients with past HBV infection(baseline HBV DNA-nega-tive)under the conditions of receiving or not receiving prophylactic antiviral therapy,respectively.Methods The clinical data of lym-phoma inpatients in 2014 were retrospectively analyzed.The essential information in the B-NHL patients with past HBV infection who received Rituximab-containing therapy was further collected,including immunological markers of HBV in serum,HBV DNA,liver function and antiviral therapy records before,during and one year after treatment.Results A tatol of 98 B-NHL patients with past HBV infection were included,who met the requirements of being baseline HBV DNA-negative,experiencing two or more consecutive treatment cycles of Rituximab-containing therapy,and receiving regular detection of serum ALT levels before each cycle of treatment.Among them,65 patients received prophylactic antiviral therapy with entecavir or lamivudine,and 33 patients did not receive prophy-lactic antiviral therapy.During the treatment,the incidence of liver injury in the two groups were 26.2%(17/65)and 18.2%(6/33)(χ^(2)=0.774,P=0.379),respectively.In the two groups,HBV DNA levels were regularly tested in 35 and 9 patients respectively with the intervals of no longer than 3 months between each test.The incidence of HBV reactivation in the two subgroups were 0%(0/35)and 11.1%(1/9)(P=0.205),respectively.One patient with HBV reactivation received entecavir for antiviral therapy.None of the 98 patients developed HBV-associated hepatitis.The medical records,including the liver function etc.,of 41 patients in the first group and 24 patients in the second group could be retrieved from doctor workstation in a year after Rituximab treatment.The incidence of liver in-jury in the two subgroups were 7.3%(3/41)and 12.5%(3/24)(χ^(2)=0.064,P=0.800),respectively.The HBV DNA levels were regularly tested in 24 and 5 patients of the two subgroups with interval no longer than 6 months,and no one was found HBV reactivation.Non of the 65 patients developed HBVassociated hepatitis.Conclusion The BNHL patients with past HBV infection even HBV DNA baselinenegative should be at the risk of HBV reactivation after treatment with Rituximabcontaining regimens.The monitoring for the levels of HBV DNA and liver function regularly is very necessary.