Liver infiltrating mononuclear cells in children with type 1 autoimmune hepatitis

Abstract

Objective: To investigate infiltrating cells in the liver of children with type 1 autoimmune hepatitis (AH-1). Methods: liver biopsies from 24 untreated AH-1 patients (14 children, 10 adults), five patients with hepatitis C virus related chronic hepatitis (HCV), and 10 control liver specimens (CL) were processed for immunohistochemical cell characterisation. Results: Two different cell distribution patterns were detected in the liver of patients with AH-1: (1) CD4 + and CD20+ cells were found in the central areas of the portal tracts (portal distribution); (2) CD8 + cells were observed at the periphery of the portal space (periportal distribution). Some cell subsets, like CD56, CD57, Fas-L, and Bak, showed a non-defined distribution pattern. The presence of two well defined patterns of cell distribution was not observed in HCV and CL (CD4 + , CD20 + , and CD8 + cells were uniformly distributed in the portal space). In AH-1 and CL, the NK markers CD56 and CD57 were found scattered throughout the liver parenchyma. However, in HCV biopsies, CD56+ cells were also clearly increased in both the portal and the periportal areas. Biopsies of AH-1 and HCV patients showed a uniform distribution of Fas-L and Bak in the portal and periportal areas, with Bak staining also detected in the hepatic parenchyma. Conclusions: Despite clinical and genetic differences, there was a similar distribution of liver infiltrating mononuclear cells in children and adults with AH-1. These results raise the possibility of reclassifying cryptogenic chronic hepatitis by immunohistochemical analysis of infiltrating liver cells.

The Role of Innate Cells Is Coupled to a Th1-Polarized Immune Response in Pediatric Nonalcoholic Steatohepatitis

“…Through the same functional study based on ROS generation, oxygen metabolism of circulating monocytes was similar to controls. The liver contains a low number of CD4 + and CD8 + cells in portal tracts and scattered through the parenchyma [28] but chronic liver injury is usually associated with inflammatory infiltrates [27,29]. The predominance of CD8 + infiltrating cells herein described and the increased expression of IFN-γ strongly suggest the presence of a local cytotoxic response in the liver of pediatric patients with NASH.…”

“…We have previously described the distribution of MN cell subpopulations in portal tracts and periportal and lobular areas of the liver [27]. Herein, the immunophenotype of MN cells infiltrating the portal tracts was characterized by immunohistochemistry and quantified in liver biopsies from ten patients with NASH.…”

Corticosteroids or not in severe acute or fulminant autoimmune hepatitis: Therapeutic brinksmanship and the point beyond salvation

“…The repertoire of triggering antigens that can stimulate T and B cell activity in autoimmune hepatitis is small,37 but other defects in the immune regulatory network can amplify or perpetuate the cytotoxicity of sensitized immunocytes 34–36. The apoptotic pathway responsible for immunocyte depletion may be impaired, and the survival of autoreactive cells may be prolonged 38.…”

Autoimmune Hepatitis: An Update on Current Animal Models

“…Others have failed to obtain evidence in support of a significant role for apoptosis in the pathogenesis of AIH. An immunohistochemical study by De Biasio et al [23], for example, has reported that Fas-L and Bak apoptotic markers are uniformly distributed through the portal and periportal areas in liver biopsy specimens from patients with AIH-1 and chronic hepatitis C virus infected patients.…”