Detection of mutations in hepatitis B virus enhancer 2/core promoter and Xprotein regions in patients with fatal hepatitis B virus infection

The enhancer 2/core promoter and the X protein regions located upstream of the precore and core regions in hepatitis B virus regulate expression of co re/e antigen peptides. Mutations in the precore and core regions have been reported to be associated closely with the severity of type B hepatitis, an d regions regulating expression of these peptides may also be involved in s evere liver damage, Mutations were examined in regions that may be related to fatal liver diseases. Nucleotide sequences and deduced amino acid sequen ces from 20 patients with fatal type 8 hepatitis (12 with fulminant hepatit is and 8 with severe exacerbation) and 10 patients with self-limited acute hepatitis were analyzed. There were 50 nucleotide alterations in the enhanc er 2/core promoter region of virus from 12 patients with fulminant hepatiti s (average 4.1/case), 37 alterations in 8 patients with severe exacerbation (4.6/case), and 10 mutations in 10 cases of acute hepatitis (1.0/case). Th e numbers of amino acid mutations in X protein were 53 in 12 cases of fulmi nant hepatitis (4.4/case), 27 in 8 cases of severe exacerbation (3.3/case), and 9 in 10 cases of acute hepatitis (0.9/case). In fatal cases, approxima tely 50% of the nucleotide mutations were located within the region spannin g nucleotides 1741-1777 (14.2% of the enhancer 2/core promoter region) and 30% of the amino acid mutations in X protein were located within the region containing codons 122-132 (7.1% of X protein). in addition to mutations in the precore and core regions, mutations in the enhancer 2/core promoter an d the X protein regions may be associated with the pathogenesis of fatal B hepatitis infection. (C) 2000 Wiley-Liss, Inc.