BACKGROUND: 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. METHODS: 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. RESULTS: (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. CONCLUSIONS: 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.
BACKGROUND: 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 FHpatients, polymorphism of the TNF gene was studied. METHODS: We analyzed 120 healthy subjects (controls), 63 patients with acute hepatitis (AH), and 32 patients with FH. Of the 32 FHpatients, 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. RESULTS: (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 FHpatients, 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 FHpatients were increased in the non-A non-B non-C group compared to controls. CONCLUSIONS:FHpatients 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.
Authors: Pavel Strnad; Qin Zhou; Shinichiro Hanada; Laura C Lazzeroni; Bi Hui Zhong; Phillip So; Timothy J Davern; William M Lee; M Bishr Omary Journal: Gastroenterology Date: 2010-06-09 Impact factor: 22.682