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

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Hauptverfasser: 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, Natalia Montiel, Ana María Domínguez Castaño, María Pilar Luzón‐García, Encarnación Ramírez Arellano, Carmen Liébana‐Martos, Francisco Franco Álvarez de Luna, María del Carmen Lozano, Begoña Palop, Antonio Sampedro, Ana Belén Pérez, Sonia Algarate, Susana Rojo Alba, Pablo Fraile, Dolores Ocete, María Jesús Alcaraz, Juan Carlos Rodríguez, Francisco Javier Hernández‐Felices, Olalla Martínez, Victoria Domínguez, Nieves Orta, Dolores Gómez, Carmen Cortell, Jorge Camacho, Susana Sabater, Luis Ángel Iglesias Sánchez, Yasmina Martín, Aldara Vallejo, Lourdes Molina, María Aroca, Beatriz Castro, Magdalena Lara, María José Pena, Ana Rodríguez‐Fernández, Alejandro González Praetorius, José Joaquín Blas, Alicia Beteta, César Gómez, María José Rodríguez, Soledad Illescas, Melanie Abreu, Julio García Díez, Inocencio Beltrán, Marta Sandoval Torrientes, Ruth Sáez, Teresa Martín, Pilar Tajada Alegre, Belén Lorenzo, María Teresa García Valero, Isabel Jiménez Sansegundo, Susana García‐de Cruz, Sonsoles Garcinuño, Miguel Ángel Sáiz, Santiago Muñoz, Isabel Fernández, Helena Miriam Lorenzo Juanes, María Reyes Vidal‐Acuña, Luz María Moldes, Noelia Calvo, Matilde Trigo, María José Gude, Patricia Ordóñez, Sandra Cortizo, Miriam Blasco, Mayra Sigcha, Iker Falces, Juan Carlos Galán, Ana Arribi, Roberto Alonso, Asunción Iborra, María Jesús del Amor Espín, Eva Cascales, Cayetano Pérez, Pablo Fernández, María Dolores Navarro, María Luz Nuñez, Jorge Galán Ros, Luis Javier Gil‐Gallardo, Ana Miqueleiz, Gabriel Reina, Luis Elorduy, Mikele Macho, Carmen Gómez, Paloma Liendo, Yolanda Salicio, Antonio Aguilera, Federico García
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author 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
Natalia Montiel
Ana María Domínguez Castaño
María Pilar Luzón‐García
Encarnación Ramírez Arellano
Carmen Liébana‐Martos
Francisco Franco Álvarez de Luna
María del Carmen Lozano
Begoña Palop
Antonio Sampedro
Ana Belén Pérez
Sonia Algarate
Susana Rojo Alba
Pablo Fraile
Dolores Ocete
María Jesús Alcaraz
Juan Carlos Rodríguez
Francisco Javier Hernández‐Felices
Olalla Martínez
Victoria Domínguez
Nieves Orta
Dolores Gómez
Carmen Cortell
Jorge Camacho
Susana Sabater
Luis Ángel Iglesias Sánchez
Yasmina Martín
Aldara Vallejo
Lourdes Molina
María Aroca
Beatriz Castro
Magdalena Lara
María José Pena
Ana Rodríguez‐Fernández
Alejandro González Praetorius
José Joaquín Blas
Alicia Beteta
César Gómez
María José Rodríguez
Soledad Illescas
Melanie Abreu
Julio García Díez
Inocencio Beltrán
Marta Sandoval Torrientes
Ruth Sáez
Teresa Martín
Pilar Tajada Alegre
Belén Lorenzo
María Teresa García Valero
Isabel Jiménez Sansegundo
Susana García‐de Cruz
Sonsoles Garcinuño
Miguel Ángel Sáiz
Santiago Muñoz
Isabel Fernández
Helena Miriam Lorenzo Juanes
María Reyes Vidal‐Acuña
Luz María Moldes
Noelia Calvo
Matilde Trigo
María José Gude
Patricia Ordóñez
Sandra Cortizo
Miriam Blasco
Mayra Sigcha
Iker Falces
Juan Carlos Galán
Ana Arribi
Roberto Alonso
Asunción Iborra
María Jesús del Amor Espín
Eva Cascales
Cayetano Pérez
Pablo Fernández
María Dolores Navarro
María Luz Nuñez
Jorge Galán Ros
Luis Javier Gil‐Gallardo
Ana Miqueleiz
Gabriel Reina
Luis Elorduy
Mikele Macho
Carmen Gómez
Paloma Liendo
Yolanda Salicio
Antonio Aguilera
Federico García
author_facet 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
Natalia Montiel
Ana María Domínguez Castaño
María Pilar Luzón‐García
Encarnación Ramírez Arellano
Carmen Liébana‐Martos
Francisco Franco Álvarez de Luna
María del Carmen Lozano
Begoña Palop
Antonio Sampedro
Ana Belén Pérez
Sonia Algarate
Susana Rojo Alba
Pablo Fraile
Dolores Ocete
María Jesús Alcaraz
Juan Carlos Rodríguez
Francisco Javier Hernández‐Felices
Olalla Martínez
Victoria Domínguez
Nieves Orta
Dolores Gómez
Carmen Cortell
Jorge Camacho
Susana Sabater
Luis Ángel Iglesias Sánchez
Yasmina Martín
Aldara Vallejo
Lourdes Molina
María Aroca
Beatriz Castro
Magdalena Lara
María José Pena
Ana Rodríguez‐Fernández
Alejandro González Praetorius
José Joaquín Blas
Alicia Beteta
César Gómez
María José Rodríguez
Soledad Illescas
Melanie Abreu
Julio García Díez
Inocencio Beltrán
Marta Sandoval Torrientes
Ruth Sáez
Teresa Martín
Pilar Tajada Alegre
Belén Lorenzo
María Teresa García Valero
Isabel Jiménez Sansegundo
Susana García‐de Cruz
Sonsoles Garcinuño
Miguel Ángel Sáiz
Santiago Muñoz
Isabel Fernández
Helena Miriam Lorenzo Juanes
María Reyes Vidal‐Acuña
Luz María Moldes
Noelia Calvo
Matilde Trigo
María José Gude
Patricia Ordóñez
Sandra Cortizo
Miriam Blasco
Mayra Sigcha
Iker Falces
Juan Carlos Galán
Ana Arribi
Roberto Alonso
Asunción Iborra
María Jesús del Amor Espín
Eva Cascales
Cayetano Pérez
Pablo Fernández
María Dolores Navarro
María Luz Nuñez
Jorge Galán Ros
Luis Javier Gil‐Gallardo
Ana Miqueleiz
Gabriel Reina
Luis Elorduy
Mikele Macho
Carmen Gómez
Paloma Liendo
Yolanda Salicio
Antonio Aguilera
Federico García
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
Natalia Montiel
Ana María Domínguez Castaño
María Pilar Luzón‐García
Encarnación Ramírez Arellano
Carmen Liébana‐Martos
Francisco Franco Álvarez de Luna
María del Carmen Lozano
Begoña Palop
Antonio Sampedro
Ana Belén Pérez
Sonia Algarate
Susana Rojo Alba
Pablo Fraile
Dolores Ocete
María Jesús Alcaraz
Juan Carlos Rodríguez
Francisco Javier Hernández‐Felices
Olalla Martínez
Victoria Domínguez
Nieves Orta
Dolores Gómez
Carmen Cortell
Jorge Camacho
Susana Sabater
Luis Ángel Iglesias Sánchez
Yasmina Martín
Aldara Vallejo
Lourdes Molina
María Aroca
Beatriz Castro
Magdalena Lara
María José Pena
Ana Rodríguez‐Fernández
Alejandro González Praetorius
José Joaquín Blas
Alicia Beteta
César Gómez
María José Rodríguez
Soledad Illescas
Melanie Abreu
Julio García Díez
Inocencio Beltrán
Marta Sandoval Torrientes
Ruth Sáez
Teresa Martín
Pilar Tajada Alegre
Belén Lorenzo
María Teresa García Valero
Isabel Jiménez Sansegundo
Susana García‐de Cruz
Sonsoles Garcinuño
Miguel Ángel Sáiz
Santiago Muñoz
Isabel Fernández
Helena Miriam Lorenzo Juanes
María Reyes Vidal‐Acuña
Luz María Moldes
Noelia Calvo
Matilde Trigo
María José Gude
Patricia Ordóñez
Sandra Cortizo
Miriam Blasco
Mayra Sigcha
Iker Falces
Juan Carlos Galán
Ana Arribi
Roberto Alonso
Asunción Iborra
María Jesús del Amor Espín
Eva Cascales
Cayetano Pérez
Pablo Fernández
María Dolores Navarro
María Luz Nuñez
Jorge Galán Ros
Luis Javier Gil‐Gallardo
Ana Miqueleiz
Gabriel Reina
Luis Elorduy
Mikele Macho
Carmen Gómez
Paloma Liendo
Yolanda Salicio
Antonio Aguilera
Federico García
collection Wiley Open Access
contents 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 Natalia Montiel Ana María Domínguez Castaño María Pilar Luzón‐García Encarnación Ramírez Arellano Carmen Liébana‐Martos Francisco Franco Álvarez de Luna María del Carmen Lozano Begoña Palop Antonio Sampedro Ana Belén Pérez Sonia Algarate Susana Rojo Alba Pablo Fraile Dolores Ocete María Jesús Alcaraz Juan Carlos Rodríguez Francisco Javier Hernández‐Felices Olalla Martínez Victoria Domínguez Nieves Orta Dolores Gómez Carmen Cortell Jorge Camacho Susana Sabater Luis Ángel Iglesias Sánchez Yasmina Martín Aldara Vallejo Lourdes Molina María Aroca Beatriz Castro Magdalena Lara María José Pena Ana Rodríguez‐Fernández Alejandro González Praetorius José Joaquín Blas Alicia Beteta César Gómez María José Rodríguez Soledad Illescas Melanie Abreu Julio García Díez Inocencio Beltrán Marta Sandoval Torrientes Ruth Sáez Teresa Martín Pilar Tajada Alegre Belén Lorenzo María Teresa García Valero Isabel Jiménez Sansegundo Susana García‐de Cruz Sonsoles Garcinuño Miguel Ángel Sáiz Santiago Muñoz Isabel Fernández Helena Miriam Lorenzo Juanes María Reyes Vidal‐Acuña Luz María Moldes Noelia Calvo Matilde Trigo María José Gude Patricia Ordóñez Sandra Cortizo Miriam Blasco Mayra Sigcha Iker Falces Juan Carlos Galán Ana Arribi Roberto Alonso Asunción Iborra María Jesús del Amor Espín Eva Cascales Cayetano Pérez Pablo Fernández María Dolores Navarro María Luz Nuñez Jorge Galán Ros Luis Javier Gil‐Gallardo Ana Miqueleiz Gabriel Reina Luis Elorduy Mikele Macho Carmen Gómez Paloma Liendo Yolanda Salicio Antonio Aguilera Federico García Alimentary Pharmacology & Therapeutics ABSTRACT Background Hepatitis 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. Aims To evaluate double reflex diagnostic implementation in Spain during the retrospective phase of the Spain Double Reflex Diagnostic study. Methods Nationwide, 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. Results Among 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%). Conclusion Between 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. 10.1111/apt.70543 http://creativecommons.org/licenses/by-nc-nd/4.0/
doi_str_mv 10.1111/apt.70543
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institution Wiley Open Access
license_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
publishDate 2026
publisher Wiley
record_format wiley_oa
spellingShingle 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
Natalia Montiel
Ana María Domínguez Castaño
María Pilar Luzón‐García
Encarnación Ramírez Arellano
Carmen Liébana‐Martos
Francisco Franco Álvarez de Luna
María del Carmen Lozano
Begoña Palop
Antonio Sampedro
Ana Belén Pérez
Sonia Algarate
Susana Rojo Alba
Pablo Fraile
Dolores Ocete
María Jesús Alcaraz
Juan Carlos Rodríguez
Francisco Javier Hernández‐Felices
Olalla Martínez
Victoria Domínguez
Nieves Orta
Dolores Gómez
Carmen Cortell
Jorge Camacho
Susana Sabater
Luis Ángel Iglesias Sánchez
Yasmina Martín
Aldara Vallejo
Lourdes Molina
María Aroca
Beatriz Castro
Magdalena Lara
María José Pena
Ana Rodríguez‐Fernández
Alejandro González Praetorius
José Joaquín Blas
Alicia Beteta
César Gómez
María José Rodríguez
Soledad Illescas
Melanie Abreu
Julio García Díez
Inocencio Beltrán
Marta Sandoval Torrientes
Ruth Sáez
Teresa Martín
Pilar Tajada Alegre
Belén Lorenzo
María Teresa García Valero
Isabel Jiménez Sansegundo
Susana García‐de Cruz
Sonsoles Garcinuño
Miguel Ángel Sáiz
Santiago Muñoz
Isabel Fernández
Helena Miriam Lorenzo Juanes
María Reyes Vidal‐Acuña
Luz María Moldes
Noelia Calvo
Matilde Trigo
María José Gude
Patricia Ordóñez
Sandra Cortizo
Miriam Blasco
Mayra Sigcha
Iker Falces
Juan Carlos Galán
Ana Arribi
Roberto Alonso
Asunción Iborra
María Jesús del Amor Espín
Eva Cascales
Cayetano Pérez
Pablo Fernández
María Dolores Navarro
María Luz Nuñez
Jorge Galán Ros
Luis Javier Gil‐Gallardo
Ana Miqueleiz
Gabriel Reina
Luis Elorduy
Mikele Macho
Carmen Gómez
Paloma Liendo
Yolanda Salicio
Antonio Aguilera
Federico García
Alimentary Pharmacology & Therapeutics
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 Natalia Montiel Ana María Domínguez Castaño María Pilar Luzón‐García Encarnación Ramírez Arellano Carmen Liébana‐Martos Francisco Franco Álvarez de Luna María del Carmen Lozano Begoña Palop Antonio Sampedro Ana Belén Pérez Sonia Algarate Susana Rojo Alba Pablo Fraile Dolores Ocete María Jesús Alcaraz Juan Carlos Rodríguez Francisco Javier Hernández‐Felices Olalla Martínez Victoria Domínguez Nieves Orta Dolores Gómez Carmen Cortell Jorge Camacho Susana Sabater Luis Ángel Iglesias Sánchez Yasmina Martín Aldara Vallejo Lourdes Molina María Aroca Beatriz Castro Magdalena Lara María José Pena Ana Rodríguez‐Fernández Alejandro González Praetorius José Joaquín Blas Alicia Beteta César Gómez María José Rodríguez Soledad Illescas Melanie Abreu Julio García Díez Inocencio Beltrán Marta Sandoval Torrientes Ruth Sáez Teresa Martín Pilar Tajada Alegre Belén Lorenzo María Teresa García Valero Isabel Jiménez Sansegundo Susana García‐de Cruz Sonsoles Garcinuño Miguel Ángel Sáiz Santiago Muñoz Isabel Fernández Helena Miriam Lorenzo Juanes María Reyes Vidal‐Acuña Luz María Moldes Noelia Calvo Matilde Trigo María José Gude Patricia Ordóñez Sandra Cortizo Miriam Blasco Mayra Sigcha Iker Falces Juan Carlos Galán Ana Arribi Roberto Alonso Asunción Iborra María Jesús del Amor Espín Eva Cascales Cayetano Pérez Pablo Fernández María Dolores Navarro María Luz Nuñez Jorge Galán Ros Luis Javier Gil‐Gallardo Ana Miqueleiz Gabriel Reina Luis Elorduy Mikele Macho Carmen Gómez Paloma Liendo Yolanda Salicio Antonio Aguilera Federico García Alimentary Pharmacology & Therapeutics ABSTRACT Background Hepatitis 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. Aims To evaluate double reflex diagnostic implementation in Spain during the retrospective phase of the Spain Double Reflex Diagnostic study. Methods Nationwide, 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. Results Among 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%). Conclusion Between 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. 10.1111/apt.70543 http://creativecommons.org/licenses/by-nc-nd/4.0/
title Nationwide Implementation of Double Reflex Testing for Hepatitis Delta in Spain: Results From the Retrospective Phase of the Spain‐DDR Study
topic Alimentary Pharmacology & Therapeutics
url https://onlinelibrary.wiley.com/doi/10.1111/apt.70543