Hepatitis B surface antigen seroconversion is associated with favourable long-term clinical outcomes during lamivudine treatment in HBeAg-negative chronic hepatitis B patients

J Viral Hepat. 2012 Mar;19(3):220-6. doi: 10.1111/j.1365-2893.2011.01542.x. Epub 2011 Oct 19.


The aims of this study were to assess hepatitis B surface antigen (HBsAg) seroconversion and to determine its impact on the natural course of the disease in patients with HBeAg-negative chronic hepatitis B (CHB) during lamivudine (LMV) treatment. A total of 183 consecutive patients with HBeAg-negative CHB who were treated with LMV were included in the study. Data were retrospectively collected from outpatient visit charts. The primary endpoint was HBsAg seroconversion to anti-HBs. The secondary endpoint was to determine the development of cirrhosis. Loss of HBsAg was confirmed in 10 patients and seroconversion to anti-HBs in nine patients during LMV treatment or after its discontinuation. HBsAg seroconversion was achieved on-treatment in four patients after a median treatment duration of 30 months and off-treatment in the remaining five patients in a median 61 months after LMV discontinuation. The cumulative probability of HBsAg seroconversion increased from 0.6% at 1 year and 1.9% at 5 years to 21.5% at 10 years of LMV during and after LMV treatment. HBsAg clearance was preceded by undetectable serum hepatitis B virus (HBV) DNA. The majority of the patients responding to treatment had undetectable HBV DNA levels at 24 weeks of treatment. The cumulative probability of LMV resistance increased from 2.2% at 1 year to 37.3% at 5 years. No baseline parameter predicting either HBsAg seroconversion or the emergence of LMV resistance was identified. None of the patients with HBsAg seroconversion experienced virological breakthrough or disease progression during the follow-up period. These results indicate that HBsAg seroclearance can occur in patients with HBeAg-negative CHB under LMV therapy and predicts better clinical outcome.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / blood
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • Female
  • Fibrosis / pathology
  • Fibrosis / virology
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B e Antigens / blood*
  • Hepatitis B e Antigens / immunology
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Humans
  • Interferon-alpha / therapeutic use
  • Lamivudine / administration & dosage
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Treatment Outcome
  • Young Adult


  • Antibodies, Viral
  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Interferon-alpha
  • Lamivudine