Association of HBsAg levels and HBV relapse patterns with HBsAg seroclearance following entecavir or tenofovir cessation.

BACKGROUND

This study investigated the association between HBsAg levels at end of treatment (EOT) and different HBV relapse patterns or HBsAg seroclearance after discontinuing entecavir or tenofovir disoproxil fumarate (TDF).

METHODS

A total of 900 non-cirrhotic patients (616 HBeAg-negative and 284 HBeAg-positive at initiation) who had discontinued entecavir or TDF for at least 12 months were retrospectively analyzed.

RESULTS

HBeAg-negative patients achieved significantly higher rates of HBsAg seroclearance than HBeAg-positive patients (10 years: 29.8% vs. 19.7%, p=0.007), despite comparable rates of clinical relapse and retreatment. Among the 118 HBeAg-negative and 35 HBeAg-positive patients who experienced HBsAg seroclearance, 39 (33.1%) and 8 (22.8%) did experience clinical relapse prior to HBsAg seroclearance, respectively. In HBeAg-negative patients who achieved seroclearance, different HBV relapse patterns were associated with distinct HBsAg kinetic profiles. An HBsAg threshold of ≤20 and 20-100 IU/mL identifies patients with a high likelihood of HBsAg loss (10-year cumulative incidence of 82.7% and 50.4%, respectively) with 0% and 31.0% clinical relapse, respectively. In HBeAg-positive patients, those with an EOT HBsAg ≤100 IU/mL achieved the highest rate of HBsAg loss (10-year cumulative incidence of 64.8%) with only 6.7% (1/15) clinical relapse. There was no significant difference in HBsAg seroclearance rates between the initial and subsequent finite therapies. Eight patients developed hepatic decompensation upon clinical relapse (annual incidence rate of 0.13 per 100 person-years).

CONCLUSION

HBV relapse patterns strongly affect HBsAg kinetics and HBsAg seroclearance. EOT HBsAg levels predict both HBsAg seroclearance and clinical relapse rates prior to HBsAg seroclearance.