Real‐World Outcomes of Opti‐Hep‐D: An Innovative, Multicentre and Multidisciplinary Program Improving Hepatitis D Cascade of Care

BACKGROUND AND AIM: Hepatitis D virus (HDV) infection remains underdiagnosed, and real-world data on screening and linkage to care are limited. We assessed the implementation of Opti-Hep-D, a publicly funded initiative for HDV management in the Spanish region of Catalonia. METHODS: In this prospective multicentre study conducted between January 2024 and April 2025, all HBsAg-positive samples underwent reflex anti-HDV and HDV-RNA testing, with subsequent active linkage to care of individuals testing positive. Clinical data were collected in their electronic medical records. Patient characteristics, risk factors, and bulevirtide initiation wereanalysed. RESULTS: Of 369 581 HBsAg determinations, 6100 were positive. Anti-HDV testing was completed in 5399 (89%), identifying 305 (5.6%) positive individuals. HDV-RNA was assessed in 285 patients, of whom 86 (30%) were viremic. Among 2945 first-time anti-HDV tests, 130 (4.4%) were positive and 26 (20%) were viremic. Notably, 42% of positive patients had no documented risk factors or elevated ALT. HDV prevalence varied across settings (2.3%-14%) and was highest in prisons. Newly diagnosed individuals tended to be younger with milder disease. Among 86 viremic individuals, 95% were successfully linked to care and 43% initiated bulevirtide; 57% remained untreated due to patient-related or reimbursement barriers. No prison inmates received bulevirtide, mainly because of complex social situations. CONCLUSIONS: Large-scale double reflex HDV screening with active linkage to care is feasible and effective in real-world practice and may serve as a model for other healthcare settings. Although care engagement is high, treatment initiation remained limited by structural and social barriers.