Soluble apoptosis molecules in primary biliary cirrhosis: analysis and commitment of the Fas and tumor necrosis factor-related apoptosis-inducing ligand systems in comparison with chronic hepatitis C.

Apoptosis in the liver is generated mainly by the Fas system. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has been proposed recently as a new apoptotic inducer. In the liver environment hepatocytes and biliary epithelial cells express TRAIL receptors which are up-regulated by increased levels of bile acids and during viral hepatitis. As for FasL, a soluble form of TRAIL has been described. To explore the commitment and level of activation of these two apoptotic systems in patients affected by primary biliary cirrhosis (PBC) or chronic hepatitis C (CH-C), a comparative study was drawn. Thirty patients with PBC on ursodeoxycholic acid have been enrolled. This group was compared with 30 patients with CH-C and with 20 healthy subjects. Soluble Fas ligand (sFasL) and soluble TRAIL (sTRAIL) levels were evaluated by double determinant immune assay and enzyme-linked immunosorbent assay (ELISA), respectively. Soluble FasL molecules were higher in PBC compared to CH-C (P=0 x 009). Soluble FasL was not detected in controls. Soluble TRAIL was significantly higher in CH-C patients compared to PBC (P=0 x 0001). Soluble TRAIL levels were higher in PBC and in CH-C than in controls (P=0 x 015 and P<0 x 001, respectively). No correlation between sFasL and sTRAIL, stage of disease, liver histology in each disease and cytolysis was present. Our data show different levels of commitment of TRAIL and Fas apoptosis-inducing systems in CH-C and PBC. Thus a different prominent role of TRAIL and Fas systems in the pathogenesis of these two conditions can be speculated: the former by inducing the death of infected hepatocytes, the latter by mediating the disappearance of bile duct.