Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients

World J Gastroenterol. 2011 Feb 14;17(6):708-16. doi: 10.3748/wjg.v17.i6.708.

Abstract

Aim: To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.

Methods: Sixty-four patients with chronic hepatitis, 65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study. HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing. Viral load was measured by real-time polymerase chain reaction.

Results: Of 179 patients, 108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted. The A1896 mutation was not found in HBeAg(+) patients, however, this mutation was detected in 70.7% of HBeAg(-) patients. This mutation was frequently found when HBeAg was not expressed (87.7%), compared to that found in HBeAg seroconverted patients (65.1%). The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P = 0.004). The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients, however, the prevalence of this mutation did not significantly differ among the two groups (P = 0.054). In HBeAg(+) patients, the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001). The A1899 mutation did not correlate with HBV DNA (P = 0.609). In HBeAg(-) patients, the T1762/A1764 mutation alone was not correlated with HBV DNA (P = 0.095), however, the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).

Conclusion: The percentage of HBeAg(-) patients is high in Indonesia, and most of the HBeAg(-) patients had been seroconverted. The A1896 mutation was most likely the major cause of HBeAg loss. The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients, but not in HBeAg(-) patients.

Keywords: Hepatitis B e antibody; Hepatitis B e antigen; Hepatitis B virus; Indonesia; Precore/core promoter mutations; Viral load.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / metabolism
  • DNA, Viral / blood
  • Female
  • Genotype
  • Hepatitis B e Antigens / blood*
  • Hepatitis B e Antigens / genetics*
  • Hepatitis B e Antigens / immunology
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / genetics
  • Hepatitis B, Chronic / immunology
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Promoter Regions, Genetic / genetics*
  • Viral Load*

Substances

  • DNA, Viral
  • Hepatitis B e Antigens
  • Alanine Transaminase