BACKGROUND: This study investigated whether genetic polymorphisms in the tumor necrosis factor alpha (TNFalpha) gene's promoter region play a role in severe acute alcoholic hepatitis (AAH). METHODS: One-hundred and fifty patients (58 AAH patients, 45 cirrhosis group free-AAH, 47 healthy group) were genotyped for 3 TNFalpha polymorphisms (-238, -308, -863) using a polymerase chain reaction-restriction fragment length polymorphism technique. Serum TNFalpha levels were determined. RESULTS: The TNFalpha-308 allele A frequency was significantly lower in AAH group (0.09), than cirrhosis (0.28) (p < 0.001), and healthy groups (p < 0.001). The TNFalpha-308 A/G, A/A genotypes were significantly lower in AAH group, than cirrhosis (p = 0.005), and healthy groups (p < 0.001). For AAH group, there were no clinical, biological, and serum TNFalpha differences between the -308 G/G and A/G, A/A genotype patients, apart higher transaminase in the former group (p = 0.02). AAH and cirrhosis groups did not differ for the frequency of TNFalpha-238, -863 polymorphisms. The specific genotype did not appear to have any influence on the therapeutic response following corticotherapy or posttreatment 6-month survival. In the AAH group, nonsurvivors had higher TNFalpha levels than survivors (7.9 +/- 8.8 vs. 3.3 +/- 1.6 pg/ml, p = 0.01). CONCLUSIONS: These results attest to the involvement of TNFalpha-related genetic factors in susceptibility to AAH.