Oral Microbiome Diversity Predicts Outcomes After NUC Therapy Discontinuation in CHB
Overview
This longitudinal study of 18 HBeAg-negative chronic hepatitis B patients undergoing nucleos(t)ide analogue (NUC) cessation found that higher oral microbiome diversity correlates with favorable virological outcomes. Oral microbial profiles predicted treatment success better than clinical markers alone, suggesting a novel prognostic role for oral microbiome analysis in CHB management.
Background
Chronic hepatitis B (CHB) affects millions worldwide and is treated primarily with nucleos(t)ide analogues (NUCs) that suppress viral replication but rarely achieve functional cure marked by HBsAg loss. Discontinuation of NUC therapy in HBeAg-negative patients may induce immune reactivation and functional cure but carries risks of relapse and hepatic flares. The gut microbiome influences CHB progression and treatment response, yet the role of the oral microbiome during NUC cessation remains unexplored. Understanding oral microbial dynamics could provide insights into host-virus interactions and support prognostication of treatment outcomes.
Data Highlights
Parameter
Favorable Outcome
Unfavorable Outcome
Statistical Significance
Alpha Diversity of Oral Microbiome
Consistently Higher
Lower
P < .001
Intersample Variation
Lower
Higher
P < .05
Correlation with HBsAg, ALT, AST
Inverse with Prevotella taxa (ρ < -0.5)
Positive with Haemophilus parainfluenzae, Porphyromonas catoniae
P < .01
Random Forest Model AUC
0.79 (Microbial markers)
0.66 (Clinical markers alone)
Not specified
Key Findings
Patients with favorable outcomes after NUC cessation exhibited significantly higher oral microbiome alpha diversity from baseline through 36 months.
Lower intersample variation in oral microbiome composition was observed in favorable outcome patients, indicating microbial stability.
Inverse correlations were found between HBsAg, ALT, AST levels and several Prevotella taxa, suggesting protective microbial associations.
Unfavorable outcomes and higher HBsAg levels correlated with opportunistic taxa such as Haemophilus parainfluenzae and Porphyromonas catoniae.
A random forest model incorporating oral microbial markers predicted favorable versus unfavorable outcomes with greater accuracy (AUC 0.79) than clinical markers alone (AUC 0.66).
The oral microbiome remained overall stable during the 3-year follow-up, emphasizing the significance of baseline microbial profiles.
Clinical Implications
Oral microbiome profiling at the time of NUC therapy cessation may serve as a valuable prognostic tool to identify CHB patients likely to achieve functional cure or maintain viral suppression off therapy. Integrating microbial markers with clinical parameters could enhance risk stratification and guide personalized management strategies to optimize safe discontinuation of antiviral treatment.
Conclusion
This study provides novel evidence that oral microbiome diversity and composition are associated with virological outcomes following NUC discontinuation in HBeAg-negative CHB. Oral microbiome analysis holds promise as a noninvasive biomarker to support clinical decision-making in hepatitis B management.
by Mahin Ghorbani, Agne Kvedaraite, Khaled Al-Manei, Choon Boon Too, Susanne Cederberg, Asgeir Johannessen, Dag Henrik Reikvam, Davide Valentini, Christopher Maucourant, Niklas K Björkström, Soo Aleman, Margaret Sällberg Chen
