Influence of TNF gene polymorphism in patients with acute and fulminant hepatitis

Tumor necrosis factor (TNF) is involved in liver damage, especially in fulminant hepatitis (FH). Our previous data showed that the serum level of TNF-alpha was markedly increased in FH. To investigate the mechanism of the overproduction of TNF in FH patients, polymorphism of the TNF gene was studied. We analyzed 120 healthy subjects (controls), 63 patients with acute hepatitis (AH), and 32 patients with FH. Of the 32 FH patients, 21 died or received liver transplantation (FH-D), and 11 survived with intensive therapy (FH-S). The TNF-alpha promoter region at -1031, -863, -857, -308, and -238, and TNF-beta Nco1 polymorphism sites were studied. (1) The four groups showed no differences in polymorphisms of positions -857, -308, and -238. The allelic frequencies of positions -1031C and -863A in the FH-D patients were significantly higher compared to findings in control subjects. (2) The allelic frequency of B2 in the TNF-beta gene was significantly higher in FH patients, and particularly in the FH-D patients, compared to control subjects. (3) When the patients were divided into four groups by etiology, hepatitis A virus (HAV), HBV, HCV, and non-A non-B non-C, the allelic frequencies of positions -863A and TNF-beta B2 in FH patients were increased in the non-A non-B non-C group compared to controls. FH patients with a poor prognosis had higher frequencies of positions -1031C and -863A in the TNF-alpha promoter region, and higher frequencies of the B2 allele of the TNF-beta gene. These data suggest that the genomic background may be associated with the prognosis of acute liver failure.