靶免联合经动脉插管化疗栓塞术治疗原发性肝癌相关肝损伤的临床研究

A clinical study of targeted immunotherapy combined with hepatic arterial chemoembolization in the treatment of liver injury associated with primary liver cancer

目的探明分子靶向药物、免疫检查点抑制剂联合经动脉插管化疗栓塞术(TACE)治疗原发性肝癌导致肝损伤的发生情况及其影响因素。方法选择2020年1月至2023年6月河北医科大学第三医院住院原发性肝癌105例,分析患者应用靶向药物+TACE和靶向药物+免疫检查点抑制剂(ICIs)+TACE治疗前后肝脏生物化学指标变化情况、2级以上肝损伤及其独立危险因素,并建立精准预测及评估模型。计量资料组间比较采用独立样本t检验、方差分析、秩和检验;计数资料组间比较采用χ^(2)检验。结果105例患者在治疗过程中共有50例(47.62%)发生肝损伤,1级肝损伤26例(52%),2级肝损伤16例(32%),3级肝损伤8例(16%),无4级肝损伤发生。两组患者肝损伤发生率差异无统计学意义(χ^(2)=1.299,P=0.637)。多因素logistic回归分析显示,总胆红素、前白蛋白及凝血酶原活动度为肝损伤发生的独立危险因素;建立总胆红素-前白蛋白-凝血酶原活动度(TAP)模型,TAP诊断2级以上肝损伤的受试者操作特征曲线下面积为0.935,当截断值为1.24时,灵敏度为84.35%、特异度为92.31%,诊断效能显著优于白蛋白-胆红素分级模型。结论靶向药物+TACE治疗组和靶向药物+ICIs+TACE治疗组患者严重肝损伤发生率低,耐受性均良好。TAP模型可作为评估靶免联合TACE治疗患者发生2级以上肝损伤风险的新方法。

Objective To investigate the conditions of occurrence and factors influencing liver injury caused by molecular targeted drugs and immune checkpoint inhibitors combined with hepatic arterial chemoembolization(TACE)in the treatment of primary liver cancer.Methods 105 cases of primary liver cancer admitted to the Third Hospital of Hebei Medical University from January 2020 to June 2023 were selected.Patients liver biochemical indicators conditional changes before and after treatment with targeted drugs+TACE and targeted drugs+immune checkpoint inhibitors(ICIs)+TACE were analyzed.Liver injuries above grade 2 and its independent risk factors to predict and evaluate model accuracy were established.Independent samples t-test,analysis of variance,and rank sum test were used for comparison of measurement data between groups.Count data were compared with aχ^(2)test between groups.Results A total of 50(47.62%)of the 105 cases developed liver injury during the treatment course,with 26(52%)cases of first-grade liver injury,16(32%)cases of second-grade liver injury,8(16%)cases of third-grade liver injury,and none of fourth-grade liver injury.There was no statistically significant difference in the incidence of liver injury between the two groups of patients(χ2=1.299,P=0.637).Multivariate logistic regression analysis showed that total bilirubin,prealbumin,and prothrombin activity were independent risk factors for the occurrence of liver injury.The total bilirubin-prealbumin-prothrombin activity(TAP)model was established.TAP diagnosis of grade 2 or higher liver injury had an area under the receiver characteristic curve of 0.935,sensitivity of 84.35%,and specificity of 92.31%at a cut-off value of 1.24,and significantly better diagnostic performance than albumin-bilirubin(ALBI)grade.Conclusion The occurrence of severe liver injury is minimal and well tolerated in the targeted drug+TACE treatment group and targeted drug+ICIs+TACE treatment group.The TAP model can be used as a new method to assess the risk of liver injury above grade 2 in patients treated with targeted immunotherapy combined with TACE.