HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alfa-2a for HBeAg-positive chronic hepatitis B

Hepatology. 2008 Feb;47(2):428-34. doi: 10.1002/hep.22065.


The aims of this study were to evaluate the usefulness of quantitative hepatitis B e antigen (HBeAg) values for predicting HBeAg seroconversion in patients treated with peginterferon alfa-2a and to assess the dynamic changes in quantitative HBeAg during therapy, compared with conventional measures of serum hepatitis B virus DNA. Data were analyzed from a large, randomized, multinational phase III registration trial involving 271 HBV-infected HBeAg-positive patients who received peginterferon alfa-2a plus oral placebo for 48 weeks. HBeAg levels were measured serially during therapy using a microparticle enzyme immunoassay validated with in-house reference standards obtained from the Paul Ehrlich Institute (PEIU/mL). In patients who achieved HBeAg seroconversion, levels of HBeAg consistently decreased during treatment and remained at their lowest level during the 24 weeks of posttreatment follow-up. After 24 weeks of treatment, 4% of patients with the highest levels of HBeAg (>or=100 PEIU/mL) achieved HBeAg seroconversion, yielding a negative predictive value of 96%, which was greater than that obtained for levels of HBV DNA (86%). Late responders to peginterferon alfa-2a could also be differentiated from nonresponders by continued decrease in HBeAg values, which were not evident by changes in HBV DNA.

Conclusion: These analyses suggest quantitative HBeAg is a useful adjunctive measurement for predicting HBeAg seroconversion in patients treated with peginterferon when considering both sensitivity and specificity compared with serum HBV DNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • DNA, Viral / blood*
  • Drug Monitoring / methods
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Lamivudine / therapeutic use
  • Polyethylene Glycols / therapeutic use*
  • Predictive Value of Tests
  • Recombinant Proteins
  • Treatment Outcome


  • Antiviral Agents
  • Biomarkers
  • DNA, Viral
  • Hepatitis B e Antigens
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Lamivudine
  • Polyethylene Glycols
  • peginterferon alfa-2a