Scientific letter
Acute pancreatitis secondary to partial multidrug resistance 3 p-glycoprotein deficit
Pancreatitis aguda secundaria a déficit parcial de multidrug resistance 3 p-glycoprotein
Héctor Miguel Marcos Prieto, Daniel Pérez Corte, M. Concepción Piñero Pérez
, María Cristina Revilla Morato, Ana María Mora Soler, Rosa Virgina Acosta Materán, Andrea Jiménez Jurado, Valeria Calabuig Mazzola, Antonio Rodríguez Pérez
Corresponding author
Servicio de Aparato Digestivo, Complejo Asistencial Universitario de Salamanca, Hospital Clínico, Salamanca, Spain
Read
1311
Timeswas read the article
444
Total PDF
867
Total HTML
Share statistics
array:24 [ "pii" => "S2444382416300451" "issn" => "24443824" "doi" => "10.1016/j.gastre.2016.06.004" "estado" => "S300" "fechaPublicacion" => "2016-08-01" "aid" => "909" "copyright" => "Elsevier España, S.L.U. and AEEH y AEG" "copyrightAnyo" => "2015" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Gastroenterol Hepatol. 2016;39:465-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 340 "formatos" => array:2 [ "HTML" => 268 "PDF" => 72 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0210570515001466" "issn" => "02105705" "doi" => "10.1016/j.gastrohep.2015.06.002" "estado" => "S300" "fechaPublicacion" => "2016-08-01" "aid" => "909" "copyright" => "Elsevier España, S.L.U. y AEEH y AEG" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Gastroenterol Hepatol. 2016;39:465-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 682 "formatos" => array:2 [ "HTML" => 456 "PDF" => 226 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta científica</span>" "titulo" => "Pancreatitis aguda secundaria a déficit parcial de multidrug resistance 3 p-glycoprotein" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "465" "paginaFinal" => "466" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Acute pancreatitis secondary to partial multidrug resistance 3 p-glycoprotein deficit" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Héctor Miguel Marcos Prieto, Daniel Pérez Corte, M. Concepción Piñero Pérez, María Cristina Revilla Morato, Ana María Mora Soler, Rosa Virgina Acosta Materán, Andrea Jiménez Jurado, Valeria Calabuig Mazzola, Antonio Rodríguez Pérez" "autores" => array:9 [ 0 => array:2 [ "nombre" => "Héctor Miguel" "apellidos" => "Marcos Prieto" ] 1 => array:2 [ "nombre" => "Daniel" "apellidos" => "Pérez Corte" ] 2 => array:2 [ "nombre" => "M. Concepción" "apellidos" => "Piñero Pérez" ] 3 => array:2 [ "nombre" => "María Cristina" "apellidos" => "Revilla Morato" ] 4 => array:2 [ "nombre" => "Ana María" "apellidos" => "Mora Soler" ] 5 => array:2 [ "nombre" => "Rosa Virgina" "apellidos" => "Acosta Materán" ] 6 => array:2 [ "nombre" => "Andrea" "apellidos" => "Jiménez Jurado" ] 7 => array:2 [ "nombre" => "Valeria" "apellidos" => "Calabuig Mazzola" ] 8 => array:2 [ "nombre" => "Antonio" "apellidos" => "Rodríguez Pérez" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2444382416300451" "doi" => "10.1016/j.gastre.2016.06.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444382416300451?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570515001466?idApp=UINPBA00004N" "url" => "/02105705/0000003900000007/v1_201607220358/S0210570515001466/v1_201607220358/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S244438241630044X" "issn" => "24443824" "doi" => "10.1016/j.gastre.2016.06.003" "estado" => "S300" "fechaPublicacion" => "2016-08-01" "aid" => "908" "copyright" => "Elsevier España, S.L.U. and AEEH y AEG" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Gastroenterol Hepatol. 2016;39:466-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 317 "formatos" => array:2 [ "HTML" => 232 "PDF" => 85 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Metastatic intestinal obstruction secondary to a primary lung tumour" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "466" "paginaFinal" => "468" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Obstrucción intestinal por metástasis de cáncer de pulmón" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1270 "Ancho" => 953 "Tamanyo" => 216589 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(A) Chest X-ray: mass in right upper lobe. (B) Computed tomography with oral and intravenous contrast, where a poorly defined mass with spiculated margins can be seen (measuring 50<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>27<span class="elsevierStyleHsp" style=""></span>mm in axial plane), extending from the right hilar region with obstruction of the right superior lobe bronchus and posterior segmental bronchus, associated with right hilar lymphadenopathies.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Elena Romera-Barba, Juan Castañer-Ramón-Llín, Inmaculada Navarro-Garcia, María Jose Carrillo López, Ainhoa Sánchez Pérez, José Luis Vazquez-Rojas" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Elena" "apellidos" => "Romera-Barba" ] 1 => array:2 [ "nombre" => "Juan" "apellidos" => "Castañer-Ramón-Llín" ] 2 => array:2 [ "nombre" => "Inmaculada" "apellidos" => "Navarro-Garcia" ] 3 => array:2 [ "nombre" => "María Jose" "apellidos" => "Carrillo López" ] 4 => array:2 [ "nombre" => "Ainhoa" "apellidos" => "Sánchez Pérez" ] 5 => array:2 [ "nombre" => "José Luis" "apellidos" => "Vazquez-Rojas" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210570515001454" "doi" => "10.1016/j.gastrohep.2015.06.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570515001454?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S244438241630044X?idApp=UINPBA00004N" "url" => "/24443824/0000003900000007/v2_201704060210/S244438241630044X/v2_201704060210/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2444382416300463" "issn" => "24443824" "doi" => "10.1016/j.gastre.2016.06.005" "estado" => "S300" "fechaPublicacion" => "2016-08-01" "aid" => "910" "copyright" => "Elsevier España, S.L.U. and AEEH y AEG" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Gastroenterol Hepatol. 2016;39:463-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 646 "formatos" => array:2 [ "HTML" => 486 "PDF" => 160 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Endometriosis of the appendix" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "463" "paginaFinal" => "465" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Endometriosis del apéndice" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 975 "Ancho" => 975 "Tamanyo" => 117742 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Irregular, distended and inflamed appendix.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Eduardo Reyna-Villasmil, Duly Torres-Cepeda, María Labarca-Acosta" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Eduardo" "apellidos" => "Reyna-Villasmil" ] 1 => array:2 [ "nombre" => "Duly" "apellidos" => "Torres-Cepeda" ] 2 => array:2 [ "nombre" => "María" "apellidos" => "Labarca-Acosta" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210570515001478" "doi" => "10.1016/j.gastrohep.2015.06.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570515001478?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444382416300463?idApp=UINPBA00004N" "url" => "/24443824/0000003900000007/v2_201704060210/S2444382416300463/v2_201704060210/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Acute pancreatitis secondary to partial multidrug resistance 3 p-glycoprotein deficit" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "465" "paginaFinal" => "466" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Héctor Miguel Marcos Prieto, Daniel Pérez Corte, M. Concepción Piñero Pérez, María Cristina Revilla Morato, Ana María Mora Soler, Rosa Virgina Acosta Materán, Andrea Jiménez Jurado, Valeria Calabuig Mazzola, Antonio Rodríguez Pérez" "autores" => array:9 [ 0 => array:2 [ "nombre" => "Héctor Miguel" "apellidos" => "Marcos Prieto" ] 1 => array:2 [ "nombre" => "Daniel" "apellidos" => "Pérez Corte" ] 2 => array:4 [ "nombre" => "M. Concepción" "apellidos" => "Piñero Pérez" "email" => array:1 [ 0 => "conxipi@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 3 => array:2 [ "nombre" => "María Cristina" "apellidos" => "Revilla Morato" ] 4 => array:2 [ "nombre" => "Ana María" "apellidos" => "Mora Soler" ] 5 => array:2 [ "nombre" => "Rosa Virgina" "apellidos" => "Acosta Materán" ] 6 => array:2 [ "nombre" => "Andrea" "apellidos" => "Jiménez Jurado" ] 7 => array:2 [ "nombre" => "Valeria" "apellidos" => "Calabuig Mazzola" ] 8 => array:2 [ "nombre" => "Antonio" "apellidos" => "Rodríguez Pérez" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Aparato Digestivo, Complejo Asistencial Universitario de Salamanca, Hospital Clínico, Salamanca, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Pancreatitis aguda secundaria a déficit parcial de multidrug resistance 3 p-glycoprotein" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Increasing numbers of young patients are being seen for abdominal pain and laboratory findings suggestive of cholestasis. Even after ruling out infectious, metabolic and autoimmune disease, and performing radiological examinations, a conclusive cause is often not identified.</p><p id="par0010" class="elsevierStylePara elsevierViewall">With the intention of highlighting a disease that has been emerging in the literature in the last 10 years, but with no cases reported in Spain, we present the case of an 18-year-old patient who presented symptoms of acute pancreatitis and cholestasis related to a partial deficiency of <span class="elsevierStyleItalic">multidrug-resistance P-glycoprotein 3</span> (MDR3).</p><p id="par0015" class="elsevierStylePara elsevierViewall">The patient had no personal history of interest. His maternal grandfather had died of pancreatic cancer, while his mother had undergone cholecystectomy for acute cholecystitis at 30 years of age.</p><p id="par0020" class="elsevierStylePara elsevierViewall">He was admitted for sudden onset epigastric pain, radiating to the lumbar region. He reported having presented similar but less intense episodes during the previous year.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Laboratory tests on samples taken in the emergency department showed cholestasis (bilirubin 5.79 [direct 2.22; indirect 3.57], aspartate aminotransferase [AST] 318, alanine aminotransferase [ALT] 671, alkaline phosphatase [ALP] 261 and gamma glutamyl transferase [GGT] 347) and high serum amylase levels (1763 IU). Complete blood count and coagulation parameters, acute phase reactants, lipid, thyroid and iron profiles were normal. Abdominal ultrasound performed in the emergency department showed liver parenchyma with no abnormalities, acalculous gall bladder with no signs of inflammation, and intra- and extrahepatic bile ducts of normal calibre and echogenicity.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The clinical picture was interpreted as mild acalculous acute pancreatitis, and the patient was discharged 72<span class="elsevierStyleHsp" style=""></span>hours later.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Before reassessment in outpatients, though, he was readmitted for a new episode of abdominal pain, with abnormal liver function tests in a cholestatic pattern but no elevated serum amylase. Autoimmune and immunoglobulin tests, as well as hepatotropic virus serology tests were negative. Repeat abdominal ultrasound was requested, with no findings of interest. Magnetic resonance cholangiography showed distal segmental dilatation of the intrahepatic bile duct, with contrast uptake in segments V, VI and VIII, with hepatic and pancreatic parenchyma of normal morphology and intensity. The gallbladder was acalculous with no signs of inflammation; the extrahepatic bile duct was normal in calibre and intensity.</p><p id="par0040" class="elsevierStylePara elsevierViewall">He was discharged after 7 days and scheduled for endoscopic ultrasound (EU).</p><p id="par0045" class="elsevierStylePara elsevierViewall">However, a few days later, his mother came to the clinic with clinical reports on 2 maternal first cousins who had recently been placed on the transplant waiting list as a result of liver cirrhosis secondary to familial intrahepatic cholestasis type 3, due to a complete deficiency of MDR3 secondary to a homozygous mutation in <span class="elsevierStyleItalic">ABCB4</span>.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Consequently, given the family history, a genetic test was requested for <span class="elsevierStyleItalic">ABCB4</span> gene expression in peripheral blood, isolating DNA from lymphocytes and then sequencing exon 4 of the <span class="elsevierStyleItalic">ABCB4</span> gene and the adjacent intronic regions. Results showed a heterozygous mutation in nucleotide 202, which involves the substitution of glycine 68 for arginine, consistent with partial MDR3 deficiency.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Treatment with urosdeoxycolic acid (UDCA) 12<span class="elsevierStyleHsp" style=""></span>mg/kg/day was started immediately; laboratory parameters returned to normal, except for bilirubin, which has fluctuated since then (1-year follow-up), with increases at the expense of indirect bilirubin, probably related with Gilbert syndrome. He has presented no new episodes of abdominal pain. Owing to the risk of fibrosis due to chronic cholestasis in these patients, liver elastography was performed, with a result of 5.5<span class="elsevierStyleHsp" style=""></span>kPa (F0–F1). Given the patient's improvement, the EU was postponed. So far, no genetic studies have been conducted in first degree relatives.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Over the last few years, several clinical cases and studies have been published highlighting the role of various hereditary disorders that affect membrane transport proteins in cholestatic syndromes.</p><p id="par0065" class="elsevierStylePara elsevierViewall">MDR3 is a protein that has been isolated in the canalicular membrane of the hepatocyte. It acts as an ATP-dependent pump, releasing phosphatidyl choline to the small bile ducts which, together with cholesterol and bile acids, enables formation of mixed micelles.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">ABCB4</span> (7q21) gene has been identified as responsible for its synthesis, with more than 60 different mutations having been described,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> both homozygous and heterozygous. These will result in truncated (<span class="elsevierStyleItalic">nonsense mutation</span>), immature or nonfunctional proteins (<span class="elsevierStyleItalic">missense mutation</span>) that will determine the severity of the deficiency.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Bile salt-induced cholangiocyte damage has been observed in cases of MDR3 deficiency, as well as increased formation of calculi, both in the gallbladder and intra- and extrahepatic bile ducts.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> This deficiency is currently related with the following syndromes: progressive familial intrahepatic cholestasis type 3, low phospholipid-associated cholelithiasis (LPAC) syndrome, intrahepatic cholestasis of pregnancy, transient neonatal cholestasis, drug-induced liver disease, as well as fibrosis and cirrhosis in adults.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Our patient met 2 of the following criteria for LPAC syndrome: (1) onset of symptoms before 40 years of age; (2) chronic mild cholestasis; (3) intrahepatic hyperechoic foci, biliary sludge or microlithiasis; (4) low biliary phospholipid concentration, and (5) recurrence of biliary symptoms after cholecystectomy.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">6,7</span></a> Once the mutation had been confirmed, the presence of complicated biliary colic and chronic mild cholestasis led us to believe that this was a compound heterozygous patient, resulting in synthesis of immature or nonfunctional — but not truncated — MDR3 protein.</p><p id="par0085" class="elsevierStylePara elsevierViewall">It is important to assess this possible aetiology in young patients who present repeated episodes of biliary colic for several reasons: first, because genetic tests are available that can confirm the diagnosis and avoid invasive tests with their associated risks; second, because it is an entity with a high response rate to UDCA,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> an inexpensive, well-tolerated drug; third, because patients can present complications, such as complicated biliary colic or progressive fibrosis<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a>; and finally, given its genetic nature, screening can be performed in first and second degree relatives who present compatible symptoms.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Marcos Prieto HM, Pérez Corte D, Piñero Pérez MC, Revilla Morato MC, Mora Soler AM, Acosta Materán RV, et al. Pancreatitis aguda secundaria a déficit parcial de multidrug resistance 3 p-glycoprotein. Gastroenterol Hepatol. 2016;39:465–466.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatic canalicular membrane 1: the role of MDR2 P-glycoprotein in hepatobiliary lipid transport" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.P. Eferink" 1 => "G.N. Tytgat" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "FASEB J" "fecha" => "1997" "volumen" => "11" "paginaInicial" => "19" "paginaFinal" => "28" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9034162" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0045" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genotype-phenotype relationships in the low-phospholipid-associated cholelithiasis syndrome: a study of 156 consecutive patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Poupon" 1 => "O. Rosmorduc" 2 => "P.Y. Boëlle" 3 => "Y. Chrétien" 4 => "C. Corpechot" 5 => "O. Chazouillères" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.26424" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2013" "volumen" => "58" "paginaInicial" => "1105" "paginaFinal" => "1110" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23533021" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0050" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Progressive familial intrahepatic cholestasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "E. Jacquemin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2210-7401(12)70018-9" "Revista" => array:7 [ "tituloSerie" => "Clin Res Hepatol Gastroenterol" "fecha" => "2012" "volumen" => "36" "numero" => "Suppl 1" "paginaInicial" => "S26" "paginaFinal" => "S35" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23141890" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0055" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Progressive familial intrahepatic cholestasis and benign recurrent intrahepatic cholestasis: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "B. Strubbe" 1 => "A. Geerts" 2 => "H. van Vlierberghe" 3 => "I. Colle" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Acta Gastroenterol Belg" "fecha" => "2012" "volumen" => "75" "paginaInicial" => "75" "paginaFinal" => "80" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0060" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The spectrum of liver diseases related to ABCB4 gene mutations: pathophysiology and clinical aspects" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Davit-Spraul" 1 => "E. Gonzales" 2 => "C. Baussan" 3 => "E. Jacquemin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1055/s-0030-1253223" "Revista" => array:6 [ "tituloSerie" => "Semin Liver Dis" "fecha" => "2010" "volumen" => "30" "paginaInicial" => "134" "paginaFinal" => "146" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20422496" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0065" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The cholangiographic features of severe forms of ABCB4/MDR3 deficiency-associated cholangiopathy in adults" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R. Poupon" 1 => "L. Arrive" 2 => "O. Rosmorduc" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.gcb.2010.04.011" "Revista" => array:6 [ "tituloSerie" => "Gastroenterol Clin Biol" "fecha" => "2010" "volumen" => "34" "paginaInicial" => "380" "paginaFinal" => "387" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20537830" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0070" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Wang D, Afdhal N. Sleisenger and Fordtran's Gastrointestinal Liver Disease. Feldman & Friedman & Brandt. Volume 2. Sección IX. Liver Chapter 65, p. 1100–1133." ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/24443824/0000003900000007/v2_201704060210/S2444382416300451/v2_201704060210/en/main.assets" "Apartado" => array:4 [ "identificador" => "48446" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/24443824/0000003900000007/v2_201704060210/S2444382416300451/v2_201704060210/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444382416300451?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 1 | 1 | 2 |
| 2024 September | 10 | 3 | 13 |
| 2024 August | 5 | 1 | 6 |
| 2024 July | 9 | 0 | 9 |
| 2024 June | 10 | 3 | 13 |
| 2024 May | 10 | 3 | 13 |
| 2024 April | 8 | 2 | 10 |
| 2024 March | 10 | 5 | 15 |
| 2024 February | 14 | 2 | 16 |
| 2024 January | 10 | 1 | 11 |
| 2023 December | 9 | 4 | 13 |
| 2023 November | 9 | 2 | 11 |
| 2023 October | 13 | 4 | 17 |
| 2023 September | 3 | 2 | 5 |
| 2023 August | 8 | 1 | 9 |
| 2023 July | 9 | 4 | 13 |
| 2023 June | 20 | 0 | 20 |
| 2023 May | 24 | 1 | 25 |
| 2023 April | 18 | 1 | 19 |
| 2023 March | 16 | 1 | 17 |
| 2023 February | 12 | 10 | 22 |
| 2023 January | 8 | 9 | 17 |
| 2022 December | 7 | 6 | 13 |
| 2022 November | 19 | 21 | 40 |
| 2022 October | 10 | 12 | 22 |
| 2022 September | 13 | 10 | 23 |
| 2022 August | 9 | 13 | 22 |
| 2022 July | 11 | 4 | 15 |
| 2022 June | 9 | 7 | 16 |
| 2022 May | 17 | 7 | 24 |
| 2022 April | 11 | 8 | 19 |
| 2022 March | 8 | 7 | 15 |
| 2022 February | 8 | 6 | 14 |
| 2022 January | 16 | 6 | 22 |
| 2021 December | 13 | 14 | 27 |
| 2021 November | 9 | 8 | 17 |
| 2021 October | 12 | 10 | 22 |
| 2021 September | 10 | 11 | 21 |
| 2021 August | 8 | 9 | 17 |
| 2021 July | 7 | 4 | 11 |
| 2021 June | 12 | 12 | 24 |
| 2021 May | 13 | 7 | 20 |
| 2021 April | 20 | 16 | 36 |
| 2021 March | 7 | 11 | 18 |
| 2021 February | 13 | 9 | 22 |
| 2021 January | 7 | 15 | 22 |
| 2020 December | 13 | 6 | 19 |
| 2020 November | 8 | 9 | 17 |
| 2020 October | 7 | 4 | 11 |
| 2020 September | 6 | 7 | 13 |
| 2020 August | 8 | 4 | 12 |
| 2020 July | 4 | 4 | 8 |
| 2020 June | 8 | 19 | 27 |
| 2020 May | 14 | 9 | 23 |
| 2020 April | 12 | 12 | 24 |
| 2020 March | 9 | 5 | 14 |
| 2020 February | 9 | 6 | 15 |
| 2020 January | 4 | 6 | 10 |
| 2019 December | 17 | 6 | 23 |
| 2019 November | 9 | 10 | 19 |
| 2019 October | 12 | 0 | 12 |
| 2019 September | 13 | 3 | 16 |
| 2019 August | 8 | 0 | 8 |
| 2019 July | 11 | 7 | 18 |
| 2019 June | 27 | 10 | 37 |
| 2019 May | 73 | 8 | 81 |
| 2019 April | 23 | 2 | 25 |
| 2019 March | 8 | 1 | 9 |
| 2019 February | 19 | 2 | 21 |
| 2019 January | 5 | 4 | 9 |
| 2018 December | 3 | 2 | 5 |
| 2018 November | 14 | 3 | 17 |
| 2018 October | 9 | 2 | 11 |
| 2018 September | 5 | 0 | 5 |
| 2018 August | 4 | 0 | 4 |
Show all
