HBV感染相关肝癌患者ICI治疗后HBV再激活及其与肝损伤事件的关系  

HBV reactivation after ICI treatment in patients with HBV infection-related hepatocellular carcinoma and its relationship with hepatic injury events

作　　者：王璐 李婉 王漾漾 郭嘉惠 张金龙 WANG Lu;LI Wan;WANG Yang-yang;GUO Jia-hui;ZHANG Jin-long(Zhongda Hospital Affiliated to Southeast University,Nanjing,Jiangsu 210003,China)

机构地区：[1]东南大学附属中大医院药学部,江苏南京210003

出　　处：《中华医院感染学杂志》2024年第19期2937-2941,共5页Chinese Journal of Nosocomiology

基　　金：江苏省卫健委科研基金资助项目(P2022240)。

摘　　要：目的探讨乙型肝炎病毒(HBV)感染相关肝癌患者免疫检查点抑制剂(ICI)治疗后HBV再激活及其与肝损伤事件的关系。方法选取东南大学附属中大医院2020年5月-2022年5月120例肝细胞癌患者,所有患者均接受ICI治疗。根据治疗前及治疗4个周期后患者HBV-DNA载量,将HBV-DNA绝对值超过10^(5)copies/ml或与基础值相比增加10倍以上者纳入再激活组,未达到上述标准者纳入非再激活组。分析HBV再激活的危险因素,对比两组肝损伤事件发生率,分析治疗后HBV-DNA载量与肝损伤程度的关系。结果120例HBV感染相关肝癌患者ICI治疗后,有19例(15.83%)出现HBV再激活;治疗前HBV-DNA载量≥10^(3)copies/ml是ICI治疗后HBV再激活的危险因素,接受抗病毒治疗是预防HBV再激活的保护因素(P<0.05);再激活组肝功能损伤发生率为36.84%高于非再激活组(P=0.016);两组严重肝功能损伤发生率比较差异无统计学意义(P=0.462);再激活组与非再激活组ICI治疗前肝功能指标水平差异无统计学意义;再激活组应用ICI治疗后肝功能指标谷草转氨酶(AST)、谷丙转氨酶(ALT)和总胆红素(TBIL)分别为(77.51±9.15)U/L、(73.44±8.27)U/L和(34.66±4.93)μmol/L高于未再激活组(P<0.05);Pearson相关性分析结果显示ICI治疗后HBVDNA复制水平与患者肝功能指标ALT、AST、TBIL水平呈正相关(r=0.623、0.548、0.517,P均<0.05)。结论ICI治疗在一定程度上增加了HBV感染相关肝癌患者HBV再激活的风险,HBV再激活可引发患者肝损伤事件的发生,加重患者肝损伤程度。OBJECTIVE To explore hepatitis B virus(HBV)reactivation after immune checkpoint inhibitor(ICI)treatment in patients with HBV infection-related hepatocellular carcinoma and its relationship with hepatic injury events.METHODS A total of 120 patients with hepatocellular carcinoma between May 2020 and May 2022 in Zhongda Hospital Affiliated to Southeast University were selected,and all of whom treated with ICI.According to the patients'HBV-DNA loads before and after 4 cycles of treatment,those with an absolute value of HBV DNA exceeding 10^(5) copies/ml or with an increase of more than 10^(-3) fold compared with the basal value were included in the reactivation group,and those who did not meet the above criteria were included in the non-reactivation group.The risk factors of HBV reactivation were analyzed,the incidence of hepatic injury events was compared between the two groups,and the relationship between HBV-DNA load and the degree of liver injury after treatment was analyzed.RESULTS After 120 patients with HBV infection-related hepatocellular carcinoma were treated with ICI,there were 19 cases(15.83%)with HBV reactivation.Pre-treatment HBV DNA load≥10^(3) copies/ml was a risk factor for HBV reactivation after ICI treatment,and receiving antiviral therapy was a protective factor for preventing HBV reactivation(P<0.05).The incidence of liver injury in reactivation group was 36.84%,higher than that in non-reactivation group(P=0.016),the difference in the incidence of severe liver injury was not statistically significant(P=0.462).The difference in the level of liver function indexes before ICI treatment between the reactivation group and the non-reactivation group was not statistically significant.After ICI treatment,the liver function indicators of aspartate aminotransferase(AST),alanine aminotransferase(ALT),and total bilirubin(TBIL)in the reactivated group were(77.51±9.15)U/L,(73.44±8.27)U/L,and(34.66±4.93)μmol/L,respectively,higher than those in the non-reactivated group(P<0.05).The results of Pearson corre

关 键 词：肝癌 乙型肝炎病毒 免疫检查点抑制剂 病毒再激活 肝损伤事件 

分 类 号：R735.7[医药卫生—肿瘤]