Editorial: HDV Diagnosis Implementation: Gains in Systematic Screening, Gaps in Standardisation

Chronic hepatitis delta virus (HDV) infection represents the most severe form of viral hepatitis, characterised by rapidly progressive liver disease. In Spain, the prevalence of anti-HDV in HBsAg positive subjects is estimated at approximately 4.9% [1]. Despite clear recommendations from major international guidelines [2, 3] advocating systematic HDV screening in all HBsAg carriers, testing remains largely suboptimal, with reported screening rates below 20% in several countries [4, 5]. The diagnostic gap persists even though early identification of HDV infection enables timely linkage to care and has become increasingly relevant following the recent approval of effective antiviral therapies, which have demonstrated clinical benefit in reducing severe liver-related complications, with the potential for substantial healthcare cost saving [6-8]. The nationwide analysis by Alberola et al. [9] provides a timely and highly relevant assessment of the real-world implementation of double reflex diagnostic (DDR) testing for HDV across Spain. The study includes nearly 66,000 HBsAg-positive individuals from 80 centres across almost all but one Spanish Autonomous Communities and convincingly demonstrates that double reflex testing can be scaled at national level. Anti-HDV uptake rose from 55% in 2022 to 86% in 2024, while RNA confirmation improved from 73% to over 90%, reflecting a substantial strengthening of the diagnostic cascade. However, the study also highlights two persistent structural challenges that must be addressed if DDR is to deliver consistent clinical and epidemiological value: heterogeneity of HDV diagnostic assays and marked inter-regional variability in implementation. The diversity of platforms used for both serological screening and HDV-RNA quantification introduces variability in analytical sensitivity, limits of detection and result comparability, directly affecting prevalence estimates and the longitudinal interpretation of surveillance data [10]. Even more important is the heterogeneity observed among Autonomous Communities. Several regions rapidly achieved near-universal uptake of reflex testing, whereas others showed irregular trajectories or persistent gaps. These differences likely reflect organisational factors, such as laboratory centralization, availability of on-site molecular testing, information system integration, local leadership and resource allocation, beyond epidemiological variations. From a health-system perspective, this fragmentation undermines equity of access, delays diagnosis in certain populations and complicates coordinated public health planning. Homogenization of reflex testing therefore requires a coordinated, multi-level strategy. First, national consensus on preferred HDV-RNA platforms, minimum analytical performance standards and traceable calibration should be established. Secondly, reflex algorithms should be formally embedded into laboratory information systems with standardised triggers, reporting formats and automated audit indicators to minimise local variability in workflow execution. Third, continuous professional training for microbiology, hepatology and laboratory informatics teams is essential to sustain adherence and to rapidly integrate methodological updates (Figure 1). In summary, the Spain-DDR experience demonstrates that nationwide DDR implementation is feasible and impactful, but also that diagnostic harmonisation and organisational alignment are now the critical next steps. Standardised assays and uniform reflex pathways are prerequisites to ensuring equitable patient access, reliable epidemiological surveillance and maximal clinical benefit from emerging HDV therapies. The ongoing prospective phase of the study will further clarify the clinical and health-system impact of systematic double reflex testing. Sara Battistella: conceptualization, writing – original draft. Francesco Paolo Russo: conceptualization, writing – review and editing. The authors have nothing to report. This article is linked to Alberola et al. paper. To view this article, visit https://doi.org/10.1111/apt.70543. The authors have nothing to report.