Double reflex testing improves the efficacy and cost effectiveness of hepatitis delta diagnosis in southern Spain
This study aims to evaluate the prevalence of undiagnosed hepatitis delta in southern Spain (Andalusia) and assess the effectiveness and cost-efficiency of implementing reflex testing for hepatitis D detection in HBsAg-positive patients. A multicenter ambispective study was conducted in 17 Andalusian hospitals. The retrospective phase (January 2018-June 2022) analyzed diagnostic processes for hepatitis delta in HBsAg-positive patients. The prospective phase (October 2022-March 2023) implemented reflex testing, performing anti-HDV serology on all HBsAg-positive patients without prior testing. HDV RNA testing followed for those who tested anti-HDV-positive. In the retrospective phase, out of 18,583 HBsAg-positive patients, anti-HDV tests were performed on 3,436 (18%), identifying 205 (6%) positive cases. HDV RNA was tested in 158 (77%) anti-HDV-positive patients, with 69 (44%) testing positive. In the prospective phase, out of 2,384 HBsAg-positive patients without prior anti-HDV testing, 2,293 (96%) were tested, identifying 109 (4.7%) positive cases. HDV RNA was analyzed in 97 (89%) anti-HDV-positive patients, with 30 (31%) testing positive. Reflex testing increased anti-HDV detection by 77%, resulting in a fourfold increase in detecting anti-HDV-positive patients and a threefold increase in detecting HDV RNA-positive patients, reducing undiagnosed HDV RNA-positive cases to 4% compared to 45% with clinical practice. Cost analysis indicated a saving of €265,954 with reflex testing. Reflex testing improves HDV detection, reduces costs, and simplifies diagnosis, making it an efficient strategy for managing chronic hepatitis D patients.
Authors
- Natalia Montiel (ORCID: https://orcid.org/0000-0003-2503-3960)
- Pilar Barrera (ORCID: https://orcid.org/0000-0003-3797-1532)
- Juan Carlos Alados (ORCID: https://orcid.org/0000-0001-5361-3968)
- Patricia Cordero (ORCID: https://orcid.org/0000-0002-8173-6401)
- Carolina Roldán
- Antonio Sampedro
- María D. Lozano (ORCID: https://orcid.org/0000-0002-6796-9380)
- Adolfo de Salazar (ORCID: https://orcid.org/0000-0002-4318-858X)
- Carolina Freyre
- Féderico García (ORCID: https://orcid.org/0000-0001-7611-781X)
- J. M. Pinazo Bandera
- Ana Fuentes (ORCID: https://orcid.org/0000-0002-2057-2730)
- Ana Belén Pérez (ORCID: https://orcid.org/0000-0001-9655-817X)
- M. Garrido
- Anny Camelo‐Castillo (ORCID: https://orcid.org/0000-0002-4080-6346)
- Teresa Cabezas
- Marta Casado (ORCID: https://orcid.org/0000-0001-6457-4650)
- Isabel Viciana
- Begoña Palop
- Juan Cristóbal Aguilar
- José Miguel Rosales Zábal (ORCID: https://orcid.org/0000-0001-6751-6720)
- Elena Ruiz Escolano
- María Pilar Luzón-García (ORCID: https://orcid.org/0000-0001-5260-7072)
- Álvaro Giráldez Gallego (ORCID: https://orcid.org/0000-0001-6849-9272)
- Pilar del Pino
- Joaquín Salas-Coronas (ORCID: https://orcid.org/0000-0002-4302-7022)
- Fernando Fernández Sánchez (ORCID: https://orcid.org/0000-0001-7522-5720)
- Fernando García (ORCID: https://orcid.org/0000-0002-9953-0452)
- Alberto de la Iglesia (ORCID: https://orcid.org/0000-0002-6989-2807)
- María del Carmen Domínguez
- Encarnación Ramírez de Arellano
- Carlota Jimeno Maté
- Matías Estévez-Escobar
- Germán Santamaría Rodríguez
- Manuel Macías
- Francisco Franco Álvarez De La Luna
- Domingo Pérez
- Rocío González Grande
Institutions
- Hospital Costa del Sol (ES)
- Hospital Universitario Virgen Macarena (ES)
- Hospital Regional Universitario de Málaga (ES)
- Hospital de Poniente (ES)
- Instituto de Investigación Biosanitaria de Granada (ES)
- Centro de Investigación Biomédica en Red (ES)
- Hospital Universitario Virgen de las Nieves (ES)
- Complejo Hospitalario de Jaén (ES)
- Biomedical Research and Innovation Institute of Cadiz (ES)
- Hospital Universitario Reina Sofía (ES)
- Hospital Juan Ramón Jiménez (ES)
- Hospital Universitario Puerto Real (ES)
- Hospital Universitario Puerta del Mar (ES)
- Hospital Universitario de Valme (ES)
- Complejo Hospitalario Torrecárdenas (ES)
- Hospital Universitario Virgen del Rocío (ES)
- Hospital Jerez Puerta del Sur (ES)
- Hospital Clínico Universitario Virgen de la Victoria (ES)
- Pharmacoeconomics and Health Outcomes Research Iberia (Spain) (ES)
- Hospital Universitario Infanta Leonor (ES)
- University of Almería (ES)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-05-02
- DOI
- https://doi.org/10.1038/s41598-025-00101-7
- Citations
- 4
- Primary Topic
- Hepatitis B Virus Studies
- Type
- article
- Field-Weighted Citation Impact
- 5.42
Funders
- Gilead Sciences
- Instituto de Salud Carlos III