Stopping nucleos(t)ide analogue treatment in Caucasian hepatitis B patients after HBeAg seroconversion is associated with high relapse rates and fatal outcomes

Aliment Pharmacol Ther. 2018 Apr;47(8):1170-1180. doi: 10.1111/apt.14560. Epub 2018 Mar 2.

Abstract

Background: Stopping nucleos(t)ide analogues (NA) after hepatitis B e antigen (HBeAg) seroconversion is associated with high relapse rates in Asian patients, but data in Caucasian cohorts are scarce. Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ substantially between distinct ethnicities.

Aim: The aim of this study was to determine relapse rates, factors predicting relapse and clinical outcomes after nucleos(t)ide analogue cessation in a large, predominantly Caucasian cohort of chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion.

Methods: This is a nationwide observational cohort study including HBeAg positive, mono-infected chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion from 18 centres in Belgium.

Results: A total of 98 patients with nucleo(s)tide analogue-induced HBeAg seroconversion were included in the study. Of the 62 patients who stopped treatment after a median consolidation treatment of 8 months, 30 relapsed. Higher gamma-glutamyl transferase levels at both treatment initiation (HR 1.004; P = 0.001 per unit increment) and HBeAg seroconversion (HR 1.006; P = 0.013 per unit increment) were associated with an increased risk of clinically significant relapse in a multivariate Cox regression model. Treatment cessation led to liver-related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg seroconversion, none relapsed or developed severe hepatic outcomes.

Conclusion: Treatment withdrawal in Caucasian chronic hepatitis B patients after nucleos(t)ide analogue-induced HBeAg seroconversion results in viral relapses in more than half of patients with potential fatal outcomes. These real-world data further lend support to preferentially continue NA treatment after HBeAg seroconversion until HBsAg loss.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Antiviral Agents / therapeutic use*
  • Cohort Studies
  • Female
  • Hepatitis B e Antigens / immunology*
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Humans
  • Male
  • Middle Aged
  • Nucleosides / therapeutic use*
  • Recurrence
  • Seroconversion
  • Treatment Outcome
  • Withholding Treatment

Substances

  • Antibodies, Viral
  • Antiviral Agents
  • Hepatitis B e Antigens
  • Nucleosides