Discrimination Of Drug-induced Autoimmune Hepatitis Versus Idiopathic Autoimmune Hepatitis Through Serobiochemical And Histological Assessment

Background and Aims:The diagnosis of drug-induced autoimmune hepatitis?DIAIH?and its differentiation from idiopathic autoimmune hepatitis?AIH?is challenging.Our aim was to identify hallmarks for differentiation of DIAIH from AIH by comprehensive serobiochemical,histological and immunocytological analysis.Methods:A total of 15 DIAIH patients and 24 AIH patients who underwent liver biopsies at initial presentation were enrolled in this study.The patients in this study were diagnosed with DIAIH and AIH according to the diagnostic scoring system of the International Autoimmune Hepatitis Group in 1999.Some specific cases will be excluded from this study.Such as overlap syndromes,viral hepatitis and metabolic disease.Clinical and laboratory data was collected and liver histopathological features of DIAIH and AIH were analysed in these patients.HE stain of liver tissues was used to assess the histological changes.The phenotypic recognition and distribution of CD4⁺Foxp3+CD25^+/-regulatory T cells?Tregs?in liver tissues was determined by single/double immunostains in serial sections.The frequency of CD4⁺Foxp3+CD25^+/-Tregs in peripheral bloods was detected by Flow Cytometry.The treatment and prognosis of patients were followed up.Results:All patients with DIAIH were females with a median age of 52?interquartile range,44-57?.The main clinical manifestations of patients with DIAIH were nausea,vomiting,anorexia,right upper abdominal discomfort.Some DIAIH patients presented with extra hepatic manifestations,such as arthritis,atopic dermatitis.Elevated serum ALT,AST,globulin and Ig G levels were determined in all of these patients.Higher levels of serum AST and ALT,more severe degree of lobular inflammation,higher frequencies of zone 3 necrosis the higher number of lobular CD4⁺Fosp3+CD25-Tregs were found in DIAIH versus AIH?P<0.01,P<0.05,P<0.05,and P<0.01?.Furthermore,there were positive correlations in DIAIH between the degree of lobular inflammation and either the AST/ALT level or the number of lobular CD4⁺Fosp3+CD25-Tregs?P<0.05,P<0.01,P<0.01?.Finally,the intralobular eosinophilic and lymphocytic infiltrations and portal biliary proliferation were more common in DIAIH versus AIH?All P<0.05?.However,the frequency of peripheral blood CD4⁺Fosp3+CD25^+/-Tregs were not significantly different between DIAIH,AIH and healthy control.Conclusion:The differences identified between patients with DIAIH versus AIH are clinically helpful for discriminating between two diseases and for aiding diagnosis of each disease in their early stages.