Reduced risk of relapse after long-term nucleos(t)ide analogue consolidation therapy for chronic hepatitis B

Background: Before stopping nucleos(t)ide analogue (NA) treatment in chronic hepatitis B (CHB), 6-12 months of consolidation therapy is recommended.

Aim: To investigate the effect of consolidation therapy on off-treatment outcomes in CHB patients.

Methods: We included 94 patients who stopped NA after at least 1 year of therapy. Patients could be HBeAg-positive or HBeAg-negative at start-of-treatment, but were HBeAg-negative and had undetectable HBV DNA at time of discontinuation. Consolidation therapy was defined as treatment after the first undetectable HBV DNA (and HBeAg loss for HBeAg-positive patients) until NA cessation.

Results: At 3 years, 74% of the start-of-treatment HBeAg-positive and 75% of the start-of-treatment HBeAg-negative patients developed HBV DNA >2000 IU/mL at a single time point, whereas a persistent virological relapse (≥2 tests of HBV DNA >2000 IU/mL 6 months apart within 1 year) developed in 49% of the start-of-treatment HBeAg-positive and 53% of the start-of-treatment HBeAg-negative patients. For both HBeAg-positive and HBeAg-negative patients, consolidation therapy of ≥3 years was associated with lower persistent virological relapse rates compared to <1 year (1-year relapse rate: 25% vs. 54%; P = 0.063 and 24% vs. 57%; P = 0.036, respectively). At 3 years, 9% of the HBeAg-positive and 14% of the HBeAg-negative patients became HBsAg-negative. Prolonged consolidation therapy increased the likelihood of HBsAg loss. Two cirrhotic patients developed hepatic decompensation but both recovered.

Conclusions: After nucleos(t)ide analogue discontinuation, relapse was common in patients with chronic hepatitis B. Prolongation of consolidation therapy beyond 3 years decreased the risk of persistent virological relapse and increased the likelihood of HBsAg loss.