沙利度胺及其类似物相关肝损伤文献病例分析  

Literature case analysis of thalidomide and its analogs-associated liver injury

作　　者：梁瑜[1] 赵俊[1] 倪倍倍[1] 李晓[1] 郭切[1] 孟真[2] Liang Yu;Zhao Jun;Ni Beibei;Li Xiao;Guo Qie;Meng Zhen(Department of Pharmacy,Affiliated Hospital of Qingdao University,Shandong Province,Qingdao 266003,China;Department of Intervention,Affiliated Hospital of Qingdao University,Shandong Province,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院药学部,青岛266003 [2]青岛大学附属医院介入科,青岛266003

出　　处：《药物不良反应杂志》2023年第2期89-94,共6页Adverse Drug Reactions Journal

基　　金：山东省自然科学基金(ZR2021QH205)。

摘　　要：目的了解沙利度胺及其类似物相关肝损伤的临床特征。方法检索国内外相关数据库(截至2022年8月31日),收集沙利度胺及其类似物来那度胺、泊马度胺相关肝损伤的病例报告类文献,记录患者性别、年龄、原发病、用药情况、肝损伤发生情况(发生时间、临床表现、肝功能状况、肝损伤分型等)以及处置和转归情况,进行描述性统计分析。结果纳入分析的患者共18例,男性11例,女性7例;年龄36~93岁,平均60岁;原发病为多发性骨髓瘤者16例,浆细胞白血病和骨髓增生异常综合征各1例;应用沙利度胺者9例,来那度胺6例,泊马度胺3例;开始用药至发生肝损伤的时间为4~232 d,≤60 d者15例;肝细胞损伤型9例,胆汁淤积型7例,因缺少数据未判定分型2例。18例患者均有不同程度肝功能异常,主要为丙氨酸转氨酶和天冬氨酸转氨酶升高(16例)、总胆红素升高(14例)、碱性磷酸酶升高(12例);15例有临床表现记录,主要为黄疸(13例)、乏力(7例)和恶心(4例)。诊断肝损伤后18例患者均停用沙利度胺或其类似物,其中4例予对症支持治疗;13例停药后7~28 d肝功能好转或恢复正常,5例死亡(2例死于肝衰竭,3例死于原发病或其他合并症)。结论沙利度胺及其类似物相关肝损伤多发生在用药2个月内,临床表现与其他药物所致肝损伤相似;停药后多数患者肝功能可好转或恢复正常,但少数可进展为肝衰竭致死亡。Objective To know the clinical characteristics of liver injury related to thalidomide and its analogs.Methods The relevant databases at home and abroad(up to August 31,2022)were searched and the case reports on thalidomide and its analogs‑associated liver injury were collected.The patients′gender,age,primary disease,drug use,occurrence of liver injury(onset time,clinical manifesta‑tions,liver function status,liver injury classification,etc.),treatment and outcome were recorded and de‑scriptively analyzed.Results A total of 18 patients were enrolled,including 11 males and 7 females,aged from 36 to 93 years with an average age of 60 years.The primary disease was multiple myeloma in 16 patients,plasma cell leukemia and myelodysplastic syndrome in 1 patient each.Thalidomide was used in 9 patients,lenalidomide in 6 patients and pomalidomide in 3 patients.The time from the beginning of medication to the occurrence of liver injury ranged from 4 to 232 days and it was≤60 days in15patients.The classification ofliver injury was hepatocellular type in 9 patients,cholestasis type in 7 patients,and unable to be determined due to lack of data in 2 patients.Different degrees of abnormal liver function appeared in 18 patients,mainly including elevated alanine aminotransferase and aspartate aminotransferase(in 16 patients),elevated total bilirubin(in 14 patients),and elevated alkaline phosphatase(in 12 patients).Clinical symptoms were recorded in 15 patients,including jaundice(in 13 cases),fatigue(in 7 cases)and nausea(in 4 cases).After diagnosis of liver injury,thalidomide or its analogues were discontinued in all 18 patients,and 4 cases received symp tomatic and supportive therapy.Liver function in 13 patients was improved or returned to normal within 7 to 28 days after drug withdrawal,and 5 patients died(2 cases died of liver failure,3 cases died of prima‑ry diseases or other complications).Conclusions Thalidomide and its analogs associated liver injury most‑ly occurs within 2 months after drug administration and

关 键 词：化学及药物性肝损伤 沙利度胺 来那度胺 泊马度胺 

分 类 号：R575[医药卫生—消化系统]