Background and Aims:Immune-mediated liver injury is a fatal side effect of sintilimab.This study aimed to shed light on the associated risk factors and characteristics of this adverse event.Methods:The clinical record...Background and Aims:Immune-mediated liver injury is a fatal side effect of sintilimab.This study aimed to shed light on the associated risk factors and characteristics of this adverse event.Methods:The clinical records of 772 patients treated with sintilimab were retrospectively reviewed to investigate risk factors associated with sintilimab immune-related hepatotoxicity,as well as its incidence and outcome.The Roussel Uclaf Causality Assessment Method was used o identify cases of sintilimab-induced hepatotoxicity.Furthermore,logistic regressions were performed to compare the clinical and bloodwork characteristics of patients with and without immune-mediated liver injury caused by checkpoint inhibitors.Resu/ts:Of the 585 patients included in the study,71(12.1%)developed liver injury during sintili-mab use.The median RUCAM score with interquartile range was 7(6,8).Hypoproteinemia,dyslipidemia,and the pres-ence of thyroid peroxidase antibodies were risk factors for sintilimab-related hepatotoxicity.A nomogram model was constructed for sintilimab-induced immune-mediated liver injury based on these risk factors,which had a C-index value of 0.713 and a good calibration curve.When applied o patients with grade≥3 and≥4 sintilimab-induced immune-mediated liver injury,it achieved C-index values of 0.752 and 0.811,respectively.The nomogram model also showed a good prediction potential in patients≥65 years and males.Six of the patients with sintilimab-related hepatotoxicity showed improved liver function upon treatment with steroids.Conclusions:This study demonstrated that hypoproteinemia,dyslipidemia,and the presence of thyroid peroxidase antibodies were clinically feasible prognostic biomarkers to predict liver injury in patients treated with sintilimab.展开更多
基金supported by the Startup Fund for Scientific Research,Fujian Medical University(2020QH1346 and 2020QH1345)Fujian Provincial Health Technology Project(2021QNA018)+3 种基金Fuzhou Health Science and Technology Project(grant numbers 2022-S-wq1)the Natural Science Foundation of Fujian Province(2021J011304)Joint Funds for the Innovation of Science and Technology,Fujian Province(Grant number:2018Y9045)Key Project for Youth Academic Talents(2019-ZQN-39)from Health and Family Planning Commission of Fujian Province.
文摘Background and Aims:Immune-mediated liver injury is a fatal side effect of sintilimab.This study aimed to shed light on the associated risk factors and characteristics of this adverse event.Methods:The clinical records of 772 patients treated with sintilimab were retrospectively reviewed to investigate risk factors associated with sintilimab immune-related hepatotoxicity,as well as its incidence and outcome.The Roussel Uclaf Causality Assessment Method was used o identify cases of sintilimab-induced hepatotoxicity.Furthermore,logistic regressions were performed to compare the clinical and bloodwork characteristics of patients with and without immune-mediated liver injury caused by checkpoint inhibitors.Resu/ts:Of the 585 patients included in the study,71(12.1%)developed liver injury during sintili-mab use.The median RUCAM score with interquartile range was 7(6,8).Hypoproteinemia,dyslipidemia,and the pres-ence of thyroid peroxidase antibodies were risk factors for sintilimab-related hepatotoxicity.A nomogram model was constructed for sintilimab-induced immune-mediated liver injury based on these risk factors,which had a C-index value of 0.713 and a good calibration curve.When applied o patients with grade≥3 and≥4 sintilimab-induced immune-mediated liver injury,it achieved C-index values of 0.752 and 0.811,respectively.The nomogram model also showed a good prediction potential in patients≥65 years and males.Six of the patients with sintilimab-related hepatotoxicity showed improved liver function upon treatment with steroids.Conclusions:This study demonstrated that hypoproteinemia,dyslipidemia,and the presence of thyroid peroxidase antibodies were clinically feasible prognostic biomarkers to predict liver injury in patients treated with sintilimab.
