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La prevalencia de la EHNA no es bien conocida y probablemente est&#233; infravalorada debido a que la mayor&#237;a de los pacientes permanecen asintom&#225;ticos&#44; a la ausencia de marcadores serol&#243;gicos precisos y a la necesidad de realizar biopsia para el diagn&#243;stico definitivo&#46; Se estima que esta enfermedad afecta al 20&#8211;30&#37; de la poblaci&#243;n adulta<a class="elsevierStyleCrossRef" href="#bib2"><span class="elsevierStyleSup">2</span></a> y su prevalencia se eleva hasta el 57&#44;5&#37; en los pacientes con obesidad<a class="elsevierStyleCrossRef" href="#bib3"><span class="elsevierStyleSup">3</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">El conocimiento sobre esta enfermedad en la edad pedi&#225;trica es limitado<a class="elsevierStyleCrossRefs" href="#bib4"><span class="elsevierStyleSup">4&#8211;10</span></a> y la prevalencia de la enfermedad&#44; en este grupo de edad&#44; es todav&#237;a desconocida&#46; La evoluci&#243;n de la EHNA&#44; a largo plazo&#44; es incierta&#46; En los pacientes obesos&#44; la EHNA asintom&#225;tica ser&#237;a el primer estadio de da&#241;o hep&#225;tico y la ganancia de peso facilitar&#237;a la progresi&#243;n a mayor da&#241;o celular&#46; Por tanto&#44; es esencial la detecci&#243;n precoz de los estadios iniciales y el fomento de h&#225;bitos saludables&#46;</p><p class="elsevierStylePara elsevierViewall">La fisiopatolog&#237;a de la EHNA no est&#225; totalmente esclarecida&#46; Tiene una naturaleza multifactorial en la que participan factores metab&#243;licos y de estr&#233;s oxidativo&#44; y la RI desempe&#241;a un papel fundamental en su desarrollo<a class="elsevierStyleCrossRefs" href="#bib11"><span class="elsevierStyleSup">11&#44;12</span></a>&#46; La adiponectina est&#225; relacionada con la RI y el desarrollo del SM<a class="elsevierStyleCrossRef" href="#bib13"><span class="elsevierStyleSup">13</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">Los objetivos del presente estudio son establecer la relaci&#243;n entre la EHNA y los par&#225;metros cl&#237;nicos y anal&#237;ticos de RI en un grupo de ni&#241;os y adolescentes con obesidad&#44; y estudiar si la adiponectina s&#233;rica se relaciona con la EHNA&#44; independientemente de la RI&#44; en dichos pacientes&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Pacientes y m&#233;todos</span><p class="elsevierStylePara elsevierViewall">Realizamos un estudio prospectivo en ni&#241;os y adolescentes remitidos a nuestra unidad por obesidad&#46; El estudio incluy&#243; 290 pacientes y el Comit&#233; &#201;tico de nuestro centro lo aprob&#243;&#46; Los criterios de inclusi&#243;n fueron los siguientes&#58; edad entre 4 y 18 a&#241;os y un &#237;ndice de masa corporal &#40;IMC&#41;&#177;desviaci&#243;n est&#225;ndar &#40;DE&#41; superior a 2DE seg&#250;n las tablas de Hern&#225;ndez et al<a class="elsevierStyleCrossRef" href="#bib14"><span class="elsevierStyleSup">14</span></a>&#46; Los pacientes con diabetes conocida&#44; tratamiento hipoglucemiante&#44; tratamiento con corticoides&#44; consumo de alcohol u otras enfermedades hep&#225;ticas previas se excluyeron del estudio&#46;</p><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Valoraci&#243;n cl&#237;nica</span><p class="elsevierStylePara elsevierViewall">El IMC &#40;peso &#91;kg&#93;&#47;altura<span class="elsevierStyleSup">2</span> &#91;m<span class="elsevierStyleSup">2</span>&#93;&#41; 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Se realizaron proyecciones longitudinal&#44; subcostal&#44; ascendente y oblicua&#46;</p><p class="elsevierStylePara elsevierViewall">La ecograf&#237;a muestra un incremento homog&#233;neo y difuso en la ecogenicidad del h&#237;gado cuando existe ac&#250;mulo intrahep&#225;tico de grasa&#44; el h&#237;gado aparece m&#225;s brillante que los ri&#241;ones y se identifican con dificultad las venas hep&#225;ticas y porta&#46; Para el diagn&#243;stico de la EHNA el radi&#243;logo se bas&#243; en los criterios&#58; discrepancia h&#237;gado-ri&#241;ones&#44; penetrancia en profundidad hep&#225;tica y claridad de venas hep&#225;ticas&#46; Los pacientes se clasificaron en 2 grupos&#58; presencia de esteatosis hep&#225;tica o ecograf&#237;a normal&#46;</p><p class="elsevierStylePara elsevierViewall">Como la EHNA es un diagn&#243;stico de exclusi&#243;n&#44; fue necesario realizar una historia y una exploraci&#243;n detallada&#44; as&#237; como pruebas complementarias para descartar consumo de alcohol en adolescentes y otras enfermedades hep&#225;ticas &#40;infecciones virales o enfermedad de Wilson&#41;&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Estudio metab&#243;lico</span><p class="elsevierStylePara elsevierViewall">Se obtuvieron muestras en ayunas para bioqu&#237;mica completa con glucosa&#44; insulina&#44; perfil lip&#237;dico y hep&#225;tico&#44; &#225;cido &#250;rico y adiponectina s&#233;rica&#46; Adem&#225;s&#44; se realiz&#243; a todos los pacientes un test de sobrecarga oral de glucosa&#46;</p><p class="elsevierStylePara elsevierViewall">Se utiliz&#243; un m&#233;todo enzim&#225;tico para la dosificaci&#243;n de l&#237;pidos&#44; AEROSET&#47;ARCHITECT c8000 &#40;Abbott&#41;&#46; Definimos dislipidemia con cHDL &#8804;40<span class="elsevierStyleHsp" style=""></span>mg&#47;dl o triglic&#233;ridos &#40;TG&#41; &#8805;110<span class="elsevierStyleHsp" style=""></span>mg&#47;dl<a class="elsevierStyleCrossRef" href="#bib18"><span class="elsevierStyleSup">18</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">Las determinaciones de alanin-aminotransferasa &#40;ALT&#41;&#44; aspartato-aminotranferasa &#40;AST&#41; y gamma-glutamil transferasa &#40;GGT&#41; se realizaron con sistema AEROSET&#47;ARCHITECT c8000 &#40;Abbott&#41; y definimos alteraci&#243;n enzim&#225;tica con ALT &#8805;40<span class="elsevierStyleHsp" style=""></span>U&#47;l<a class="elsevierStyleCrossRefs" href="#bib6"><span class="elsevierStyleSup">6&#44;19&#44;20</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">La adiponectina s&#233;rica se midi&#243; por radioinmunoensayo &#40;RIA&#41; &#40;Linco Research&#44; Inc&#46;&#44; St&#46; Charles&#44; Missouri&#44; EE&#46; UU&#46;&#41;&#46; Las muestras se diluyeron &#40;500 veces&#41; previo al an&#225;lisis&#46; La sensibilidad del m&#233;todo es de 2<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; Los coeficientes de variaci&#243;n intraensayo e interensayo fueron inferiores al 5&#37;&#46;</p><p class="elsevierStylePara elsevierViewall">Para la determinaci&#243;n de la glucosa plasm&#225;tica se utiliz&#243; el m&#233;todo de glucosa oxidasa del analizador AEROSET c8000&#46; La insulina se midi&#243; mediante inmunoan&#225;lisis &#40;Immunolite 2000&#41;&#44; sin reacci&#243;n cruzada significativa con proinsulina&#46;</p><p class="elsevierStylePara elsevierViewall">La alteraci&#243;n en el metabolismo hidrocarbonado se defini&#243; seg&#250;n los &#250;ltimos criterios de la Asociaci&#243;n Americana de Diabetes<a class="elsevierStyleCrossRef" href="#bib17"><span class="elsevierStyleSup">17</span></a>&#46; El &#237;ndice HOMA se calcul&#243; mediante la f&#243;rmula&#58; glucosa basal &#40;mmol&#47;l&#41;&#215;insulina basal &#40;&#956;U&#47;ml&#41;&#47;22&#44;5<a class="elsevierStyleCrossRef" href="#bib21"><span class="elsevierStyleSup">21</span></a>&#46; Clasificamos a los pacientes como resistentes a la insulina cuando el HOMA o la insulina basal fue mayor del P95 para nuestra poblaci&#243;n<a class="elsevierStyleCrossRef" href="#bib16"><span class="elsevierStyleSup">16</span></a>&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">M&#233;todos estad&#237;sticos</span><p class="elsevierStylePara elsevierViewall">Se utiliz&#243; el paquete estad&#237;stico SPSS 12&#46;0 para Windows &#40;SPSS&#44; Inc&#46;&#44; Chicago&#44; Illinois&#44; EE&#46; UU&#46;&#41; para realizar el an&#225;lisis estad&#237;stico&#46; Se presentan los datos como media&#177;DE para las variables continuas&#46; El <span class="elsevierStyleItalic">Z-score</span> se calcul&#243; como valor-media&#47;DE&#46; Se utiliz&#243; el test de la t de Student&#44; el test de la U de Mann-Witney&#44; la prueba de la &#967;<span class="elsevierStyleSup">2</span> y el test de Fisher cuando correspond&#237;a&#46; Se analizaron las correlaciones entre variables &#40;Spearman&#41; y se realiz&#243; un an&#225;lisis de regresi&#243;n m&#250;ltiple para estudiar los factores predictores de la EHNA&#46; Se incluyeron en el modelo m&#225;ximo las siguientes variables&#58; edad&#44; IMC&#177;DE&#44; HOMA&#44; &#225;cido &#250;rico&#44; TG y adiponectina&#46; Se analiz&#243; la colinearidad por los criterios de Belsley&#46; Todos los valores de p son para 2 colas&#59; se consider&#243; significancia estad&#237;stica valores de p&#60;0&#44;05&#46;</p></span></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStylePara elsevierViewall">Se estudi&#243; a un total de 290 pacientes &#40;147 varones&#47;143 mujeres&#41;&#44; con una edad media de 11&#177;3 a&#241;os &#40;el 91&#37; de raza cauc&#225;sica y el 9&#37; eran hispanos&#41;&#46; Cincuenta y dos pacientes mostraron esteatosis en la ecograf&#237;a hep&#225;tica &#40;18&#37;&#41;&#46; Los datos cl&#237;nicos y bioqu&#237;micos de la poblaci&#243;n se resumen en la <a class="elsevierStyleCrossRef" href="#tbl1">tabla 1</a>&#46;</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">Todos los pacientes con EHNA estaban cl&#237;nicamente asintom&#225;ticos y sin hepatomegalia&#46; Veintid&#243;s pacientes &#40;8&#37;&#41; ten&#237;an niveles plasm&#225;ticos de ALT elevados&#46; La frecuencia de hiperaminotransferasemia fue significativamente mayor en los pacientes con EHNA que en los pacientes con ecograf&#237;a normal &#40;el 21 frente al 5&#37;&#59; p&#60;0&#44;005&#41;&#46; Se encontraron diferencias significativas en ALT y GGT&#44; pero no en AST&#44; entre los 2 grupos &#40;<a class="elsevierStyleCrossRef" href="#tbl1">tabla 1</a>&#41;&#46;</p><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Caracter&#237;sticas de los pacientes con esteatosis hep&#225;tica no alcoh&#243;lica</span><p class="elsevierStylePara elsevierViewall">Como muestra la <a class="elsevierStyleCrossRef" href="#tbl1">tabla 1</a>&#44; los pacientes con EHNA ten&#237;an mayor IMC global y en DE que los sujetos sin esteatosis &#40;30&#177;4<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> frente a 27&#177;3 y 4&#44;5&#177;1&#44;5 frente a 3&#44;8&#177;1&#44;3&#44; respectivamente&#44; ambos p&#60;0&#44;005&#41;&#46; Encontramos tambi&#233;n diferencia significativa en la edad&#44; pero no en sexo&#44; estadio puberal o raza&#46; La acantosis nigricans y los par&#225;metros bioqu&#237;micos de RI fueron significativamente m&#225;s frecuentes en el grupo con esteatosis&#46; En la poblaci&#243;n global estudiada se encontr&#243; un 40&#37; de pacientes con RI&#44; frecuencia que aumentaba a un 70&#37; en el grupo con EHNA&#46; Asimismo&#44; la frecuencia del SM fue mayor en los pacientes con esteatosis &#40;31&#37;&#41; que en aqu&#233;llos con ecograf&#237;a normal &#40;18&#37;&#41; &#40;p&#60;0&#44;05&#41;&#46; Los pacientes con EHNA tuvieron niveles significativamente m&#225;s bajos de adiponectina que el grupo sin EHNA &#40;8&#44;7&#177;4<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml frente a 11&#44;3&#177;4&#44;7<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#59; p&#60;0&#44;005&#41;&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Correlaciones y an&#225;lisis de regresi&#243;n log&#237;stica</span><p class="elsevierStylePara elsevierViewall">No encontramos correlaci&#243;n significativa entre ALT y el grado de obesidad &#40;<a class="elsevierStyleCrossRef" href="#tbl2">tabla 2</a>&#41;&#44; pero s&#237; con par&#225;metros de RI y &#225;cido &#250;rico &#40;p&#60;0&#44;05&#41;&#46; Los niveles de adiponectina se correlacionaron de forma directa con cHDL&#44; y negativamente con edad&#44; ALT&#44; GGT&#44; &#225;cido &#250;rico y HOMA &#40;p&#60;0&#44;005&#41;&#46;</p><elsevierMultimedia ident="tbl2"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">En el an&#225;lisis de regresi&#243;n log&#237;stica m&#250;ltiple &#40;<a class="elsevierStyleCrossRef" href="#tbl3">tabla 3</a>&#41; solamente se asociaron a EHNA&#44; de forma significativa e independiente&#44; IMC&#177;DE&#44; HOMA y adiponectina &#40;&#40;<span class="elsevierStyleItalic">odds ratio</span>&#58; 1&#44;4 &#91;1&#44;1-1&#44;9&#93;&#59; 1&#44;3 &#91;1&#44;1-1&#44;6&#93; y 0&#44;9 &#91;0&#44;8-0&#44;9&#93;&#44; respectivamente&#41;&#46;</p><elsevierMultimedia ident="tbl3"></elsevierMultimedia></span></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discusi&#243;n</span><p class="elsevierStylePara elsevierViewall">Los resultados de este estudio ponen de manifiesto la relaci&#243;n entre la esteatosis hep&#225;tica&#44; en ni&#241;os y adolescentes obesos&#44; y el grado de obesidad y de RI&#46; Adem&#225;s&#44; indican una relaci&#243;n estrecha entre los niveles de adiponectina y el riesgo en el desarrollo de la EHNA en dicha poblaci&#243;n&#46;</p><p class="elsevierStylePara elsevierViewall">La EHNA se ha relacionado con la obesidad en varios estudios pedi&#225;tricos<a class="elsevierStyleCrossRefs" href="#bib20"><span class="elsevierStyleSup">20&#44;22&#8211;26</span></a>&#46; La frecuencia de dicha enfermedad en nuestra cohorte &#40;18&#37;&#41; es menor que en otros estudios<a class="elsevierStyleCrossRefs" href="#bib5"><span class="elsevierStyleSup">5&#44;7&#44;9&#44;27&#8211;30</span></a>&#44; probablemente porque nuestros pacientes no alcanzaban el grado de obesidad de otras poblaciones y por la variabilidad en los criterios diagn&#243;sticos utilizados&#46; Aunque el <span class="elsevierStyleItalic">gold standard</span> para el diagn&#243;stico sigue siendo la biopsia hep&#225;tica&#44; no se realiz&#243; en nuestro estudio por ser invasiva y de mayor coste&#46; Actualmente se est&#225;n desarrollando otras pruebas no invasivas&#44; como el test del aliento con metacolina&#44; pero se precisan estudios en la poblaci&#243;n infantil para establecer su indicaci&#243;n y seguridad&#46; En nuestra muestra realizamos el diagn&#243;stico ecogr&#225;fico por su f&#225;cil acceso&#44; inocuidad y excelente sensibilidad para el diagn&#243;stico de esteatosis<a class="elsevierStyleCrossRefs" href="#bib31"><span class="elsevierStyleSup">31&#44;32</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">En los ni&#241;os obesos la elevaci&#243;n de ALT se ha utilizado como indicador del dep&#243;sito de grasa hep&#225;tica<a class="elsevierStyleCrossRef" href="#bib33"><span class="elsevierStyleSup">33</span></a>&#46; La elevaci&#243;n de ALT puede ser el &#250;nico hallazgo bioqu&#237;mico en pacientes con EHNA<a class="elsevierStyleCrossRef" href="#bib34"><span class="elsevierStyleSup">34</span></a> aunque suele ocurrir en casos de mayor ac&#250;mulo graso y no de esteatosis leve&#46; En nuestra poblaci&#243;n estudiada existi&#243; hiperaminotransferasemia en el 8&#37;&#59; Strauss et al<a class="elsevierStyleCrossRef" href="#bib35"><span class="elsevierStyleSup">35</span></a> han encontrado una frecuencia similar en 2&#46;450 adolescentes con sobrepeso y obesidad&#46; En algunos estudios la frecuencia de hiperaminotransferasemia alcanza el 25&#37;<a class="elsevierStyleCrossRefs" href="#bib9"><span class="elsevierStyleSup">9&#44;5</span></a>&#46; La hiperaminotransferasemia fue significativamente mayor en el grupo de EHNA que en el grupo con ecograf&#237;a normal &#40;p&#60;0&#44;005&#41;&#44; pero s&#243;lo alcanz&#243; el 21&#37;&#44; por tanto&#44; la determinaci&#243;n aislada de aminotransferasas no es indicador suficiente de EHNA y es recomendable realizar ecograf&#237;a en pacientes de riesgo para su diagn&#243;stico&#46;</p><p class="elsevierStylePara elsevierViewall">Al contrario de otras publicaciones<a class="elsevierStyleCrossRefs" href="#bib5"><span class="elsevierStyleSup">5&#44;6&#44;35</span></a>&#44; no encontramos diferencias significativas en el da&#241;o hep&#225;tico seg&#250;n el sexo&#46;</p><p class="elsevierStylePara elsevierViewall">Numerosos factores se han asociado al desarrollo de la EHNA<a class="elsevierStyleCrossRef" href="#bib3"><span class="elsevierStyleSup">3</span></a>&#46; En nuestra experiencia&#44; la prevalencia de EHNA se incrementa con la edad y con el grado de obesidad&#44; sobre todo cuando asocian otros datos de SM&#44; como la RI&#59; otros autores<a class="elsevierStyleCrossRef" href="#bib11"><span class="elsevierStyleSup">11</span></a> tambi&#233;n han evidenciado este hecho&#46; La frecuencia de EHNA fue del 28&#37; en los pacientes que cumpl&#237;an criterios de SM frente al 15&#37; en aqu&#233;llos sin criterios del SM &#40;p&#60;0&#44;005&#41;&#46; Hay que resaltar que estos datos se deben interpretar con cautela&#44; dado que las distintas definiciones del SM pueden ser la causa de las diferencias en los resultados con respecto a otros trabajos&#46;</p><p class="elsevierStylePara elsevierViewall">La RI parece desempe&#241;ar un papel fundamental en el desarrollo de la esteatosis&#44; tanto en los adultos<a class="elsevierStyleCrossRefs" href="#bib11"><span class="elsevierStyleSup">11&#44;36&#44;37</span></a> como en la poblaci&#243;n pedi&#225;trica<a class="elsevierStyleCrossRefs" href="#bib6"><span class="elsevierStyleSup">6&#44;26&#44;38&#8211;40</span></a>&#46; La teor&#237;a patog&#233;nica m&#225;s aceptada es la del doble impacto<a class="elsevierStyleCrossRef" href="#bib41"><span class="elsevierStyleSup">41</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig1">fig&#46; 1</a>&#41;&#46; Estudios recientes indican que el hiperinsulinismo produce alteraciones en las v&#237;as de captaci&#243;n&#44; s&#237;ntesis&#44; degradaci&#243;n y secreci&#243;n de &#225;cidos grasos libres en forma de TG&#46; Esto conlleva una mayor susceptibilidad hep&#225;tica a los cambios inflamatorios y al da&#241;o tisular<a class="elsevierStyleCrossRef" href="#bib42"><span class="elsevierStyleSup">42</span></a>&#46; El mayor estr&#233;s oxidativo resultante de la disfunci&#243;n mitocondrial y de las citoquinas proinflamatorias participa en la progresi&#243;n de la simple esteatosis a la esteatohepatitis y cirrosis&#46; Sin embargo&#44; adem&#225;s de la obesidad y de la RI se requieren otros factores ambientales o gen&#233;ticos para la progresi&#243;n a esteatohepatitis&#46;</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">En los &#250;ltimos a&#241;os se ha destacado el papel de la adiponectina como regulador del metabolismo lip&#237;dico y de la acci&#243;n de la insulina<a class="elsevierStyleCrossRef" href="#bib43"><span class="elsevierStyleSup">43</span></a>&#44; incluso en estudios pedi&#225;tricos<a class="elsevierStyleCrossRef" href="#bib44"><span class="elsevierStyleSup">44</span></a>&#46; La adiponectina recientemente ha sido considerada como un importante regulador del da&#241;o tisular en la EHNA<a class="elsevierStyleCrossRefs" href="#bib11"><span class="elsevierStyleSup">11&#44;45</span></a>&#46; En nuestra serie&#44; los niveles de adiponectina se correlacionaron negativamente con HOMA&#44; AST&#44; ALT y &#225;cido &#250;rico&#44; y de forma positiva con los niveles de cHDL&#46; Estudios previos han asociado niveles bajos de adiponectina con el desarrollo de los componentes del SM&#44; tanto en adultos<a class="elsevierStyleCrossRef" href="#bib46"><span class="elsevierStyleSup">46</span></a> como en ni&#241;os y en adolescentes<a class="elsevierStyleCrossRefs" href="#bib13"><span class="elsevierStyleSup">13&#44;44</span></a>&#46; Nuestros datos&#44; coincidentes con los de otros estudios<a class="elsevierStyleCrossRef" href="#bib27"><span class="elsevierStyleSup">27</span></a>&#44; indican un papel protector de la adiponectina en el desarrollo de la EHNA en los ni&#241;os obesos&#46;</p><p class="elsevierStylePara elsevierViewall">Los &#225;cidos grasos libres inducen directamente la expresi&#243;n de factor de necrosis tumoral alfa &#40;TNF-&#945;&#41; en el hepatocito y promueven la esteatosis y el da&#241;o hep&#225;tico<a class="elsevierStyleCrossRef" href="#bib47"><span class="elsevierStyleSup">47</span></a>&#46; Recientemente se ha identificado a la apoptosis del hepatocito como componente clave en la progresi&#243;n de la esteatohepatitis&#46; La adiponectina podr&#237;a prevenir el da&#241;o hep&#225;tico por la modulaci&#243;n de TNF-&#945;<a class="elsevierStyleCrossRefs" href="#bib48"><span class="elsevierStyleSup">48&#44;49</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">En conclusi&#243;n&#44; la obesidad y la RI son factores de riesgo para el desarrollo de la EHNA en ni&#241;os y adolescentes&#46; Los niveles disminuidos de adiponectina s&#233;rica est&#225;n fuertemente asociados con la esteatosis hep&#225;tica en los ni&#241;os con obesidad&#46;</p></span></span>"
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        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introducci&#243;n</span><p class="elsevierStyleSimplePara elsevierViewall">Estudiar la prevalencia de esteatosis hep&#225;tica no alcoh&#243;lica &#40;EHNA&#41; en una poblaci&#243;n pedi&#225;trica obesa y su relaci&#243;n con par&#225;metros clinicoanal&#237;ticos de resistencia a la insulina &#40;RI&#41; y con niveles de adiponectina&#46;</p> <span class="elsevierStyleSectionTitle">Pacientes y m&#233;todos</span><p class="elsevierStyleSimplePara elsevierViewall">Se estudi&#243; a 290 ni&#241;os &#40;4&#8211;18 a&#241;os&#41; con obesidad&#46; Se analiz&#243; el &#237;ndice de masa corporal &#40;IMC&#41; y la desviaci&#243;n est&#225;ndar &#40;DE&#41;&#44; la acantosis nigricans&#44; la presi&#243;n arterial&#44; el perfil lip&#237;dico&#44; las aminotransferasas y la adiponectina&#46; Se realiz&#243; un test de sobrecarga oral de glucosa y se defini&#243; la RI mediante el <span class="elsevierStyleItalic">homeostasis model assessment</span> &#40;HOMA&#41; y la esteatosis hep&#225;tica por ecograf&#237;a&#46; Definimos el s&#237;ndrome metab&#243;lico &#40;SM&#41; como la presencia de 3 o m&#225;s de los siguientes criterios&#58; obesidad&#44; hipertensi&#243;n&#44; hipertrigliceridemia&#44; colesterol ligado a lipoprote&#237;nas de alta densidad &#40;cHDL&#41; bajo y alteraci&#243;n hidrocarbonada&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">Cincuenta y dos &#40;18&#37;&#41; pacientes presentaban EHNA en la ecograf&#237;a&#44; 22 &#40;8&#37;&#41; pacientes ten&#237;an elevaci&#243;n de alanin-aminotransferasa &#40;ALT&#41; &#40;&#8805;40<span class="elsevierStyleHsp" style=""></span>U&#47;l&#41;&#46; Los pacientes con EHNA fueron significativamente mayores &#40;12&#44;2&#177;2&#44;4 frente a 11&#44;1&#177;2&#44;9 a&#241;os&#41;&#44; m&#225;s obesos &#40;IMC&#177;DE&#58; 4&#44;5&#177;1&#44;5 frente a 3&#44;8&#177;1&#44;3&#41;&#44; y presentaron niveles m&#225;s elevados de HOMA &#40;3&#44;7&#177;1&#44;5 frente a 2&#44;4&#177;1&#44;4&#41; que los pacientes con ecograf&#237;a normal&#46; No se encontr&#243; diferencia significativa en sexo&#44; raza y estadio puberal&#46; La prevalencia del SM y la acantosis nigricans fue significativamente mayor en los ni&#241;os con EHNA&#46; Encontramos una correlaci&#243;n inversa entre los niveles s&#233;ricos de adiponectina y edad&#44; HOMA&#44; ALT y &#225;cido &#250;rico&#44; y encontramos una correlaci&#243;n directa con cHDL&#46; En el an&#225;lisis de regresi&#243;n m&#250;ltiple&#44; las variables que se asociaron de forma independiente con la EHNA fueron IMC&#177;DE&#44; HOMA y adiponectina &#40;<span class="elsevierStyleItalic">odds ratio</span>&#58; 1&#44;4 &#91;1&#44;1-1&#44;9&#93;&#59; 1&#44;3 &#91;1&#44;1-1&#44;6&#93; y 0&#44;9 &#91;0&#44;8-0&#44;9&#93;&#44; respectivamente&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">La obesidad y la RI son factores de riesgo de la EHNA en ni&#241;os y adolescentes&#46; Los niveles bajos de adiponectina est&#225;n fuertemente asociados al desarrollo de EHNA en dichos pacientes&#46;</p>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introduction</span><p class="elsevierStyleSimplePara elsevierViewall">To study the clinical and laboratory relationships of fatty liver disease in a group of obese children and to investigate whether circulating adiponectin is related to fatty liver disease&#46;</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p class="elsevierStyleSimplePara elsevierViewall">Two hundred-ninety obese patients &#40;age 4&#8211;18 years&#41; were studied&#46; Baseline body mass index-standard deviation score &#40;BMI-SDS&#41;&#44; acanthosis nigricans&#44; blood pressure&#44; plasma lipids&#44; uric acid&#44; alanine aminotransferase &#40;ALT&#41; and adiponectin were assessed&#44; and a standard oral glucose tolerance test was performed&#46; Insulin resistance &#40;RI&#41; was estimated by the homeostasis model assessment &#40;HOMA&#41; and liver steatosis was assessed by ultrasound &#40;US&#41;&#46; Children were classified as having metabolic syndrome if they met three or more of the following criteria&#58; obesity&#44; hypertension&#44; hypertriglyceridemia&#44; low HDL-cholesterol and impaired glucose metabolism&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">Fifty-two subjects &#40;18&#37;&#41; had fatty liver by US and 22 &#40;8&#37;&#41; had elevated ALT levels &#40;&#8805;40<span class="elsevierStyleHsp" style=""></span>U&#47;L&#41;&#46; Subjects with steatosis were significantly older &#40;12&#46;2&#177;2&#46;4 frente a 11&#46;1&#177;2&#46;9<span class="elsevierStyleHsp" style=""></span>yr&#41;&#44; heavier &#40;BMI-SDS&#58; 4&#46;5&#177;1&#46;5 frente a 3&#46;8&#177;1&#46;3&#41;&#44; and more RI &#40;HOMA&#58; 3&#46;7&#177;1&#46;5 frente a 2&#46;4&#177;1&#46;4&#41;&#44; but were comparable in gender&#44; pubertal status and racial distribution to those with normal US&#46; The prevalence of metabolic syndrome and acanthosis nigricans were also higher in the steatosis frente a the normal US group&#46; Serum adiponectin concentration was inversely correlated with age&#44; HOMA&#44; ALT and uric acid and directly correlated with HDL-cholesterol&#46; In a multiple logistic regression analysis&#44; BMI-SDS&#44; HOMA and serum adiponectin&#44; but not age&#44; uric acid or triglycerides&#44; were the covariates independently associated with the presence of steatosis &#40;odds ratio 1&#46;4 &#91;1&#46;1-1&#46;9&#93;&#59; 1&#46;3 &#91;1&#46;1-1&#46;6&#93; and 0&#46;9 &#91;0&#46;8-0&#46;9&#93;&#44; respectively&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStyleSimplePara elsevierViewall">Obesity and RI are risk factors for liver steatosis in children and adolescents&#46; Decreased serum adiponectin is closely and independently associated with steatosis&#46;</p>"
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "fig1"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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            "imagen" => "gr1.jpeg"
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        "descripcion" => array:1 [
          "es" => "<p class="elsevierStyleSimplePara elsevierViewall">Esquema de la patogenia de las esteatosis hep&#225;tica no alcoh&#243;lica<a class="elsevierStyleCrossRef" href="#bib41"><span class="elsevierStyleSup">41</span></a>&#46; Factor de necrosis tumoral alfa &#40;TNF-&#945;&#41;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl1"
        "etiqueta" => "Tabla 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p class="elsevierStyleSimplePara elsevierViewall">AGA&#58; alteraci&#243;n de la glucosa en ayunas&#59; AHC&#58; alteraci&#243;n hidrocarbonada&#59; ALT&#58; alanin-aminotransferasa&#59; AST&#58; aspartato-aminotransferasa&#59; ATG&#58; alteraci&#243;n de la tolerancia a la glucosa&#59; cHDL&#58; colesterol ligado a lipoprote&#237;nas de alta densidad&#59; GGT&#58; gamma-glutamil transferasa&#59; HOMA&#58; homeostatic model assessment&#59; HTA&#58; hipertensi&#243;n arterial&#59; RI&#58; resistencia a la insulina&#59; SM&#58; s&#237;ndrome metab&#243;lico&#59; TG&#58; triglic&#233;ridos&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Global&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">Esteatosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sin esteatosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">n &#61; 290&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">n &#61; 52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">n &#61; 238&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">Edad &#40;a&#241;os&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">11&#44;3&#177;2&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;2&#177;2&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#44;1&#177;2&#44;9<a class="elsevierStyleCrossRef" href="#tblfn1b"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sexo&#44; m&#47;f&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">147&#47;143&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#47;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">117&#47;121&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prepuberales &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IMC &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#47;IMC&#177;DE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#44;9&#177;3&#44;6&#47;3&#44;9&#177;1&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#44;2&#177;4&#44;2&#47;4&#44;5&#177;1&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#44;4&#177;3&#44;3<a class="elsevierStyleCrossRef" href="#tblfn1c"><span class="elsevierStyleSup">c</span></a>&#47;3&#44;8&#177;1&#44;3<a class="elsevierStyleCrossRef" href="#tblfn1c"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acantosis nigricans &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30<a class="elsevierStyleCrossRef" href="#tblfn1c"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HTA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AST &#40;U&#47;l&#41;&#44; media&#177;DE &#40;rango&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#177;7 &#40;12-78&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&#177;12 &#40;12-78&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#177;5 &#40;12-44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ALT &#40;U&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#177;15 &#40;5-166&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#177;29 &#40;9-166&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#177;9<a class="elsevierStyleCrossRef" href="#tblfn1c"><span class="elsevierStyleSup">c</span></a> &#40;5-68&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ALT &#62;40<span class="elsevierStyleHsp" style=""></span>U&#47;l &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5<a class="elsevierStyleCrossRef" href="#tblfn1c"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GGT &#40;U&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">HOMA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">cHDL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">TG&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&#193;cido &#250;rico&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Adiponectina&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ALT&nbsp;\t\t\t\t\t\t\n
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Original
Esteatosis hepática, resistencia a la insulina y adiponectina en una población con obesidad
Fatty liver disease, insulin resistance and adiponectin in an obese pediatric population
M. López-Capapéa,
Autor para correspondencia
martalopezcapape@eresmas.com

Autor para correspondencia.
, A. López-Bermejob, M. Alonso Blancod, E. Lara Orejasd, J. Corbatón Blascoc, R. Barrio Castellanosd
a Unidad de Endocrinología Pediátrica, Servicio de Pediatría, Hospital La Moraleja, Madrid, España
b Servicio de Pediatría, Hospital Dr. Josep Trueta, Girona, España
c Unidad de Radiología Pediátrica, Hospital Universitario Ramón y Cajal, Madrid, España
d Unidad de Endocrinología Pediátrica, Hospital Universitario Ramón y Cajal, Madrid, España
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    "textoCompleto" => "<span class="elsevierStyleSections"><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introducci&#243;n</span><p class="elsevierStylePara elsevierViewall">La prevalencia de la obesidad y sus consecuencias metab&#243;licas est&#225; aumentando r&#225;pidamente a nivel mundial<a class="elsevierStyleCrossRef" href="#bib1"><span class="elsevierStyleSup">1</span></a>&#46; La esteatosis hep&#225;tica&#44; as&#237; como la diabetes de tipo 2&#44; la dislipidemia y otros par&#225;metros de resistencia a la insulina &#40;RI&#41; est&#225;n fuertemente asociados a la obesidad&#46; La esteatosis hep&#225;tica no alcoh&#243;lica &#40;EHNA&#41;&#44; incluso&#44; se ha considerado como el componente hep&#225;tico del s&#237;ndrome metab&#243;lico &#40;SM&#41;&#46; Abarca un amplio espectro de anomal&#237;as histol&#243;gicas como resultado de la acumulaci&#243;n grasa en los hepatocitos&#44; que engloba desde la esteatosis asintom&#225;tica hasta la esteatohepatitis y fibrosis-cirrosis hep&#225;tica&#46; La prevalencia de la EHNA no es bien conocida y probablemente est&#233; infravalorada debido a que la mayor&#237;a de los pacientes permanecen asintom&#225;ticos&#44; a la ausencia de marcadores serol&#243;gicos precisos y a la necesidad de realizar biopsia para el diagn&#243;stico definitivo&#46; Se estima que esta enfermedad afecta al 20&#8211;30&#37; de la poblaci&#243;n adulta<a class="elsevierStyleCrossRef" href="#bib2"><span class="elsevierStyleSup">2</span></a> y su prevalencia se eleva hasta el 57&#44;5&#37; en los pacientes con obesidad<a class="elsevierStyleCrossRef" href="#bib3"><span class="elsevierStyleSup">3</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">El conocimiento sobre esta enfermedad en la edad pedi&#225;trica es limitado<a class="elsevierStyleCrossRefs" href="#bib4"><span class="elsevierStyleSup">4&#8211;10</span></a> y la prevalencia de la enfermedad&#44; en este grupo de edad&#44; es todav&#237;a desconocida&#46; La evoluci&#243;n de la EHNA&#44; a largo plazo&#44; es incierta&#46; En los pacientes obesos&#44; la EHNA asintom&#225;tica ser&#237;a el primer estadio de da&#241;o hep&#225;tico y la ganancia de peso facilitar&#237;a la progresi&#243;n a mayor da&#241;o celular&#46; Por tanto&#44; es esencial la detecci&#243;n precoz de los estadios iniciales y el fomento de h&#225;bitos saludables&#46;</p><p class="elsevierStylePara elsevierViewall">La fisiopatolog&#237;a de la EHNA no est&#225; totalmente esclarecida&#46; Tiene una naturaleza multifactorial en la que participan factores metab&#243;licos y de estr&#233;s oxidativo&#44; y la RI desempe&#241;a un papel fundamental en su desarrollo<a class="elsevierStyleCrossRefs" href="#bib11"><span class="elsevierStyleSup">11&#44;12</span></a>&#46; La adiponectina est&#225; relacionada con la RI y el desarrollo del SM<a class="elsevierStyleCrossRef" href="#bib13"><span class="elsevierStyleSup">13</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">Los objetivos del presente estudio son establecer la relaci&#243;n entre la EHNA y los par&#225;metros cl&#237;nicos y anal&#237;ticos de RI en un grupo de ni&#241;os y adolescentes con obesidad&#44; y estudiar si la adiponectina s&#233;rica se relaciona con la EHNA&#44; independientemente de la RI&#44; en dichos pacientes&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Pacientes y m&#233;todos</span><p class="elsevierStylePara elsevierViewall">Realizamos un estudio prospectivo en ni&#241;os y adolescentes remitidos a nuestra unidad por obesidad&#46; El estudio incluy&#243; 290 pacientes y el Comit&#233; &#201;tico de nuestro centro lo aprob&#243;&#46; Los criterios de inclusi&#243;n fueron los siguientes&#58; edad entre 4 y 18 a&#241;os y un &#237;ndice de masa corporal &#40;IMC&#41;&#177;desviaci&#243;n est&#225;ndar &#40;DE&#41; superior a 2DE seg&#250;n las tablas de Hern&#225;ndez et al<a class="elsevierStyleCrossRef" href="#bib14"><span class="elsevierStyleSup">14</span></a>&#46; Los pacientes con diabetes conocida&#44; tratamiento hipoglucemiante&#44; tratamiento con corticoides&#44; consumo de alcohol u otras enfermedades hep&#225;ticas previas se excluyeron del estudio&#46;</p><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Valoraci&#243;n cl&#237;nica</span><p class="elsevierStylePara elsevierViewall">El IMC &#40;peso &#91;kg&#93;&#47;altura<span class="elsevierStyleSup">2</span> &#91;m<span class="elsevierStyleSup">2</span>&#93;&#41; se calcul&#243; en global y en DE&#46; Se realiz&#243; una exploraci&#243;n completa y se valor&#243; la presencia de acantosis nigricans en el cuello&#44; las axilas y la regi&#243;n inguinal&#46; La pubertad se valor&#243; seg&#250;n los estadios de Tanner&#46; La presi&#243;n arterial &#40;PA&#41; se midi&#243; mediante el aparato Dynamap con el paciente sentado en reposo&#44; se cogi&#243; como dato la cifra m&#225;s baja de 3 mediciones y se tom&#243; como referencia los percentiles &#40;P&#41; de la Task Force<a class="elsevierStyleCrossRef" href="#bib15"><span class="elsevierStyleSup">15</span></a>&#46; Definimos hipertensi&#243;n arterial &#40;HTA&#41; como una PA diast&#243;lica o sist&#243;lica &#8805;P95 para edad&#44; sexo y talla&#44; y definimos SM como el cumplimiento de al menos 3 de los siguientes criterios<a class="elsevierStyleCrossRef" href="#bib16"><span class="elsevierStyleSup">16</span></a>&#58; obesidad &#40;IMC&#8805;2DE&#41;&#44; HTA &#40;PA sist&#243;lica o diast&#243;lica &#8805;P95&#41;&#44; hipertrigliceridemia &#40;&#8805;110<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#44; colesterol ligado a lipoprote&#237;nas de alta densidad &#40;cHDL&#41; bajo &#40;&#8804;40<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41; y alteraci&#243;n hidrocarbonada<a class="elsevierStyleCrossRef" href="#bib17"><span class="elsevierStyleSup">17</span></a>&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Diagn&#243;stico de esteatosis</span><p class="elsevierStylePara elsevierViewall">La ecograf&#237;a es una t&#233;cnica sensible y no invasiva que resulta muy &#250;til para determinar el da&#241;o hep&#225;tico y su evoluci&#243;n<a class="elsevierStyleCrossRef" href="#bib5"><span class="elsevierStyleSup">5</span></a>&#46; El estudio ecogr&#225;fico se realiz&#243; en todos los sujetos por el mismo radi&#243;logo&#44; con ec&#243;grafo &#40;TOSBEE TOSHIBA&#41; equipado con sonda convexa de 3&#44;5 y 5<span class="elsevierStyleHsp" style=""></span>MHz&#46; Se realizaron proyecciones longitudinal&#44; subcostal&#44; ascendente y oblicua&#46;</p><p class="elsevierStylePara elsevierViewall">La ecograf&#237;a muestra un incremento homog&#233;neo y difuso en la ecogenicidad del h&#237;gado cuando existe ac&#250;mulo intrahep&#225;tico de grasa&#44; el h&#237;gado aparece m&#225;s brillante que los ri&#241;ones y se identifican con dificultad las venas hep&#225;ticas y porta&#46; Para el diagn&#243;stico de la EHNA el radi&#243;logo se bas&#243; en los criterios&#58; discrepancia h&#237;gado-ri&#241;ones&#44; penetrancia en profundidad hep&#225;tica y claridad de venas hep&#225;ticas&#46; Los pacientes se clasificaron en 2 grupos&#58; presencia de esteatosis hep&#225;tica o ecograf&#237;a normal&#46;</p><p class="elsevierStylePara elsevierViewall">Como la EHNA es un diagn&#243;stico de exclusi&#243;n&#44; fue necesario realizar una historia y una exploraci&#243;n detallada&#44; as&#237; como pruebas complementarias para descartar consumo de alcohol en adolescentes y otras enfermedades hep&#225;ticas &#40;infecciones virales o enfermedad de Wilson&#41;&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Estudio metab&#243;lico</span><p class="elsevierStylePara elsevierViewall">Se obtuvieron muestras en ayunas para bioqu&#237;mica completa con glucosa&#44; insulina&#44; perfil lip&#237;dico y hep&#225;tico&#44; &#225;cido &#250;rico y adiponectina s&#233;rica&#46; Adem&#225;s&#44; se realiz&#243; a todos los pacientes un test de sobrecarga oral de glucosa&#46;</p><p class="elsevierStylePara elsevierViewall">Se utiliz&#243; un m&#233;todo enzim&#225;tico para la dosificaci&#243;n de l&#237;pidos&#44; AEROSET&#47;ARCHITECT c8000 &#40;Abbott&#41;&#46; Definimos dislipidemia con cHDL &#8804;40<span class="elsevierStyleHsp" style=""></span>mg&#47;dl o triglic&#233;ridos &#40;TG&#41; &#8805;110<span class="elsevierStyleHsp" style=""></span>mg&#47;dl<a class="elsevierStyleCrossRef" href="#bib18"><span class="elsevierStyleSup">18</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">Las determinaciones de alanin-aminotransferasa &#40;ALT&#41;&#44; aspartato-aminotranferasa &#40;AST&#41; y gamma-glutamil transferasa &#40;GGT&#41; se realizaron con sistema AEROSET&#47;ARCHITECT c8000 &#40;Abbott&#41; y definimos alteraci&#243;n enzim&#225;tica con ALT &#8805;40<span class="elsevierStyleHsp" style=""></span>U&#47;l<a class="elsevierStyleCrossRefs" href="#bib6"><span class="elsevierStyleSup">6&#44;19&#44;20</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">La adiponectina s&#233;rica se midi&#243; por radioinmunoensayo &#40;RIA&#41; &#40;Linco Research&#44; Inc&#46;&#44; St&#46; Charles&#44; Missouri&#44; EE&#46; UU&#46;&#41;&#46; Las muestras se diluyeron &#40;500 veces&#41; previo al an&#225;lisis&#46; La sensibilidad del m&#233;todo es de 2<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; Los coeficientes de variaci&#243;n intraensayo e interensayo fueron inferiores al 5&#37;&#46;</p><p class="elsevierStylePara elsevierViewall">Para la determinaci&#243;n de la glucosa plasm&#225;tica se utiliz&#243; el m&#233;todo de glucosa oxidasa del analizador AEROSET c8000&#46; La insulina se midi&#243; mediante inmunoan&#225;lisis &#40;Immunolite 2000&#41;&#44; sin reacci&#243;n cruzada significativa con proinsulina&#46;</p><p class="elsevierStylePara elsevierViewall">La alteraci&#243;n en el metabolismo hidrocarbonado se defini&#243; seg&#250;n los &#250;ltimos criterios de la Asociaci&#243;n Americana de Diabetes<a class="elsevierStyleCrossRef" href="#bib17"><span class="elsevierStyleSup">17</span></a>&#46; El &#237;ndice HOMA se calcul&#243; mediante la f&#243;rmula&#58; glucosa basal &#40;mmol&#47;l&#41;&#215;insulina basal &#40;&#956;U&#47;ml&#41;&#47;22&#44;5<a class="elsevierStyleCrossRef" href="#bib21"><span class="elsevierStyleSup">21</span></a>&#46; Clasificamos a los pacientes como resistentes a la insulina cuando el HOMA o la insulina basal fue mayor del P95 para nuestra poblaci&#243;n<a class="elsevierStyleCrossRef" href="#bib16"><span class="elsevierStyleSup">16</span></a>&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">M&#233;todos estad&#237;sticos</span><p class="elsevierStylePara elsevierViewall">Se utiliz&#243; el paquete estad&#237;stico SPSS 12&#46;0 para Windows &#40;SPSS&#44; Inc&#46;&#44; Chicago&#44; Illinois&#44; EE&#46; UU&#46;&#41; para realizar el an&#225;lisis estad&#237;stico&#46; Se presentan los datos como media&#177;DE para las variables continuas&#46; El <span class="elsevierStyleItalic">Z-score</span> se calcul&#243; como valor-media&#47;DE&#46; Se utiliz&#243; el test de la t de Student&#44; el test de la U de Mann-Witney&#44; la prueba de la &#967;<span class="elsevierStyleSup">2</span> y el test de Fisher cuando correspond&#237;a&#46; Se analizaron las correlaciones entre variables &#40;Spearman&#41; y se realiz&#243; un an&#225;lisis de regresi&#243;n m&#250;ltiple para estudiar los factores predictores de la EHNA&#46; Se incluyeron en el modelo m&#225;ximo las siguientes variables&#58; edad&#44; IMC&#177;DE&#44; HOMA&#44; &#225;cido &#250;rico&#44; TG y adiponectina&#46; Se analiz&#243; la colinearidad por los criterios de Belsley&#46; Todos los valores de p son para 2 colas&#59; se consider&#243; significancia estad&#237;stica valores de p&#60;0&#44;05&#46;</p></span></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStylePara elsevierViewall">Se estudi&#243; a un total de 290 pacientes &#40;147 varones&#47;143 mujeres&#41;&#44; con una edad media de 11&#177;3 a&#241;os &#40;el 91&#37; de raza cauc&#225;sica y el 9&#37; eran hispanos&#41;&#46; Cincuenta y dos pacientes mostraron esteatosis en la ecograf&#237;a hep&#225;tica &#40;18&#37;&#41;&#46; Los datos cl&#237;nicos y bioqu&#237;micos de la poblaci&#243;n se resumen en la <a class="elsevierStyleCrossRef" href="#tbl1">tabla 1</a>&#46;</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">Todos los pacientes con EHNA estaban cl&#237;nicamente asintom&#225;ticos y sin hepatomegalia&#46; Veintid&#243;s pacientes &#40;8&#37;&#41; ten&#237;an niveles plasm&#225;ticos de ALT elevados&#46; La frecuencia de hiperaminotransferasemia fue significativamente mayor en los pacientes con EHNA que en los pacientes con ecograf&#237;a normal &#40;el 21 frente al 5&#37;&#59; p&#60;0&#44;005&#41;&#46; Se encontraron diferencias significativas en ALT y GGT&#44; pero no en AST&#44; entre los 2 grupos &#40;<a class="elsevierStyleCrossRef" href="#tbl1">tabla 1</a>&#41;&#46;</p><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Caracter&#237;sticas de los pacientes con esteatosis hep&#225;tica no alcoh&#243;lica</span><p class="elsevierStylePara elsevierViewall">Como muestra la <a class="elsevierStyleCrossRef" href="#tbl1">tabla 1</a>&#44; los pacientes con EHNA ten&#237;an mayor IMC global y en DE que los sujetos sin esteatosis &#40;30&#177;4<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> frente a 27&#177;3 y 4&#44;5&#177;1&#44;5 frente a 3&#44;8&#177;1&#44;3&#44; respectivamente&#44; ambos p&#60;0&#44;005&#41;&#46; Encontramos tambi&#233;n diferencia significativa en la edad&#44; pero no en sexo&#44; estadio puberal o raza&#46; La acantosis nigricans y los par&#225;metros bioqu&#237;micos de RI fueron significativamente m&#225;s frecuentes en el grupo con esteatosis&#46; En la poblaci&#243;n global estudiada se encontr&#243; un 40&#37; de pacientes con RI&#44; frecuencia que aumentaba a un 70&#37; en el grupo con EHNA&#46; Asimismo&#44; la frecuencia del SM fue mayor en los pacientes con esteatosis &#40;31&#37;&#41; que en aqu&#233;llos con ecograf&#237;a normal &#40;18&#37;&#41; &#40;p&#60;0&#44;05&#41;&#46; Los pacientes con EHNA tuvieron niveles significativamente m&#225;s bajos de adiponectina que el grupo sin EHNA &#40;8&#44;7&#177;4<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml frente a 11&#44;3&#177;4&#44;7<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;ml&#59; p&#60;0&#44;005&#41;&#46;</p></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Correlaciones y an&#225;lisis de regresi&#243;n log&#237;stica</span><p class="elsevierStylePara elsevierViewall">No encontramos correlaci&#243;n significativa entre ALT y el grado de obesidad &#40;<a class="elsevierStyleCrossRef" href="#tbl2">tabla 2</a>&#41;&#44; pero s&#237; con par&#225;metros de RI y &#225;cido &#250;rico &#40;p&#60;0&#44;05&#41;&#46; Los niveles de adiponectina se correlacionaron de forma directa con cHDL&#44; y negativamente con edad&#44; ALT&#44; GGT&#44; &#225;cido &#250;rico y HOMA &#40;p&#60;0&#44;005&#41;&#46;</p><elsevierMultimedia ident="tbl2"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">En el an&#225;lisis de regresi&#243;n log&#237;stica m&#250;ltiple &#40;<a class="elsevierStyleCrossRef" href="#tbl3">tabla 3</a>&#41; solamente se asociaron a EHNA&#44; de forma significativa e independiente&#44; IMC&#177;DE&#44; HOMA y adiponectina &#40;&#40;<span class="elsevierStyleItalic">odds ratio</span>&#58; 1&#44;4 &#91;1&#44;1-1&#44;9&#93;&#59; 1&#44;3 &#91;1&#44;1-1&#44;6&#93; y 0&#44;9 &#91;0&#44;8-0&#44;9&#93;&#44; respectivamente&#41;&#46;</p><elsevierMultimedia ident="tbl3"></elsevierMultimedia></span></span><span class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discusi&#243;n</span><p class="elsevierStylePara elsevierViewall">Los resultados de este estudio ponen de manifiesto la relaci&#243;n entre la esteatosis hep&#225;tica&#44; en ni&#241;os y adolescentes obesos&#44; y el grado de obesidad y de RI&#46; Adem&#225;s&#44; indican una relaci&#243;n estrecha entre los niveles de adiponectina y el riesgo en el desarrollo de la EHNA en dicha poblaci&#243;n&#46;</p><p class="elsevierStylePara elsevierViewall">La EHNA se ha relacionado con la obesidad en varios estudios pedi&#225;tricos<a class="elsevierStyleCrossRefs" href="#bib20"><span class="elsevierStyleSup">20&#44;22&#8211;26</span></a>&#46; La frecuencia de dicha enfermedad en nuestra cohorte &#40;18&#37;&#41; es menor que en otros estudios<a class="elsevierStyleCrossRefs" href="#bib5"><span class="elsevierStyleSup">5&#44;7&#44;9&#44;27&#8211;30</span></a>&#44; probablemente porque nuestros pacientes no alcanzaban el grado de obesidad de otras poblaciones y por la variabilidad en los criterios diagn&#243;sticos utilizados&#46; Aunque el <span class="elsevierStyleItalic">gold standard</span> para el diagn&#243;stico sigue siendo la biopsia hep&#225;tica&#44; no se realiz&#243; en nuestro estudio por ser invasiva y de mayor coste&#46; Actualmente se est&#225;n desarrollando otras pruebas no invasivas&#44; como el test del aliento con metacolina&#44; pero se precisan estudios en la poblaci&#243;n infantil para establecer su indicaci&#243;n y seguridad&#46; En nuestra muestra realizamos el diagn&#243;stico ecogr&#225;fico por su f&#225;cil acceso&#44; inocuidad y excelente sensibilidad para el diagn&#243;stico de esteatosis<a class="elsevierStyleCrossRefs" href="#bib31"><span class="elsevierStyleSup">31&#44;32</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">En los ni&#241;os obesos la elevaci&#243;n de ALT se ha utilizado como indicador del dep&#243;sito de grasa hep&#225;tica<a class="elsevierStyleCrossRef" href="#bib33"><span class="elsevierStyleSup">33</span></a>&#46; La elevaci&#243;n de ALT puede ser el &#250;nico hallazgo bioqu&#237;mico en pacientes con EHNA<a class="elsevierStyleCrossRef" href="#bib34"><span class="elsevierStyleSup">34</span></a> aunque suele ocurrir en casos de mayor ac&#250;mulo graso y no de esteatosis leve&#46; En nuestra poblaci&#243;n estudiada existi&#243; hiperaminotransferasemia en el 8&#37;&#59; Strauss et al<a class="elsevierStyleCrossRef" href="#bib35"><span class="elsevierStyleSup">35</span></a> han encontrado una frecuencia similar en 2&#46;450 adolescentes con sobrepeso y obesidad&#46; En algunos estudios la frecuencia de hiperaminotransferasemia alcanza el 25&#37;<a class="elsevierStyleCrossRefs" href="#bib9"><span class="elsevierStyleSup">9&#44;5</span></a>&#46; La hiperaminotransferasemia fue significativamente mayor en el grupo de EHNA que en el grupo con ecograf&#237;a normal &#40;p&#60;0&#44;005&#41;&#44; pero s&#243;lo alcanz&#243; el 21&#37;&#44; por tanto&#44; la determinaci&#243;n aislada de aminotransferasas no es indicador suficiente de EHNA y es recomendable realizar ecograf&#237;a en pacientes de riesgo para su diagn&#243;stico&#46;</p><p class="elsevierStylePara elsevierViewall">Al contrario de otras publicaciones<a class="elsevierStyleCrossRefs" href="#bib5"><span class="elsevierStyleSup">5&#44;6&#44;35</span></a>&#44; no encontramos diferencias significativas en el da&#241;o hep&#225;tico seg&#250;n el sexo&#46;</p><p class="elsevierStylePara elsevierViewall">Numerosos factores se han asociado al desarrollo de la EHNA<a class="elsevierStyleCrossRef" href="#bib3"><span class="elsevierStyleSup">3</span></a>&#46; En nuestra experiencia&#44; la prevalencia de EHNA se incrementa con la edad y con el grado de obesidad&#44; sobre todo cuando asocian otros datos de SM&#44; como la RI&#59; otros autores<a class="elsevierStyleCrossRef" href="#bib11"><span class="elsevierStyleSup">11</span></a> tambi&#233;n han evidenciado este hecho&#46; La frecuencia de EHNA fue del 28&#37; en los pacientes que cumpl&#237;an criterios de SM frente al 15&#37; en aqu&#233;llos sin criterios del SM &#40;p&#60;0&#44;005&#41;&#46; Hay que resaltar que estos datos se deben interpretar con cautela&#44; dado que las distintas definiciones del SM pueden ser la causa de las diferencias en los resultados con respecto a otros trabajos&#46;</p><p class="elsevierStylePara elsevierViewall">La RI parece desempe&#241;ar un papel fundamental en el desarrollo de la esteatosis&#44; tanto en los adultos<a class="elsevierStyleCrossRefs" href="#bib11"><span class="elsevierStyleSup">11&#44;36&#44;37</span></a> como en la poblaci&#243;n pedi&#225;trica<a class="elsevierStyleCrossRefs" href="#bib6"><span class="elsevierStyleSup">6&#44;26&#44;38&#8211;40</span></a>&#46; La teor&#237;a patog&#233;nica m&#225;s aceptada es la del doble impacto<a class="elsevierStyleCrossRef" href="#bib41"><span class="elsevierStyleSup">41</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig1">fig&#46; 1</a>&#41;&#46; Estudios recientes indican que el hiperinsulinismo produce alteraciones en las v&#237;as de captaci&#243;n&#44; s&#237;ntesis&#44; degradaci&#243;n y secreci&#243;n de &#225;cidos grasos libres en forma de TG&#46; Esto conlleva una mayor susceptibilidad hep&#225;tica a los cambios inflamatorios y al da&#241;o tisular<a class="elsevierStyleCrossRef" href="#bib42"><span class="elsevierStyleSup">42</span></a>&#46; El mayor estr&#233;s oxidativo resultante de la disfunci&#243;n mitocondrial y de las citoquinas proinflamatorias participa en la progresi&#243;n de la simple esteatosis a la esteatohepatitis y cirrosis&#46; Sin embargo&#44; adem&#225;s de la obesidad y de la RI se requieren otros factores ambientales o gen&#233;ticos para la progresi&#243;n a esteatohepatitis&#46;</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><p class="elsevierStylePara elsevierViewall">En los &#250;ltimos a&#241;os se ha destacado el papel de la adiponectina como regulador del metabolismo lip&#237;dico y de la acci&#243;n de la insulina<a class="elsevierStyleCrossRef" href="#bib43"><span class="elsevierStyleSup">43</span></a>&#44; incluso en estudios pedi&#225;tricos<a class="elsevierStyleCrossRef" href="#bib44"><span class="elsevierStyleSup">44</span></a>&#46; La adiponectina recientemente ha sido considerada como un importante regulador del da&#241;o tisular en la EHNA<a class="elsevierStyleCrossRefs" href="#bib11"><span class="elsevierStyleSup">11&#44;45</span></a>&#46; En nuestra serie&#44; los niveles de adiponectina se correlacionaron negativamente con HOMA&#44; AST&#44; ALT y &#225;cido &#250;rico&#44; y de forma positiva con los niveles de cHDL&#46; Estudios previos han asociado niveles bajos de adiponectina con el desarrollo de los componentes del SM&#44; tanto en adultos<a class="elsevierStyleCrossRef" href="#bib46"><span class="elsevierStyleSup">46</span></a> como en ni&#241;os y en adolescentes<a class="elsevierStyleCrossRefs" href="#bib13"><span class="elsevierStyleSup">13&#44;44</span></a>&#46; Nuestros datos&#44; coincidentes con los de otros estudios<a class="elsevierStyleCrossRef" href="#bib27"><span class="elsevierStyleSup">27</span></a>&#44; indican un papel protector de la adiponectina en el desarrollo de la EHNA en los ni&#241;os obesos&#46;</p><p class="elsevierStylePara elsevierViewall">Los &#225;cidos grasos libres inducen directamente la expresi&#243;n de factor de necrosis tumoral alfa &#40;TNF-&#945;&#41; en el hepatocito y promueven la esteatosis y el da&#241;o hep&#225;tico<a class="elsevierStyleCrossRef" href="#bib47"><span class="elsevierStyleSup">47</span></a>&#46; Recientemente se ha identificado a la apoptosis del hepatocito como componente clave en la progresi&#243;n de la esteatohepatitis&#46; La adiponectina podr&#237;a prevenir el da&#241;o hep&#225;tico por la modulaci&#243;n de TNF-&#945;<a class="elsevierStyleCrossRefs" href="#bib48"><span class="elsevierStyleSup">48&#44;49</span></a>&#46;</p><p class="elsevierStylePara elsevierViewall">En conclusi&#243;n&#44; la obesidad y la RI son factores de riesgo para el desarrollo de la EHNA en ni&#241;os y adolescentes&#46; Los niveles disminuidos de adiponectina s&#233;rica est&#225;n fuertemente asociados con la esteatosis hep&#225;tica en los ni&#241;os con obesidad&#46;</p></span></span>"
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          "titulo" => array:5 [
            0 => "Resumen"
            1 => "Introducci&#243;n"
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          "titulo" => array:5 [
            0 => "Abstract"
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        5 => array:2 [
          "titulo" => "Pacientes y m&#233;todos"
          "secciones" => array:4 [
            0 => array:1 [
              "titulo" => "Valoraci&#243;n cl&#237;nica"
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            1 => array:1 [
              "titulo" => "Diagn&#243;stico de esteatosis"
            ]
            2 => array:1 [
              "titulo" => "Estudio metab&#243;lico"
            ]
            3 => array:1 [
              "titulo" => "M&#233;todos estad&#237;sticos"
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          ]
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        6 => array:2 [
          "titulo" => "Resultados"
          "secciones" => array:2 [
            0 => array:1 [
              "titulo" => "Caracter&#237;sticas de los pacientes con esteatosis hep&#225;tica no alcoh&#243;lica"
            ]
            1 => array:1 [
              "titulo" => "Correlaciones y an&#225;lisis de regresi&#243;n log&#237;stica"
            ]
          ]
        ]
        7 => array:1 [
          "titulo" => "Discusi&#243;n"
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          "titulo" => "Bibliograf&#237;a"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2009-06-17"
    "fechaAceptado" => "2009-08-03"
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          "clase" => "keyword"
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          "palabras" => array:5 [
            0 => "Esteatosis hep&#225;tica no alcoh&#243;lica"
            1 => "Obesidad"
            2 => "Resistencia a la insulina"
            3 => "Adiponectina"
            4 => "S&#237;ndrome metab&#243;lico"
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      ]
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec92612"
          "palabras" => array:5 [
            0 => "Fatty liver disease"
            1 => "Obesity"
            2 => "Insulin resistance"
            3 => "Adiponectin"
            4 => "Metabolic syndrome"
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    "resumen" => array:2 [
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introducci&#243;n</span><p class="elsevierStyleSimplePara elsevierViewall">Estudiar la prevalencia de esteatosis hep&#225;tica no alcoh&#243;lica &#40;EHNA&#41; en una poblaci&#243;n pedi&#225;trica obesa y su relaci&#243;n con par&#225;metros clinicoanal&#237;ticos de resistencia a la insulina &#40;RI&#41; y con niveles de adiponectina&#46;</p> <span class="elsevierStyleSectionTitle">Pacientes y m&#233;todos</span><p class="elsevierStyleSimplePara elsevierViewall">Se estudi&#243; a 290 ni&#241;os &#40;4&#8211;18 a&#241;os&#41; con obesidad&#46; Se analiz&#243; el &#237;ndice de masa corporal &#40;IMC&#41; y la desviaci&#243;n est&#225;ndar &#40;DE&#41;&#44; la acantosis nigricans&#44; la presi&#243;n arterial&#44; el perfil lip&#237;dico&#44; las aminotransferasas y la adiponectina&#46; Se realiz&#243; un test de sobrecarga oral de glucosa y se defini&#243; la RI mediante el <span class="elsevierStyleItalic">homeostasis model assessment</span> &#40;HOMA&#41; y la esteatosis hep&#225;tica por ecograf&#237;a&#46; Definimos el s&#237;ndrome metab&#243;lico &#40;SM&#41; como la presencia de 3 o m&#225;s de los siguientes criterios&#58; obesidad&#44; hipertensi&#243;n&#44; hipertrigliceridemia&#44; colesterol ligado a lipoprote&#237;nas de alta densidad &#40;cHDL&#41; bajo y alteraci&#243;n hidrocarbonada&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">Cincuenta y dos &#40;18&#37;&#41; pacientes presentaban EHNA en la ecograf&#237;a&#44; 22 &#40;8&#37;&#41; pacientes ten&#237;an elevaci&#243;n de alanin-aminotransferasa &#40;ALT&#41; &#40;&#8805;40<span class="elsevierStyleHsp" style=""></span>U&#47;l&#41;&#46; Los pacientes con EHNA fueron significativamente mayores &#40;12&#44;2&#177;2&#44;4 frente a 11&#44;1&#177;2&#44;9 a&#241;os&#41;&#44; m&#225;s obesos &#40;IMC&#177;DE&#58; 4&#44;5&#177;1&#44;5 frente a 3&#44;8&#177;1&#44;3&#41;&#44; y presentaron niveles m&#225;s elevados de HOMA &#40;3&#44;7&#177;1&#44;5 frente a 2&#44;4&#177;1&#44;4&#41; que los pacientes con ecograf&#237;a normal&#46; No se encontr&#243; diferencia significativa en sexo&#44; raza y estadio puberal&#46; La prevalencia del SM y la acantosis nigricans fue significativamente mayor en los ni&#241;os con EHNA&#46; Encontramos una correlaci&#243;n inversa entre los niveles s&#233;ricos de adiponectina y edad&#44; HOMA&#44; ALT y &#225;cido &#250;rico&#44; y encontramos una correlaci&#243;n directa con cHDL&#46; En el an&#225;lisis de regresi&#243;n m&#250;ltiple&#44; las variables que se asociaron de forma independiente con la EHNA fueron IMC&#177;DE&#44; HOMA y adiponectina &#40;<span class="elsevierStyleItalic">odds ratio</span>&#58; 1&#44;4 &#91;1&#44;1-1&#44;9&#93;&#59; 1&#44;3 &#91;1&#44;1-1&#44;6&#93; y 0&#44;9 &#91;0&#44;8-0&#44;9&#93;&#44; respectivamente&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">La obesidad y la RI son factores de riesgo de la EHNA en ni&#241;os y adolescentes&#46; Los niveles bajos de adiponectina est&#225;n fuertemente asociados al desarrollo de EHNA en dichos pacientes&#46;</p>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introduction</span><p class="elsevierStyleSimplePara elsevierViewall">To study the clinical and laboratory relationships of fatty liver disease in a group of obese children and to investigate whether circulating adiponectin is related to fatty liver disease&#46;</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p class="elsevierStyleSimplePara elsevierViewall">Two hundred-ninety obese patients &#40;age 4&#8211;18 years&#41; were studied&#46; Baseline body mass index-standard deviation score &#40;BMI-SDS&#41;&#44; acanthosis nigricans&#44; blood pressure&#44; plasma lipids&#44; uric acid&#44; alanine aminotransferase &#40;ALT&#41; and adiponectin were assessed&#44; and a standard oral glucose tolerance test was performed&#46; Insulin resistance &#40;RI&#41; was estimated by the homeostasis model assessment &#40;HOMA&#41; and liver steatosis was assessed by ultrasound &#40;US&#41;&#46; Children were classified as having metabolic syndrome if they met three or more of the following criteria&#58; obesity&#44; hypertension&#44; hypertriglyceridemia&#44; low HDL-cholesterol and impaired glucose metabolism&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">Fifty-two subjects &#40;18&#37;&#41; had fatty liver by US and 22 &#40;8&#37;&#41; had elevated ALT levels &#40;&#8805;40<span class="elsevierStyleHsp" style=""></span>U&#47;L&#41;&#46; Subjects with steatosis were significantly older &#40;12&#46;2&#177;2&#46;4 frente a 11&#46;1&#177;2&#46;9<span class="elsevierStyleHsp" style=""></span>yr&#41;&#44; heavier &#40;BMI-SDS&#58; 4&#46;5&#177;1&#46;5 frente a 3&#46;8&#177;1&#46;3&#41;&#44; and more RI &#40;HOMA&#58; 3&#46;7&#177;1&#46;5 frente a 2&#46;4&#177;1&#46;4&#41;&#44; but were comparable in gender&#44; pubertal status and racial distribution to those with normal US&#46; The prevalence of metabolic syndrome and acanthosis nigricans were also higher in the steatosis frente a the normal US group&#46; Serum adiponectin concentration was inversely correlated with age&#44; HOMA&#44; ALT and uric acid and directly correlated with HDL-cholesterol&#46; In a multiple logistic regression analysis&#44; BMI-SDS&#44; HOMA and serum adiponectin&#44; but not age&#44; uric acid or triglycerides&#44; were the covariates independently associated with the presence of steatosis &#40;odds ratio 1&#46;4 &#91;1&#46;1-1&#46;9&#93;&#59; 1&#46;3 &#91;1&#46;1-1&#46;6&#93; and 0&#46;9 &#91;0&#46;8-0&#46;9&#93;&#44; respectively&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStyleSimplePara elsevierViewall">Obesity and RI are risk factors for liver steatosis in children and adolescents&#46; Decreased serum adiponectin is closely and independently associated with steatosis&#46;</p>"
      ]
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                  \t\t\t\t">cHDL &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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ISSN: 16954033
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