Serum levels of soluble Fas ligand in patients with acute and fulminant hepatitis: relationship with soluble Fas, tumor necrosis factor α and TNF receptor-1

Abstract

We measured the serum levels of soluble Fas ligand (sFasL) using a newly developed ELISA system in patients with acute hepatitis (AH), acute severe hepatitis (ASH) and fulminant hepatitis (FH). In addition, we also evaluated the relationship between the serum levels of sFasL, soluble Fas (sFas), soluble tumor necrosis factor α (sTNFα), and soluble TNF receptor-1 (sTNFR1). The median serum sFasL level was significantly increased in patients with acute liver disease compared to that in normal subjects; however, there were no significant differences among patients with AH, ASH, and FH. The serum sFasL levels varied according to the cause of hepatitis and were particularly high in patients with hepatitis A viral infection. On the other hand, the median serum sFas level was also significantly increased in patients with acute liver disease compared to that in normal subjects; however, there were no significant differences among patients with the three clinical forms or various causes of hepatitis. The serum sFasL levels decreased rapidly following improvement in liver functions, whereas the serum sFas levels decreased more gradually and remained abnormally high even at follow-up. The serum sFasL levels were not correlated with the levels of serum transaminases or sFas, but were significantly correlated with those of sTNFα ( r=0.483, P<0.001) and sTNFR1 ( r=0.324, P<0.05). On the other hand, serum sFas levels were significantly correlated with those of sTNFR1 ( r=0.319, P<0.05) alone. Our results suggest that the serum sFasL level increases in the acute phase of hepatitis and the level varies according to the cause of hepatitis. Our findings also suggest that the Fas-FasL system and cytokine networks may be closely associated with early process of hepatic necrosis.