药物性肝损伤合并自身免疫病患者的临床特点  

Clinical characteristics of drug-induced liver injury combined with autoimmune disease

作　　者：孙月 曾湛 杨柳 毕潇月 林妍洁 张维燕 邓雯 蒋婷婷 李明慧 谢尧 Sun Yue;Zeng Zhan;Yang Liu;Bi Xiaoyue;Lin Yanjie;Zhang Weiyan;Deng Wen;Jiang Tingting;Li Minghui;Xie Yao(Department of Infection,The First Hospital of Tsinghua University,Beijing 100016,China;Department of Hepatology Division 2,Peking University Ditan Teaching Hospital,Beijing 100015,China;Department of Hepatology Division 2,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China)

机构地区：[1]清华大学第一附属医院感染科,北京100016 [2]北京大学地坛医院教学医院肝病二科,北京100015 [3]首都医科大学附属北京地坛医院肝病二科,北京100015

出　　处：《中国肝脏病杂志（电子版）》2023年第4期28-32,共5页Chinese Journal of Liver Diseases：Electronic Version

基　　金：国家重点研发计划(2022YFC2603500、2022YFC2603505);北京市医院管理中心临床医学发展专项经费资助(XMLX202127);北京市医院管理中心消化内科学科协同发展中心资助课题(XXZ0302);首都卫生发展专项公共卫生项目(首发2022-1-2172)。

摘　　要：目的 分析药物性肝损伤(drug induced liver injury,DILI)合并自身免疫病患者的临床特点。方法 以2014年12月至2018年12月首都医科大学附属北京地坛医院收治的肝功能异常并经肝穿刺诊断为DILI的403例患者为研究对象。将入组患者根据肝组织病理结果分为DILI组和DILI合并自身免疫病组,比较两组患者的人口学信息及实验室检查结果,包括丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotansferase,AST)、国际标准化比值(international normalized ratio,INR)、凝血酶原活动度(prothrombin time activity,PTA)、免疫球蛋白G(immunoglobulins G,IgG)、免疫球蛋白A(immunoglobulins A,IgA)等。比较两组患者6个月后DILI慢性化率。结果共入组403例患者,其中DILI组376例,DILI合并自身免疫病组27例,DILI合并自身免疫病组中中年患者(45~59岁)占66.7%(18/27),女性占88.9%(24/27),黄疸患者占77.8%(21/27),自身抗体阳性患者占74.1%(20/27)。DILI合并自身免疫病组患者年龄[(52.3±9.9)岁vs(44.8±13.2)岁;t=-3.71,P=0.001]、女性患者比例[88.9%(24/27)vs 67.0%(252/376);χ^(2)=5.581,P=0.018]及自身抗体阳性比例[74.1%(20/27) vs48.9%(184/376);χ^(2)=6.368,P=0.012]均显著高于DILI组患者。DILI合并自身免疫病组患者ALT(中位数:154.5 U/L vs 382.0 U/L;z=-2.197,P=0.028)和PTA [(80.7±27.9)%vs (89.8±21.3)%;t=2.098,P=0.037]水平显著低于DILI组患者;INR(中位数:1.09 vs 1.03;z=-2.047,P=0.041)、IgG(中位数:19.6 g/L vs 13.4 g/L;z=-3.595,P <0.001)和Ig A(中位数:3.01 g/L vs 2.47 g/L;z=-2.167,P=0.03)水平显著高于DILI组患者。DILI组与DILI合并自身免疫病组患者发生慢性化比例差异无统计学意义[34.8%(131/376) vs 33.3%(9/27);χ^(2)=0.025,P=0.874]。结论 DILI合并自身免疫病组患者年龄更大,女性患者占比更高,IgG水平较高,但ALT水平较低。Objective To analyze the clinical characteristics of drug-induced liver injury(DILI)patients combined with autoimmune disease.Methods Total of 403 patients with abnormal liver function and diagnosed by liver puncture as DILI in Beijing Ditan Hospital,Capital Medical University from December 2014 to December 2018 were selected and divided into DILI group and DILI with autoimmune disease group according to the results of liver biopsy.The clinical characteristics including alanine aminotransferase(ALT),aspartate aminotansferase(AST),international normalized ratio(INR),prothrombin time activity(PTA),immunoglobulins G(IgG)and immunoglobulins A(IgA)were compared between patients in two groups.The rate of DILI chronicity after 6 months was compared between the two groups.Results A total of 403 patients were enrolled in the study,including 376 cases in DILI group and 27 cases in DILI with autoimmune disease group.In DILI with autoimmune disease group,middle-aged patients(45~59 years old)accounted for 66.7%(18/27),women accounted for 88.9%(24/27),patients with jaundice accounted for 77.8%(21/27)and patients with autoantibody positive accounted for 74.1%(20/27).The age[(52.3±9.9)years old vs(44.8±13.2)years old;t=-3.71,P=0.001],proportion of female[88.9%(24/27)vs 67.0%(252/376);χ^(2)=5.581,P=0.018]and positive rate of autoantibody[74.1%(20/27)vs 48.9%(184/376);χ^(2)=6.368,P=0.012]of patients in DILI with autoimmune disease group were significantly higher than those of DILI group.ALT(median:154.5 U/L vs 382.0 U/L;z=-2.197,P=0.028)and PTA[(80.7±27.9)%vs(89.8±21.3)%;t=2.098,P=0.037]levels of patients in DILI with autoimmune disease group were significantly lower than those of DILI group,INR(median:1.09 vs 1.03;z=-2.047,P=0.041),IgG(median:19.6 g/L vs 13.4 g/L;z=-3.595,P<0.001)and IgA(median:3.01 g/L vs 2.47 g/L;z=-2.167,P=0.03)levels were significantly higher.There was no difference in the rate of chronicity between patients in DILI group and DILI with autoimmune disease group[34.8%(131/376)vs 33.3%(9/27);χ^(2)=0.025,P

关 键 词：药物性肝损伤 自身免疫病 肝活组织检查 

分 类 号：R575[医药卫生—消化系统] R593.2[医药卫生—内科学]