419例药物性肝损伤患者临床特点与自身抗体特征分析

Clinical features and autoantibody characteristics of patients with drug-induced liver injury:An analysis of 419 cases

目的研究药物性肝损伤(DILI)患者的临床特点与自身抗体特征。方法回顾性分析2014年9月—2018年9月首都医科大学附属北京地坛医院收治的肝功能异常且通过RUCAM评分临床诊断为DILI的患者,收集入院时的基线肝功能、肾功能、血常规、免疫五项、自身抗体、肝穿刺活检结果。计量资料满足正态性2组间比较使用t检验;计量资料不满足正态性2组间比较使用Mann-Whitney U检验。采用卡方检验研究不同性别、肝损伤类型之间的自身抗体检出率是否存在差异;用logistic回归方法分析自身抗体与性别、年龄、损伤类型之间是否存在回归关系;以各项基线化验结果做自变量,ANA的滴度分级作为因变量做有序logistic回归分析。结果共入组419例DILI患者,中位年龄47(35~55)岁,其中男性占32.5%(136/419),女性占67.5%(283/419);肝细胞型有88例(21.5%),混合型87例(21.2%),胆汁淤积型235例(57.3%)。自身抗体检出率为50.6%(212/419),其中抗核抗体检出率为42.9%(180/419),抗体滴度以1∶100为主(104/180)。不同性别(χ^(2)=2.658,P=0.103)与不同损伤类型(χ^(2)=0.859,P=0.651)之间的自身抗体检出率差异均无统计学意义。二元logistics回归提示性别、年龄和损伤类型与自身抗体之间均不存在回归关系(P值均>0.05)。自身抗体阳性组和阴性组患者的PTA和INR存在显著差异(t=2.161,P=0.031;Z=-3.010,P=0.003)。有序logistics回归提示INR和IgG与ANA分级有相关性(OR=3.101,P=0.040;OR=1.043,P=0.014)。结论DILI患者自身抗体检出率较高,但自身抗体检出率与性别、损伤类型、年龄无关,自身抗体阳性与阴性患者之间的PTA和INR存在差异,INR和IgG水平与ANA抗体滴度有相关性。

Objective To investigate the clinical features and autoantibody characteristics of patients with drug-induced liver injury(DILI).Methods A retrospective analysis was performed for the patients with abnormal liver function who were admitted to Beijing Ditan Hospital,Capital Medical University,from September 2014 to September 2018 and were diagnosed with DILI based on RUCAM score,and related data on admission were collected,including baseline liver function,renal function,routine blood test results,five immune indices,autoantibody,and liver biopsy results.The t-test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used to compare the detection rate of autoantibody between the patients with different sexes or types of liver injury.A logistic regression analysis was used to investigate whether autoantibody had a regression relationship with sex,age,and type of injury,and an ordinal logistic regression analysis was performed with baseline laboratory results as independent variables and anti-nuclear antibody(ANA)titer as the dependent variable.Results A total of 419 patients with DILI were enrolled in the study,with a median age of 47(35-55)years,among whom male patients accounted for 32.5%(136/419)and female patients accounted for 67.5%(283/419).Among these 419 patients,88(21.5%)had hepatocellular-type liver injury,87(21.2%)had mixed-type liver injury,and 235(57.3%)had cholestasis-type liver injury.The detection rate of autoantibodies was 50.6%(212/419),and the detection rate of ANA was 42.9%(180/419),with a titer of mainly 1∶100(104/180).There was no significant difference in the detection rate of autoantibodies between the patients with different sexes(χ^(2)=2.658,P=0.103)or different types of injury(χ^(2)=0.859,P=0.651).The binary logistic regression analysis showed that autoantibody did not have a regression relationship with sex,age,and type of injury(all P>0.05)There were significant differences in prothrombin time activity(PTA)and international normalized ratio(INR)between the positive autoantibody group and the negative autoantibody group(t=2.161,P=0.031;Z=-3.010,P=0.003).The ordinal logistic regression analysis showed that INR(odds ratio[OR]=3.101,P=0.040)and IgG(OR=1.043,P=0.014)were associated with ANA grade.Conclusion There is a relatively high detection rate of autoantibodies in patients with DILI,and the detection rate of autoantibodies is not associated with sex,age,or type of injury.There are differences in PTA and INR between autoantibody-positive patients and autoantibody-negative patients,and the levels of INR and IgG are correlated with antibody titer.