Activated lymphocytes and high liver expression of IFN-? are associated with fulminant hepatic failure in patients

Background & Aims: To study immunological mechanisms of fulminant hepatic failure (FHF) derived from extensive liver lesions, 14 patients with FHF induced by different aetiologies were investigated by observance of both lymphocyte phenotyping and cytokine levels. Methods: Five patients bearing benign acute hepatitis B (AHB) and seven healthy liver donors (HC) were used as controls. Samples of liver and blood from both FHF patients and HC were obtained during transplantation procedures. Plasma levels of IL-1 beta, IL-4, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, MCP-1, RANTES and MIP-1 alpha were quantified using a multiplex immunoassay. Cell characterization was carried out by flow cytometry. IFN-gamma staining was performed on liver sections using immunofluorescence methods. Results: An increase of peripheral frequency of natural killer (NK) cells expressing early activation markers (CD69, HLADR and CD38) and adhesion molecule CD44 was observed in FHF patients. Elevated frequency of T lymphocytes CD4(+) and CD8(+) expressing CD38 and adhesion molecules CD29 and CD44 was also observed in FHF. Additionally, an increase of natural killer T cells (NKT) was detected in FHF patients. High plasma cytokine levels were not statistically different between FHF and AHB patients. In comparison to HC, a strong liver expression of IFN-gamma was detected in FHF patients. The increased frequency of CD4(+) CD44(+) and IL-8 cytokine was found in patients with poor prognosis. Conclusions: These findings indicate the involvement of NK and NKT cells as well as T lymphocytes CD4(+) and CD8(+) in the inflammatory process inducing FHF, confirmed by the high hepatic expression of IFN-gamma.