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Estudio retrospectivo de la capacidad de evaluación de fibrosis hepática del FibroScan®, APRI, FIB-4 y FORNS con referencia a la biopsia hepática de pacientes con hepatitis crónica C, mono y coinfectados con VIH
Retrospective study of FibroScan®, APRI, FIB-4 and FORNS indexes compared with liver biopsy in the evaluation of liver fibrosis in patients with chronic hepatitis C monoinfection and HIV coinfection
Maria Isabel González Guilaberta,
Autor para correspondencia
isabel46@ono.com

Autor para correspondencia.
, Carmen Hinojosa Mena-Bernala, Jorge del Pozo Gonzálezb, Miguel Angel del Pozo Péreza
a Unidad de Enfermedades Infecciosas, Hospital Clínico Universitario de Valladolid, Valladolid, España
b Royal Dick Veterinary School, University of Edinburgh, Easter Bush Veterinary Centre, Midlothian, Escocia, Reino Unido
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    "textoCompleto" => "<span class="elsevierStyleSections"><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introducci&#243;n</span><p class="elsevierStylePara elsevierViewall">La infecci&#243;n por el VHC afecta a unos 170 millones de personas en el mundo&#44; con una prevalencia estimada entre el 2&#8211;3&#37; y gran variabilidad geogr&#225;fica<a class="elsevierStyleCrossRef" href="#bib1"><span class="elsevierStyleSup">1</span></a>&#46; La fibrosis hep&#225;tica &#40;FH&#41; se usa frecuentemente como indicador de la evoluci&#243;n de la hepatitis cr&#243;nica C &#40;HCC&#41; y se utiliza en algoritmos de decisi&#243;n de tratamiento antiviral<a class="elsevierStyleCrossRefs" href="#bib2"><span class="elsevierStyleSup">2&#8211;4</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">Hist&#243;ricamente&#44; la biopsia hep&#225;tica &#40;BH&#41; ha sido la prueba de referencia para determinar el grado de FH histol&#243;gicamente &#40;Ej&#46; escala METAVIR5&#41;&#46; Sin embargo&#44; esta t&#233;cnica es invasiva&#44; se basa en una muestra limitada&#44; puede presentar complicaciones<a class="elsevierStyleCrossRefs" href="#bib6"><span class="elsevierStyleSup">6&#44;7</span></a> y su interpretaci&#243;n puede variar seg&#250;n el pat&#243;logo<a class="elsevierStyleCrossRefs" href="#bib8"><span class="elsevierStyleSup">8&#44;9</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">Se han propuesto diferentes alternativas no invasivas a la biopsia&#44; entre ellas el uso de marcadores bioqu&#237;micos y elastograf&#237;a&#46; Los marcadores bioqu&#237;micos propuestos son Actitest<a class="elsevierStyleCrossRef" href="#bib10"><span class="elsevierStyleSup">10</span></a>&#44; APRI<a class="elsevierStyleCrossRef" href="#bib11"><span class="elsevierStyleSup">11</span></a>&#44; FIB-4<a class="elsevierStyleCrossRef" href="#bib12"><span class="elsevierStyleSup">12</span></a>&#44; FibroIndex<a class="elsevierStyleCrossRef" href="#bib13"><span class="elsevierStyleSup">13</span></a>&#44; FibroTest<a class="elsevierStyleCrossRef" href="#bib14"><span class="elsevierStyleSup">14</span></a>&#44; HALT-C<a class="elsevierStyleCrossRef" href="#bib15"><span class="elsevierStyleSup">15</span></a> y Forns<a class="elsevierStyleCrossRef" href="#bib16"><span class="elsevierStyleSup">16</span></a>&#46; Estos &#237;ndices tienen capacidad para predecir grados de FH leve o ausente y avanzadas siendo menos precisos para los grados intermedios<a class="elsevierStyleCrossRef" href="#bib17"><span class="elsevierStyleSup">17</span></a>&#46; En cuanto a la elastograf&#237;a&#44; el FibroScan<span class="elsevierStyleSup">&#174;</span> &#40;FS&#41; es una t&#233;cnica sencilla&#44; indolora y reproducible que determina la rigidez hep&#225;tica utilizando elastograf&#237;a unidimensional &#40;Echosens&#44; Paris&#44; France&#41;<a class="elsevierStyleCrossRef" href="#bib18"><span class="elsevierStyleSup">18</span></a>&#46; Los primeros ensayos realizados para comparar la elasticidad medida por FS y la fibrosis hep&#225;tica valorada en BH mostraron una correlaci&#243;n significativa<a class="elsevierStyleCrossRefs" href="#bib18"><span class="elsevierStyleSup">18&#44;19</span></a> y la capacidad predictiva de fibrosis significativa &#40;F&#8805;2&#41; del FS se ha evaluado en varias ocasiones con resultados satisfactorios<a class="elsevierStyleCrossRefs" href="#bib20"><span class="elsevierStyleSup">20&#44;21</span></a>&#46; El FS presenta algunas limitaciones&#58; no se puede realizar en pacientes con espacios intercostales estrechos&#44; ascitis u obesidad<a class="elsevierStyleCrossRefs" href="#bib18"><span class="elsevierStyleSup">18&#44;22</span></a>&#44; no aporta informaci&#243;n sobre la actividad necroinflamatoria de la hepatitis<a class="elsevierStyleCrossRef" href="#bib23"><span class="elsevierStyleSup">23</span></a> y hay solapamiento entre estad&#237;os adyacentes de FH&#44; especialmente en los grados m&#225;s bajos<a class="elsevierStyleCrossRefs" href="#bib17"><span class="elsevierStyleSup">17&#8211;19</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">Se ha propuesto utilizar de forma combinada marcadores bioqu&#237;micos con el FS&#44; con el objetivo de aumentar la eficacia diagn&#243;stica conjunta<a class="elsevierStyleCrossRefs" href="#bib17"><span class="elsevierStyleSup">17&#44;18</span></a> y evitar la realizaci&#243;n de biopsia hep&#225;tica en el mayor n&#250;mero de casos posibles&#46; El prop&#243;sito de este estudio es evaluar la exactitud diagn&#243;stica de varios marcadores bioqu&#237;micos &#40;APRI&#44; FIB-4 Y FORNS&#41; y el FS con referencia a la biopsia hep&#225;tica en pacientes monoinfectados con HCC y coinfectados con HCC-VIH conjuntamente&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material y m&#233;todos</span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Pacientes</span><p class="elsevierStylePara elsevierViewall">Para realizar este estudio&#44; revisamos las historias cl&#237;nicas de 154 pacientes del Hospital Cl&#237;nico Universitario de Valladolid&#46; El examen cl&#237;nico de estos pacientes se realiz&#243; entre agosto&#8211;octubre del 2008&#46; Se tomaron las siguientes muestras&#58; a&#41; biopsia hep&#225;tica por punci&#243;n transcut&#225;nea intercostal guiada por ecograf&#237;a&#59; b&#41; 10 mediciones con FS&#44; y c&#41; suero y plasma en ayunas&#46; Los criterios de inclusi&#243;n en el estudio fueron los siguientes&#58; edad superior a 18 a&#241;os&#44; consentimiento para la realizaci&#243;n del estudio&#44; presencia en suero de Ac anti-VHC &#40;detectada por serolog&#237;a de VHC por enzimoinmunoan&#225;lisis de tercera generaci&#243;n&#41;&#44; RNA del VHC detectable por reacci&#243;n cuantitativa en cadena de la polimerasa &#40;PCR&#44; sistema Roche Amplicor<span class="elsevierStyleSup">&#174;</span>&#41;&#44; incremento de la alanina aminotransferasa &#40;ALT&#41; durante 6 meses como m&#237;nimo y medici&#243;n con FS satisfactoria&#46; En todos los pacientes se determin&#243; la presencia&#47;ausencia de Ac anti-VIH en suero con serolog&#237;a y Western-blot&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Evaluaci&#243;n histol&#243;gica</span><p class="elsevierStylePara elsevierViewall">Todas las biopsias se valoraron por el servicio de patolog&#237;a del Hospital Cl&#237;nico Universitario de Valladolid&#46; Las muestras de tejido hep&#225;tico se fijaron en parafina y se ti&#241;eron con hematoxilina-eosina y tricr&#243;mico de Masson&#46; El sistema de clasificaci&#243;n usado fue el sistema Metavir5&#44; el cual clasifica las FH por estadios en una escala del 0&#8211;4 como sigue&#58; FH&#61;0 &#40;no fibrosis&#41;&#44; FH&#61;1 &#40;fibrosis portal sin septos&#41;&#44; FH&#61;2 &#40;aumento de tractos portales con rara formaci&#243;n de septos&#41;&#44; FH&#61;3 &#40;septos numerosos sin fibrosis&#41;&#44; FH&#61;4 &#40;cirrosis histol&#243;gica&#41;&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Marcadores bioqu&#237;micos</span><p class="elsevierStylePara elsevierViewall">Las muestras de suero y plasma se analizaron usando m&#233;todos validados para los siguientes par&#225;metros&#58; Plaquetas &#40;x10<span class="elsevierStyleSup">9</span>&#41;&#59; aspartato transaminasa &#40;AST&#59; UI&#47;l&#41;&#59; alanino aminotransferasa &#40;ALT&#44; UI&#47;l&#41;&#59; &#947;-glutamil transpeptidasa &#40;GGT&#59; UI&#47;l&#41;&#59; colesterol &#40;mg&#47;dl&#41;&#46; Estos valores se usaron para la obtenci&#243;n de los &#237;ndices APRI11&#44; FIB-412 y FORNS16 como sigue&#58; APRI&#58; AST&#47;&#40;l&#237;mite superior de normalidad de AST&#41;&#215;100&#47;plaquetas&#59; FIB-4&#58; &#91;edad &#40;a&#241;os&#41;&#215;AST&#93;&#47;&#40;plaquetas&#215;<span class="elsevierStyleSup">2</span>&#8730;ALT&#41;&#59; FORNS&#58; 7&#44;881&#8722;3&#44;131&#215;plaquetas&#43;0&#44;781&#215;ln GGT&#43;3&#44;467&#215;ln edad &#40;a&#241;os&#41;&#8722;0&#44;014&#215;colesterol&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Fibroscan</span><p class="elsevierStylePara elsevierViewall">El valor final de Fibroscan<span class="elsevierStyleSup">&#174;</span> para cada paciente se obtuvo calculando la mediana de 10 mediciones tomadas por v&#237;a intercostal en el mismo lugar del l&#243;bulo derecho hep&#225;tico&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">An&#225;lisis estad&#237;sticos</span><p class="elsevierStylePara elsevierViewall">Todos los datos de este estudio se recogieron en una hoja de c&#225;lculo en MS Excel<span class="elsevierStyleSup">&#174;</span> &#40;Microsoft<span class="elsevierStyleSup">&#174;</span>&#44; USA&#41; y se analizaron con MedCalc<span class="elsevierStyleSup">&#174;</span> 3&#46;0 &#40;MedCalc Software&#44; Mariakerke&#44; Belgium&#41;&#46; Inicialmente&#44; calculamos los valores para APRI&#44; FORNS&#44; FIB-4 y la estad&#237;stica descriptiva&#46; Para las variables cualitativas se utiliz&#243; la frecuencia absoluta y la frecuencia relativa en porcentaje&#46; Para las variables cuantitativas&#44; inicialmente se determin&#243; la normalidad con el test de Kolmogorov-Smirnov&#46; Seguidamente se utiliz&#243; la media y la DE para las variables param&#233;tricas&#44; y la mediana y los p 25 y 75 para las no param&#233;tricas&#46; Para evaluar las pruebas&#44; la prueba de referencia fue la biopsia hep&#225;tica&#44;y los pacientes se clasificaron en presencia de fibrosis &#40;FH&#8805;1&#41;&#44; fibrosis significativa &#40;FH&#8805;2&#41;&#44; fibrosis grave &#40;FH&#8805;3&#41; y cirrosis &#40;FH&#61;4&#41;&#46; Las diferencias entre grupos respecto a las caracter&#237;sticas de los pacientes se analizaron con el test de la t de student para variables param&#233;tricas y con el test de la u de Mann-Whitney para las no param&#233;tricas&#46; La asociaci&#243;n entre el grado de fibrosis y cada prueba se analiz&#243; mediante la prueba de Kruskal Wallis&#46; Posteriormente se usaron curvas operativas de rendimiento para evaluar cada prueba respecto a la BH&#44; usando el ABC como indicaci&#243;n de la capacidad predictiva&#46; El punto de corte &#243;ptimo de cada prueba para cada grado de fibrosis se determin&#243; como el punto en que la media de la especificidad y la sensibilidad era m&#225;xima&#46; Tras establecer este punto&#44; se calcul&#243; la sensibilidad&#44; valor predictivo positivo y negativo y las razones de verosimilitud positiva y negativa&#46; Finalmente&#44; se calcul&#243; el &#237;ndice de kappa para cada punto de corte&#44; a fin de evaluar la concordancia con la biopsia hep&#225;tica&#46;</p></span></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Resultados</span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Pacientes y evaluaci&#243;n histol&#243;gica</span><p class="elsevierStylePara elsevierViewall">La <a class="elsevierStyleCrossRef" href="#tbl1">tabla 1</a> contiene las caracter&#237;sticas epidemiol&#243;gicas de la muestra y los resultados de las anal&#237;ticas seg&#250;n el grado de fibrosis hep&#225;tica seg&#250;n la biopsia&#46; Un total de 154 pacientes fueron examinados&#44; con una edad media de 43&#44;6&#177;8&#44;2 a&#241;os&#44; de los cuales la mayor&#237;a eran varones &#40;76&#44;6&#37;&#41;&#46;</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">Los pacientes de mayor edad&#44; coinfectados con VIH presentaron significativamente mayores grados de fibrosis&#46; En cuanto a los resultados de las anal&#237;ticas&#44; todos los par&#225;metros variaron significativamente respecto al grado de FH exceptuando el colesterol&#46;</p><p class="elsevierStylePara elsevierViewall">La <a class="elsevierStyleCrossRef" href="#fig1">figura 1</a> muestra los valores de la mediana&#44; la distribuci&#243;n de los cuartiles y los valores marginales de cada estadio de FH para todas las pruebas&#46; En todos los casos los valores de la prueba aumentaron significativamente respecto al grado de FH&#46;</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">La capacidad predictiva de cada grado de FH de las pruebas&#44; estimada mediante el ABC&#44; se muestra en la <a class="elsevierStyleCrossRef" href="#fig2">figura 2</a> y las <a class="elsevierStyleCrossRef" href="#tbl2">tablas 2</a><a class="elsevierStyleCrossRefs" href="#tbl3">tablas 3&#8211;5</a> &#40;Fibroscan&#41;&#44; 3 &#40;APRI&#41;&#44; 4 &#40;FIB-4&#41; y 5 &#40;FORNS&#41;&#46;</p><elsevierMultimedia ident="fig2"></elsevierMultimedia><elsevierMultimedia ident="tbl2"></elsevierMultimedia><elsevierMultimedia ident="tbl3"></elsevierMultimedia><elsevierMultimedia ident="tbl4"></elsevierMultimedia><elsevierMultimedia ident="tbl5"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">Los valores de rigidez hep&#225;tica por FS abarcaron desde 3&#44;6&#8211;69&#44;1 kPas &#40;mediana&#58; 7&#44;8 kPas&#41;&#46; Los valores de los &#237;ndices bioqu&#237;micos abarcaron de 0&#44;12&#8211;4&#44;7 &#40;mediana&#58; 0&#44;48&#41; para APRI&#44; de 0&#44;40&#8211;9&#44;5 &#40;mediana&#58; 1&#44;4&#41; para FIB-4 y de &#8722;0&#44;1&#8211;15&#44;2 &#40;mediana&#58; 5&#44;3&#41; para FORNS&#46; El ABC de todas las pruebas oscil&#243; entre 0&#44;61&#8211;0&#44;79&#44; y en todos los casos aument&#243; gradualmente con el grado de FH detectado&#46; Todas las pruebas tuvieron ABC menores que 0&#44;7 para la detecci&#243;n de presencia&#47;ausencia de FH &#40;FH&#8805;1&#41; y en el caso de APRI y FORNS el ABC no era significativamente diferente a 0&#44;5&#46; Sin embargo&#44; la capacidad predictiva de las pruebas para grados mayores de FH fue significativa en todos los casos&#46; El grado de concordancia de las pruebas con los resultados &#40;&#954;&#41; de la biopsia fue pobre para la detecci&#243;n de FH&#8805;1 &#40;&#954;&#60;0&#44;20&#41; e increment&#243; gradualmente para la detecci&#243;n de mayores grados de FH en todas las pruebas&#46; En ning&#250;n caso fue mayor que 0&#44;50&#44; indicando concordancia moderada con la biopsia&#46; Cuatro pacientes mostraron valores at&#237;picos de APRI y FIB-4&#44; que no se incluyeron en el an&#225;lisis&#46; De estos&#44; 2 pacientes tuvieron FH&#61;4 y los otros 2 FH&#61;0 y FH&#61;3 respectivamente&#46; Todos estos pacientes ten&#237;an valores de plaquetas de 11&#8211;52 &#40;&#215;10<span class="elsevierStyleSup">9</span>&#41; significativamente menores que la media del resto &#40;P&#60;0&#44;001&#44; ANOVA&#41;&#46;</p></span></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discusi&#243;n</span><p class="elsevierStylePara elsevierViewall">Hemos utilizado los resultados del estudio cl&#237;nico de 154 pacientes con VHC para evaluar la capacidad diagn&#243;stica de FH de varios marcadores bioqu&#237;micos &#40;APRI&#44; FIB-4 y FORNS&#41; y del FS&#44; usando la BH como prueba de referencia&#46; La presencia de grados intermedios o mayores de FH &#40;FH&#8805;1&#8211;2&#41; se usa como referencia para el tratamiento de FH en pacientes con VHC<a class="elsevierStyleCrossRefs" href="#bib3"><span class="elsevierStyleSup">3&#44;4</span></a>&#46; M&#225;s de la mitad de los pacientes &#40;54&#44;6&#37;&#41; de este estudio ten&#237;an grados intermedios de FH<a class="elsevierStyleCrossRef" href="#bib24"><span class="elsevierStyleSup">24</span></a> indicando que estos datos son &#250;tiles para la evaluaci&#243;n de la capacidad diagn&#243;stica de estas pruebas no invasivas en el rango de inter&#233;s cl&#237;nico&#46;</p><p class="elsevierStylePara elsevierViewall">En esta muestra&#44; los pacientes de mayor edad tuvieron significativamente mayores grados de FH&#44; en consistencia con estudios previos<a class="elsevierStyleCrossRefs" href="#bib25"><span class="elsevierStyleSup">25&#44;26</span></a>&#46; M&#225;s de la mitad estaban coinfectados VHC&#47;VIH&#44; los cuales generalmente presentan una evoluci&#243;n peor de la FH 5 y esto se reflej&#243; en significativamente mayores grados de FH en coinfectados VHC&#47;VIH&#46; Los valores de colesterol no variaron significativamente seg&#250;n el grado de FH&#44; indicando que esta variable&#44; utilizada en el &#237;ndice FORNS 16&#44; no ten&#237;a valor predictivo de FH para estos datos&#46; El an&#225;lisis de valores at&#237;picos de APRI y FIB-4 sugiere que valores bajos de plaquetas pueden resultar en incremento de estos valores no correlacionado con la FH y en estos casos se deber&#237;a contrastar el resultado de estos &#237;ndices con el de otra prueba que no utilice el n&#250;mero de plaquetas&#46;</p><p class="elsevierStylePara elsevierViewall">El objetivo principal de este estudio es la evaluaci&#243;n del FS y marcadores bioqu&#237;micos para reducir en la medida de lo posible la necesidad de BH&#46; Seg&#250;n algunos autores&#44; el tratamiento de FH en pacientes coinfectados con VIH se comienza cuando FH&#8805;1 4&#46; En estos datos&#44; solo el FS y el FIB-4 tuvieron una capacidad predictiva de FH&#8805;1 significativa&#44; y m&#225;s de 94&#37; de los pacientes con &#62;6&#44;7<span class="elsevierStyleHsp" style=""></span>kPas en FS o &#62;1&#44;3 en Fib-4 ten&#237;an FH&#8805;1&#46; Sin embargo&#44; la sensibilidad de estas pruebas para FH&#8805;1 fue baja y 37&#37; &#40;FS&#41; y 44&#37; &#40;Fib-4&#41; de los pacientes con FH no fueron detectados&#46; Otras gu&#237;as de consensos indican el comienzo del tratamiento de FH cuando FH&#8805;2 en pacientes con VHC 3&#46; En este caso&#44; todas las pruebas tuvieron una capacidad predictiva de FH&#8805;2 significativa&#44; y entre 77&#8211;86&#37; de los pacientes con &#62;6&#44;8<span class="elsevierStyleHsp" style=""></span>kPas en FS&#44; 0&#44;6 en APRI&#44; 1&#44;4 en FIB-4 y 5&#44;6 en FORNS tuvieron FH&#8805;2&#46; De nuevo&#44; el FS tuvo una sensibilidad relativamente baja y no detect&#243; a 30&#37; de los pacientes con FH&#8805;2&#46; Los &#237;ndices bioqu&#237;micos tuvieron una sensibilidad m&#225;s pobre y no detectaron entre 41&#8211;46&#37; de los pacientes con FH&#8805;2&#46; En cuanto a la detecci&#243;n de fibrosis avanzada&#44; todas las pruebas fueron &#250;tiles para excluir a los pacientes que no presentaban FH&#61;4&#44; con valores predictivos negativos &#40;91&#8211;92&#37;&#41;&#44; y especificidades &#40;86&#8211;92&#37;&#41; altos&#46; El valor de ABC de para la detecci&#243;n de cirrosis con FS es inferior a los datos publicados previamente &#40;0&#44;79&#41;&#46; Esto puede haber sido consecuencia de diferencias en la distribuci&#243;n del grado de actividad necro inflamatoria en esta muestra respecto a otros estudios&#44; ya que este factor tiene influencia significativa en la rigidez hep&#225;tica<a class="elsevierStyleCrossRef" href="#bib23"><span class="elsevierStyleSup">23</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">Los resultados de este an&#225;lisis indican que todas las pruebas tuvieron una capacidad aceptable de predicci&#243;n de la presencia&#47;ausencia de fibrosis significativa &#40;FH&#8805;2&#41; y de ausencia de fibrosis avanzada &#40;FH&#61;4&#41;&#44; en consistencia con estudios previos<a class="elsevierStyleCrossRefs" href="#bib10"><span class="elsevierStyleSup">10&#44;23&#44;25&#44;27</span></a>&#46; Sin embargo&#44; los resultados indican un grado de concordancia moderado con la BH y valores bajos de sensibilidad&#44; para FH&#8805;2&#46; Varios autores han propuesto combinar estas pruebas para mejorar la detecci&#243;n de FH significativa y cirrosis<a class="elsevierStyleCrossRefs" href="#bib17"><span class="elsevierStyleSup">17&#44;28&#8211;30</span></a> y se ha observado que de esta manera es posible evitar la BH en hasta un tercio de pacientes con HCC&#46; Concluyendo&#44; los resultados de este estudio apoyan las recomendaciones de las &#171;AASLD Practice Guidelines 2009&#187;<a class="elsevierStyleCrossRef" href="#bib31"><span class="elsevierStyleSup">31</span></a>&#44; las cuales indican que los m&#233;todos no invasivos son &#250;tiles en definir ausencia o presencia de FH avanzada pero sin reemplazar totalmente la BH en la rutina de la pr&#225;ctica cl&#237;nica&#46; Con la informaci&#243;n disponible en la actualidad&#44; la BH sigue siendo necesaria en caso de discordancia o resultados indeterminados usando m&#233;todos no invasivos&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicto de intereses</span><p class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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          "titulo" => array:5 [
            0 => "Abstract"
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        5 => array:2 [
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              "titulo" => "Pacientes"
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            1 => array:1 [
              "titulo" => "Evaluaci&#243;n histol&#243;gica"
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            2 => array:1 [
              "titulo" => "Marcadores bioqu&#237;micos"
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            3 => array:1 [
              "titulo" => "Fibroscan"
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            4 => array:1 [
              "titulo" => "An&#225;lisis estad&#237;sticos"
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        6 => array:2 [
          "titulo" => "Resultados"
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            0 => array:1 [
              "titulo" => "Pacientes y evaluaci&#243;n histol&#243;gica"
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          "titulo" => "Discusi&#243;n"
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        8 => array:1 [
          "titulo" => "Conflicto de intereses"
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          "identificador" => "xack43888"
          "titulo" => "Agradecimientos"
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        10 => array:1 [
          "titulo" => "Bibliograf&#237;a"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2009-04-28"
    "fechaAceptado" => "2010-02-16"
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec151111"
          "palabras" => array:6 [
            0 => "Virus de la hepatitis C"
            1 => "Virus de la inmunodeficiencia humana"
            2 => "Coinfectados"
            3 => "Fibrosis hep&#225;tica"
            4 => "Biomarcadores"
            5 => "Fibroscan biopsia hep&#225;tica"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec151110"
          "palabras" => array:7 [
            0 => "HCV"
            1 => "HIV"
            2 => "Coinfection"
            3 => "Liver fibrosis"
            4 => "Biomarkers"
            5 => "Fibroscan"
            6 => "Liver biopsy"
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        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p class="elsevierStyleSimplePara elsevierViewall">Evaluaci&#243;n de la capacidad predictiva de fibrosis hep&#225;tica &#40;FH&#41; del FibroScan<span class="elsevierStyleSup">&#174;</span> y APRI&#44; FIB-4 y FORNS&#44; con la biopsia hep&#225;tica como prueba de referencia&#46;</p> <span class="elsevierStyleSectionTitle">M&#233;todos</span><p class="elsevierStyleSimplePara elsevierViewall">El grado de fibrosis hep&#225;tica &#40;FH&#41; se determin&#243; en 154 pacientes con hepatitis cr&#243;nica C usando el sistema METAVIR&#46; Se tomaron medidas de FibroScan<span class="elsevierStyleSup">&#174;</span> &#40;FS&#41; y muestras sangu&#237;neas simult&#225;neamente a la biopsia&#46; Las pruebas se evaluaron usando curvas COR y los valores de concordancia&#44; sensibilidad&#44; especificidad&#44; razones de verosimilitud y valores predictivos&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">Los pacientes de mayor edad y los coinfectados con VIH ten&#237;an significativamente mayores grados de fibrosis&#46; El FS y el FIB-4 tuvieron una capacidad predictiva de FH&#8805;1 significativa&#44; y m&#225;s de 94&#37; de los pacientes con FS&#62;6&#44;7kPas o FIB-4&#62;1&#44;3 ten&#237;an FH&#8805;1 en BH&#44; con sensibilidades bajas &#40;63&#37;FS&#59; 56&#37;Fib-4&#41;&#46; Para la detecci&#243;n de FH&#8805;2&#44; todas las pruebas tuvieron una capacidad predictiva significativa&#44; y entre 77&#8211;86&#37; de los pacientes con FS&#62;6&#44;8kPas&#44; APRI&#62;0&#44;6&#44; FIB-4&#62;1&#44;4 y FORNS&#62;5&#44;6 ten&#237;an FH&#8805;2&#44; con sensibilidades bajas &#40;70&#37;FS&#59; 54&#37;APRI&#59; 59&#37;FIB-4&#59; 54&#37;FORNS&#41;&#46; Todas las pruebas tuvieron valores predictivos negativos &#40;91&#8211;92&#37;&#41;&#44; y especificidades &#40;86&#8211;92&#37;&#41; altos para la detecci&#243;n de fibrosis avanzada &#40;FH&#61;4&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusi&#243;n</span><p class="elsevierStyleSimplePara elsevierViewall">Todas las pruebas tuvieron una capacidad aceptable de predicci&#243;n de la presencia&#47;ausencia de fibrosis leve &#40;FH&#8805;2&#41; y de ausencia de fibrosis avanzada &#40;FH&#61;2&#41;&#46; Sin embargo&#44; grados de concordancia con la BH bajos a moderados y valores bajos de sensibilidad para la detecci&#243;n de fibrosis leve indican que la BH sigue siendo necesaria en caso de discordancia o resultados indeterminados usando estos m&#233;todos&#46;</p>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p class="elsevierStyleSimplePara elsevierViewall">To assess the ability of FibroScan<span class="elsevierStyleSup">&#174;</span> &#40;FS&#41; and the APRI&#44; FIB-4 and FORNS indexes to predict liver fibrosis &#40;LF&#41;&#44; using liver biopsy as the gold standard&#46;</p> <span class="elsevierStyleSectionTitle">Methods</span><p class="elsevierStyleSimplePara elsevierViewall">LF stage was determined in 154 patients with chronic hepatitis C virus infection using the METAVIR system&#46; Fibroscan<span class="elsevierStyleSup">&#174;</span> measurements and blood samples were taken simultaneously with biopsy&#46; The tests were evaluated using ROC curves and the concordance&#44; sensitivity&#44; specificity and predictive values and likelihood ratios&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">Significantly higher LF stages were found in older patients and in those with HIV coinfection&#46; FS and FIB-4 were able to predict significant LF&#8805;1 and more than 94&#37; of patients with FS&#62;6&#46;7 kPas or FIB-4&#62;1&#46;3 had LF&#8805;1 in liver biopsy&#44; with low sensitivities &#40;63&#37; FS&#59; 56&#37; Fib-4&#41;&#46; For the detection of LF&#8805;2&#44; all the tests had significant predictive capacity and between 77&#37; and 86&#37; of the patients with FS&#62;6&#46;8kPas&#44; APRI&#62;0&#46;6&#44; FIB-4&#62;1&#46;4 and FORNS&#62;5&#46;6 had LF&#8805;2&#44; with low sensitivities &#40;70&#37;FS&#59; 54&#37;APRI&#59; 59&#37;FIB-4&#59; 54&#37;FORNS&#41;&#46; All tests had high negative predictive values &#40;91&#8211;92&#37;&#41; and specificities &#40;86&#8211;92&#37;&#41; in the detection of advanced fibrosis &#40;FH&#61;4&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusion</span><p class="elsevierStyleSimplePara elsevierViewall">All tests were acceptable in predicting the presence or absence of mild fibrosis <span class="elsevierStyleBold">&#40;</span>LF&#8805;2&#41; and the absence of advanced fibrosis &#40;LF&#61;2&#41;&#46; However&#44; the low or moderate agreement with liver biopsy and low sensitivities in the detection of mild fibrosis indicate that liver biopsy continues to be required when the results of other methods are discordant or indeterminate&#46;</p>"
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                  \t\t\t\t">178&#44;5 &#40;70&#8211;232&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;8&#44;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p class="elsevierStyleSimplePara elsevierViewall">FH&#58; fibrosis hep&#225;tica&#59; &#205;ndice &#954;&#58; concordancia con grado de FH determinado mediante biopsia&#59; N&#58; 150&#59; VPN&#58; valor predictivo negativo&#59; VPP&#58; valor predictivo positivo&#59; RVN&#58; raz&#243;n de verosimilitud negativa&#59; RVP&#58; raz&#243;n de verosimilitud positiva&#46;</p>"
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                  \t\t\t\t</td></tr></tbody></table>
                  """
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Información del artículo
ISSN: 02105705
Idioma original: Español
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2020 Mayo 67 23 90
2020 Abril 80 30 110
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2020 Enero 102 9 111
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2019 Noviembre 85 14 99
2019 Octubre 92 6 98
2019 Septiembre 119 22 141
2019 Agosto 90 12 102
2019 Julio 99 27 126
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2019 Mayo 292 59 351
2019 Abril 124 30 154
2019 Marzo 54 15 69
2019 Febrero 44 19 63
2019 Enero 26 8 34
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2018 Octubre 42 9 51
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2018 Agosto 16 3 19
2018 Julio 20 3 23
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2018 Mayo 24 5 29
2018 Abril 13 2 15
2018 Marzo 24 2 26
2018 Febrero 13 2 15
2018 Enero 27 1 28
2017 Diciembre 15 3 18
2017 Noviembre 39 3 42
2017 Octubre 14 3 17
2017 Septiembre 33 0 33
2017 Agosto 31 2 33
2017 Julio 20 2 22
2017 Junio 17 9 26
2017 Mayo 23 3 26
2017 Abril 15 2 17
2017 Marzo 25 1 26
2017 Febrero 32 4 36
2017 Enero 12 1 13
2016 Diciembre 40 4 44
2016 Noviembre 56 4 60
2016 Octubre 65 6 71
2016 Septiembre 73 7 80
2016 Agosto 53 4 57
2016 Julio 43 1 44
2016 Junio 55 12 67
2016 Mayo 55 13 68
2016 Abril 54 20 74
2016 Marzo 58 16 74
2016 Febrero 48 20 68
2016 Enero 41 16 57
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2014 Mayo 36 5 41
2014 Abril 48 3 51
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