<Original article>Serum Soluble Fas as a Seromarker of Disease Activity in Chronic Hepatitis C and the Possible Involvement of Peripheral Blood Mononuclear Cells in the Production of Serum Soluble Fas

Fas-mediated apoptosis is considered to be a major form of liver cell death in chronic hepatitis C. Recently, serum soluble Fas has become measurable although its clinical significance in chronic liver diseases is not fully understood. We measured serum soluble Fas (sFas) levels in 22 normal volunteers, in 10 cases with autoimmune hepatitis type 1 (AIH), in 18 cases with chronic hepatitis C with autoimmune features (C-AIH), in 34 cases with chronic hepatitis without such features (C-CH) and in 17 cases with systemic lupus erythematosus. The mean sFas level in C-AIH was significantly higher (p<0.05) than C-CH and normal volunteers. As a whole, the serum sFas level positively correlated with aspartate aminotransferase (AST) (p<0.05) and alanine aminotransferase (ALT) (p<0.05), and inversely with peripheral platelet counts (p<0.05). Only C-CH showed a striking correlation between serum sFas and AST/ALT levels while other disease groups with autoimmune features did not, suggesting the possible involvement of lymphocytes in sFas production in these groups. The serum sFas level also significantly correlated with the histological activity indexes of chronic inflammation in liver sections. Fas and sFas mRNAs were both detectable by reverse-transcription-polymerase chain reaction amplification in peripheral blood mononuclear cells (PBMC) that were collected from these patients. The intensity of sFas mRNA expression was higher than that of full-length Fas mRNA in half of the cases examined. Among these, the expression intensity of both mRNAs was highest in AIH. After the stimulation of PBMC with phytohemoagglutinin and interleukin-2, the intensity of Fas mRNA expression was consistently higher than that of sFas mRNA. The Fas and sFas mRNA expressions in 3 C-CH liver samples were both more up-regulated than in the normal liver. Nuclear DNA fragmentation visualized by terminal deoxyuridine transferase-mediated nick end labeling was detectable in mononuclear cells infiltrating portal triads of the AIH, C-AIH and C-CH liver. In conclusion, serum sFas levels can be a possible seromarker of disease activity in chronic hepatitis C. Moreover, peripheral blood mononuclear cells are possibly involved in the production of serum sFas, especially in chronic hepatitis C with autoimmune features.