Nucleotide sequence analysis of the precore region in patients with fulminant hepatitis B in the United States

Background: A precore defective hepatitis B virus (HBV) mutant unable to produce hepatitis B e antigen (HBeAg) has been associated with fulminant hepatitis B. We have studied the etiologic contribution of precore mutants among North American patients with this disorder. Methods: We studied 39 patients with fulminant hepatitis B. The precore and proximal core regions of HBV from 37 of 39 patients were sequenced. Results: Four patients (10.8%) harbored nonsense mutants likely to produce an HBeAg negative HBV infection; two such mutants had a G to A substitution at position 1896, one lost the precore initiation codon, and one harbored a stop codon immediately downstream of the precore initiation codon. Recovered sequences from seven additional patients displayed silent or missense mutations in these regions. All delta coinfected patients harbored known wild type strains of HBV. A significantly poorer survival was associated with antibody to HBe positivity and presence of nucleotide substitutions in the precore/core region. Conclusions: The prevalence of precore mutations in 37 patients from the United States was lower than reported elsewhere; only two patients were found to have the G to A transition mutation in the precore region at position 1896. We conclude that HBeAg negative HBV mutants do not play a predominant etiologic role among North American patients with fulminant hepatitis B.