程序性死亡受体1抑制剂治疗晚期肝癌导致免疫性肝毒性的临床特点及影响因素分析

Clinical characteristics and influencing factors of immunological hepatotoxicity induced by programmed death-1 inhibitors in the treatment of advanced liver cancer

目的分析程序性死亡受体1(programmeddeath-1,PD-1)抑制剂治疗晚期肝癌患者导致免疫性肝毒性的临床特点及影响因素,为免疫性肝毒性的治疗管理提供理论依据。方法回顾性分析2020年9月至2022年9月在海南省肿瘤医院接受PD-1抑制剂治疗的135例晚期肝癌患者的临床资料,统计分析免疫性肝毒性发生的影响因素。结果在接受免疫治疗的135例肝癌患者中,46例出现免疫性肝毒性,发生率为34.1%,其中男性33例,女性13例;发生时间为3~26周,中位发生时间为25d;年龄为34~73岁,中位年龄为62岁。肝毒性分级G1组11例,G2组27例,G3组6例,G4组2例。单因素分析显示,发生免疫性肝毒性患者与未发生免疫性肝毒性患者的年龄、总胆红素水平和Child-Pugh分级的差异具有统计学意义(P<0.05)。多因素Logistic回归分析提示肝功能Child-Pugh分级B级是影响患者发生免疫性肝毒性的独立危险因素。结论肝功能Child-Pugh分级B级是PD-1抑制剂治疗晚期肝癌患者发生免疫性肝毒性的危险因素。

Objective To analyze the clinical characteristics and influencing factors of immunological hepatotoxicity in advanced liver cancer patients undergoing programmed death-1(PD-1)inhibitor treatment,in order to provide a theoretical basis for the treatment of immunological hepatotoxicity in this patient population.Method A retrospective analysis was conducted on clinical data from September 2018 to September 2022 of patients with advanced liver cancer who received PD-1 inhibitor treatment in Hainan Cancer Hospital.The influencing factors of immunological hepatotoxicity associated with immune therapy were statistically analyzed.Result Among the 135 patients with liver cancer who received immune therapy,46 cases experienced immunological hepatotoxicity,with an incidence rate of 34.1%.Among them,33 cases were male and 13 cases were female.The occurrence time of hepatotoxicity ranged from 3 to 26 weeks,with a median occurrence time of 25 days.The age range was 34-73 years old,with a median age of 62.The grading of hepatotoxicity was as follows:11 cases in grade G1,27 cases in grade G2,6 cases in grade G3,and 2 cases in grade G4.Univariate analysis showed that there were statistically differences in age,total bilirubin level,and Child-Pugh classification between the patients with immunological hepatotoxicity and the patients without immunological hepatotoxicity(P<0.05).Multifactor logistic regression analysis suggested that Child-Pugh B classification of liver function was an independent risk factor influencing the occurrence of immunological hepatotoxicity in patients.Conclusion The Child-Pugh B classification of liver function is a risk factor for the occurrence of immunological hepatotoxicity in advanced liver cancer patients undergoing PD-1 inhibitor treatment.