Presence of hepatitis B virus core promoter mutations pre-seroconversion predict persistent viral replication after HBeAg loss

J Clin Virol. 2007 Jul;39(3):199-204. doi: 10.1016/j.jcv.2007.04.008. Epub 2007 May 29.

Abstract

Background: In patients with chronic hepatitis B virus (HBV) infection DNA levels do not always fall after anti-hepatitis B e (anti-HBe) seroconversion.

Objectives: 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.

Study design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • DNA, Viral / blood
  • Female
  • Genotype
  • Hepatitis B Antibodies / blood
  • Hepatitis B Core Antigens / genetics*
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / classification
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B virus / physiology*
  • Hepatitis B, Chronic / virology
  • Humans
  • Male
  • Mutation*
  • Phenotype
  • Promoter Regions, Genetic*
  • Viral Load
  • Virus Replication*

Substances

  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Core Antigens
  • Hepatitis B e Antigens