Why and when could nucleos(t)ide analogues treatment be withdrawn?

Area of Science:

• Hepatology
• Virology
• Immunology

Background:

• Oral antiviral nucleos(t)ide analogues (NUCs) effectively suppress hepatitis B virus (HBV) replication, improving clinical outcomes.
• Functional cure, defined by hepatitis B surface antigen (HBsAg) clearance, remains rare despite long-term NUC therapy.
• New treatments with finite durations are being investigated for chronic hepatitis B (CHB).

Purpose of the Study:

• To explore strategies for achieving HBsAg loss and functional cure in CHB patients.
• To evaluate the risks and benefits of NUC discontinuation.
• To investigate biomarkers and AI-driven approaches for personalized NUC treatment decisions.

Main Methods:

• Review of available data on NUC therapy outcomes, including HBsAg loss and relapse rates.
• Analysis of risks associated with NUC discontinuation in patients with cirrhosis.
• Exploration of viral and immune biomarkers for relapse risk stratification.
• Consideration of artificial intelligence (AI) and viral kinetics modeling for treatment optimization.

Main Results:

• HBsAg loss occurs in 10-20% of patients post-NUC discontinuation, but with significant risks of virological relapse (50-80%) and retreatment (40-55%).
• NUC treatment should not be stopped in patients with cirrhosis due to high risks of hepatic decompensation and mortality.
• Biomarkers for predicting relapse risk after NUC cessation are under investigation.

Conclusions:

• Achieving functional cure of HBV remains a challenge, with NUC discontinuation posing significant relapse risks.
• Personalized medicine approaches, including AI-powered monitoring of viral kinetics, show promise for optimizing NUC treatment duration and improving patient outcomes.
• Further research into predictive biomarkers and advanced modeling is crucial for guiding individualized treatment decisions in CHB management.