Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection

Am J Gastroenterol. 2002 Feb;97(2):406-12. doi: 10.1111/j.1572-0241.2002.05478.x.


Objectives: We aimed to study the relationship between the hepatitis B virus (HBV) genotypes, core promoter/precore stop codon mutations, and histological liver damage among hepatitis B e antigen (HBeAg)-negative patients.

Methods: Liver biopsy specimens of 55 HBeAg-negative chronic HBV-infected patients were studied. A histological activity index was scored for degree of necroinflammation (HAI-NI) and fibrosis (HAI-F) as described by Knodell et al. HBV DNA was determined by a cross-linking assay and polymerase chain reaction (PCR) at the core promoter/precore region and the S region. PCR-positive samples were directly sequenced for core promoter and precore mutations and examined by restriction fragment length polymorphism for genotyping.

Results: Forty-one males and 14 females at a median age of 43 were studied. HBV DNA was detectable in 32 (58%) and 37 (67%) patients by the cross-linking assay and PCR, respectively, at the time of liver biopsy. The median (range) HAI-NI and HAI-F scores were 5 (1-10) and 2 (0-4), respectively. HBV DNA detectable by either the cross-linking assay or PCR was associated with a higher HAI-NI score. Eleven and 31 patients had genotypes B and C HBV, respectively. Genotype C HBV was associated with higher HAI-NI than genotype B HBV. Core promoter mutations and precore stop codon mutation were detected in 74% and 40% patients, respectively, but they were not associated with higher HAI-NI or HAI-F scores.

Conclusions: Detectable HBV DNA and genotype C HBV, but not core promoter or precore stop codon mutations, are associated with more severe liver damage in HBeAg-negative patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Biopsy, Needle
  • Culture Techniques
  • DNA, Viral / analysis
  • DNA, Viral / genetics*
  • Female
  • Genotype
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / pathology*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Polymerase Chain Reaction
  • Probability
  • Promoter Regions, Genetic
  • Sensitivity and Specificity
  • Serologic Tests
  • Severity of Illness Index
  • Statistics, Nonparametric


  • DNA, Viral
  • Hepatitis B e Antigens