Fas/FasL system, IL-1β expression and apoptosis in chronic HBV and HCV liver disease

The Fas/Fas-ligand (FasL) system is an important death signal pathway in the liver. An enhanced local inflammatory response prompted by FasL expression, which contributes to neutrophil recruitment and interleukin-1 beta (IL-1 beta) release, seems to be crucial to chronic liver damage, persistence of viral infections, and probably initiation and/or promotion of HCC. In order to evaluate the expression of Fas, FasL, and IL-1 beta in different stages of human liver disease and to determine whether hepatitis B virus (HBV) and hepatitis C virus (HCV) infections modulate their expression, also in relation to apoptosis, we examined 87 liver samples obtained from patients with: chronic hepatitis (CH) (n.42), cirrhosis (n.9) and hepatocellular carcinoma (HCC) (n.16) and corresponding peritumoural tissues (n.16); histologically-normal liver (n.4) as controls. Fas, FasL and IL-1 beta mRNA were quantified using reverse transcriptase-polymerase chain reaction. The apoptotic index was evaluated by TUNEL analysis. Our data showed a progressive Fas/FasL increase from CH to cirrhosis followed by a decline from the latter to HCC. In histological sections apoptosis was detected in HCC. A significant difference emerged between HCV and HBV-related disease for IL-1 beta expression only in CH. A significant positive correlation between IL-1 beta and FasL in HCV-related disease (P = 0.014) and an inverse correlation between IL-1 beta and Fas in HBV-related disease (P = 0.021) were observed. The different pattern of IL-1 beta, Fas and FasL expression found in HCV- and HBV-mediated liver disease, points to a different modulation of immune response B and C virus induced, while the decline in Fas/FasL expression in HCC may be related to defence mechanisms adopted by HCC cells against the immune system.