CD4+Foxp3+CD25+/-Tregs characterize liver tissue specimens of patients suffering from drug-induced autoimmune hepatitis:A clinical-pathological study  

作　　者：Li-Mei Qu Shu-Hua Wang Kun Yang David R.Brigstock Li Su Run-Ping Gao 

机构地区：[1]Department of Hepatic-Biliary-Pancreatic Medicine,First Hospital of Jilin University,Changchun 130021,China [2]Department of Surgical Gastroenterology,First Hospital of Jilin University,Changchun 130021,China [3]The Research Institute at Nationwide Children’s Hospital,Columbus,OH 43205,USA [4]Division of Pediatric Surgery,Department of Surgery,The Ohio State University,Columbus,OH 43205,USA

出　　处：《Hepatobiliary & Pancreatic Diseases International》2018年第2期133-139,共7页国际肝胆胰疾病杂志（英文版）

基　　金：supported by a grant from the National Natural Science Foundation of China(81270544)

摘　　要：Background: The diagnosis of drug-induced autoimmune hepatitis(DIAIH) and its differentiation from idiopathic autoimmune hepatitis(AIH) is challenging. This study aimed to differentiate DIAIH from AIH by comparing the biochemical changes, histological features, and frequencies of CD4~+Foxp3~+CD25+/-regulatory T cells(Tregs) in liver tissues or peripheral blood lymphocytes.Methods: A total of 15 DIAIH patients and 24 AIH patients who underwent liver biopsies at initial presentation were enrolled in this study. The liver histological changes were assessed by HE staining. The phenotypic recognition and distribution of CD4~+Foxp3~+CD25+/-Tregs in liver tissues were evaluated by single/double immunostains in serial sections. The CD4~+Foxp3~+CD25+/-Tregs in peripheral blood were analyzed by flow cytometry.Results: The median values of ALT and AST were 404.50 U/L and 454.10 U/L in DIAIH patients and309.50 U/L and 315.00 U/L in AIH patients, respectively. More importantly, for the first time we found that patients with DIAIH had higher levels of serum ALT and AST, more severe degree of lobular inflammation,higher frequencies of zone 3 necrosis and higher number of lobular CD4~+Foxp3~+CD25~-Tregs compared with AIH(P < 0.05). 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~+Foxp3~+CD25~-Tregs(P < 0.05).However, the frequency of peripheral blood CD4~+Foxp3~+CD25+/-Tregs were not significantly different between DIAIH and AIH.Conclusions: The differences of ALT, AST and the number of lobular CD4~+Foxp3~+CD25~-Tregs between patients with DIAIH and those with AIH are clinically helpful in differentiating these two diseases in their early stage.Background: The diagnosis of drug-induced autoimmune hepatitis(DIAIH) and its differentiation from idiopathic autoimmune hepatitis(AIH) is challenging. This study aimed to differentiate DIAIH from AIH by comparing the biochemical changes, histological features, and frequencies of CD4^+Foxp3^+CD25^(+/-)regulatory T cells(Tregs) in liver tissues or peripheral blood lymphocytes.Methods: A total of 15 DIAIH patients and 24 AIH patients who underwent liver biopsies at initial presentation were enrolled in this study. The liver histological changes were assessed by HE staining. The phenotypic recognition and distribution of CD4^+Foxp3^+CD25^(+/-)Tregs in liver tissues were evaluated by single/double immunostains in serial sections. The CD4^+Foxp3^+CD25^(+/-)Tregs in peripheral blood were analyzed by flow cytometry.Results: The median values of ALT and AST were 404.50 U/L and 454.10 U/L in DIAIH patients and309.50 U/L and 315.00 U/L in AIH patients, respectively. More importantly, for the first time we found that patients with DIAIH had higher levels of serum ALT and AST, more severe degree of lobular inflammation,higher frequencies of zone 3 necrosis and higher number of lobular CD4^+Foxp3^+CD25^-Tregs compared with AIH(P < 0.05). 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^+Foxp3^+CD25^-Tregs(P < 0.05).However, the frequency of peripheral blood CD4^+Foxp3^+CD25^(+/-)Tregs were not significantly different between DIAIH and AIH.Conclusions: The differences of ALT, AST and the number of lobular CD4^+Foxp3^+CD25^-Tregs between patients with DIAIH and those with AIH are clinically helpful in differentiating these two diseases in their early stage.

关 键 词：Drug-induced liver injury Autoimmune hepatitis Drug-induced autoimmune hepatitis Liver biopsy Regulatory T cells 

分 类 号：R[医药卫生]