Clinical Scorecard: The Role of Oral Microbiome Diversity in Discontinuing Nucleos(t)ide Analogue Therapy for Chronic Hepatitis B

At a Glance

Key Highlights

• Higher oral microbiome alpha diversity at NUC cessation correlates with favorable virological outcomes including HBsAg loss or sustained low HBV DNA levels.
• Specific oral taxa such as Prevotella inversely correlate with HBsAg, ALT, and AST levels, while opportunistic taxa like Haemophilus parainfluenzae associate with unfavorable outcomes.
• Oral microbiome profiling improves prediction of off-therapy outcomes beyond clinical markers alone (AUC 0.79 vs 0.66).

Guideline-Based Recommendations

Diagnosis

• Classify patients as HBeAg-negative CHB with at least 2 years of NUC therapy and full viral suppression before considering NUC cessation.
• Exclude patients with cirrhosis or hepatocellular carcinoma prior to NUC discontinuation.

Management

• Consider planned NUC cessation in selected HBeAg-negative CHB patients with mild liver disease under close monitoring.
• Use oral microbiome diversity assessment as a potential prognostic tool to support decision-making on NUC withdrawal.

Monitoring & Follow-up

• Monitor alanine transaminase (ALT) and HBV DNA levels regularly post-NUC cessation to detect hepatic flares or viral relapse.
• Define hepatic flare as ALT > 80 U/L or doubling from baseline.
• Follow patients longitudinally for at least 36 months to assess sustained off-therapy outcomes.

Risks

• NUC discontinuation carries risk of hepatic flares and viral relapse, especially in patients with low oral microbiome diversity or high HBsAg levels.
• Older age, male sex, and tenofovir-based therapy are additional risk factors for relapse.

Patient & Prescribing Data

18 adult HBeAg-negative CHB patients with >2 years NUC therapy and no cirrhosis

Patients with higher oral microbiome diversity at NUC cessation had better virological outcomes; oral microbiome markers may guide personalized NUC discontinuation strategies.

Clinical Best Practices

• Perform comprehensive baseline assessment including liver function tests and viral markers before NUC cessation.
• Incorporate oral microbiome profiling to enhance prognostication of treatment outcomes.
• Maintain long-term follow-up with serial biochemical and virological monitoring post-NUC withdrawal.
• Educate patients on signs of hepatic flare and ensure prompt clinical evaluation if symptoms arise.

References

• ClinicalTrials.gov NCT03681132