The Clinical Characteristics Of Autoimmune-like Drug Induced Liver Injury

Background:Drug induced liver injury(DILI)is one of the most common and severe drug adverse reactions.The clinical manifestations of DILI are diverse.There are no specific diagnostic criteria and indicators.The factors mentioned above result in making a diagnosis and identification of DILI become a problem.The mechanisms of DILI are still not fully understood.The development of DILI is considered to be the result of metabolism,immune response,genetic mechanism and other factors.Autoimmune-like drug induced liver injury(AL-DILI)is a sub-type of DILI.AL-DILI is developed from DILI which is mainly immune-mediated.AL-DILI and autoimmune hepatitis(AIH)share common characteristics in clinical symptoms,serological examinations and histological findings.Correctly diagnosed AL-DILI remains a challenge in clinical practice.Objective:To provide evidence for the identification of AL-DILI in clinical practice by analyzing its clinical characteristics and the related risk factors.Methods:A retrospective analysis was performed based on the clinical data of patients from January 2015 to January 2020 who were diagnosed as DILI and admitted to the second affiliated hospital of Dalian Medical University.Pathological examinations of the liver biopsy were performed on all patients.All the patients were divided into two groups:AL-DILI group and simple DILI group.The diagnosis procedure of DILI accorded with the “Guidelines for the diagnosis and treatment of drug-induced liver injury(2015)”:According to the Roussel Uclaf Causality Assessment Method,patients who had a score greater than or equal to 6 were diagnosed with DILI and enrolled in our research.Diagnosis of AL-DILI was based on following criteria: patients who had a score between 10 and 15 before the treatment of glucocorticoids according to International Autoimmune Hepatitis Scoring System(1999),accompanied by typical histopathological findings,recovery after withdrawal of the insulted drugs or glucocorticoids and without any relapse during follow up.Clinical data of all patients were collected and analyzed statistically.The features and differences of gender,age,clinical symptoms,clinical classification,laboratory examinations,immunological indexes and histological features were compared between two groups.Results:1.Gender and age: AL-DILI group and simple DILI group were common in female population.There was no significant difference in gender composition between two groups.The patients with AL-DILI had a mean age of 56.65±9.59 years old.It was elderly than simple DILI group whose mean age was 48.38 ± 16.76 years old.The difference was statistically significant(P<0.05).2.The causative agents: The most common causative agents in both AL-DILI group and simple DILI group were traditional Chinese medicines.There was no significant difference in the composition of various drugs between AL-DILI group and simple DILI group(P>0.05).3.Clinical symptoms: The common symptoms of AL-DILI was anorexia(9,52.9%),nausea and vomiting(9,52.9%),fatigue(7,41.2%).Simple DILI were presented with darken urine(23,59.0%),fatigue(21,53.8%),nausea and vomiting(14,35.9%)and so on.There showed no significance difference between two groups(P>0.05).4.Laboratory examinations: AST in AL-DILI group was 609.58(180.85~1012.60)U/L.It was higher than simple DILI group which was 171.10(83.06~647.50)U/L.The difference was statistically significant(P<0.05).AST could predict AL-DILI.When the value of AST more than 466.50 U/L,it indicated patients may have AL-DILI.There showed no significance difference on ALT,ALP,GGT,TBil,CB,UCB,Alb,PT,PTR,INR,TT,APTT,FIB,PTA between two groups(P>0.05).5.Clinical classification of DILI: Hepatocellular injury was the most common type of liver injury in both of these two groups.There were 14 cases with hepatocellular injury in AL-DILI group,accounting for 82.4%.26 cases in simple DILI were hepatocellular injury,accounting for 66.7%.There was no significant difference in clinical classification of DILI between two groups(P>0.05).6.Immunological indexes: The level of globulin averaged 34.10(30.24~37.63)g/L in AL-DILI group was higher than simple DILI which was 28.32(25.55~32.06)g/L.The level of Ig G averaged 16.10(14.35~21.05)g/L in AL-DILI group was also higher than simple DILI which was 13.07(11.10~14.10)g/L.For both of them,the difference was statistically significant(P<0.05).To identify AL-DILI and simple DILI,the best threshold value of globulin and Ig G was 31.08 g/L and 14.65 g/L respectively,the sensitivity was 76.5% and 76.5%,and corresponding specific degree was 74.4% and82.1%.Positive rate of ANA in AL-DILI(94.1%)was higher than simple DILI group(48.7%),and the difference was statistically significant(P<0.05).Ig A,lg M and Ig E comparisons between groups showed no significant difference(P>0.05).7.Histological features: In AL-DILI group,16 cases(94.1%)were observed with interface hepatitis and 15 cases(88.2%)were observed with lymphoplasmacytic cell infiltration in portal area.However,hepatocytes necrosis(28,71.8%),cholestasis(17,43.6%)were common in simple DILI group.Interface hepatitis and lymphoplasmacytic cell infiltration in portal area were common among patients with AL-DILI and reached statistical significance(P<0.05).Patients accompanied with interface hepatitis suggested may have AL-DILI.Conclusions:1.Patients with AL-DILI tended to be older than simple DILI.2.The level of AST in AL-DILI was higher than simple DILI.For the patients with DILI,AST could predict AL-DILI.When the value of AST more than 466.50 U/L,it indicated patients may have AL-DILI.3.The level of globulin,Ig G,and positive rate of ANA were higher in AL-DILI,which could be used to distinguish between AL-DILI and simple DILI.When the value of globulin and Ig G exceeded 31.08 g/L and 14.65 g/L respectively,it would tend to be diagnosed with AL-DILI.4.Liver biopsy was of great value in the identification of AL-DILI and DILI.Interface hepatitis and lymphoplasmacytic cell infiltration in portal area were specific for AL-DILI.When interface hepatitis was observed on patients with DILI,AL-DILI should be the consideration of choice.