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array:24 [ "pii" => "S2387020617301882" "issn" => "23870206" "doi" => "10.1016/j.medcle.2017.03.013" "estado" => "S300" "fechaPublicacion" => "2017-03-22" "aid" => "3905" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2017" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2017;148:277-82" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0025775316307102" "issn" => "00257753" "doi" => "10.1016/j.medcli.2016.12.018" "estado" => "S300" "fechaPublicacion" => "2017-03-22" "aid" => "3905" "copyright" => "Elsevier España, S.L.U." 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"documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Clin. 2017;148:283-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Risk-benefit balance assessment of colchicine use during pregnancy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "283" "paginaFinal" => "285" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Evaluación del balance riesgo-beneficio del empleo de colchicina durante el embarazo" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Gabriel Horta-Baas" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Gabriel" "apellidos" => "Horta-Baas" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775316306868" "doi" => "10.1016/j.medcli.2016.12.013" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775316306868?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020617301766?idApp=UINPBA00004N" "url" => "/23870206/0000014800000006/v1_201704120030/S2387020617301766/v1_201704120030/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S238702061730181X" "issn" => "23870206" "doi" => "10.1016/j.medcle.2017.03.009" "estado" => "S300" "fechaPublicacion" => "2017-03-22" "aid" => "3822" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2017;148:271-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1 "HTML" => 1 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Diagnosis and treatment</span>" "titulo" => "Gout: Diagnosis and treatment" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "271" "paginaFinal" => "276" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Diagnóstico y tratamiento de la gota" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3307 "Ancho" => 1500 "Tamanyo" => 474726 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Synovial fluid microscopy at 600-magnification with ordinary light (top image), where a needle-shape crystal is shown inside a leucocyte. Under simple polarized light (middle image), the glass shows strong birefringence which, after applying the first order red compensator (below), is confirmed as negative birefringence–as it is yellow in colour and is positioned parallel to the compensator's axis (arrow)–. Photographs courtesy of Prof. Eliseo Pascual.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Francisca Sivera, Mariano Andrés, Neus Quilis" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Francisca" "apellidos" => "Sivera" ] 1 => array:2 [ "nombre" => "Mariano" "apellidos" => "Andrés" ] 2 => array:2 [ "nombre" => "Neus" "apellidos" => "Quilis" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775316305280" "doi" => "10.1016/j.medcli.2016.10.019" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775316305280?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S238702061730181X?idApp=UINPBA00004N" "url" => "/23870206/0000014800000006/v1_201704120030/S238702061730181X/v1_201704120030/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>" "titulo" => "Elimination of hepatitis C in Spain: Adaptation of a mathematical model based on the public health strategic plan for addressing hepatitis C in the National Health System" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "277" "paginaFinal" => "282" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "María Buti, Jose Luis Calleja, Javier García-Samaniego, Miguel Ángel Serra, Javier Crespo, Manuel Romero, Miguel Ángel Simón, Juan Turnes, Antonio Javier Blasco, Pablo Lázaro, Sarah Robbins, Homie Razavi" "autores" => array:13 [ 0 => array:3 [ "nombre" => "María" "apellidos" => "Buti" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Jose Luis" "apellidos" => "Calleja" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:4 [ "nombre" => "Javier" "apellidos" => "García-Samaniego" "email" => array:1 [ 0 => "javiersamaniego@telefonica.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 3 => array:3 [ "nombre" => "Miguel Ángel" "apellidos" => "Serra" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Javier" "apellidos" => "Crespo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "Manuel" "apellidos" => "Romero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] 6 => array:3 [ "nombre" => "Miguel Ángel" "apellidos" => "Simón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 7 => array:3 [ "nombre" => "Juan" "apellidos" => "Turnes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] ] ] 8 => array:3 [ "nombre" => "Antonio Javier" "apellidos" => "Blasco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">i</span>" "identificador" => "aff0045" ] ] ] 9 => array:3 [ "nombre" => "Pablo" "apellidos" => "Lázaro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">i</span>" "identificador" => "aff0045" ] ] ] 10 => array:3 [ "nombre" => "Sarah" "apellidos" => "Robbins" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">j</span>" "identificador" => "aff0050" ] ] ] 11 => array:3 [ "nombre" => "Homie" "apellidos" => "Razavi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">j</span>" "identificador" => "aff0050" ] ] ] 12 => array:1 [ "colaborador" => "on behalf of the Grupo para el Estudio y Modelización Epidemiológica de la Hepatitis C en España (GEMEHCE)" ] ] "afiliaciones" => array:10 [ 0 => array:3 [ "entidad" => "Hospital Universitario Vall d’Hebron, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hospital Universitario Puerta de Hierro, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad Autónoma de Madrid, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hospital Universitario La Paz, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Hospital Clínico Universitario de Valencia, Valencia, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Hospital Universitario Marqués de Valdecilla, Santander, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Hospital Universitario Virgen Macarena-Virgen del Rocío, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Sevilla, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Hospital Clínico Universitario de Zaragoza, Zaragoza, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Hospital Universitario de Pontevedra, Pontevedra, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Investigador independiente en Servicios de Salud, Madrid, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Center for Disease Analysis (CDA), Louisville, CO, USA" "etiqueta" => "j" "identificador" => "aff0050" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Eliminación de la hepatitis C en España: adaptación de un modelo matemático de salud pública partiendo del plan estratégico para el abordaje de la hepatitis C en el Sistema Nacional de Salud" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1284 "Ancho" => 1626 "Tamanyo" => 131607 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Prevalent cases of hepatitis C according to various strategies. SPAHC, strategic plan for addressing hepatitis C.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hepatitis C virus (HCV) infection is a public health problem in most countries.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> The effects of chronic HCV infection, including the development of liver cirrhosis and hepatocellular carcinoma have a negative impact on the population's health and use a considerable amount of the already limited health resources.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> According to a systematic review of the year 2011, the estimated prevalence of hepatitis C (HC) in Spain is among the highest in Europe,<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> which is expected to lead to a high disease burden in the coming years, and has shown that HCV is the leading cause of death from infectious disease in Spain.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> Based on data from recent publications available in Spain, the prevalence of antibodies in adults is estimated at 1.7%, and the prevalence of viremia in adults at 1.2%, which corresponds, in absolute terms, to approximately 688,000 adults with positive serology in total and 472,000 adults with viremia in 2014.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Fortunately, to prevent disease progression to advanced stages is possible through the early detection of HCV infection and the availability of increasingly more effective treatments. With the advent of direct antiviral agents (DAAs) administered orally, HCV can be eliminated in 90% of treated patients with an excellent safety profile.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> For these reasons, many countries have developed strategies that combine public health interventions with the efficacy of the new treatments, decreasing HC prevalence and its negative consequences on health.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7,8</span></a> In Spain, in May 2015, the Ministry of Health, Social Services and Equality (MHSSE) published the strategic plan for addressing hepatitis C (SPAHC) in the National Health System.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> Throughout 2015, 38,067 patients with HC were treated in Spain with the implementation of SPAHC.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The aim of this study is to estimate the effects on HC-related disease burden that would occur in Spain in the next 10 years considering three strategies: (<span class="elsevierStyleSmallCaps">1</span>) Apply SPAHC; (<span class="elsevierStyleSmallCaps">2</span>) Incremental strategy (applying the SPAHC while increasing the number of patients diagnosed and treated), and (<span class="elsevierStyleSmallCaps">3</span>) Strategy to eliminate the disease.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Methodology</span><p id="par0020" class="elsevierStylePara elsevierViewall">At the beginning of the project, a scientific committee (SC) was established, composed of the authors of this paper except AJB, PL, SR and HR. The SC advised on clinical aspects of the study and provided information when there was no scientific evidence or when it was contradictory.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Hepatitis C progression model</span><p id="par0025" class="elsevierStylePara elsevierViewall">HC progression was modeled through a previously described system dynamic model<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> in which population and epidemiological data in Spain were updated.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> HC progression was modeled as transitions between stages: HC (acute and chronic F0, F1, F2 and F3), cirrhosis (F4), hepatocellular carcinoma, liver transplantation and death. The transition probabilities between stages and the values of model variables were obtained from scientific evidence.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1,11</span></a> The model considers the decreased prevalence of HC as epidemiological outcome, and the decrease in cases of cirrhosis, hepatocellular carcinoma, liver transplantation, and mortality related to liver disease as clinical outcomes.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Characteristics of the Spanish population infected with hepatitis C virus</span><p id="par0030" class="elsevierStylePara elsevierViewall">No publications were found about population-based prevalence at national level. The most recent publication estimated a prevalence of 2.6% of anti-HCV antibodies in adults over 25 years from data collected in Catalonia between 1994 and 1996.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> Due to the limitations in national estimates and the well-known regional variability, the SC estimated a mean prevalence of anti-HCV antibodies of 1.7% in 2015, and a rate of viremia was assumed to be 68.6%.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> Applying prevalence figures by gender and age group in the national population, 426,998 people were estimated to have chronic infection in Spain in 2015. To estimate the distribution by age and sex of the infected population, data from Catalonia were used,<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> assuming that the distribution by age and sex of the HCV infected population in Catalonia is similar to the distribution in Spain. To apply the distribution of HCV genotypes in the model, we started from the most recent publication in Spain,<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> assigning the following distribution: 77.6, 2.7, 12.3 and 7.4% for genotypes G1 and other, G2, G3 and G4, respectively.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Annual population data for Spain, structured by age and sex, were obtained from the National Statistics Institute (Instituto Nacional de Estadística, INE).<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">It was estimated that between 1994 and 1996, transfusion accounted for 25.5% of the transmission of HCV infection while using intravenous drugs (IDUs) past or present accounted for about 10%.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> The transmission of HCV infection through transfusion and IDUs has declined steadily since 1996.</p><p id="par0045" class="elsevierStylePara elsevierViewall">As information on the incidence of HCV in Spain is scarce, the incidence curve to estimate the occurrence of new cases was developed through consensus with the SC from data about the natural history of HCV disease in Spain. It was considered that the annual number of new cases in Spain peaked in 1991, before the implementation of protocols for blood transfusions, and began to decline thereafter. It is assumed that the number of new cases per year is relatively stable for nosocomial transmission.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> In 2015, it was estimated that 2738 HCV incident cases occurred in Spain.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Mortality and liver transplantation</span><p id="par0050" class="elsevierStylePara elsevierViewall">Mortality statistics provided by the Spanish National Statistics Institute distributed by sex and 5-year sections for age were used to calculate mortality figures between the years 1970–2015.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> The increased mortality in patients with infection acquired by transfusion or IDUs was corrected by applying a standard mortality rate of 1.5 and 10.0%, depending on the age group affected.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17,18</span></a> Data on the number of liver transplants performed and the proportion of transplants attributable to HCV were obtained from the National Transplant Organization.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> The proportion of liver transplants performed in Spain due to HC is 31.6% of the total, and corresponds to 359 transplants a year. It was assumed that this figure will remain constant in the coming years, as it has occurred in recent years in Spain.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">The strategies</span><p id="par0055" class="elsevierStylePara elsevierViewall">3 strategies were designed: apply the SPAHC, the incremental strategy and the elimination strategy.<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">(I)</span><p id="par0060" class="elsevierStylePara elsevierViewall">Application of SPAHC during 10 years (2015–2024). This strategy assumes that: (1) from 2015–2024 there will be 5500 new cases diagnosed annually (estimated in 2015); (2) in 2015 and 2016, the proportion of eligible patients is 85% for all genotypes; (3) in the years 2017 and beyond, the proportion of eligible patients for each genotype is 90%; (4) every year it is treated from stage F2, included; (5) there is capacity to treat 38,000 patients in 2015 and 2016, and 20,000 patients in the years 2017–2024 (it is designed in that way because no more than 20,000 patients can be treated a year due to not having enough new patients diagnosed and also because it is treated from a stage equal or higher than F2).</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">(II)</span><p id="par0065" class="elsevierStylePara elsevierViewall">Incremental strategy. This strategy adds to the SPAHC strategy that, during the 10 years, 15,000 new cases will be diagnosed annually and there is a capacity to treat 38,000 patients a year.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">(III)</span><p id="par0070" class="elsevierStylePara elsevierViewall">Elimination strategy: aims to eliminate the disease in 10 years, defining elimination as having a prevalence of HC in Spain lower than 20,000 cases. This objective can be achieved if, with respect to the strategy of SPAHC: (1) from 2016, the diagnosis effort increases to 40,000 new cases annually; (2) from 2016 it increases the capacity to treat 50,000 patients annually, and 90% of all genotypes are eligible; (3) from 2017 it is treated from F1, and (4) from the year 2022 it is treated from F0.</p></li></ul></p><p id="par0075" class="elsevierStylePara elsevierViewall">In the three strategies, it is assumed that: (1) 2738 incident cases occur annually; (2) the age of treatment is 15 to 84 years; (3) the distribution of genotypes is the same over the years; (4) in the years 2015 and 2016, the sustained viral response (SVR) is 95% for genotypes G1, G2 and G4<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> and 85% for G3,<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> and 6) in the years 2017 and beyond, the SVR is 98% for all genotypes.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">With the SPAHC, from the year 2019 the number of treatable patients (diagnosed with treatment criteria and eligible) is less than that which is allowed by the strategy's capacity: despite being able to treat 20,000 patients annually in the years 2019, 2020, 2021, 2022, 2023 and 2024, treatable patients were 8533, 6337, 6112, 6099, 6077 and 6034, respectively. For the same reasons, with the incremental strategy, despite being able to treat 38,000 patients a year in the years 2018, 2019, 2020, 2021, 2022, 2023 and 2024, eligible patients were 20,049, 13,215, 12,654, 12,980, 13,393, 13,740 and 14,029, respectively. With the elimination strategy in the years 2017, 2021 and 2022 only 45,544, 43,401 and 37,130 patients can be treated, respectively. During the rest of the years, 50,000 patients can be treated, until 2024, in which 36,777 patients are treated, achieving elimination as there remain 14,753 prevalent cases.</p><p id="par0085" class="elsevierStylePara elsevierViewall">With the updated population data, it is estimated that in 2015 there were 426,998 prevalent cases of HC in Spain. The 3 strategies produce a continued decline in prevalence, so that in 2024, with the SPAHC strategy, the prevalence would be 291,196 cases, 237,662 with the incremental strategy, and 14,753 cases with the elimination strategy. With the elimination strategy, in 2024 there would be, for the first time, less than 20,000 prevalent cases of HC and therefore, the elimination goal would be achieved (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In the 10 years of strategy implementation (2015–2024), both incremental and elimination, would achieve a decrease in prevalence of 53,534 (18.38%) and 276,443 (94.93%) cases, respectively, with respect to SPAHC.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">It is estimated that in 2015, 2032 deaths have occurred related to liver disease due to HC. In 2016 and 2017 there is a small increase in deaths because it increases the number of diagnosed patients who had not been treated previously, observing that the decreased mortality effect occurs from 2017. In 2024, 1643 deaths will occur with SPAHC, 1223 with the incremental strategy and 626 with the elimination strategy (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The increase observed in 2024 compared to 2023 with the SPAHC is because since 2021 there are not enough patients meeting the treatment criteria, even if there is capacity to treat them, thereby increasing mortality due to progression of the disease in prevalent cases that have not been diagnosed and, therefore, have not had the opportunity to access treatment. That is, the limiting factor is the number of patients diagnosed. As accumulated results, over the 10 years of implementation of the strategies (2015–2024) 17,815 deaths would have occurred related to liver disease with SPAHC, 16,394 with the incremental strategy and 14,423 with the elimination strategy. Therefore, the incremental and elimination strategies, compared to SPAHC, would achieve a decrease in the number of deaths related to liver disease in 1421 (7.98%) and 3.393 (19.04%), respectively.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">In 2015, there were 1.393 incident cases of decompensated cirrhosis due to HC. In 2024, 1.023 would occur with SPAHC, 613 with the incremental strategy and 87 with the elimination strategy (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). As in the case of deaths, decompensated cirrhosis increases which appear with the first 2 strategies are due to not having enough patients diagnosed with treatment criteria in previous years. In the 10 years of implementation of the strategies (2015–2024), decompensated cirrhosis would have occurred 9547 with SPAHC, 7926 with incremental strategy and 5691 with the elimination strategy. Therefore, with respect to SPAHC, the incremental and elimination strategies would achieve a decrease in the number of decompensated cirrhosis of 1622 (16.99%) and 3.875 (40.39%), respectively.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">As for hepatocellular carcinoma, in 2015 there were 1131 cases. In 2024, an estimated 834 will occur with SPAHC, 504 with the incremental strategy and 70 with the elimination strategy (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). Increases in the incidence of hepatocellular carcinoma appearing in SPAHC and incremental strategies occur because, as in the case of cirrhosis and mortality, there are not enough patients diagnosed with treatment criteria in previous years. In the 10 years of implementation of the strategies (2015–2024) they would have been 7837 cases of hepatocellular carcinoma with SPAHC, 6523 with the incremental strategy and 4671 with the elimination strategy. Therefore, compared to SPAHC, the incremental and elimination strategies would achieve a decrease in the number of hepatocellular carcinoma in 1314 (16.76%) and 3.166 (40.39%), respectively.</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">In 2015 there were 1562 patients on the waiting list for liver transplantation due to HC. In 2024, with the SPAHC, the waiting list would be of 1038 patients, 492 patients with the incremental strategy, and 44 with the elimination strategy. The annual performance of 359 liver transplants, which has been assumed constant, has contributed to this decrease in the waiting list (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">The incremental strategy and the elimination strategy reduce the need for transplants: with respect to SPAHC, for the year 2024, the incremental strategy decreases the waiting list for liver transplantation in 546 (53%) patients, and the elimination strategy in 994 (96%) patients. The number of liver transplants performed due to HC is not reduced with the SPAHC and the incremental strategy, since there are less organs available compared to those needed, but, with the elimination strategy, 722 (20%) less transplants would be performed between the year 2022 and 2024, which could be available to patients who need liver transplantation for other reasons (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).</p><p id="par0115" class="elsevierStylePara elsevierViewall">To achieve these reductions in disease burden in 10 years, 155,274 patients would need to be treated with the SPAHC, 214,065 with the incremental strategy and 450,845 with the elimination strategy.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">SPAHC was launched in April 2015 and is still an important breakthrough that has allowed access to treatment to 38,000 patients in the first year of its implementation. At first, a quick identification of patients most likely to benefit from short-term treatment (stage F4 and decompensated cirrhosis) was necessary. However, one of the most important challenges for the control and elimination of HCV infection is the diagnosis of asymptomatic cases. HC is a silent disease and a high percentage of subjects does not know that they are infected with HCV. Since the SPAHC does not explicitly propose to increase the number of undiagnosed prevalent cases or treat patients with lower degrees of fibrosis (below F2), from the year 2019 there will not be many patients who meet the treatment access criteria established in SPAHC compared to the first 2 years, so its health benefits are lower than those potentially achievable. The SPAHC is able to reduce the prevalence of 426,998 cases in 2015 to 291,196 cases in 2024, which is a remarkable achievement, but the incremental strategy, which increases the effort to diagnose new cases and maintains the treatment capacity originally designed in the SPAHC, achieves a prevalence of 237,662 cases in 2024 (18.38% less than the SPAHC). In 2024, the elimination strategy achieves the elimination of the disease (defined as less than 20,000 prevalent cases), with 14,753 prevalent cases (94.93% less than the SPAHC).</p><p id="par0125" class="elsevierStylePara elsevierViewall">Also, the number of deaths related to liver disease, decompensated cirrhosis and hepatocellular carcinoma are significantly lower with the incremental strategy and the strategy of elimination. The incremental strategy reduces the number of transplants required, but always above the maximum transplants that can be performed each year in Spain, so even though it decreases the waiting list, it does not leave organs available for other diseases. However, the elimination strategy not only reduces the need for transplants (considerably decreases the waiting list), but also the number of transplants required becomes less than the number of possible transplants, a situation observed in the year 2022, so that from this year, the reduced need for livers for patients with HC would leave 722 organs available for patients who need liver transplantation for other diseases. The finding of leaving the waiting list for liver transplant of patients treated with DAAs, even in advanced stages of fibrosis, has also been shown in other studies.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">The findings of this study suggest that if the SPAHC maintains the resources to treat 38,000 patients each year, it can only reach that number of treated patients if detection policies are designed for prevalent cases of undiagnosed HC and access to treatment is offered in earlier stages (F0 and F1) without decreasing the number of patients treated at more advanced stages. In fact, the increase in mortality, decompensated cirrhosis, hepatocellular carcinoma and liver transplants shown in <a class="elsevierStyleCrossRefs" href="#fig0015">Figs. 3–5</a> with SPAHC, as described in the results section, is due to a decrease in the number of patients who are candidates to be treated.</p><p id="par0135" class="elsevierStylePara elsevierViewall">The effort to increase the detection of undiagnosed prevalent cases, and therefore of treated cases, is essential to the effectiveness of the plan and explains the success of the HC project developed by the government of Scotland.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> For this, it would be necessary to implement a screening program for silent cases of HC aimed at the general population in certain age groups or those with risk infection factors. Recent estimates show that the implementation of this program can be cost-effective.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">With new DAAs and new screening techniques, the elimination of HC is possible.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> However, the resources required for elimination are substantial. According to the findings of this study, the elimination of HC in 10 years would require treating 450,845 patients if this figure is confirmed by the data of new epidemiological studies, but in return, at the end of 10 years, Spain would have reduced the prevalence from 426,998 to 14,753 cases, and with respect to SPAHC, it would have prevented 3393 deaths, 3857 decompensated cirrhosis, 3166 hepatocellular carcinomas and 722 liver transplants. It would be interesting to compare the costs related to the disease elimination strategy in 10 years with those of the no elimination in Spain. It seems plausible to assume that the sum of the costs saved over 10 years due to the decrease prevalence in 276,443 cases and their consequences is greater than the cost of diagnosing and treating 426,988 patients over 10 years. With scientific evidence available from published studies about economic evaluation, cost-effectiveness ratios depend on the genotype, stage of disease and DAAs treatment cost.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6,27,28</span></a> Considering the group of patients with HC, the efficiency ratio normally used -which is the cost per quality-adjusted life year-is within the range considered socially acceptable, and obviously, the efficiency will increase to the extent that DAAs treatment prices decrease with time.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> For these reasons, strategies to eliminate HC are starting to be proposed and articulated.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">7,8,26</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">This study has some limitations, among them, the fact that expert opinion (SC) has been used as a source of information to assign values to some variables that had no scientific evidence to support them, and to establish some of the clinical assumptions used in the mathematical model. However, the opinion of the SC has been used only when scientific evidence did not exist or was contradictory. Therefore, the best possible methodological approach has been used, that of the best available scientific evidence and the opinion of experienced clinicians who provide their best clinical assessment when there is no evidence. Similar studies in various countries have used the same methodology.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1,2,29,30</span></a> However, if the actual HCV prevalence figures in Spain were to become available in the near future, the calculations would be different, but the elimination strategy would remain the most effective option. Another limitation may be related to the fact that the model establishes a staging defined by the degree of fibrosis and contemplates treating patients in stages F0–F1 separately. In clinical practice, the sensitivity and specificity of elastography does not allow for a clear distinction between the two stages, so that in the elimination strategy, it might be reasonable to treat the F0 stages from 2017.</p><p id="par0150" class="elsevierStylePara elsevierViewall">In short, the SPAHC is an excellent initiative of the MHSSE, but, with the current design, it is estimated to decrease the incidence and prevalence of the disease and its consequences in a measure, not only less than desirable, but less than possible if the dedicated resources in its first year of maintenance were to be kept over the next 10 years. If the resources dedicated by the SPAHC in 2015 are maintained over the next 10 years, an active early detection policy of undiagnosed prevalent cases aimed at the general population of certain age groups is required in order to maximize health outcomes, especially for the population with risk factors. The elimination of the HC is possible if the effectiveness of new DAAs is combined with public health policies that emphasize the identification of undiagnosed cases and treatment to patients in need. With the model used in this study, the HC can be eliminated within 10 years. Other countries have considered elimination in 2030. Although the cost of elimination can be high, the savings to the health system in health costs saved by cirrhosis, hepatocellular carcinoma and liver transplants may outweigh the elimination costs. If the social costs saved by lost productivity and death at an early age are taking into account, efficiency from a social perspective will be even greater than efficiency from a health system perspective.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflict of interests</span><p id="par0155" class="elsevierStylePara elsevierViewall">This project has received financial support from Gilead Sciences.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Maria Buti: Grants: Gilead, Consultant: Gilead, MSD, Abbvie, Janssen, Sponsored conferences: Gilead, MSD, Abbvie, Janssen.</p><p id="par0165" class="elsevierStylePara elsevierViewall">José Luis Calleja: Consultant/Sponsored Conferences: Abbvie, Gilead, BMS, MSD.</p><p id="par0170" class="elsevierStylePara elsevierViewall">Javier García Samaniego: Consultant: Gilead, Abbvie, Janssen, BMS, Sponsored conferences: Gilead, Abbvie, Janssen, BMS.</p><p id="par0175" class="elsevierStylePara elsevierViewall">Miguel Angel Serra: Consultant: AbbVie, Gilead, BMS, Janssen, Sponsored conferences: Abbvie, Gilead, BMS, Janssen.</p><p id="par0180" class="elsevierStylePara elsevierViewall">Javier Crespo: Grant: MSD, Gilead, Consultant: MSD, Gilead, AbbVie, BMS, Sponsored conferences: MSD, Gilead, Abbvie, BMS.</p><p id="par0185" class="elsevierStylePara elsevierViewall">Manuel Romero: None.</p><p id="par0190" class="elsevierStylePara elsevierViewall">Miguel Angel Simon None.</p><p id="par0195" class="elsevierStylePara elsevierViewall">Juan Turnes: has participated as an advisory board member and sponsored conferences for Abbvie, Gilead, Janssen and BMS; and sponsored conferences for MSD.</p><p id="par0200" class="elsevierStylePara elsevierViewall">Pablo Lazaro and Antonio Javier Blasco: have received financial support without restrictions from Gilead Sciences for the methodological development of this project.</p><p id="par0205" class="elsevierStylePara elsevierViewall">Sarah Robbins and Homie Razavi: They have not received funding for consulting or conferences, or reimbursement for their traveling expenses. Sarah and Homie are employees of CDA. CDA has received research grants from Gilead and Abbvie. Homie is the founder and owner of CDA.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:3 [ "identificador" => "sec0010" "titulo" => "Methodology" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Hepatitis C progression model" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Characteristics of the Spanish population infected with hepatitis C virus" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Mortality and liver transplantation" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "The strategies" ] ] ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interests" ] 5 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-10-04" "fechaAceptado" => "2016-12-27" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Buti M, Calleja JL, García-Samaniego J, Serra MÁ, Crespo J, Romero M, et al. Eliminación de la hepatitis C en España: adaptación de un modelo matemático de salud pública partiendo del plan estratégico para el abordaje de la hepatitis C en el Sistema Nacional de Salud. Med Clin (Barc). 2017;148:277–282.</p>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1284 "Ancho" => 1626 "Tamanyo" => 131607 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Prevalent cases of hepatitis C according to various strategies. SPAHC, strategic plan for addressing hepatitis C.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1255 "Ancho" => 1555 "Tamanyo" => 114662 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Deaths due to hepatitis C according to various strategies. SPAHC, strategic plan for addressing hepatitis C.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1232 "Ancho" => 1578 "Tamanyo" => 116833 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Decompensated cirrhosis due to hepatitis C according to various strategies. SPAHC, strategic plan for addressing hepatitis C.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1220 "Ancho" => 1561 "Tamanyo" => 119260 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Hepatocarcinomas due to hepatitis C according to various strategies. SPAHC, strategic plan for addressing hepatitis C.</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1203 "Ancho" => 1595 "Tamanyo" => 136178 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Needed liver transplants due to hepatitis C (patients on a waiting list), according to various strategies, and performed transplants. 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