Evidence map›Paper›PMID 41603079›Full record

ArticleAlimentary pharmacology & therapeutics2026

Nationwide Implementation of Double Reflex Testing for Hepatitis Delta in Spain: Results From the Retrospective Phase of the Spain-DDR Study.

Ana Alberola, Adolfo de Salazar, Ana Fuentes, Raquel Carracedo, Marta Illescas-López, María Del Carmen Rodríguez Baños, Carolina Freyre, Berta Becerril, Isabel Viciana, Inmaculada López-Rodríguez and 86 more

Abstract readMulticenter Study
In one paragraph

Article in Alimentary pharmacology & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. From Diagnosis to Durability: A Review of the European Bulevirtide Experience and Practical Learnings for CHD Management.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

96 authors.

Ana AlberolaHospital Universitario Clínico San Cecilio, Granada, Spain.ORCID https://orcid.org/0009-0005-9403-2824
Adolfo de SalazarHospital Universitario Clínico San Cecilio, Granada, Spain.ORCID https://orcid.org/0000-0002-4318-858X
Ana FuentesHospital Universitario Clínico San Cecilio, Granada, Spain.
Raquel CarracedoComplexo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain.
Marta Illescas-LópezHospital Universitario Clínico San Cecilio, Granada, Spain.
María Del Carmen Rodríguez BañosHospital Torrecárdenas, Almería, Spain.
Carolina FreyreHospital Universitario Puerto Real, Cádiz, Spain.
Berta BecerrilHospital Universitario de Jerez, Jerez, Spain.
Isabel VicianaHospital Clínico Universitario Virgen de La Victoria, Málaga, Spain.
Inmaculada López-RodríguezHospital Costa del Sol, Marbella, Spain.
Natalia MontielHospital Universitario Puerta del Mar, Cádiz, Spain.
Ana María Domínguez CastañoHospital Universitario de Valme, Seville, Spain.
María Pilar Luzón-GarcíaCentro de Investigación Biomédica en Red Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
Encarnación Ramírez ArellanoHospital Universitario Virgen Macarena, Sevilla, Spain.
Carmen Liébana-MartosComplejo Hospitalario de Jaén, Jaén, Spain.
Francisco Franco Álvarez de LunaHospital Universitario Juan Ramón Jiménez, Huelva, Spain.
María Del Carmen LozanoHospital Universitario Virgen del Rocío, Sevilla, Spain.
Begoña PalopHospital Regional Universitario Carlos Haya, Málaga, Spain.
Antonio SampedroHospital Universitario Virgen de Las Nieves, Granada, Spain.
Ana Belén PérezCentro de Investigación Biomédica en Red Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain.
Sonia AlgarateHospital Clínico Universitario Lozano Blesa, Zaragoza, Spain.
Susana Rojo AlbaHospital Universitario Central de Asturias, Oviedo, Spain.
Pablo FraileHospital Universitario Son Espases, Palma de Mallorca, Spain.
Dolores OceteConsorcio Hospital General Universitario de Valencia, Valencia, Spain.
María Jesús AlcarazHospital Clínico Universitario de Valencia, Valencia, Spain.
Juan Carlos RodríguezHospital General Universitario de Alicante, Alicante, Spain.
Francisco Javier Hernández-FelicesHospital Universitario Vega Baja, Orihuela, Spain.ORCID https://orcid.org/0000-0003-1843-8521
Olalla MartínezHospital Universitario de La Ribera, Alzira, Spain.
Victoria DomínguezHospital Arnau de Vilanova, Valencia, Spain.
Nieves OrtaHospital Universitario Francesc De Borja, Gandia, Spain.
Dolores GómezHospital Universitario y Politécnico La Fe, Valencia, Spain.
Carmen CortellUnidad de Conductas Adictivas San Isidro, Valencia, Spain.
Jorge CamachoInstituto Valenciano de Oncología, Valencia, Spain.ORCID https://orcid.org/0000-0002-6602-0966
Susana SabaterHospital General de Castellón, Castellón, Spain.
Luis Ángel Iglesias SánchezHospital Nuestra Señora de Guadalupe, La Gomera, Spain.
Yasmina MartínHospital Universitario Doctor José Molina Orosa, Lanzarote, Spain.
Aldara VallejoHospital General de Fuerteventura, Fuerteventura, Spain.
Lourdes MolinaHospital Universitario de La Palma, La Palma, Spain.
María ArocaHospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain.
Beatriz CastroComplejo Hospitalario Universitario de Canarias, La Laguna, Spain.
Magdalena LaraHospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain.
María José PenaHospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain.
Ana Rodríguez-FernándezHospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain.
Alejandro González PraetoriusHospital Universitario de Guadalajara, Guadalajara, Spain.
José Joaquín BlasHospital General de Albacete, Albacete, Spain.
Alicia BetetaHospital General Nuestra Señora del Prado, Talavera de la Reina, Spain.
César GómezComplejo Hospitalario Universitario de Toledo, Toledo, Spain.
María José RodríguezHospital Virgen de la Luz, Cuenca, Spain.
Soledad IllescasHospital General Universitario de Ciudad Real, Ciudad Real, Spain.
Melanie AbreuHospital Público Santa Bárbara, Puertollano, Spain.
Julio García DíezHospital General de Valdepeñas, Valdepeñas, Spain.
Inocencio BeltránHospital Virgen de Altagracia, Manzanares, Spain.
Marta Sandoval TorrientesHospital Santiago Apostol, Miranda de Ebro, Spain.
Ruth SáezComplejo Asistencial Universitario de Burgos, Burgos, Spain.
Teresa MartínHospital Virgen de la Concha, Zamora, Spain.
Pilar Tajada AlegreHospital General de Segovia, Segovia, Spain.
Belén LorenzoHospital Río Hortega, Valladolid, Spain.
María Teresa García ValeroComplejo Asistencial de Palencia, Palencia, Spain.
Isabel Jiménez SansegundoHospital Nuestra Señora De Sonsoles, Ávila, Spain.
Susana García-de CruzComplejo Asistencial de Soria, Soria, Spain.
Sonsoles GarcinuñoHospital Clínico Universitario de Valladolid, Valladolid, Spain.
Miguel Ángel SáizHospital Santos Reyes, Aranda de Duero, Spain.
Santiago MuñozHospital Universitario de Salamanca, Salamanca, Spain.
Isabel FernándezHospital de León, León, Spain.
Helena Miriam Lorenzo JuanesHospital El Bierzo, Ponferrada, Spain.
María Reyes Vidal-AcuñaComplejo Hospitalario Universitario de Cáceres, Cáceres, Spain.
Luz María MoldesComplexo Hospitalario Universitario de A Coruña, La Coruña, Spain.
Noelia CalvoComplexo Hospitalario Universitario de Ourense, Ourense, Spain.
Matilde TrigoComplexo Hospitalario de Pontevedra, Pontevedra, Spain.
María José GudeHospital Universitario Lucus Augusti, Lugo, Spain.
Patricia OrdóñezComplexo Hospitalario Arquitecto Marcide-Profesor Novoa Santos, Ferrol, Spain.
Sandra CortizoComplexo Hospitalario Universitario de Vigo, Vigo, Spain.
Miriam BlascoHospital San Pedro, Logroño, Spain.
Mayra SigchaHospital Universitario 12 de Octubre, Madrid, Spain.
Iker FalcesHospital Universitario La Paz, Madrid, Spain.
Juan Carlos GalánHospital Universitario Ramón y Cajal, Madrid, Spain.
Ana ArribiHospital Clínico San Carlos, Madrid, Spain.
Roberto AlonsoHospital General Universitario Gregorio Marañón, Madrid, Spain.
Asunción IborraHospital Virgen de la Arrixaca, Murcia, Spain.
María Jesús Del Amor EspínHospital General Universitario Santa Lucía, Cartagena, Spain.
Eva CascalesHospital General Universitario Rafael Méndez, Lorca, Spain.
Cayetano PérezHospital Comarcal del Noroeste, Caravaca de la Cruz, Spain.
Pablo FernándezHospital Virgen del Castillo, Yecla, Spain.
María Dolores NavarroHospital General Universitario Morales Meseguer, Murcia, Spain.
María Luz NuñezHospital General Universitario Reina Sofía, Murcia, Spain.
Jorge Galán RosHospital General Universitario Los Arcos del Mar Menor, Murcia, Spain.
Luis Javier Gil-GallardoHospital de la Vega Lorenzo Guirao, Cieza, Spain.
Ana MiqueleizHospital Universitario de Navarra, Pamplona, Spain.
Gabriel ReinaClínica Universidad de Navarra, Pamplona, Spain.
Luis ElorduyHospital Universitario Cruces, Barakaldo, Spain.
Mikele MachoHospital Universitario Galdakao-Usansolo, Galdakao, Spain.
Carmen GómezHospital Universitario de Álava, Vitoria-Gasteiz, Spain.
Paloma LiendoHospital Universitario de Basurto, Bilbao, Spain.
Yolanda SalicioHospital Universitario Donostia, San Sebastián, Spain.
Antonio AguileraComplexo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain.
Federico GarcíaHospital Universitario Clínico San Cecilio, Granada, Spain.ORCID https://orcid.org/0000-0001-7611-781X

Funding

Gilead Sciences IN-ES-980-7036
6 · The paper itself

Abstract

backgroundHepatitis delta virus accelerates liver disease progression in chronic hepatitis B, yet remains underdiagnosed. Guidelines recommend double reflex diagnostic testing with antibody testing followed by viral load testing, but uptake remains inconsistent.

aimsTo evaluate double reflex diagnostic implementation in Spain during the retrospective phase of the Spain Double Reflex Diagnostic study.

methodsNationwide, multicenter retrospective analysis of individuals positive for hepatitis B surface antigen (2022-2024) from 80 centers. Laboratory data included hepatitis B surface antigen, hepatitis delta virus antibody and hepatitis delta virus viral load. Uptake rates, hepatitis delta virus antibody positivity, viral load confirmation and viral load-confirmed prevalence were calculated with 95% confidence intervals.

resultsAmong 65,763 individuals positive for hepatitis B surface antigen, hepatitis delta virus antibody testing uptake increased from 55.1% (54.4-55.8) in 2022 (n = 18,986) to 72.5% (71.9-73.1) in 2023 (n = 22,463) and 85.8% (85.1-86.4) in 2024 (n = 24,314; p < 0.0001). Antibody positivity remained stable (5.6%, 4.9%, 5.3%). Viral load confirmation among antibody-positive patients improved from 72.6% in 2022 to 90.8% in 2023 and 91.0% in 2024. Viral load-confirmed prevalence among antibody-positive individuals was 40.3% in 2022, 31.6% in 2023, and 30.1% in 2024. Regional heterogeneity was marked, with several autonomous communities achieving near-universal uptake (> 95%).

conclusionBetween 2022 and 2024, double reflex diagnostic implementation expanded rapidly, demonstrating national feasibility and describing hepatitis D virus seroprevalence. However, regional inequities persist. Sustained uptake will require standardised reflex protocols, harmonization of viral load assays and continuous training to reduce underdiagnosis and improve care of coinfected patients.

Indexed as

Hepatitis DHepatitis Delta VirusAdultFemaleHepatitis AntibodiesHepatitis B, ChronicHepatitis B Surface AntigensHumansMaleMiddle AgedPrevalenceRetrospective StudiesSpainViral LoadHepatitis AntibodiesHepatitis B Surface Antigensanti‐HDVHDV‐RNAhepatitis delta virusprevalencereflex diagnostic

Identifiers

PMID41603079
PMCPMC13127840

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