利妥昔单抗联合CHOP化疗对HBsAg阴性/抗-HBc阳性弥漫大B细胞淋巴瘤患者乙型肝炎病毒再激活的影响

Effect of rituximab combined with CHOP chemotherapy on hepatitis B virus reactivation in patients with HBsAg negative/anti-HBc positive diffuse large B-cell lymphoma

目的探讨利妥昔单抗联合CHOP化疗(R-CHOP)对乙型肝炎表面抗原(HBsAg)阴性/乙型肝炎核心抗体(抗-HBc)阳性的弥漫大B细胞淋巴瘤(DLBCL)患者乙型肝炎病毒(HBV)再激活的影响。方法回顾分析2010-2018年北京大学第三医院血液内科收治的187例HBsAg阴性/抗-HBc阳性DLBCL患者的临床资料,所有患者均接受R-CHOP化疗方案,且未接受预防性抗病毒治疗。根据是否发生HBV再激活分为HBV未激活组(n=174)与HBV激活组(n=13)。分析两组患者的临床特点、免疫化疗对HBV再激活的影响及预后情况。结果HBV激活组患者年龄明显高于HBV未激活组[71(66,80)岁vs.65(54,75)岁],差异有统计学意义(P<0.05),13例(13/13,100.0%)患者HBV DNA由基线不可测转为可测,2例患者HBsAg或乙型肝炎e抗原(HBeAg)转为阳性的时间先于可测及HBV DNA的时间。13例HBV再激活患者中,2例出现HBV再激活相关肝炎,未发生HBV再激活相关暴发性肝炎;7例(7/13,53.8%)HBsAg由阴性转为阳性,其中3例(3/13,23.1%)HBeAg由阴性转为阳性。HBV再激活后,10例患者在随访中HBV DNA恢复至不可测水平,其中7例接受抗病毒治疗;2例HBsAg阳性患者在随访中HBsAg转为阴性。结论HBsAg阴性/抗-HBc阳性DLBCL患者接受R-CHOP化疗后HBV再激活为中度风险,密切监测HBV DNA及HBV血清学标志物对于早期发现HBV再激活具有重要的临床意义。

Objective To investigate hepatitis B virus(HBV)reactivation in patients with diffuse large B-cell lymphoma(DLBCL)who were hepatitis B surface antigen negative/antibody to hepatitis B core antigen positive(HBsAg negative/anti-HBc positive)and received rituximab combined with CHOP(R-CHOP)chemotherapy regimen.Methods In this retrospective study,clinical data of 187 HBsAg negative/anti-HBc positive patients with DLBCL were collated and analyzed respectively from Hematology Department of Peking University Third Hospital from 2010 to 2018.All the patients received R-CHOP chemotherapy and did not receive prophylactic antiviral therapy.According to whether HBV was reactivated or not,these patients were divided into non-HBV reactivation group(174 cases)and HBV reactivation group(13 cases).Results The age of the patients in HBV reactivation group was significantly higher than that in non-HBV reactivation group[71(66,80)years vs.65(54,75)years,P<0.05].HBV DNA changed from undetectable baseline to detectable level in 13 patients(13/13,100.0%).The time when HBsAg or HBeAg became positive in 2 patients was earlier than the time when HBV DNA could be detected.In 13 patients with HBV reactivation,2 patients developed hepatitis related to HBV reactivation,and there was no fulminant hepatitis related to HBV reactivation.Serum HBsAg became positive in 7 of the 13 patients(7/13,53.8%)with HBV reactivation,whereas serum HBeAg became positive in 3 patients(3/13,23.1%).After HBV reactivation,HBV DNA reached an undetectable level again in 10 patients during follow-up,of which 7 patients received antiviral treatment.HBsAg became negative again in 2 HBsAg positive patients during follow-up.Conclusion DLBCL patients who were HBsAg negative/anti-HBc positive and treated with R-CHOP chemotherapy had a moderate risk of HBV reactivation.Close monitoring of HBV DNA levels and HBV serological markers should be performed in lymphoma patients who received R-CHOP chemotherapy.