Presence of hepatitis B virus core promoter mutations pre-seroconversion predict persistent viral replication after HBeAg loss.
BACKGROUND
In patients with chronic hepatitis B virus (HBV) infection DNA levels do not always fall after anti-hepatitis B e (anti-HBe) seroconversion.


OBJECTIVE
To follow longitudinally through HB e antigen (HBeAg) loss HBV DNA levels and core promoter/precore sequences in a cohort of 21 chronic HBV carriers.


METHODS
Treatment-naïve HBeAg seropositive HBV carriers were monitored through HBeAg loss for between 2 and 22 years (mean 9.3). Core promoter/precore sequences, genotypes, HBV DNA levels and HBe status were determined.


RESULTS
Patients were grouped into those in whom serum/plasma HBV DNA remained high after HBeAg loss (group 1, n=11; HBV DNA>5log(10)IU/ml) and those in whom HBV DNA declined (group 2, n=10). Re-appearance of HBeAg was seen in seven group 1 patients. Pre-seroconversion mutations in the core promoter region including A1762T and/or G1764A were detected more frequently in group 1 (P=0.031). Overall sequence changes at sites other than 1762/1764 were more common post-seroconversion in group 1 than group 2 patients (P=0.037).


CONCLUSIONS
The presence of core promoter mutations prior to HBeAg loss identified those patients in whom HBV DNA persisted at high levels and was associated with temporary re-emergence of serum HBeAg. These patients may benefit from early anti-viral treatment.
Ferns
R Bridget
RB
Centre for Virology, Department of Infection, University College, Windeyer Building, 46 Cleveland Street, London W1T 4JF, United Kingdom. r.ferns@ucl.ac.uk
Naoumov
Nikolai V
NV
Gilson
Richard J
RJ
Tedder
Richard S
RS
D000293:Adolescent; D000328:Adult; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005838:Genotype; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000821:virology; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D011401:Promoter Regions, Genetic; D019562:Viral Load; D014779:Virus Replication
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens