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array:25 [ "pii" => "S2341287922001181" "issn" => "23412879" "doi" => "10.1016/j.anpede.2022.04.009" "estado" => "S300" "fechaPublicacion" => "2022-05-01" "aid" => "3262" "copyright" => "Asociación Española de Pediatría" "copyrightAnyo" => "2022" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2022;96:448.e1-448.e11" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:20 [ "pii" => "S1695403322000601" "issn" => "16954033" "doi" => "10.1016/j.anpedi.2022.04.002" "estado" => "S300" "fechaPublicacion" => "2022-05-01" "aid" => "3262" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2022;96:448.e1-448.e11" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Asociación Española de Pediatría</span>" "titulo" => "Actuación diagnóstica ante hipertransaminasemia en pediatría: documento de consenso de Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP), Asociación Española de Pediatría de Atención Primaria (AEPap) y Sociedad Española de Pediatría de Atención Primaria (SEPEAP)" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "448.e1" "paginaFinal" => "448.e11" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Diagnostic action against hypertransaminasemia in paediatrics: Consensus document of Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP), Asociación Española de Pediatría de Atención Primaria (AEPap) and Sociedad Española de Pediatría de Atención Primaria (SEPEAP)" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1621 "Ancho" => 3000 "Tamanyo" => 607812 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Algoritmo diagnóstico. Ac. Anti-VHC: anticuerpos antivirus de hepatitis C; ALT: alanina aminotransferasa; AMA: anticuerpos antimitocondriales; ANA: anticuerpos antinucleares; Anti-LC-1: anticuerpos anti citosol hepático tipo 1; Anti-LKM-1: anticuerpos microsomales de hígado y riñon tipo 1; Anti-SLA: anticuerpos contra los antígenos hepáticos solubles; AST: aspartato aminotransferasa; ATGt: anticuerpos antitransglutaminasa; CMV: citomegalovirus; CPK: creatina fosfoquinasa; GGT: gammaglutamil transpeptidasa; HBsAg: antígeno de superficie del virus de hepatitis B; Ig: inmunoglobulinas; LAL: lipasa ácida lisosomal; p-ANCA: anticuerpos anticitoplasma de neutrófilos de patrón perinuclear; VEB: virus de Epstein-Barr; TORCH: toxoplasma, rubeola, CMV, herpes simple y VIH; SMA: anticuerpos antimúsculo liso; Test de CDT: test de transferrina deficiente en carbohidrato; TSH: hormona estimulante de la tiroides; T4 libre: tiroxina libre; VIH: virus de inmunodeficiencia humana.</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span>Correlacionar con valores normales según edad.</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">b</span>Valorar hacer en el segundo nivel en el lactante.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ignacio Ros Arnal, Joaquín Reyes Andrade, María Mercadal Hally, Luis Carlos Blesa Baviera, Diana García Tirado, Samuel Héctor Campuzano Martín, Estela de la Calle Navarro, Ana María Vegas Álvarez" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Ignacio" "apellidos" => "Ros Arnal" ] 1 => array:2 [ "nombre" => "Joaquín" "apellidos" => "Reyes Andrade" ] 2 => array:2 [ "nombre" => "María" "apellidos" => "Mercadal Hally" ] 3 => array:2 [ "nombre" => "Luis Carlos" "apellidos" => "Blesa Baviera" ] 4 => array:2 [ "nombre" => "Diana" "apellidos" => "García Tirado" ] 5 => array:2 [ "nombre" => "Samuel Héctor" "apellidos" => "Campuzano Martín" ] 6 => array:2 [ "nombre" => "Estela" "apellidos" => "de la Calle Navarro" ] 7 => array:2 [ "nombre" => "Ana María" "apellidos" => "Vegas Álvarez" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2341287922001181" "doi" => "10.1016/j.anpede.2022.04.009" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287922001181?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403322000601?idApp=UINPBA00005H" "url" => "/16954033/0000009600000005/v1_202205150557/S1695403322000601/v1_202205150557/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2341287922000795" "issn" => "23412879" "doi" => "10.1016/j.anpede.2021.01.011" "estado" => "S300" "fechaPublicacion" => "2022-05-01" "aid" => "3083" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "An Pediatr (Barc). 2022;96:449-51" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "The Paediatric Palliative Care Unit has been transformed into Home Care Unit during the COVID-19 pandemic. Is this transformation here to stay?" "subtitulo" => "Transformación de una Unidad de Cuidados Paliativos Pediátricos en Unidad de Atencion Domiciliaria a raíz de la pandemia COVID-19. ¿Llegó para quedarse?" 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=> array:9 [ "pii" => "S1695403321002095" "doi" => "10.1016/j.anpedi.2021.05.021" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403321002095?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287922000849?idApp=UINPBA00005H" "url" => "/23412879/0000009600000005/v3_202207070640/S2341287922000849/v3_202207070640/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Spanish Association of Paediatrics</span>" "titulo" => "Diagnostic action against hypertransaminasemia in paediatrics: Consensus document of Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP), Asociación Española de Pediatría de Atención Primaria (AEPap) and Sociedad Española de Pediatría de Atención Primaria (SEPEAP)" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "448.e1" "paginaFinal" => "448.e11" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Ignacio Ros Arnal, Joaquín Reyes Andrade, María Mercadal Hally, Luis Carlos Blesa Baviera, Diana García Tirado, Samuel Héctor Campuzano Martín, Estela de la Calle Navarro, Ana María Vegas Álvarez" "autores" => array:8 [ 0 => array:4 [ "nombre" => "Ignacio" "apellidos" => "Ros Arnal" "email" => array:1 [ 0 => "iros@salud.aragon.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Joaquín" "apellidos" => "Reyes Andrade" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 2 => array:3 [ "nombre" => "María" "apellidos" => "Mercadal Hally" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 3 => array:3 [ "nombre" => "Luis Carlos" "apellidos" => "Blesa Baviera" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 4 => array:3 [ "nombre" => "Diana" "apellidos" => "García Tirado" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] ] ] 5 => array:3 [ "nombre" => "Samuel Héctor" "apellidos" => "Campuzano Martín" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">i</span>" "identificador" => "aff0045" ] ] ] 6 => array:3 [ "nombre" => "Estela" "apellidos" => "de la Calle Navarro" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">j</span>" "identificador" => "aff0050" ] ] ] 7 => array:3 [ "nombre" => "Ana María" "apellidos" => "Vegas Álvarez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">k</span>" "identificador" => "aff0055" ] ] ] ] "afiliaciones" => array:11 [ 0 => array:3 [ "entidad" => "Unidad de Gastroenterología, Hepatología y Nutrición Pediátrica, Hospital Universitario Miguel Servet, Zaragoza, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "En representación de la Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica, Grupo de trabajo Hepatología de la SEGHNP" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Gastroenterología, Hepatología y Nutrición Pediátrica, Instituto Hispalense de Pediatría, Sevilla, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "En representación de la Sociedad Española de Pediatría de Atención Primaria, Grupo de trabajo Gastroenterología y Nutrición SEPEAP" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Unidad de Hepatología y Trasplante Hepático, Hospital Universitario Vall d’Hebron, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Centro de Salud Serrería 2, Valencia, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "En representación de la Asociación Española de Pediatría de Atención Primaria, Grupo de trabajo Gastroenterología y Nutrición AEPAP" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Unidad de Gastroenterología, Hepatología y Nutrición Pediátrica, Corporación Parc Taulí Hospital Universitario, Sabadell, Barcelona, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Centro de Salud Casco Vello, Vigo, Pontevedra, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Unidad de Gastroenterología, Hepatología y Nutrición Pediátrica, Hospital Universitario Donostia, Gipuzkoa, Donostia-San Sebastián, Spain" "etiqueta" => "j" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Unidad de Gastroenterología, Hepatología y Nutrición Pediátrica, Hospital Universitario Río Hortega, Valladolid, Spain" "etiqueta" => "k" "identificador" => "aff0055" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Actuación diagnóstica ante hipertransaminasemia en pediatría: documento de consenso de Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP), Asociación Española de Pediatría de Atención Primaria (AEPap) y Sociedad Española de Pediatría de Atención Primaria (SEPEAP)" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1754 "Ancho" => 3008 "Tamanyo" => 581993 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">ALT, alanine aminotransferase; AMA, antimitochondrial antibodies; ANA, antinuclear antibodies; anti-LC-1, anti-liver cytosol type 1 antibodies; anti-LKM-1, liver-kidney microsomal type 1 antibodies; anti-SLA, anti-soluble liver antigen antibodies; anti-tTG, anti-tissue transglutaminase antibodies; ASMA, anti-smooth muscle antibody; AST, aspartate aminotransferase; CDT, carbohydrate deficient transferrin; CMV, cytomegalovirus; CPK, creatine phosphokinase; EBV, Epstein-Barr virus; fT<span class="elsevierStyleInf">4</span>, free thyroxine; GGT, gamma-glutamyl transferase; HIV, human immunodeficiency virus; HTRA, hypertransaminasaemia; Ig, immunoglobulin; LAL, lysosomal acid lipase; p-ANCA, perinuclear anti-neutrophil cytoplasmic antibodies; TORCH, toxoplasmosis, rubella, CMV, herpes simplex and HIV; TSH, thyroid-stimulating hormone.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">1</span>Compare to normal range for age. <span class="elsevierStyleSup">2</span>Consider inclusion in second-tier testing in infants.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Transaminases are intracellular enzymes found in hepatocytes and other cells. The most important ones are aspartate aminotransferase (AST), also known as glutamic oxaloacetic transaminase (GOT), which is less specific due to its ubiquity, and alanine aminotransferase (ALT), also known as glutamic-pyruvic transaminase (GPT), which is more specific to the liver.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Hypertransaminasaemia can be detected in the evaluation of liver disease or can be an incidental finding in blood tests performed for other reasons.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Mild elevations of transaminase levels frequently lead to performance of incomplete evaluations.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Persistent hypertransaminasaemia calls for performance of a comprehensive evaluation to determine the specific aetiology.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In developing this document, the objective was to establish the steps to take from the initial detection of hypertransaminasaemia in a blood test to the completion of the diagnostic process through a consensus process involving paediatricians specialised in primary care and in gastroenterology, hepatology and nutrition. It includes the sequence of tests to include in the initial diagnostic evaluation (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). This document does not address the evaluation of patients with isolated cholestasis or cholestasis associated with hypertransaminasaemia, the diagnosis process for each specific disease once it is suspected, the treatment of the different causes of hypertransaminasaemia or the management of abnormal liver function or acute liver failure.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">A working group (WG) was established that comprised 8 members that represented the Sociedad Española de Gastroenterología, Hepatología y Nutrición (Spanish Society of Gastroenterology, Hepatology and Nutrition, SEGHNP), Asociación Española de Pediatría de Atención Primaria (Spanish Association of Primary Care Paediatrics, AEPap) and Sociedad Española de Pediatría Extrahospitalaria y Atención Primaria (Spanish Society of Outpatient and Primary Care Paediatrics, SEPEAP). The group broached 15 clinical questions regarding what, when and how to do from the moment of the initial detection of hypertransaminasaemia to the completion of its evaluation in both the primary care and hospital settings.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The WG conducted a systematic literature search in PubMed for articles published between January 2010 and January 2020 with the search terms “liver test” “liver disease” in patients aged 0–18 years, articles published at any time with the search terms “aminotransferase” “hypertransaminasemia” in ages 0–18 years, and articles published at any time with the terms “genetic liver disease” “histology liver disease”. We conducted a second search for articles published between January 2020 and September 2020 with the same approach. We used the Zotero 5.0 open-source citation management system. The search yielded 248 articles in English or Spanish, for which the group obtained the full text. Of this total, 113 were considered relevant to the consensus documents and selected because they were helpful in addressing the questions posed for development of the guideline.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Development of the document</span><p id="par0030" class="elsevierStylePara elsevierViewall">The WG answered each of the clinical questions (each of which was addressed by 2 members) based on the available evidence and with the aim of establishing a structured approach to the diagnostic evaluation of hypertransaminasaemia based on the consensus of the group. The group did not perform a systematic review or meta-analysis of the contemplated diagnostic tests. The full document was revised 5 times by every member of the group, with a virtual meeting conducted after each of the revisions through Gotomeeting (access granted by the SEGHNP and Zoom). All the recommendations presented in this document were reached by consensus and approved by the members of the group (informal consensus). The full consensus document can be consulted in the webpage of any of the participating professional associations.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Definition of hypertransaminasaemia and its main causes</span><p id="par0035" class="elsevierStylePara elsevierViewall">Given the absence of a widely accepted abbreviation for hypertransaminasaemia, it was agreed that HTRA would be used for this document.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Hypertransaminasaemia (HTRA) is defined as elevation of serum levels of transaminases past the upper limit of normal (ULN)<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> established in a healthy and representative sample of the population of interest. These levels exhibit substantial physiological variability within and between individuals. Their elevation reflects the lysis or increased permeability of the membrane of cells that contain them.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5,6</span></a> In the paediatric population, through extrapolation of the threshold traditionally used in adults, HTRA is usually defined as levels greater than 40 U/L, but different authors have published thresholds that may differ to some extent and with some variations<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10–19</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). There is considerable overlap between healthy and unhealthy populations, which hinders the establishment of cut-off points with an adequate sensitivity and specificity.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In addition, some authors note that in adolescence normal levels are too high and therefore this threshold loses sensitivity when used for initial screening of fatty liver or chronic hepatitis caused by hepatitis C virus (HCV), so that a lower ULN should be applied in these circumstances.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">There is no reliable correlation between the degree of transaminase elevation and its severity or prognosis. Nevertheless, very high levels are usually associated with extensive injury, which has led to the arbitrary categorization of HTRA into 3 degrees: mild (< 5 × ULN), moderate (=5−10 × ULN) and very high (>10 × ULN). On the other hand, based on experience and long-lasting consensus, HTRA is considered chronic if it lasts longer than 6 months.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The detection of HTRA, transient as it may be in some cases, should be considered a potential marker of disease and be interpreted in the clinical context of the patient. Therefore, it should always be confirmed and monitored until the levels normalize or the cause is identified.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,20</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In the paediatric population, there are multiple possible causes of HTRA, hepatic and extrahepatic, so its differential diagnosis is broad (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,20</span></a> Isolated or disproportionate elevation of AST usually has an extrahepatic aetiology: difficult blood draw, haemolysis, rhabdomyolysis, etc. It may also be due to the formation of macro-AST.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">The most frequent cause of acute mild-to-moderate elevation that normalises within 6 months is viral respiratory or gastrointestinal infection in infants, and infection by cytomegalovirus or Epstein-Barr virus in older children.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> A pharmacological or toxic aetiology should also be considered. The drugs most frequently involved in HTRA are antibiotic and antiepileptic agents, but there is a broad range of pharmaceuticals that can cause it. Other possible causative substances are illicit drugs (such as alcohol or cocaine), solvents, pesticides or natural remedies (such as St John’s wort, ephedra or gentian).</p><p id="par0065" class="elsevierStylePara elsevierViewall">The main cause of persistent HTRA of hepatic aetiology in older children and adolescents is non-alcoholic fatty liver disease (NAFLD) associated with overweight or obesity.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Recommendations:</span><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1</span><p id="par0075" class="elsevierStylePara elsevierViewall">We recommend the following ALT cut-off points for the healthy European paediatric population, stratified by age and sex: age less than 18 months, >60 U/L in boys and > 55 U/L in girls, and age greater than 18 months, >40 U/L in boys and >35 U/L in girls. We propose the following ALT thresholds for initial screening of hepatic steatosis or chronic hepatitis caused by HCV in adolescents: 26 U/L in male adolescents and 22 U/L in female adolescents.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2</span><p id="par0080" class="elsevierStylePara elsevierViewall">We recommend the following AST cut-off points, stratified by age: >65 U/L up to age 12 months, >55 U/L for ages 1−4 years, >50 U/L for ages 5−8 years and >40 U/L for ages 9−18 years.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3</span><p id="par0085" class="elsevierStylePara elsevierViewall">The aetiology of HTRA may be hepatic and/or extrahepatic. We recommend a stepwise diagnostic evaluation based on age and the most frequent hepatic and extrahepatic causes.</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Initial assessment following detection of HTRA</span><p id="par0090" class="elsevierStylePara elsevierViewall">The history-taking and physical examination are the first tools to use in the diagnostic evaluation of HTRA.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,21,22</span></a> Their findings sometimes provide information on the aetiology or severity of the disease (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,20–22</span></a> The history taking should include the personal and family medical history, use of pharmaceuticals or drugs, performance of vigorous activity, results of previous blood tests and systemic symptoms.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20,22</span></a> The physical examination will include a thorough review of systems, as there is a broad range of extrahepatic conditions that may manifest with HTRA<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">When it comes to diagnostic tests, the first step is to confirm the presence of HTRA.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The comprehensive liver panel includes markers of hepatocellular liver injury, cholestasis and hepatic synthesis (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,20</span></a> An abdominal ultrasound examination may be useful to assess liver and bile duct morphology, rule out tumours and, in adolescents with excess weight, indicate the possibility of fatty liver. Serological tests for viral detection will be performed based on the history of the patient.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Many episodes of HTRA are self-limited, but there is variability in the time elapsed to resolution (weeks or months).<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,22</span></a> There is no evidence to establish how much time should elapse before retesting. Traditionally, an interval of 2–4 weeks is recommended in the case of HTRA in the absence of any other warning signs.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,20–22</span></a> This interval should be individualised in the context of transient HTRA (associated with consumption of hepatotoxic pharmaceuticals or herbal remedies, infection, vigorous physical activity) likely to take longer to resolve.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,20</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">If additional warning signs are present (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>), the patient should be referred to a hospital on an urgent basis. It is particularly important to rule out acute liver failure (inability of the liver to perform its biosynthesis, regulation and detoxification functions).<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> If there are signs of encephalopathy, impaired renal function requiring dialysis, haemodynamic instability or respiratory failure, the patient should be treated in an intensive care unit, and, in the presence of encephalopathy, hypoglycaemia, renal failure or an international normalised ratio (INR) greater than 2.5,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> transfer to a hospital that can perform liver transplantation should be contemplated.</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Recommendations:</span><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4</span><p id="par0115" class="elsevierStylePara elsevierViewall">Performance of a thorough anamnesis and physical examination, which in some cases may reveal information that can guide the diagnosis and the assessment of severity.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">5</span><p id="par0120" class="elsevierStylePara elsevierViewall">We recommend considering detection of HTRA, even if transient, as a potential marker of disease to be evaluated taking into account the clinical context of the patient and with performance of a comprehensive liver panel for initial screening (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">6</span><p id="par0125" class="elsevierStylePara elsevierViewall">Hypertransaminasaemia should always be confirmed. In the absence of other warning signs, we suggest performance of a confirmatory test 2–4 weeks after the initial detection. If a specific temporary cause is suspected, the follow-up test can be delayed to up to 8 weeks if resolution of the transient process is expected within that timeframe. If there are clinical or laboratory features suggestive of severity, the follow-up test will be performed on an urgent basis.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">7</span><p id="par0130" class="elsevierStylePara elsevierViewall">We recommend screening for the most frequent or relevant causes of HTRA by means of blood tests and an ultrasound examination (first-tier tests) following confirmation of HTRA or at the time the confirmatory test is performed (<a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>).</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">8</span><p id="par0135" class="elsevierStylePara elsevierViewall">We recommend assessment of every warning sign that would warrant urgent referral to a hospital (severe liver disease, infantile cholestasis or suspected tumour) in ever follow-up visit. Children with cholestasis (excluding infants) should be referred for assessment on a priority basis.</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">9</span><p id="par0140" class="elsevierStylePara elsevierViewall">If acute liver failure is suspected, we recommend considering admission to the intensive care unit and transfer to a hospital with an active paediatric liver transplantation programme.</p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Evaluation of confirmed HTRA of unknown aetiology</span><p id="par0145" class="elsevierStylePara elsevierViewall">In the absence of signs or symptoms that could guide the diagnostic evaluation, it is important to conduct an organised and systematic evaluation, with inclusion of specific diseases in the differential diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25–28</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">It must be taken into account that NAFLD is currently the most frequent cause of HTRA in children aged more than 10 years. Obesity and/or liver hyperechogenicity in the initial ultrasound scan suggest, but do not confirm, the presence of NAFLD and require evaluation according to the established protocol.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Doppler ultrasonography allows diagnosis of diseases that could manifest with abnormal hepatic vascularization<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> and is useful for screening of portal hypertension.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">The assessment of other diseases that are less frequent or that do not chiefly manifest with isolated HTRA should be personalised based on the age, clinical context, existing symptoms and associated clinical features (<a class="elsevierStyleCrossRef" href="#tbl0035">Table 7</a>). <a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a> details the first, second and third-tier diagnostic tests.</p><elsevierMultimedia ident="tbl0035"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Recommendations</span>:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">10</span><p id="par0170" class="elsevierStylePara elsevierViewall">After performance of first-tier tests, if HTRA persists and its aetiology is unknown, we propose performance of laboratory tests for assessment of autoimmune hepatitis, Wilson disease, alpha-1-antitrypsin deficiency, lysosomal acid lipase deficiency, bile acid synthesis disorders, congenital disorders of glycosylation and urea cycle defects and repetition of serology tests for hepatitis B virus (HBV) and HCV.</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">11</span><p id="par0175" class="elsevierStylePara elsevierViewall">In children with sonographic features compatible with fatty liver and/or with excess weight, we recommend following the specific protocol for these diseases to complete the evaluation of HTRA.</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">12</span><p id="par0180" class="elsevierStylePara elsevierViewall">In the case of persistent HTRA, we propose completing the imaging assessment with a liver Doppler ultrasound scan to evaluate hepatic venous and arterial vascularization.</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">13</span><p id="par0185" class="elsevierStylePara elsevierViewall">In the presence of findings compatible with metabolic disease, and depending on the type of newborn screening performed, the clinical presentation, the age of the patient and the laboratory findings, we recommend performance of a targeted metabolomic analysis with participation of a specialist in metabolic disorders. In the cases of suspected cystic fibrosis, we recommend the sweat chloride test and, depending on the results, genetic testing to screen for variants in the <span class="elsevierStyleItalic">CFTR</span> gene.</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">14</span><p id="par0190" class="elsevierStylePara elsevierViewall">In the case of children with risk factors for HBV or HCV (immunocompromised, from high-prevalence areas, of parents who are carriers of HBV or HCV), even if the hepatitis B surface antigen or HCV antibody test turn out negative, we recommend performance of PCR tests for detection of HBV DNA and HCV RNA.</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">15</span><p id="par0195" class="elsevierStylePara elsevierViewall">In certain epidemiological situations, especially in children of immigrant origin, patients with suspected or known immunosuppression or undergoing evaluation of a systemic disease, the search for infectious aetiologies should be expanded in collaboration with a specialist in infectious disease.</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">16</span><p id="par0200" class="elsevierStylePara elsevierViewall">In the case of isolated and sustained elevation of AST, we recommend testing for detection of macro-AST.</p></li></ul></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Diagnostic tests for follow-up of confirmed isolated HTRA</span><p id="par0205" class="elsevierStylePara elsevierViewall">Specific studies have not been performed to validate the appropriate timing of follow-up tests in the management of HTRA. The specific circumstances of the patient are very important in determining when to perform follow-up tests. Normal transaminase levels at a single time point do not rule out liver disease, as some of these diseases have a fluctuating course.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In addition, some diseases may manifest with mild transaminase elevation and still cause acute liver failure.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–32</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">In the absence of alarming findings (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>), patients should be referred to the hospital to complete the diagnostic evaluation or treatment when investigation or therapeutic options are exhausted in primary care or if there are findings indicative of severe disease (such as HTRA > 10 × ULN, cholestasis).<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Recommendations</span>: <ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">17</span><p id="par0220" class="elsevierStylePara elsevierViewall">We recommend follow-up testing in 3–6 months in patients with unexplained HTRA that resolved after its detection, avoiding collection of the blood sample in the context of situations that may cause secondary hypertransaminasaemia (infection, medication, physical activity…).</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">18</span><p id="par0225" class="elsevierStylePara elsevierViewall">In asymptomatic patients with HTRA, in the absence of red flags, we recommend performance of first- and second-tier tests in the first 3–6 months. If HTRA persists and its aetiology remains unknown, we suggest a comprehensive evaluation (first-, second- and third-tier tests) within 12 months of the initial detection of HTRA.</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">19</span><p id="par0230" class="elsevierStylePara elsevierViewall">Patients with associated cholestasis or very high transaminase elevation (>10 × ULN) should be referred for assessment by a paediatric gastroenterologist/hepatologist on a priority basis.</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">20</span><p id="par0235" class="elsevierStylePara elsevierViewall">In the absence of alarming signs, we recommend referral to a paediatric gastroenterologist/hepatologist of patients with HTRA and a suspected diagnosis requiring specific diagnostic procedures or treatment or with HTRA of unknown aetiology requiring performance of third-tier tests. The care setting where the second-tier tests are performed will depend on the organization, experience and resources of health care facilities in the region.</p></li></ul></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Other investigations in the evaluation of sustained and asymptomatic HTRA</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Genetic testing</span><p id="par0240" class="elsevierStylePara elsevierViewall">The results of previous tests, the phenotype of the patient and the study of the case with a geneticist will guide the selection of the genetic tests to be performed. At present, genetic testing is performed by means of next-generation sequencing (NGS) techniques. Next-generation sequencing allows detection of point mutations, microdeletions and intragenic insertions in several genes at once. The NGS tests used in clinical practice are targeted gene panels,<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> clinical exome sequencing (CES), which may be targeted based on the key phenotypic features of the patient using the Human Phenotype Ontology (HPO) nomenclature<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> and whole-exome sequencing (WES).<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> Due to advances in molecular genetics and the increasing availability of these techniques, NGS will be used increasingly frequently and at earlier stages in clinical practice.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Liver biopsy (LB)</span><p id="par0245" class="elsevierStylePara elsevierViewall">Since this is an invasive procedure, it is only performed after an exhaustive initial evaluation with non-invasive methods. The ultrasound-guided needle biopsy of the liver is the criterion standard procedure for sampling liver tissue, using cutting or suction needles of varying gauge based on age.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> Persistent HTRA is the main indication for performance of LB in children.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> The right time to perform it is not as clearly established. Some authors have reported a low diagnostic yield of LB in the case of sustained HTRA of unknown aetiology, and performance of this procedure could be delayed to 14–16 months after initial detection of HTRA.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The parents or legal guardians must be informed of the potential benefits and risks of the procedure based on the nature of the liver disorder experienced by the child.</p><p id="par0250" class="elsevierStylePara elsevierViewall">The LB specimen can provide information on specific pathological and histological features of different liver diseases.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">38,39</span></a> This technique is also useful in the prognostic assessment of chronic liver disease through the determination of histological activity indices (inflammation, fibrosis, necrosis, steatosis etc). Different techniques may be used in the histological examination: basic staining with haematoxylin and eosin, special histochemical stains and immunostains or electron microscopy.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> Adequate communication between the pathology and clinical teams is crucial to ensure the correct processing and assessment of histological samples.</p><p id="par0255" class="elsevierStylePara elsevierViewall">In recent years, non-invasive techniques have been developed to assess liver fibrosis by ultrasound elastography. Although this approach provides relevant information in the followup, due to the absence of established normal ranges validated in the paediatric population or specific cut-off values for the different diseases that may be present, ultrasound elastography cannot currently replace performance of a LB.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Recommendations</span>:<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">21</span><p id="par0265" class="elsevierStylePara elsevierViewall">In the case of persistent HTRA without an aetiological diagnosis, genetic testing should be performed in collaboration with specialists in clinical genetics. In these patients in whom HTRA is the only warning sign, we recommend clinical exome sequencing.</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">22</span><p id="par0270" class="elsevierStylePara elsevierViewall">We recommend performance of an additional LB (preferably guided by ultrasound) at 12–18 months from initial detection of asymptomatic and persistent HTRA, in the absence of other warning signs, in patients in whom the previous diagnostic evaluation did not establish the aetiology of HTRA.</p></li></ul></p></span></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflicts of interest</span><p id="par0275" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres1744600" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1537355" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1744601" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1537354" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Development of the document" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Definition of hypertransaminasaemia and its main causes" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Initial assessment following detection of HTRA" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Evaluation of confirmed HTRA of unknown aetiology" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Diagnostic tests for follow-up of confirmed isolated HTRA" ] 5 => array:3 [ "identificador" => "sec0040" "titulo" => "Other investigations in the evaluation of sustained and asymptomatic HTRA" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Genetic testing" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Liver biopsy (LB)" ] ] ] ] ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflicts of interest" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-09-06" "fechaAceptado" => "2022-04-07" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1537355" "palabras" => array:5 [ 0 => "Hypertransaminasemia" 1 => "Pediatrics" 2 => "Consensus" 3 => "Algorithm" 4 => "Diagnosis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1537354" "palabras" => array:5 [ 0 => "Hipertransaminasemia" 1 => "Pediatría" 2 => "Consenso" 3 => "Algoritmo" 4 => "Diagnóstico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Hypertransaminasemia is a frequent finding in pediatrics, which could reflect potentially treatable serious disease. The aim of this document is to establish, by reviewing the available evidence, a consensus for an adequate management of hypertransaminasemia, from its detection until the study is complete. To this end, a working group was formed with the participation of members of the Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP), the Spanish Association of Primary Care Pediatrics (AEPap) and the Spanish Society of Primary Care Pediatrics (SEPEAP). Twenty-one recommendations are established with a marked practical component that will be useful in hospital clinical practice and primary care.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">La hipertransaminasemia es un hallazgo frecuente en pediatría, puede ser banal o reflejar enfermedad grave potencialmente tratable. El objetivo de este documento es establecer, mediante la revisión de la evidencia disponible, un consenso para un adecuado enfoque práctico desde la detección de la hipertransaminasemia hasta completar su estudio en la edad pediátrica. Para ello, se constituyó un grupo de trabajo con participación de miembros de la Sociedad de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP), Asociación Española de Pediatría de Atención Primaria (AEPap) y Sociedad Española de Pediatría de Atención Primaria (SEPEAP). Se establecieron 21 recomendaciones con el objetivo de que sirvan de utilidad en la práctica clínica habitual tanto en atención primaria como hospitalaria.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Arnal IR, Andrade JR, Hally MM, Baviera LCB, Tirado DG, Martín SHC, et al. Actuación diagnóstica ante hipertransaminasemia en pediatría: documento de consenso de Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP), Asociación Española de Pediatría de Atención Primaria (AEPap) y Sociedad Española de Pediatría de Atención Primaria (SEPEAP). An Pediatr (Barc). 2022;96:448.</p>" ] ] "multimedia" => array:10 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1754 "Ancho" => 3008 "Tamanyo" => 581993 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">ALT, alanine aminotransferase; AMA, antimitochondrial antibodies; ANA, antinuclear antibodies; anti-LC-1, anti-liver cytosol type 1 antibodies; anti-LKM-1, liver-kidney microsomal type 1 antibodies; anti-SLA, anti-soluble liver antigen antibodies; anti-tTG, anti-tissue transglutaminase antibodies; ASMA, anti-smooth muscle antibody; AST, aspartate aminotransferase; CDT, carbohydrate deficient transferrin; CMV, cytomegalovirus; CPK, creatine phosphokinase; EBV, Epstein-Barr virus; fT<span class="elsevierStyleInf">4</span>, free thyroxine; GGT, gamma-glutamyl transferase; HIV, human immunodeficiency virus; HTRA, hypertransaminasaemia; Ig, immunoglobulin; LAL, lysosomal acid lipase; p-ANCA, perinuclear anti-neutrophil cytoplasmic antibodies; TORCH, toxoplasmosis, rubella, CMV, herpes simplex and HIV; TSH, thyroid-stimulating hormone.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">1</span>Compare to normal range for age. <span class="elsevierStyleSup">2</span>Consider inclusion in second-tier testing in infants.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">ALT, alanine aminotransferase; AST, aspartate aminotransferase; P, percentile; ULN, upper limit of normal.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "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"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author (year) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Values in U/L, by age range and/or sex</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fraser (2007)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male and female adolescents</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT LSN = 30</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">England (2009)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><18 months, male \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><18 months, female \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>18 months, male \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">female \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 60 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 55 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 40 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 35 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lai (2009) \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 " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT 2.5−97.5 percentile = 8−38</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Schwimmer (2010)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male adolescents</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female adolescents</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 26</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 22</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rodoo (2013)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 months-8 years, male \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 months-8 years, female \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9−18 years, male \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9−18 years, female \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 23.4 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 17.4 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 30.6 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 30.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6−12 months, male and female \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1−4 years, male and female \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5−8 years, male and female \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9−18 years, male and female \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST ULN = 66 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST ULN = 55.8 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST ULN = 48 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST ULN = 43.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Zierk (2015) \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 " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT and AST expressed as a continuous reference spectrum in the form percentile curves (P2.5-P97.5) for age</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Klietherme (2017)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adolescents, male</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adolescents, female</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 28</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 21−24</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bussler (2018)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 months-16 years, male</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 months-16 years, female</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Several age ranges</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Several age ranges</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN male = 29.9−38</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN female = 24.2−31.7</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST ULN male = 41.5−68.7</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST ULN female = 35.2−62.9</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kim (2018)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adolescents, male</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adolescents, female</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 33</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 25</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Liu (2019)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 age ranges, differences based on sex only in adolescents</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ULN = 39−56</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST ULN = 32−67</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Paediatric transaminase level ranges published by different authors.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">ALT, alanine aminotransferase; AST, aspartate aminotransferase; CMPA, cow’s milk protein allergy; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HSV, herpes simplex virus; HBL, hypobetalipoproteinaemia; HIV, human immunodeficiency virus; RSV, respiratory syncytial virus; UTI, urinary tract infection; VZV, varicella-zoster virus.</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">*The most frequent aetiologies are presented in boldface.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "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"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleUnderline">Hepatic</span></th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleUnderline">Hepatic</span></th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Infectious</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute hepatitis (A, B, C, D, E) and chronic hepatitis (B, C) Systemic with hepatic tropism: <span class="elsevierStyleBold">EBV, CMV</span>, HSV, VZV, HIV, toxoplasmosis, SARS-CoV-2. Sepsis and bacteraemia. Brucellosis, leptospirosis, typhoid fever.</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neoplastic \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Primary: liver tumour (hepatoblastoma, hepatocarcinoma) Secondary neuroblastoma, lymphoma, leukaemia, metastasis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatobiliary</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Cholelithiasis, choledochal cyst</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cholestatic pattern of disease, require separate detailing and evaluation. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other (more frequent in young children): respiratory and gastrointestinal viruses (adenovirus, RSV, parvovirus, echovirus, rotavirus), gastroenteritis caused by <span class="elsevierStyleItalic">Salmonella</span>, UTI</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Traumatic \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Obstetric trauma (subcapsular haematoma), abdominal trauma \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Miscellaneous \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chromosomal disorder (Turner syndrome), amyloidosis, sarcoidosis, Reye syndrome, CMPA (in infants), vascular diseases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatotoxicity \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Prescription drugs</span>, illicit drugs, toxins, herbal and alternative medicine remedies. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Immune \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Autoimmune hepatitis</span>, autoimmune cholangitis. Liver disease associated with immune disorder: collagenosis and other \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gastrointestinal or systemic disease \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Coeliac disease, thyroid dysfunction,</span> cystic fibrosis, chronic inflammatory bowel disease, Shwachman-Diamond syndrome. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Obesity \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Non-alcoholic fatty liver disorder (hepatic steatosis, steatohepatitis)</span>. \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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleUnderline">Extrahepatic</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Metabolic</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Alpha-1 antitrypsin deficiency, Wilson disease</span>, galactosaemia, fructosaemia, tyrosinaemia, glycogenosis (I, III, IV, VI, IX), lipidosis (Gaucher, Niemann-Pick), fatty acid β-oxidation disorders, lysosomal acid lipase deficiency, congenital disorders of glycosylation, Inborn errors of bile acid synthesis, urea cycle disorders, lipoprotein metabolism disorders (HBL), porphyria, other.</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Elevation of AST and ALT</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Muscular and neuromuscular diseases (AST > ALT): Duchenne and Becker muscular dystrophy, caveolinopathies, limb-girdle muscular dystrophy, polymyositis, dermatomyositis, metabolic myopathies (glycogen storage disease type V or McArdle disease). Other disorders involving muscle: major trauma, high-degree burns, surgery, vigorous exercise. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thyroid disorders: hypothyroidism and hyperthyroidism. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Renal diseases. Adrenal insufficiency. Anorexia nervosa. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ischaemic-vascular \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Low cardiac output, hepatic artery or portal vein obstruction, congestive heart failure, Budd-Chiari syndrome. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Isolated AST elevation \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Haemolysis: difficult blood draw, haemolytic disease. Heart disease (pericarditis, myocarditis, acute myocardial infarction). Isolated macroaspartasaemia. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Causes of hypertransaminasaemia in the paediatric population.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nonspecific manifestations \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Asthenia, anorexia, nauseas, vomiting, abdominal distension, abdominal pain \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Suggestive of liver disease \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatomegaly, jaundice, acholia, choluria \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Suggestive of chronic liver disease \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Telangiectasias, palmar erythema, malnutrition, ascites, splenomegaly, collateral vessels, gastrointestinal bleeding \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dysmorphic features \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Characteristic phenotype (Alagille syndrome) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neurologic manifestations \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Irritability, changes in behaviour, changes in muscle tone, psychomotor retardation. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Manifestations of muscular involvement \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abnormal gait, myalgia, muscle hypertrophy or weakness. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Signs and symptoms in the history-taking and physical examination.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase; LDH: lactic dehydrogenase.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><elsevierMultimedia ident="202207070640576201"></elsevierMultimedia> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Comprehensive liver panel.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0030" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><elsevierMultimedia ident="202207070640576202"></elsevierMultimedia> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Red flags in patients with hypertransaminasaemia.</p>" ] ] 6 => array:8 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0035" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">ALT, alanine aminotransferase; AMA, antimitochondrial antibodies; ANA, antinuclear antibodies; anti-LC-1, anti-liver cytosol type 1 antibodies; anti-LKM-1, liver-kidney microsomal type 1 antibodies; anti-SLA, anti-soluble liver antigen antibodies; ASMA, anti-smooth muscle antibody; AST, aspartate aminotransferase; CDT, carbohydrate deficient transferrin; CPK, creatine phosphokinase; fT4, free thyroxine; GGT, gamma-glutamyl transferase; HIV, human immunodeficiency virus; Ig, immunoglobulin; LAL, lysosomal acid lipase; p-ANCA, perinuclear anti-neutrophil cytoplasmic antibodies; TORCH, toxoplasmosis, rubella cytomegalovirus, herpes simplex, and HIV; TSH, thyroid-stimulating hormone.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">First tier</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Comprehensive liver panel \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST, ALT, GGT, alkaline phosphatase, total and fractionated bilirubin, coagulation study \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blood chemistry \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glucose, total protein, albumin, total cholesterol, triglycerides, CPK \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute infectious disease \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Viral serology tests for hepatitis A, B and C, Epstein-Barr virus, cytomegalovirus and, in infants, the TORCH test \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Imaging \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abdominal ultrasound \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thyroid function (TSH and fT4), coeliac disease (tissue transglutaminase IgA), total IgA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Second tier</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Infectious disease \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Repeat serologic tests for hepatitis B and C and HIV. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autoantibodies \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ANA, ASMA, anti-LKM-1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serum ceruloplasmin, serum alpha-1 antitrypsin, serum Ig levels (IgA, IgG and IgM)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Third tier</span></td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autoantibodies \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-LC-1, anti-SLA, AMA, p-ANCA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Imaging \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abdominal Doppler ultrasound \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Plasma amino acid analysis (or ammonia)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>, venous or capillary blood gas analysis,<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> lactate,<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> CDT test, alpha-1 antitrypsin phenotype, urine copper (24 -h urine), LAL activity, bile acids (plasma and/or urine), \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Compare to normal range for age.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Consider inclusion in second-tier testing in infants.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">First-, second- and third-tier tests.</p>" ] ] 7 => array:8 [ "identificador" => "tbl0035" "etiqueta" => "Table 7" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0040" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">AST, aspartate aminotransferase; HBV, hepatitis B virus; HCV, hepatitis C virus.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "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"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Diseases \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tests \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inborn errors of metabolism \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Many are included in newborn screening protocols. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Review newborn screen results \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diagnosis guided by specialist in metabolic diseases \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">They are rarely asymptomatic, and their main manifestations (faltering growth, short stature, vomiting, psychomotor retardation, hepatomegaly, hypoglycaemia cholestasis, etc.) usually appear in infancy. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Plasma amino acids, ammonia, lactate, accumulation of metabolites in blood and/or urine, specific enzyme assays and genetic testing. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Infections</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients in risk group for HBV or HCV with initial negative screen or immunocompromised patient.</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PCR for detection of HBV DNA and HCV RNA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Opportunistic infections \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diagnosis guided by specialist in infectious disease \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">History of travel \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parasites and bacteria that with low prevalence Spain \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pancreatic involvement</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cystic fibrosis</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Review newborn screen results \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sweat chloride test/CFTR gene \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Shwachman-Diamond syndrome</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cytopenias \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Genetic testing \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Macro-AST</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Isolated, sustained and exclusive elevation of AST due to the presence of macroenzymes</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Percent polyethylene glycol precipitable activity (%PPA) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Electrophoresis \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Assessment of specific diseases.</p>" ] ] 8 => array:5 [ "identificador" => "202207070640576201" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 1640 "Ancho" => 2508 "Tamanyo" => 260658 ] ] ] 9 => array:5 [ "identificador" => "202207070640576202" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx2.jpeg" "Alto" => 2036 "Ancho" => 2508 "Tamanyo" => 422132 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:40 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alanine aminotransferase-old biomarker and new concept: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Z. Liu" 1 => "S. Que" 2 => "J. Xu" 3 => "T. Peng" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7150/ijms.8951" "Revista" => array:6 [ "tituloSerie" => "Int J Med Sci" "fecha" => "2014" "volumen" => "11" "paginaInicial" => "925" "paginaFinal" => "935" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25013373" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alanine aminotransferase: a clinical and regulatory tool for detecting liver injury-past, present, and future" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.R. Senior" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/clpt.2012.108" "Revista" => array:6 [ "tituloSerie" => "Clin Pharmacol Ther" "fecha" => "2012" "volumen" => "92" "paginaInicial" => "332" "paginaFinal" => "339" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22871997" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Exploraciones clínicas, bioquímicas y técnicas de imagen en la valoración de la patología digestiva y hepatobiliar" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D. Lledín Barbancho" 1 => "R. Vecino López" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Pediatr Integral" "fecha" => "2015" "volumen" => "XIX" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A practical approach to the child with abnormal liver tests" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "T. Lamireau" 1 => "V. McLin" 2 => "V. Nobili" 3 => "P. Vajro" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clinre.2014.02.010" "Revista" => array:6 [ "tituloSerie" => "Clin Res Hepatol Gastroenterol" "fecha" => "2014" "volumen" => "38" "paginaInicial" => "259" "paginaFinal" => "262" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24736033" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aproximación diagnóstica al paciente con enfermedad hepática" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.M. Marugán de Miguelsanz" 1 => "M.C. Torres Hinojal" 2 => "C. Alonso Vicente" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Pediatr Integral" "fecha" => "2020" "volumen" => "XXIV" "paginaInicial" => "6" "paginaFinal" => "14" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Persistent hypertransaminasemia in asymptomatic children: a stepwise approach" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Vajro" 1 => "S. Maddaluno" 2 => "C. Veropalumbo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3748/wjg.v19.i18.2740" "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2013" "volumen" => "19" "paginaInicial" => "2740" "paginaFinal" => "2751" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23687411" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Fernández Ventureira V, Ros Arnal I, Rodríguez Martínez G, García Rodríguez B, García Romero R, Ubalde Sainz E. Evaluación del seguimiento de niños con hallazgo de hipertransaminasemia. An Pediatría. 3 de septiembre de 2020. Available from: <a target="_blank" href="https://www.sciencedirect.com/science/article/pii/S1695403320302411">https://www.sciencedirect.com/science/article/pii/S1695403320302411</a>. [Accessed 16 March 2021]." ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypertransaminasemia in childhood as a marker of genetic liver disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R. Iorio" 1 => "A. Sepe" 2 => "A. Giannattasio" 3 => "F. Cirillo" 4 => "A. Vegnente" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00535-005-1635-7" "Revista" => array:6 [ "tituloSerie" => "J Gastroenterol" "fecha" => "2005" "volumen" => "40" "paginaInicial" => "820" "paginaFinal" => "826" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16143887" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Upper limit of normal for alanine aminotransferase: quo vadis?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "L. Pacifico" 1 => "F. Ferraro" 2 => "E. Bonci" 3 => "C. Anania" 4 => "S. Romaggioli" 5 => "C. Chiesa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cca.2013.03.030" "Revista" => array:6 [ "tituloSerie" => "Clin Chim Acta" "fecha" => "2013" "volumen" => "422" "paginaInicial" => "29" "paginaFinal" => "39" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23566931" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Age- and sex-related reference ranges of alanine aminotransferase levels in children: European paediatric HCV network" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K. England" 1 => "C. Thorne" 2 => "L. Pembrey" 3 => "P.A. Tovo" 4 => "M.L. Newell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MPG.0b013e31818fc63b" "Revista" => array:6 [ "tituloSerie" => "J Pediatr Gastroenterol Nutr" "fecha" => "2009" "volumen" => "49" "paginaInicial" => "71" "paginaFinal" => "77" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19465871" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An assessment of racial differences in the upper limits of normal ALT levels in children and the effect of obesity on elevated values" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Kliethermes" 1 => "M. Ma" 2 => "C. Purtell" 3 => "N. Balasubramanian" 4 => "B. Gonzalez" 5 => "T.J. Layden" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/ijpo.12152" "Revista" => array:6 [ "tituloSerie" => "Pediatr Obes" "fecha" => "2017" "volumen" => "12" "paginaInicial" => "363" "paginaFinal" => "372" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27237782" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "New pediatric percentiles of liver enzyme serum levels (alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase): effects of age, sex, body mass index, and pubertal stage" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Bussler" 1 => "M. Vogel" 2 => "D. Pietzner" 3 => "K. Harms" 4 => "T. Buzek" 5 => "M. Penke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.29542" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2018" "volumen" => "68" "paginaInicial" => "1319" "paginaFinal" => "1330" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28926121" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of elevated alanine aminotransferase among US adolescents and associated factors: NHANES 1999-2004" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Fraser" 1 => "M.P. Longnecker" 2 => "D.A. Lawlor" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2007.08.077" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2007" "volumen" => "133" "paginaInicial" => "1814" "paginaFinal" => "1820" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18054554" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pediatric reference intervals for several biochemical analytes in school children in Central Taiwan" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.S. Lai" 1 => "S.C. Chen" 2 => "Y.H. Chang" 3 => "C.Y. Chen" 4 => "J.B. Lin" 5 => "Y.J. Lin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0929-6646(10)60009-5" "Revista" => array:6 [ "tituloSerie" => "J Formos Med Assoc" "fecha" => "2009" "volumen" => "108" "paginaInicial" => "957" "paginaFinal" => "963" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20040461" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.B. Schwimmer" 1 => "W. Dunn" 2 => "G.J. Norman" 3 => "P.E. Pardee" 4 => "M.S. Middleton" 5 => "N. Kerkar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2009.12.052" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2010" "volumen" => "138" "paginaInicial" => "1357" "paginaFinal" => "1364" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20064512" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Population-based pediatric reference intervals for HbA1c, bilirubin, albumin, CRP, myoglobin and serum enzymes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P. Rödöö" 1 => "P. Ridefelt" 2 => "M. Aldrimer" 3 => "F. Niklasson" 4 => "J. Gustafsson" 5 => "D. Hellberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/00365513.2013.783931" "Revista" => array:6 [ "tituloSerie" => "Scand J Clin Lab Invest" "fecha" => "2013" "volumen" => "73" "paginaInicial" => "361" "paginaFinal" => "367" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23581477" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Age- and sex-specific dynamics in 22 hematologic and biochemical analytes from birth to adolescence" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Zierk" 1 => "F. Arzideh" 2 => "T. Rechenauer" 3 => "R. Haeckel" 4 => "W. Rascher" 5 => "M. Metzler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1373/clinchem.2015.239731" "Revista" => array:6 [ "tituloSerie" => "Clin Chem" "fecha" => "2015" "volumen" => "61" "paginaInicial" => "964" "paginaFinal" => "973" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25967371" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence and risk factors of elevated alanine aminotransferase among Korean adolescents: 2001-2014" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.W. Kim" 1 => "K.J. Lee" 2 => "H.R. Yang" 3 => "J.Y. Chang" 4 => "J.S. Moon" 5 => "Y.H. Khang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12889-018-5548-9" "Revista" => array:5 [ "tituloSerie" => "BMC Public Health" "fecha" => "2018" "volumen" => "18" "paginaInicial" => "617" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29751750" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pediatric reference intervals of liver and renal function tests from birth to adolescence in Chinese children as performed on the Olympus AU5400" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Liu" 1 => "Y. Dai" 2 => "Y. Lee" 3 => "E. Yuan" 4 => "Q. Wang" 5 => "L. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cca.2019.01.001" "Revista" => array:6 [ "tituloSerie" => "Clin Chim Acta" "fecha" => "2019" "volumen" => "490" "paginaInicial" => "142" "paginaFinal" => "146" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30611730" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Blesa Baviera L, Vegas Alvarez A, Albañil Ballesteros M. Guía de Algoritmos en Pediatría de Atención Primaria. Hipertransaminasemia. AEPap. 2016 (en línea). Available from: <a target="_blank" href="http://algoritmos.aepap.org">algoritmos.aepap.org</a>." ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aumento aislado de transaminasas: aproximación diagnóstica" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L. Lesmes Moltó" 1 => "M.R. Albañil Ballesteros" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Form Act Pediatr Aten Prim" "fecha" => "2013" "volumen" => "6" "paginaInicial" => "35" "paginaFinal" => "42" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hipertransaminasemia en Pediatría" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D. González Jiménez" 1 => "P.M. Santos Rodríguez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Bol Pediatr" "fecha" => "2013" "volumen" => "53" "paginaInicial" => "137" "paginaFinal" => "145" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pediatric acute liver failure of undetermined cause: a research workshop" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E.M. Alonso" 1 => "S.P. Horslen" 2 => "E.M. Behrens" 3 => "E. Doo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.28944" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2017" "volumen" => "65" "paginaInicial" => "1026" "paginaFinal" => "1037" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27862115" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pediatric liver injury: physical examination, fast and serum transaminases can serve as a guide" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Zeeshan" 1 => "M. Hamidi" 2 => "T. O’Keeffe" 3 => "K. Hanna" 4 => "N. Kulvatunyou" 5 => "A. Tang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jss.2019.04.021" "Revista" => array:6 [ "tituloSerie" => "J Surg Res" "fecha" => "2019" "volumen" => "242" "paginaInicial" => "151" "paginaFinal" => "156" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31078899" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Wilsonʼs disease in children: a position paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Socha" 1 => "W. Janczyk" 2 => "A. Dhawan" 3 => "U. Baumann" 4 => "L. D’Antiga" 5 => "S. Tanner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MPG.0000000000001787" "Revista" => array:6 [ "tituloSerie" => "J Pediatr Gastroenterol Nutr" "fecha" => "2018" "volumen" => "66" "paginaInicial" => "334" "paginaFinal" => "344" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29341979" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Liver involvement in children with Alpha-1 antitrypsin deficiency: a multicenter study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Cakir" 1 => "E. Sag" 2 => "A. Islek" 3 => "M. Baran" 4 => "G. Tumgor" 5 => "S. Aydogdu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5223/pghn.2020.23.2.146" "Revista" => array:6 [ "tituloSerie" => "Pediatr Gastroenterol Hepatol Nutr" "fecha" => "2020" "volumen" => "23" "paginaInicial" => "146" "paginaFinal" => "153" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32206627" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Marques-da-Silva" 1 => "V. Dos Reis Ferreira" 2 => "M. Monticelli" 3 => "P. Janeiro" 4 => "P.A. Videira" 5 => "P. Witters" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10545-016-0012-4" "Revista" => array:6 [ "tituloSerie" => "J Inherit Metab Dis" "fecha" => "2017" "volumen" => "40" "paginaInicial" => "195" "paginaFinal" => "207" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28108845" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and management of pediatric autoimmune liver disease: ESPGHAN Hepatology Committee Position Statement" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Mieli-Vergani" 1 => "D. Vergani" 2 => "U. Baumann" 3 => "P. Czubkowski" 4 => "D. Debray" 5 => "A. Dezsofi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MPG.0000000000001801" "Revista" => array:6 [ "tituloSerie" => "J Pediatr Gastroenterol Nutr" "fecha" => "2018" "volumen" => "66" "paginaInicial" => "345" "paginaFinal" => "360" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29356770" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.B. Vos" 1 => "S.H. Abrams" 2 => "S.E. Barlow" 3 => "S. Caprio" 4 => "S.R. Daniels" 5 => "R. Kohli" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MPG.0000000000001482" "Revista" => array:6 [ "tituloSerie" => "J Pediatr Gastroenterol Nutr" "fecha" => "2017" "volumen" => "64" "paginaInicial" => "319" "paginaFinal" => "334" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28107283" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Congenital extrahepatic portosystemic shunts (abernethy malformation): an international observational study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Baiges" 1 => "F. Turon" 2 => "M. Simón-Talero" 3 => "S. Tasayco" 4 => "J. Bueno" 5 => "K. Zekrini" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.30817" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2020" "volumen" => "71" "paginaInicial" => "658" "paginaFinal" => "669" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31211875" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Paediatric fatty liver disease (PeFLD): all is not NAFLD - Pathophysiological insights and approach to management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R. Hegarty" 1 => "M. Deheragoda" 2 => "E. Fitzpatrick" 3 => "A. Dhawan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2018.02.006" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2018" "volumen" => "68" "paginaInicial" => "1286" "paginaFinal" => "1299" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29471012" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guidelines on the management of abnormal liver blood tests" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.N. Newsome" 1 => "R. Cramb" 2 => "S.M. Davison" 3 => "J.F. Dillon" 4 => "M. Foulerton" 5 => "E.M. Godfrey" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gutjnl-2017-314924" "Revista" => array:6 [ "tituloSerie" => "Gut" "fecha" => "2018" "volumen" => "67" "paginaInicial" => "6" "paginaFinal" => "19" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29122851" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Next generation sequencing in pediatric hepatology and liver transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E. Nicastro" 1 => "L. D’Antiga" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/lt.24964" "Revista" => array:6 [ "tituloSerie" => "Liver Transpl" "fecha" => "2018" "volumen" => "24" "paginaInicial" => "282" "paginaFinal" => "293" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29080241" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The human phenotype ontology: semantic unification of common and rare disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Groza" 1 => "S. Köhler" 2 => "D. Moldenhauer" 3 => "N. Vasilevsky" 4 => "G. Baynam" 5 => "T. Zemojtel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajhg.2015.05.020" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2015" "volumen" => "97" "paginaInicial" => "111" "paginaFinal" => "124" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26119816" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Exome sequencing in clinical hepatology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S. Vilarinho" 1 => "P.K. Mistry" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.30826" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2019" "volumen" => "70" "paginaInicial" => "2185" "paginaFinal" => "2192" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31222768" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Liver biopsy in children: position paper of the ESPGHAN Hepatology Committee" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Dezsőfi" 1 => "U. Baumann" 2 => "A. Dhawan" 3 => "O. Durmaz" 4 => "B. Fischler" 5 => "N. Hadzic" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MPG.0000000000000632" "Revista" => array:6 [ "tituloSerie" => "J Pediatr Gastroenterol Nutr" "fecha" => "2015" "volumen" => "60" "paginaInicial" => "408" "paginaFinal" => "420" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25383787" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Contemporary evaluation of the pediatric liver biopsy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.A. Schady" 1 => "M.J. Finegold" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.gtc.2017.01.013" "Revista" => array:6 [ "tituloSerie" => "Gastroenterol Clin North Am" "fecha" => "2017" "volumen" => "46" "paginaInicial" => "233" "paginaFinal" => "252" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28506363" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 =>