Comparative Analysis of Intrahepatic Infiltration of Activated T Cells and Macrophages between Autoimmune Hepatitis and Drug-Induced Liver Injury.

Background/Aims In this study, we aimed to identify the amount and patterns of immune cell infiltration in autoimmune hepatitis (AIH), and to compare them with those of drug-induced liver injury (DILI). Methods From March 2016 to December 2018, 15 patients with AIH were prospectively enrolled in this study. For comparison, 22 patients with DILI in the same period were analyzed in the same way. Liver biopsy was performed, and immunohistochemical stain for CD3, CD68, CD20, and CD38 was done. For some patients, immune cells were harvested from fresh liver biopsy samples, and multicolor flow cytometry was used for the immunophenotyping of the infiltrated immune cells. Results First, we identified that activated CD8 and CD4 T cells were more infiltrated in the livers from patients with AIH than those from healthy controls by multicolor flow cytometry. The amounts of T cells, macrophages, and B cells infiltration had no associations with serum aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase or gamma glutamyltranspeptidase in patients with AIH. Furthermore, serum levels of IgG and IgA were not correlated with the amounts of immune cells infiltrations, either. Next, we compared the infiltration of the immune cell subsets between patients with AIH and those with DILI. Baseline serum ALT was significantly higher in patients with DILI, but the levels of activated T cells (CD3+CD38+) infiltration were not significantly different between AIH and DILI. However, a larger number of macrophages were infiltrated in the livers in DILI than those in AIH, suggesting that drug-induced injury of hepatocytes triggers innate immunity more vigorously. Conclusions Both patients with AIH and DILI have activated T cells and macrophages infiltrated in the injured liver. Higher ALT and more macrophages infiltration in DILI suggest that drug-induced injury of hepatocytes might trigger innate immunity more vigorously than autoimmunity-mediated mechanisms. [ABSTRACT FROM AUTHOR]