Clinical characteristics and outcomes of patients with recurrent chronic hepatitis B after nucleos(t)ide analog withdrawal with stringent cessation criteria: A prospective cohort study

Abstract

Aim: The aim of this study was to explore the clinical characteristics and outcomes of patients with recurrent chronic hepatitis B meeting the cessation criteria outlined by the 2008 Asian Pacific Association for the Study of the Liver guidelines.

Methods: In total, 223 chronic hepatitis B patients who met the cessation criteria and discontinued nucleos(t)ide analog therapy were prospectively included. They were monitored monthly during the first 4 months and every 3-6 months thereafter. Early relapse was defined as viral relapse (serum hepatitis B virus [HBV] DNA >10⁴ copies/mL) confirmed within 3 months after cessation.

Results: Of the 38 hepatitis B e antigen (HBeAg)-positive relapse cases, 44.7%, 65.8%, 76.3% and 89.5% occurred within 3 months, 6 months, 12 months, and 48 months, respectively; in the 49 HBeAg-negative relapse cases, 44.9%, 51.0%, 77.6% and 91.8% occurred within 3, 6, 12 and 36 months, respectively. Time to undetectable HBV DNA was a predictive factor of early relapse. Viral relapses were accompanied by elevated alanine aminotransferase in 70 (80.5%) patients. A peak alanine aminotransferase 10 times over the upper limit of normal after relapse was observed in 15.8% of the HBeAg-positive and 22.4% of the HBeAg-negative patients. Hepatic decompensation and liver failure were not observed.

Conclusions: For HBeAg-positive and HBeAg-negative patients meeting stringent cessation criteria, at least 4 years and 3 years of close follow-up are necessary. For those with a longer time to undetectable HBV DNA, more attention should be paid to the early stages after cessation. Nucleos(t)ide analog withdrawal in selected non-cirrhotic patients is generally safe, although close monitoring and timely intervention are needed.

Keywords: hepatitis B; nucleos(t)ide analogs; outcome; relapse/recurrence; safety.