The Characteristics Of Different Types Of Drug-induced Liver Injury And Its Relationship With Liver Pathology

Objective:1.To analyze the characteristics of different clinical types of drug-induced liver injury(DILI)established the Standards by Council for international organizations of medical sciences(by calculating R value).2.We compared the consistency of the diagnostic criteria for Council for international organizations of medical sciences(by calculating R value)with the criteria for diagnosis of cholestatic liver disease(EASL diagnostic criteria).3.We compared the consistency of the clinical classification(by calculating R value)with the pathological classification of liver pathology.Methods:The patients with drug-induced liver injury were collected from Tianjin Second People's Hospital of between January 2014 and January 2016.A total of 289 patients who met the above criteria were included in this study.Among them,there were 152 cases with liver pathology.According to the criteria established by the Council for International Organizations of Medical Sciences(CIOMS),the 289 patients were divided into hepatocellular injury type,cholestasis type and mixed type according to the biochemical index calculation "R value".We analyzed gender and age distribution,drug using,serum parameters,prognosis between the three types patients.The clinical classification of DILI is not static,but changed with the progress of the disease.In our study,liver function of 1 week after the onset of the disease was calculated to be subdivided.Then we compared the Classifications between admission with admission for the next 1 week in order to judge the type and development trend of liver injury more accurately.For the diagnosis of cholestatic liver disease,it is widely used in the diagnosis of EASL in 2009.In our study,the consistency of two types of criteria for the diagnosis of intrahepatic cholestasis were compared based on the clinical classification by calculating R value and the diagnostic criteria of EASL.There were152 patients going liver biopsy.They were divided into three types hepatocellular injury type,cholestasis and mixed type according to the characteristics of liver histology.And we compared the consistency between the clinical classification by calculating R value and pathological injury types.Result:1.Among the patients with drug-induced liver injury,there were 108 males(37.37%)and females(62.63%)and the ratio of male to female was 1:1.68.The ageof the patients ranged from 10 to 88 years,with an average age of(49.06±13.76)years old.female was more than male.The clinical manifestations of patients was including fatigue,jaundice,nausea,anorexia and so on.According to the calculation of "R value" of the 289 patients,the results of clinical classification were:hepatocellular injury(181cases,62.63%),cholestasis type(55cases,19.03%)and mixed type(53cases,18.34%).There was no significant difference in age,sex ratio and clinical manifestations between patients of three types(P > 0.05).2.The leading cause of DILI was Chinese herb medicine,accounting for 48.79%of cases,followed by anti-tumor drugs(10.73%),anti-tuberculosis drugs(7.27%),non steroidal anti-inflammatory drugs(7.27%),health products(6.92%)and so on.There was no significant difference between the three groups in the distribution of suspected drugs(P > 0.05).3.Some biochemical indexes(such as ALT,AST,TBIL,PT,INR)were significantly higher in patients with liver injury than the other two groups,and statistics and P values were F=58.575 P=0.00,F=26.329 P=0.00,F=10.182 P=0.06,respectively.While some biochemical indexes(such as ALP,GGT)in patients with cholestasis was significantly higher than the other two groups,and statistics and P values were F=70.38 P=0.00,F=2.071 P=0.00,respectively.There was no significant difference in TP?PT?INR?AFP and eosinophil percentage between the three groups,and statistics and P values were ?~2=4.581 P=0.285,?~2=11.203 P=0.428,?~2=7.162 P=0.102,?~2=7.29 P=0.143,?~2=0.386 P=0.68,?~2=1.593 P=0.205,respectively.4.Compared with the previous,the patients' biochemical indicators(such as ALT,AST)decreased significantly after active protecting liver treatment with 1 week(646.31±595.08 vs 150.77±135.29,372.60±371.24 vs 95.68±122.83),while ALP,GGT decreased slightly(219.75±535.92 vs 158.13±97.69,269.24±312.98 vs205.49±211.96).At the same time,according to the clinical classification criteria,the patients were redivided into three groups: hepatocellular injury type(58cases,20.07%),cholestasis type(121cases,41.87%)and mixed type(110cases,38.06%).At the end of the 1 week,compared with that of the "R" score at admission,the proportion of liver injury was decreased,and the proportion of cholestasis and mixed type was higher than before.5.According to the 2009 European Association(EASL)criteria for the diagnosis of cholestatic liver disease,a total of 92 patients with cholestasis were included in this study(31.83%)(n=289),which was no significant difference in number compared with the DILI clinical types of cholestasis and mixed type(108 cases,37.37%).The consistency between the two comparison is good(Kappa=0.058 P<0.05).6.There were 152 patients under liver biopsy and they were classified into the hepatocellular injury type(43 cases,28.29%),cholestasis type(8 cases,5.26%),and mixed type(101 cases,66.45%)by the histological changes;and were classified into the liver injury type(95 cases,62.5%),cholestasis type(29 cases,19.08%),and mixed type(28 cases,18.42%)by the calculation of "R value".So the consistency between the two comparison is poor(Kappa=0.229 P<0.05).There was no significant difference between the three types of liver pathological features(P>0.05).According to the histological changes,the mixed type was the most common type.The clinical classification of the calculated R values underestimated cholestasis.7.In 289 patients with DILI,there were 4 patients with acute liver failure(all of whom were liver cell damage type)during the period of hospitalization,and all of them were improved and discharged from hospital in the last 4 years.All patients were followed up for 10 months after the onset of the disease,with a total of 45 patients with chronic DILI,of which the hepatocellular injury type was 22 cases(12.15%),mixed type was 9 cases(16.98%),cholestasis type was 14 cases(25.45%).The proportion of cholestasis in the three groups was the highest,and the difference between cholestasis type and hepatocellular injury type was statistically significant(P=0.046 <0.05).Conclusion:1.DILI patients mainly occurred in 40~50 years of age and women more than men.Chinese herb medicine was the main cause of drug-induced liver injury.There were no significant difference in clinical features between hepatocellular injury,cholestasis and mixed DILI.2.With the prolongation of the course of disease,hepatocyte injury type would be transformed into cholestasis/mixed type,and the proportion of cholestasis type and mixed type is higher and higher.3.The diagnostic criteria established by the International Medical Council(by calculating R value)and the diagnostic criteria for cholestatic liver disease(EASL criteria)were consistent with the diagnosis of cholestatic liver disease.4.The consistency between by the International Medical Council(R calculation)clinical typing and pathological typing were poor.The most common type of liver injury in clinical classification were hepatocellular injury,while the mixed type were the largest proportion of the liver histological features.The type criterion established by the International Medical Council(by calculating R value),can not fully reflect the real liver injury,which was underestimated the occurrence of cholestasis and should be improved.5.A small number of patients with hepatocellular injury could progress to acute liver failure.Patients of cholestasis type is relatively easy to progress to chronic drug-induced liver injury.