Liver and Bile
Off-therapy response after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B: An international, multicenter, multiethnic cohort (RETRACT-B Study)
Background and 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. The aim of this study was 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 virological, 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 [HR] = 6.8; 95% confidence interval [CI]: 2.7–16.8; p < 0.001) and among patients with HBsAg levels < 100 IU/ml at end of therapy (vs. ≥ 100 IU/ml: subdistribution HR = 22.5; 95% CI: 13.1–38.7; p < 0.001). 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 nucleos(t)ide analogue withdrawal are virally suppressed, hepatitis B e antigen-negative, non-cirrhotic patients with chronic hepatitis B with low hepatitis B surface antigen levels, particularly Whites with < 1000 IU/ml and Asians with < 100 IU/ml. However, strict surveillance is recommended to prevent deterioration.