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 with and without normal alanine aminotransferase (ALT) levels who had serum hepatitis B virus (HBV) DNA detectable only by polymerase chain reaction (PCR) were examined. Viral DNA was amplified by PCR, using primers that encompassed precore and ORF-X regions and sequenced directly, to investigate whether mutations in the nucleotide sequences of X and precore gene regions of HBV-DNA might be responsible for the difference in the activity of disease and in the levels of viral replication. The HBV-DNA concentration in patients with abnormal ALT levels was higher 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-DNA harboring the 1896 precore stop mutation, and there was a negative correlation between the percentage of precore mutant genotype and the HBV-DNA concentration (P < 0.05). Thirty percent of patients had mutations in ORF-X. Patients with ORF-X mutations had lower levels of HBV-DNA than those who had wild-type virus. The presence of mutations in precore and X regions may be related to a low HBV-DNA concentration and reduced biochemical activity in patients with anti-HBe.
Cabrerizo
M
M
Department of Hepatology, Fundación Jiménez Díaz, Madrid, Spain.
Bartolomé
J
J
Iñigo
E R
ER
López-Alcorocho
J M
JM
Cotonat
T
T
Carreño
V
V
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005814:Genes, Viral; D006510:Hepatitis B Antibodies / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D015534:Trans-Activators / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D015534:Trans-Activators; D014758:Viral Core Proteins; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D000410:Alanine Transaminase