Clinical Characteristics And Pathological Analysis Of 170 Patients With Drug-induced Liver Injury

BackgroundDrug-induced liver injury(DILI)refers to liver damage caused by an individual’s hypersensitivity or reduced tolerance to drugs during drug use.It is one of the common clinical liver diseases,and it is also in the United States.Acute liver failure(ALF)is the main cause of occurrence.In recent years,with the continuous advent of new drugs,the incidence of DILI has also increased year by year.Due to its extremely diverse clinical manifestations and histological characteristics,and lack of specific serological markers,it is easy to cause misdiagnosis and misdiagnosis of DILI,which further affects the correct diagnosis and treatment choices of clinicians.ObjectiveA retrospective analysis of the clinical data of DILI patients admitted to Taizhou People’s Hospital from July 2015 to July 2020.To determine the epidemiology,risk factors,suspicious drug application,clinical manifestations,pathological types,and the relationship with clinical types of DILI,in order to improve clinicians’ understanding and diagnosis of drug-induced liver injury.MethodsThe DILI patients diagnosed and treated from July 2015 to July 2020 in the Department of Liver Diseases of Taizhou People’s Hospital were collected,and patients with complete clinical data were included in this study,a total of 170 cases.Collect demographic data(gender,age,occupation,smoking history,drinking history),medical history(drug taking history,combined underlying diseases),clinical manifestations and classification(hepatocellular type,cholestasis type,mixed type)of the patients included in the study,Laboratory indicators(liver function,coagulation function,viral hepatitis markers,autoantibodies,etc.)and pathological data,while collecting general data(sex,age,occupation,smoking history,drinking history,combined underlying diseases and Some indicators of liver function).Results1.Among the 170 patients,45 were males(26.5%)and 125 were females(73.5%).The male to female ratio was 1:2.78.The minimum age of onset was only 5months,the maximum age was 82 years,the median age was 47,and the average age46.69±13.53 years old,6 cases(3.5%)under 20 years old,40 cases(23.5%)21-40 years old,94 cases(55.3%)41-60 years old,30 cases(17.6%)over 60 years old In the occupational distribution,52 cases(30.6%)were farmers and 50 cases(29.4%)were employees;11 cases were drinkers(6.5%),and 8 cases were smokers(4.7%).The "R value" was calculated according to the serological indexes of the patients at admission,and DILI was divided into 3 types,including 118 cases(69.4%)of hepatocyte type,29 cases(17.1%)of cholestasis type,and 23 cases(13.5%)of mixed type.The three clinical types of patients were compared between groups.Among them,age and occupation have statistically significant differences in the distribution of the three types(P<0.05),while gender,smoking,and alcohol consumption have no statistically significant differences in the distribution of the three types(P>0.05).2.The clinical manifestations of 170 patients were fatigue,anorexia,nausea,abdominal distension,yellow urine,fever and other symptoms.There was no statistically significant difference among the clinical classifications of DILI(P>0.05).3.In the history of suspected drug use,Chinese herbal medicine and dietary supplements(HDS)were 102 cases(60.0%),antibacterial drugs were 28 cases(16.5%),non-steroidal anti-inflammatory drugs were 14 cases(8.2%),and antihypertensive drugs were 8 cases(4.7%).%),6 cases(3.5%)of hypolipidemic drugs,etc.The distribution ratios of various drugs among the 3 clinical types were similar,and the difference was not statistically significant(P>0.05).4.Among the underlying diseases of DILI patients when they were admitted to the hospital,19 cases of hypertension(11.2%)ranked first,followed by 7 cases of tuberculosis(4.1%),and 6 cases of type 2 diabetes(3.5%).3 cases of thrombocytopenia(1.8%),2 cases of leukemia(1.2%),etc.Among them,the difference in the distribution of diabetes among type 3 patients was statistically significant(P<0.05).There was no statistically significant difference in the distribution of other diseases(P>0.05).5.After univariate analysis of the clinical data of DILI and the healthy control group,it was found that the distribution of ALT,AST,ALP,GGT,TBIL,and TP was statistically significant(P<0.05).Further pairwise comparison found that ALT,ALP,TBIL have significant differences between the 3 clinical types and the healthy control group at the same time(P<0.05);AST,GGT,TP have significant differences between the 3 clinical types and the healthy control group(P<0.001);The distribution of Alb among the groups was not statistically significant(P>0.05).The statistically significant indicators were analyzed by collinearity to satisfy VIF<5,and further included in the Logistic regression model to obtain that the elevation of ALT and ALP has certain distinguishing value for hepatocyte type and cholestatic DILI(B>0,OR>1,P<0.05).Draw the ROC curve of a single index and a combined index,calculate the area under the curve(AUC),95% confidence interval and the combined index to detect the sensitivity and specificity of hepatocyte type DILI and cholestasis type DILI.The combination of indicators uses Logistic Regression model construction:(1)The area under the receiver operating characteristic curve for the diagnosis of hepatocellular DILI by ALT is 0.980(95% CI: 0.963-0.997),the sensitivity is 89.8%,and the specificity is 98.0%;the receiver operating characteristic curve for ALP for the diagnosis of hepatocellular type Under area AUC=0.882(95%CI: 0.830-0.934),sensitivity is 78.0%,specificity is 82.0%;AUC=0.985(95%CI: 0.927-0.999),sensitivity is92.4% for combined diagnosis,The specificity is 98%,which is greater than the area under the ROC curve for a single factor diagnosis of hepatocyte type DILI.(2)The area under the receiver operating characteristic curve for ALT diagnosis of cholestatic DILI AUC=0.860(95% CI: 0.777-0.942),the sensitivity is 79.3%,and the specificity is 84.0%;ALP diagnosis of cholestatic DILI receiver operating characteristics The area under the curve AUC=0.971(95% CI: 0.938-1.000),the sensitivity is 89.7%,and the specificity is 96.0%;the area under the receiver operating characteristic curve AUC=0.983(95% CI: 0.962)-1.000),the sensitivity is 89.7%,the specificity is 100%,the combination of ALT and ALP is greater than the area under the ROC curve for the single factor diagnosis of cholestatic DILI.In order to enhance the actual operability,the Logistic model is used to construct equations and draw ROC curves.(1)The area under the receiver operating characteristic curve for the diagnosis of hepatocellular DILI by the ALT/ALP equation is AUC=0.985(95% CI: 0.972-0.999),the sensitivity is 92.4%,the specificity is 98.0%,and the combined index is used to diagnose liver The efficiency of cell type DILI is similar,and it is believed that this equation can be used for clinical diagnosis of hepatocyte type DILI.(2)The area under the receiver operating characteristic curve for the diagnosis of cholestatic DILI by the ALT/ALP equation is AUC=0.983(95% CI: 0.962-1.000),the sensitivity is 89.7%,the specificity is 100%,and the combined index is used to diagnose bile The efficacy of stasis type DILI is similar,and it is believed that this equation can be used for the clinical diagnosis of cholestasis type DILI.6.A total of 18 of 170 patients underwent liver biopsy.The main pathological changes included watery and ballooning degeneration of liver cells,focal and bridging necrosis,infiltration of lymphocytes,plasma cells and neutrophils,and cholestasis.,Biliary thrombus formation and garland arrangement of liver cells and other manifestations.There was no statistically significant difference in the distribution of histological characteristics among the three clinical types of patients(P>0.05).The consistency of clinical and pathological types was tested,K value=0.04<0.4,the consistency of the two types was poor.7.The univariate and multivariate binary logistic regression analysis of DILI patients and healthy controls showed that there was a statistically significant difference in the distribution of patients with age ≥ 40,a history of drinking,and a history of diabetes between the two groups(P<0.05).Conclusions1.The age of onset of DILI patients admitted to Taizhou People’s Hospital in the past 5 years is mostly between 41-60 years old,and most of them are women.Elderly people over 60 are prone to cholestatic DILI,and young people under 60 are mainly hepatocellular injury DILI.The occupations of the affected population are mainly farmers and employees,and the type of injury is mostly hepatocellular injury type DILI.Clinical manifestations are more common in symptoms such as fatigue,anorexia,nausea,abdominal distension,yellow urine,and fever.2.Herbal medicines and dietary supplements(HDS)are the main drugs that cause DILI.The main ingredients involved include Polygonum multiflorum,Tripterygium wilfordii,Panax notoginseng,Houttuynia cordata,dandelion,etc;followed by antibacterial drugs,quinolones,macrolides Mainly cephalosporins.3.In terms of diagnostic efficiency of hepatocellular DILI: Compared with ALP,ALT has higher specificity and sensitivity.When ALT and ALP are combined,the sensitivity is increased without change in specificity;in terms of diagnostic efficiency of cholestatic DILI: Compared with ALT,ALP has higher specificity and sensitivity,when ALT is combined with ALP,the specificity increases,and the sensitivity does not change.4.By analyzing the correlation between basic clinical data and the onset of DILI,it is found that age,drinking,and diabetes are independent risk factors that affect DILI.