药物性肝损伤不同时间临床分型与病理损伤分型关联性分析

目的分析药物性肝损伤(drug-induced liver injury,DILI)不同时间点依据R值和新R值进行临床分型与病理损伤分型的关联性。方法选取临床确诊且经肝穿刺病理检查证实的DILI患者178例,收集患者首次发病时、疾病进程中生化指标峰值及肝脏穿刺3 d内的丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)值分别计算R值和新R值(分别为R0、R1、R2和新R0、新R1、新R2)进行临床分型。通过肝组织活检观察病理损伤靶点,分析不同时间点临床分型与病理损伤分型的关联性。结果R0、新R0、R1、新R1、R2、新R2分型与病理损伤分型的κ值分别为0.115、0.122、0.141、0.151、0.078、0.077,一致性较差。以导致DILI的可疑药物进行亚组分析,西药组R1临床分型与肝病理损伤分型的一致性最高,中药组R2及新R2临床分型与肝病理损伤分型的一致性最差。R0临床分型与肝病理损伤分型比较差异有统计学意义(P<0.05),以肝细胞损伤型一致率最高,以混合型一致率最低。以R0临床分型标准分型后,3型患者总体ALT、天冬氨酸转氨酶(AST)、ALP、总胆红素(TBIL)、γ谷氨酰转移酶(GGT)比较差异有统计学意义(P<0.01);而以肝病理损伤分型后,3型患者总体ALT、AST比较差异无统计学意义(P>0.05),总体ALP、TBIL、GGT比较差异有统计学意义(P<0.01)。结论DILI的R值临床分型与病理损伤分型一致性较差,结合患者临床表现、用药史和肝功能生化指标进行肝组织病理学检查对于明确DILI分型有重要的意义。

Association Between Clinical Classification at Different Time Points and Pathological Classification in Drug-induced Liver Injury

Objective To analyze the association between clinical classification and pathological classification of drug-induced liver injury(DILI)at different time points according toR valueandnew R value.Methods A total of 178 patients with DILI who were clinically diagnosed and pathologically confirmed by liver biopsy were enrolled.The ALT and ALP values at three time points(the first onset of the disease,the peak of biochemical indicators during the course of the disease and within 3 days of liver biopsy)were collected to calculate theR valueandnew R valuerespectively(R0,R1,R2 and new R0,new R1,new R2)for clinical classification.Liver biopsy was used to observe the pathological injury targets and analyze the correlation between clinical classification and pathological injury classification at different time points.Resultsκvalues of Kappa consistency test based on the values of R0,new R0,R1,new R1,R2,new R2.for classification and pathological injury classification were 0.115,0.122,0.141,0.151,0.078,0.077.The subgroup analysis of suspected drugs leading to DILI was conducted.The clinical classification of R1 in western medicine group had the highest consistency with classification of liver pathological damage,while that of R2 and new R2 in traditional Chinese medicine group had the lowest consistency with classification of liver pathological damage.There was a statistically significant difference between the clinical classification of R0 and liver pathological injury classification(P<0.05),with the highest consistent rate of hepatocyte injury classification and the lowest consistent rate of mixed injury classification.After the clinical classification with R0,there were statistically significant differences in ALT,AST,ALP,TBIL and GGT in patients with these 3 classifications(P<0.01).However,after the liver pathological injury classification,there was no significant difference in ALT and AST in patients with these 3 classifications(P>0.05),while there was significant difference in ALP,TBIL and GGT(P<0.01).The differences of total ALP,TBIL and GGT were statistically significant(P<0.01).Conclusion The consistency between clinical classification based on R value and pathological classification is poor.Combining the clinical manifestations,medication history and biochemical parameters of liver function to perform liver histopathological examination is of great significance in determining the DILI classification.