Sustained response and HBsAg loss after nucleo(s)tide analogue discontinuation in chronic hepatitis B patients: the prospective SNAP study

Clin Res Hepatol Gastroenterol. 2024 Feb;48(2):102257. doi: 10.1016/j.clinre.2023.102257. Epub 2023 Dec 6.

Abstract

Background & aim(s): Current guidelines suggest that nucleos(t)ide analogues (NA) can be discontinued before HBsAg loss in a selected group of chronic hepatitis B (CHB) patients. We aimed to study the safety and off-treatment response after NA cessation.

Methods: This is a prospective, multicentre, cohort study in which eligible patients discontinued NA therapy. Adult patients, with a CHB mono-infection, HBeAg-negative, without a (history of) liver cirrhosis, who had achieved long-term viral suppression were eligible. Follow-up visits were planned at week 2-4-8-12-24-36-48-72-96. Re-treatment criteria included severe hepatitis (ALT >10x ULN), signs of imminent liver failure (bilirubin >1.5x ULN or INR >1.5), or at the physician's own discretion.

Results: In total, 33 patients were enrolled. Patients were predominantly Caucasian (45.5%) and had genotype A/B/C/D/unknown in 3/4/6/10/10 (9.1/12.1/18.2/30.3/30.3%). At week 48, 15 patients (45.5%) achieved a sustained response (HBV DNA <2,000 IU/mL). At week 96, 13 patients (39.4%) achieved a sustained response, 4 (12.1%) achieved HBsAg loss, and 12 (36.4%) were re-treated. Severe hepatitis was the main reason for re-treatment (n=7, 21.2%). One patient with severe hepatitis developed jaundice, without signs of hepatic decompensation. Re-treatment was successful in all patients.

Conclusion: NA therapy can be ceased in a highly selected group of CHB patients if close follow-up can be guaranteed. Treatment cessation may increase the chance of HBsAg loss in selected patients, which is counterbalanced by a significant risk of severe hepatitis.

Keywords: Functional cure, ALT flare; HBV treatment; HBsAg seroconversion; Treatment cessation.

MeSH terms

  • Adult
  • Antiviral Agents / adverse effects
  • Cohort Studies
  • DNA, Viral
  • Hepatitis A*
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Hepatitis B virus / genetics
  • Hepatitis B* / drug therapy
  • Hepatitis B, Chronic* / diagnosis
  • Hepatitis B, Chronic* / drug therapy
  • Humans
  • Prospective Studies
  • Treatment Outcome

Substances

  • Hepatitis B Surface Antigens
  • Antiviral Agents
  • Hepatitis B e Antigens
  • DNA, Viral