Toward Precise Risk Stratification after the Functional Cure of Chronic Hepatitis B
Clinical Snapshot
PICO Framework
| P — Population | Patients with chronic hepatitis B who have achieved functional cure (HBsAg seroclearance) |
| I — Intervention | Machine learning-based risk stratification models |
| C — Comparator | Conventional prediction models for post-cure risk assessment |
| O — Outcomes | Liver-related complications, particularly hepatocellular carcinoma development after functional cure |
Bottom Line
This narrative review proposes that patients achieving hepatitis B functional cure require ongoing personalized risk assessment rather than uniform surveillance. While the concept of machine learning-enhanced risk stratification is promising, this review lacks the systematic methodology needed to provide robust evidence for practice change. The absence of quantitative synthesis, quality assessment, and clear search strategy limits its utility for evidence-based decision making. Clinicians should continue following established guidelines for post-cure surveillance while awaiting high-quality systematic reviews and validated prediction models. The core message - that functional cure represents a transition to personalized risk management rather than disease resolution - is clinically sound but requires stronger evidence synthesis.
Key Findings
Effect Size: Not quantified - narrative review
Primary Outcome: Risk of hepatocellular carcinoma after HBsAg seroclearance
Nnt Or Sensitivity: Not reported - conceptual framework only
Confidence Interval: Not provided
Clinical Application
Machine learning approaches require sophisticated infrastructure and validation Relevant to Australian hepatitis B management given significant burden in Indigenous and migrant populations; aligns with RACGP guidelines emphasizing individualized care Patients with chronic hepatitis B achieving functional cure in developed healthcare systems
Abstract
Chronic hepatitis B remains a major global health challenge despite the advances in antiviral therapy. Although hepatitis B surface antigen (HBsAg) seroclearance is considered a functional cure, liver-related complications, particularly hepatocellular carcinoma, may still occur after viral clearance. This residual risk reflects the lasting impact of host and liver factors rather than ongoing viral activity. Conventional prediction models have attempted to stratify the residual risk after a functional cure but remain limited in their ability to guide individualized management. Recent advances in machine learning have enabled more precise risk stratification by capturing complex host-driven determinants of the long-term outcomes. These approaches support a shift from uniform surveillance toward risk-adaptive monitoring strategies. Nevertheless, post-cure management is emerging as a new clinical priority as more patients achieve a functional cure. Therefore, a functional cure should be viewed not as the end of the disease, but as the beginning of a phase requiring personalized risk assessment and surveillance.
References
- 1.Hur, M. H. (2026). Toward precise risk stratification after the functional cure of chronic hepatitis B. The Korean Journal of Gastroenterology, 77(4), 123-130. https://doi.org/10.4166/kjg.2026.020
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