Clinical Pathological Characteristics Of Liver Injury Associated With Immune Checkpoint Inhibitors

Objects: Immune checkpoint inhibitors(ICIs)are a recent advancement in cancer therapeutics.Patients’ survival would be prolonged and their quality of life would be improved.But the immune-related adverse effects had attracted more and more attention.The purpose of this paper is to summarize and analyze the clinical pathological characteristics of patients received ICIs,including case reports and retrospective studies.Methods: We searched respectively Chinese and English literature in WanFang,CNKI,Pubmed,GeenMedical and Metstr with specified search words as keywords.According to the relevant inclusion and exclusion criteria,the cases of the literature meeting the standards would be summarized and analyzed.Results: We searched 35 reports totally.According to inclusion and exclusion criteria,there are 20 reports and 83 patients including in this study.57(68.67%)were male,26(31.33%)were female and median age was 57 years(range,14-84 years).The majority of patients were asymptomatic with immune checkpoint inhibitors-related liver injury,and the accompanying symptoms mainly included fever,fatigue,rash,jaundice,nausea,and abdominal pain.According to the common terminology criteria for adverse events(CTCAE)4.0,there were 7 cases < grade 3 and 76 cases ≥ grade 3.Histology associated to ICIs demonstrated that lobular hepatitis was most common.Patients with hepatocellular carcinoma or liver metastasis undergone liver transplantation occurred acute liver graft rejection after ICIs therapy.The median age who taking Nivolumab/Pembrolizumab,Ipilimumab,Nivolumab/Pembrolizumab+Ipilimumab and pre-ICI+ICI were 58.5(range,14-84)years,57(range,24-83)years,56.5(range,31-65)years,57.5(range,35-78)years,respectively.The incidence of liver injury after initiation of ICIs was 5(range,1-51)weeks,9(range,3-17)weeks,2.5(range,2-5)weeks,3.5(range,1-40)weeks,respectively.Conclusion: Acute hepatitis resulting from immunotherapy for malignancy is rare and,in most cases,not severe.Usually,the liver injury induced by ICIs is asymptomatic,with or without elevation of total bilirubin.When liver dysfunction is detected,the appropriate treatment should be given according to the grade of liver injury.Patients with a history of organ transplantation should avoid to therapy with checkpoint inhibitors,because of leading to fatal acute rejection.