Long-term follow-up of patients with hepatitis B e antigen negative chronic hepatitis B

J Gastroenterol Hepatol. 2011 Jan;26(1):122-8. doi: 10.1111/j.1440-1746.2010.06322.x.


Background and aim: After hepatitis B virus (HBV) e antigen (HBeAg) seroconversion, HBV-DNA continues to replicate, and HBeAg-negative patients still face the risk of liver disease progression. We investigated the predictive factors for alanine aminotransferase (ALT) elevation, antiviral drug use, and hepatocellular carcinoma (HCC) occurrence in HBeAg-negative patients.

Methods: Age, sex, ALT, platelet counts, HBV-DNA levels, genotype, antidiabetic drug use, body mass index, smoking, and alcohol consumption were analyzed for a total of 244 HBV carriers who were HBeAg-negative.

Results: Of 244 HBeAg-negative patients, 158 (64.8%) showed normal ALT levels at baseline. Multivariate Cox hazard regression analysis identified high HBV-DNA levels and high ALT at baseline as independent risk factors for ALT elevation in the patients with normal ALT at baseline. The threshold ALT and HBV-DNA levels were determined to be 31 IU/L and 5.3 log copies/mL, respectively. Seventeen (7.0%) patients used antiviral drugs. Multivariate Cox hazard regression analysis identified high HBV-DNA levels (threshold, 5.7 log copies/mL), the use of antidiabetic drugs, and daily alcohol consumption at baseline as an independent risk factor for the use of antiviral drugs in HBeAg-negative patients. In 10 patients (4.1%), HCC was detected, and a low platelet count (threshold, 10.0×10(4)/mm(3)) was associated with the occurrence of HCC.

Conclusion: This study identified predictors of future active liver disease in HBeAg-negative patients, i.e. ALT elevation, unavoidable use of antiviral drugs, and occurrence of HCC.

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Carcinoma, Hepatocellular / virology*
  • Chi-Square Distribution
  • DNA, Viral / blood
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Genotype
  • Hepatitis B e Antigens / blood*
  • Hepatitis B e Antigens / genetics
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / diagnosis*
  • Hepatitis B, Chronic / drug therapy
  • Humans
  • Japan
  • Kaplan-Meier Estimate
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Platelet Count
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Viral Load


  • Antiviral Agents
  • Biomarkers
  • DNA, Viral
  • Hepatitis B e Antigens
  • Alanine Transaminase