ANALYSIS OF THE HEPATITIS-B VIRUS PRECORE AND ORF-X SEQUENCES IN PATIENTS WITH ANTIBODY TO HEPATITIS-B E-ANTIGEN WITH AND WITHOUT NORMAL ALT LEVELS

Serum samples from 20 anti-hepatitis B e antigen-positive patients wit h and without normal alanine aminotransferase (ALT) levels who had ser um hepatitis B virus (HBV) DNA detectable only by polymerase chain rea tion (PCR) were examined. Viral DNA was amplified by PCR, using primer s that encompassed precore and ORF-X regions and sequenced directly, t o investigate whether mutations in the nucleotide sequences of X and p recore gene regions of HBV-DNA might be responsible for the difference in the activity of disease and in the levels of viral replication. Th e HBV-DNA concentration in patients with abnormal ALT levels was highe r than in those with normal ALT. The amount of HBV-DNA correlated with the ALT levels (P < 0.05). Seventy-two percent of patients had HBV-DN A harboring the 1896 precore stop mutation, and there was a negative c orrelation between the percentage of precore mutant genotype and the H BV-DNA concentration (P < 0.05). Thirty percent of patients had mutati ons in ORF-X. Patients with ORF-X mutations had lower levels of HBV-DN A than those who had wild-type virus. The presence of mutations in pre core and X regions may be related to a low HBV-DNA concentration and r educed biochemical activity in patients with anti-HBe. (C) 1998 Wiley- Liss, Inc.