Highlights
– Global meta-analysis of 110 cohorts shows major drop-offs across the chronic hepatitis B (HBV) care cascade, with lower treatment assessment and initiation in primary/community models versus hospital-based specialist care.
– Assessment for treatment eligibility ranged from ~33% (passive community linkage) to >85% (integrated prison services); antiviral initiation among eligible patients was highest when community screening included active linkage to specialists (~98%) and lowest in primary care (~49%).
– Retention in care was substantially higher in patients on antiviral therapy (pooled ~88% in specialist care) than in untreated patients (~47%); viral suppression on therapy in specialist care averaged ~73% after ~12 months.
Background: disease burden and health-system challenge
Chronic hepatitis B infection remains a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Despite a safe, effective, and affordable antiviral treatment arsenal that reduces disease progression and transmission, large gaps persist in diagnosis, linkage, treatment and long-term follow-up. In 2022, only an estimated 13% of the global 254 million people living with chronic HBV were diagnosed, and only 3% were on antiviral therapy — highlighting major implementation failures.
Service delivery models that improve linkage after diagnosis, simplify treatment pathways, and retain people in long-term care are central to achieving public health targets and preventing HBV-related morbidity and mortality. The Lancet Gastroenterology & Hepatology systematic review and meta-analysis by Stockdale and colleagues (2025) provides the most comprehensive, up-to-date quantitative assessment of how different care models perform across key cascade outcomes.
Study design
This review searched PubMed, Embase and Scopus for observational and interventional studies of chronic HBV service delivery models published from May 1, 2013 to July 15, 2024 and reporting care cascade outcomes. Eligible studies reported one or more cascade metrics: the proportion of diagnosed individuals assessed for treatment eligibility; the proportion of eligible people who initiated antiviral therapy; retention in care (12–48 months); and the proportion on therapy achieving HBV DNA suppression. The authors pooled outcomes across multiple service delivery models using generalized linear mixed models and presented within-study comparisons (risk ratios) using inverse-variance weighting. The final analysis included 106 studies comprising 110 cohorts from 50 countries (41% from low- and middle-income countries; 59% from high-income countries).
Key findings
The review quantified performance across multiple service models: hospital-based specialist care; co-managed primary-specialist care; primary care–led services; community screening with active linkage to specialists; community screening with passive linkage; and integrated models (antenatal, NCD clinics, HIV, prison health, harm-reduction services).
Assessment for treatment eligibility
Pooled proportions of diagnosed patients who received formal assessment for treatment eligibility were:
- Hospital-based specialist care: 73.9% (95% CI 65.8–80.6; I2 = 98.5%; 20 cohorts)
- Co-managed primary-specialist care: 63.1% (53.0–72.2; I2 = 99.9%; 23 cohorts)
- Primary care: 50.4% (25.9–74.8; I2 = 99.7%; 4 cohorts)
- Community screening with active linkage to specialist care: 82.3% (58.7–93.8; I2 = 96.1%; 10 cohorts)
- Community screening with passive linkage: 33.2% (23.1–45.1; I2 = 98.6%; 3 cohorts)
- Antenatal diagnosis with post‑delivery linkage to specialist care: 56.9% (40.2–72.1; I2 = 98.8%; 5 cohorts)
- Integrated care in harm‑reduction services: 75.0% (37.7–93.7; I2 = 0.0%; 2 cohorts)
- Integrated prison health services: 85.4% (78.0–90.6; I2 = 0.0%; 2 cohorts)
Interpretation: Specialist and actively linked community models generally achieved higher treatment assessment rates than primary-care or passive linkage models, though heterogeneity across studies was high.
Initiation of antiviral therapy among those eligible
Pooled initiation rates were:
- Hospital-based specialist care: 78.1% (68.1–85.7; I2 = 99.2%; 25 cohorts)
- Co-managed care: 67.2% (55.5–77.1; I2 = 95.8%; 11 cohorts)
- Primary care: 49.3% (32.4–66.4; I2 = 87.9%; 4 cohorts)
- Community screening with active linkage: 97.7% (80.6–99.8; I2 = 39.2%; 7 cohorts)
- Integrated with NCD clinics: 49.4% (22.1–77.0; I2 = 84.0%; 2 cohorts)
Within-study pooled comparisons showed significantly higher rates of assessment (RR 2.07, 95% CI 1.65–2.59) and antiviral initiation (RR 1.45, 95% CI 1.13–1.85) in hospital-based specialist care versus primary care (three cohorts for each comparison).
Interpretation: Primary-care led services and some integrated models initiated fewer eligible patients on treatment compared with specialist and actively linked community approaches. When active linkage mechanisms were in place after community screening, initiation among eligible patients was high.
Retention in care
Retention measured 12–48 months after assessment or treatment showed large differences by treatment status:
- Patients on antiviral therapy in hospital-based specialist care: 87.7% retained (95% CI 79.9–92.8; I2 = 96.7%; 13 cohorts)
- Patients not receiving antiviral therapy: 47.2% retained (22.2–73.6; I2 = 99.5%; 2 cohorts)
Overall, retention was higher in patients receiving antiviral therapy than those not on treatment (RR 1.72; 95% CI 1.16–2.54).
Interpretation: Antiviral therapy is associated with substantially higher retention, perhaps reflecting more frequent clinical interactions, perceived benefit, or care engagement strategies tied to therapy.
Viral suppression on therapy
Among patients on antiviral therapy in specialist settings (median follow-up ~12 months, IQR 12–33), pooled HBV DNA suppression was 73.1% (95% CI 64.3–80.4; I2 = 92.0%; 9 cohorts).
Interpretation: Virologic suppression rates are suboptimal in many settings compared with expectations from clinical trials and programmatic targets; reasons may include adherence gaps, intermittent drug access, genotypic resistance, or measurement timing/thresholds.
Expert commentary: interpretation, strengths, and limitations
This analysis is timely and valuable for policy makers and clinicians, synthesizing data from a wide range of settings and service models. Key strengths include broad geographic representation, consideration of multiple service-delivery approaches, and focus on clinically meaningful cascade outcomes.
However, several limitations must temper interpretation. Heterogeneity across cohorts was high (I2 frequently >90%), reflecting diverse health systems, case-finding approaches, eligibility criteria and follow-up durations. Many included studies were observational and at risk of selection bias; for example, specialist clinics may report better outcomes because patients attending them are already engaged or have more advanced disease. The small number of cohorts for some models (notably primary care and certain integrated services) limits precision. Outcome definitions (what constitutes ‘assessment’, ‘retention’ or viral suppression) and timing varied, complicating direct comparisons. Finally, the review largely aggregates program-level performance but cannot fully disentangle which specific components (task-shifting, point-of-care testing, patient navigation, cost removal) drive success.
Clinical and policy implications
Principal implications are clear:
- Active linkage after community testing markedly improves initiation among eligible patients; programs should invest in linkage/navigation rather than relying on passive referral.
- Primary care can potentially expand access but current primary-care models in the literature underperformed for assessment and initiation; scale-up will require training, simplified algorithms, access to HBV DNA or validated alternatives, and systems for follow-up.
- Retention is substantially better among people on antiviral therapy, underscoring the secondary prevention value of treatment beyond viral suppression. Efforts to identify and treat eligible persons will likely strengthen long‑term engagement.
- Integrated services (antenatal care, HIV programs, prisons, harm-reduction) show promise as high-yield platforms, but evidence quantity and quality vary by subtype; targeted implementation research is needed.
These findings align with recommendations in the 2024 WHO hepatitis B guidelines, which emphasise simplified care, decentralisation where safe, strengthened linkage-to-care, and interventions to support adherence and retention.
Unanswered questions and research priorities
High-priority topics include pragmatic trials of simplified treatment algorithms in primary care (including point-of-care tests and low-cost eligibility tools), implementation studies of patient navigation and digital reminders to improve linkage and retention, cost-effectiveness analyses of decentralised models in low-resource settings, and operational research into why viral suppression is not consistently achieved on therapy at scale. Evaluation of integrative approaches (antenatal, HIV, NCD clinics, prisons, harm reduction) using standardized cascade metrics is also needed.
Conclusion
Stockdale et al.’s global systematic review highlights major losses across the chronic HBV care cascade, particularly at the assessment and treatment-initiation steps in primary and passively linked community settings, and poor retention among untreated patients. Active linkage mechanisms, specialist involvement or adequately resourced and simplified primary-care pathways appear essential to close these gaps. Achieving WHO elimination targets will require pragmatic, context-adapted implementation of linkage, treatment initiation, adherence support and retention strategies, underpinned by investments in diagnostics and workforce training.
Funding and registration
The systematic review and meta-analysis were funded by the World Health Organization and registered with PROSPERO (CRD42023410009).
Selected references
1. Stockdale AJ, Holt B, Bhadoria AS, et al. Service delivery models and care cascade outcomes for people living with chronic hepatitis B: a global systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2025 Nov;10(11):1013-1027. doi: 10.1016/S2468-1253(25)00163-3.
2. World Health Organization. Global Hepatitis Report 2017. Geneva: WHO; 2017. https://www.who.int/publications/i/item/global-hepatitis-report-2017
3. World Health Organization. WHO consolidated guidelines on hepatitis B (prevention, care and treatment) — 2024 update. Geneva: WHO; 2024.
Note: Additional operational and guideline literature (EASL, AASLD, regional policy documents) should be consulted locally when adapting models to specific health systems.
