肺癌患者应用抗PD-1/PD-L1抗体导致免疫性肝损伤的临床特点

Clinical characteristics of immune-mediated liver injury in lung cancer patients treated with anti-PD-1/PD-L1 antibody

目的:总结抗程序性死亡受体-1(programmed cell death protein 1,PD-1)/程序性死亡配体-1(programmed cell death ligand 1,PD-L1)抗体导致的免疫介导的肝炎(immune mediated hepatitis,IMH)在肺癌中的临床特点,为IMH的诊治提供见解。方法:收集2022年01月至2023年01月于我院接受抗PD-1/PD-L1抗体治疗的发生IMH的肺癌患者的临床资料。连续变量由中位数和范围表示,分类变量由患者数量和百分比表示。适当时进行参数和非参数测试。结果:本研究共纳入11名患者,中位年龄为64岁,吸烟可能是IMH的危险因素,IMH的中位发病时间为在接受抗PD-1/PD-L1抗体后的2.1个月。在实验室检查中,我们发现对比谷丙转氨酶(alanine transaminase,ALT)和谷草转氨酶(aspartate aminotransferase,AST),γ-谷氨酰转肽酶(gamma-glutamyl transferase,GGT)、总胆汁酸(total bile acid,TBA)的变化更为明显,肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)的升高可能与难治性IMH相关,CD25^(+)T细胞百分比的降低或可提示IMH的发生。在治疗上,ALT/AST异常中位持续时间为26天,总胆红素(total bilirubin,TB)异常中位持续时间为45天;糖皮质激素治疗无效及时请肝病专科医生会诊,添加其他免疫抑制剂,但注意相关不良反应。结论:TNF-α的升高或许可以作为难治性IMH的标志物,外周血Treg T细胞百分比的下降可能会预测IMH的发生。在治疗上,建议在基于ALT/AST的CTCAE分级上,若患者存在TB和/或GGT的升高,增加一个CTCAE分级的干预。

Objective:To summarize the clinical characteristics of immune mediated hepatitis(IMH)caused by anti-programmed cell death protein 1(PD-1)/programmed cell death ligand 1(PD-L1)antibody in lung cancer and provide insights into the diagnosis and treatment of IMH.Methods:Clinical data of lung cancer patients who developed IMH after receiving anti-PD-1/PD-L1 antibody therapy at our hospital from January 2022 to January 2023 were collected.Continuous variables were expressed as median and range,while categorical variables were represented by the number and the percentage of patients.Parametric and non-parametric tests were performed as appropriate.Results:This study included a total of 11 patients,with a median age of 64 years.Smoking may be a risk factor for IMH,and the median time to onset of IMH was 2.1 months after receiving anti-PD-1/PD-L1 therapy.Based on laboratory examination results,we found that compared to alanine transaminase(ALT)and aspartate aminotransferase(AST),the changes in gamma-glutamyl transferase(GGT)and total bile acid(TBA)were more pronounced.The elevation of tumor necrosis factorα(TNF-α)may be associated with refractory IMH,and a decrease in CD25^(+)T cell percentage may indicate the occurrence of IMH.The median duration of abnormal ALT/AST levels was 26 days,and the median duration of abnormal total bilirubin(TB)levels was 45 days.If glucocorticoid treatment was ineffective,timely consultation with a hepatologist was recommended to consider the addition of other immunosuppressive agents,while being mindful of potential adverse reactions.Conclusion:Possibly,the elevation of TNF-αcould be used as a marker for refractory IMH.The decrease in the percentage of Treg T cells in peripheral blood may be predictive of the occurrence of IMH.In terms of treatment,we recommend to add an intervention level based on CTCAE grading if patients with the elevation of TB and/or GGT in the context of CTCAE grading based on ALT/AST.