Nucleos(t)ide analogues only induce temporary hepatitis B e antigen seroconversion in most patients with chronic hepatitis B

Gastroenterology. 2010 Aug;139(2):491-8. doi: 10.1053/j.gastro.2010.03.059. Epub 2010 Apr 8.


Background & aims: Inconsistencies in results and guideline recommendations regarding the durability of nucleos(t)ide analogue-induced hepatitis B e antigen (HBeAg) seroconversion require clarification. We studied the long-term durability of nucleos(t)ide analogue-induced HBeAg seroconversion in patients with chronic hepatitis B virus (HBV) infection.

Methods: We performed a single-center cohort study of 132 HBeAg-positive patients who had received nucleos(t)ide analogue therapy.

Results: During a median treatment duration of 26 months (range, 16-43 mo), HBeAg seroconversion occurred in 46 of 132 subjects (35%). Forty-two subjects (91%) had follow-up evaluation after HBeAg seroconversion. During a median follow-up period of 59 months (range, 28-103 mo) after HBeAg seroconversion, 13 of 42 patients (31%) showed a durable remission (defined as HBeAg negative and HBV-DNA level<10,000 copies/mL). Overall, 33 of 42 subjects (79%) continued therapy after HBeAg seroconversion; of these, 22 (67%) showed serologic and/or virologic recurrence. Nine of 42 subjects (21%) discontinued therapy after HBeAg seroconversion and at least 6 months of consolidation therapy. Only 2 patients showed a durable response in the absence of therapy. Disease recurrence in patients who continued therapy after HBeAg seroconversion was preceded by the development of resistance (80% of these patients); resistance only occurred in subjects given lamivudine monotherapy. In contrast, recurrence after treatment discontinuation or noncompliance was observed in all patients given nucleos(t)ide analogues.

Conclusions: Induction of HBeAg seroconversion by nucleos(t)ide analogues is temporary in most patients with chronic HBV infection. Long-term continuation of nucleos(t)ide analogue treatment, irrespective of the occurrence of HBeAg seroconversion, appears to be necessary.

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage*
  • Biomarkers / blood
  • Cohort Studies
  • DNA, Viral / blood
  • Drug Administration Schedule
  • Drug Resistance, Viral
  • Endpoint Determination
  • Female
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Medication Adherence
  • Middle Aged
  • Nucleosides / administration & dosage*
  • Nucleotides / administration & dosage*
  • Proportional Hazards Models
  • Recurrence
  • Risk Assessment
  • Time Factors
  • Treatment Outcome
  • Viral Load
  • Young Adult


  • Antiviral Agents
  • Biomarkers
  • DNA, Viral
  • Hepatitis B e Antigens
  • Nucleosides
  • Nucleotides