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

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 and 309.50 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. (C) 2018 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.