Off-Therapy Response After Nucleos(t)ide Analogue Withdrawal in Patients With Chronic Hepatitis B: An International, Multicenter, Multiethnic Cohort (RETRACT-B Study)

Gastroenterology. 2022 Mar;162(3):757-771.e4. doi: 10.1053/j.gastro.2021.11.002. Epub 2021 Nov 9.

Abstract

Background & aims: Functional cure, defined based on hepatitis B surface antigen (HBsAg) loss, is rare during nucleos(t)ide analogue (NA) therapy and guidelines on finite NA therapy have not been well established. We aim to analyze off-therapy outcomes after NA cessation in a large, international, multicenter, multiethnic cohort of patients with chronic hepatitis B (CHB).

Methods: This cohort study included patients with virally suppressed CHB who were hepatitis B e antigen (HBeAg)-negative and stopped NA therapy. Primary outcome was HBsAg loss after NA cessation, and secondary outcomes included virologic, biochemical, and clinical relapse, alanine aminotransferase flare, retreatment, and liver-related events after NA cessation.

Results: Among 1552 patients with CHB, cumulative probability of HBsAg loss was 3.2% at 12 months and 13.0% at 48 months of follow-up. HBsAg loss was higher among Whites (vs Asians: subdistribution hazard ratio, 6.8; 95% confidence interval, 2.7-16.8; P < .001) and among patients with HBsAg levels <100 IU/mL at end of therapy (vs ≥100 IU/mL: subdistribution hazard ratio, 22.5; 95% confidence interval, 13.1-38.7; P < .001). At 48 months of follow-up, Whites with HBsAg levels <1000 IU/mL and Asians with HBsAg levels <100 IU/mL at end of therapy had a high predicted probability of HBsAg loss (>30%). Incidence rate of hepatic decompensation and hepatocellular carcinoma was 0.48 per 1000 person-years and 0.29 per 1000 person-years, respectively. Death occurred in 7/19 decompensated patients and 2/14 patients with hepatocellular carcinoma.

Conclusions: The best candidates for NA withdrawal are virally suppressed, HBeAg- negative, noncirrhotic patients with CHB with low HBsAg levels, particularly Whites with <1000 IU/mL and Asians with <100 IU/mL. However, strict surveillance is recommended to prevent deterioration.

Keywords: Antiviral; Discontinuation; HBV; HBsAg seroconversion.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Age Factors
  • Antiviral Agents / therapeutic use*
  • Asians / statistics & numerical data*
  • Cohort Studies
  • DNA, Viral / blood
  • Female
  • Follow-Up Studies
  • Guanine / analogs & derivatives
  • Guanine / therapeutic use
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Nucleosides / analogs & derivatives
  • Nucleosides / therapeutic use*
  • Race Factors
  • Recurrence
  • Retreatment
  • Tenofovir / therapeutic use
  • Whites / statistics & numerical data*

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Nucleosides
  • entecavir
  • Guanine
  • Tenofovir