High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study

J Hepatol. 2009 Jun;50(6):1084-92. doi: 10.1016/j.jhep.2009.01.016. Epub 2009 Mar 9.


Background/aims: To assess the HBsAg seroconversion rate and its impact on the long-term outcome in chronic hepatitis B patients treated with conventional interferon, and to analyze the serum HBsAg concentration prior to seroconversion.

Methods: Ninety-seven HBeAg-positive patients were retrospectively evaluated. Sustained virological response (SVR) was defined as HBeAg seroconversion and undetectable serum HBV-DNA 48 weeks after treatment discontinuation. HBsAg level was assessed at yearly intervals until seroconversion in SVRs.

Results: Twenty-five patients (26%) achieved SVR. By multivariate analysis, SVR was associated with low serum HBV DNA level and severe liver fibrosis. During a median follow-up of 14 years (range, 5-20 years), 28 patients (29%) developed HBsAg seroconversion including 16 SVRs (64%) and 12 non-SVRs (16%), p < 0.001. HBsAg quantification showed a major decrease (median = 46%, range = 19-100%) in the first year after interferon starting in SVR patients. Six patients developed hepatocellular carcinoma, none of them had undergone HBsAg seroconversion. Liver fibrosis improved in 70% of patients with HBsAg seroconversion compared to 30% of those without HBsAg seroconversion (p < 0.01).

Conclusions: HBsAg seroconversion is achieved with a high steady rate in patients responding to interferon, and associated with excellent outcome. Prospective studies are needed to clarify the utility of on-treatment quantitative serum HBsAg in interferon-based therapy.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Carcinoma, Hepatocellular / etiology
  • DNA, Viral / blood
  • Female
  • Follow-Up Studies
  • Hepatitis B Antibodies / blood
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / immunology
  • Hepatitis B virus / isolation & purification
  • Hepatitis B virus / pathogenicity
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / virology
  • Humans
  • Interferons / therapeutic use*
  • Liver / pathology
  • Liver Neoplasms / etiology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Young Adult


  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Interferons