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Anti-parietal cell autoantibodies (PCA) in primary biliary cirrhosis: a putative marker for recurrence after orthotopic liver transplantation?
Sandra Ciesek*, Thomas Becker**, Michael P. Manns*, Christian P. Strassburg*,*
* Department of Gastroenterology, Hepatology and Endocrinology, Medical School, Hannover, Germany
** Department of General, Visceral and Transplant Surgery, Medical School, Hannover, Germany
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          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A&#46;</span> Detection of &#945;nti-PCA&#58; Anti-PCA was significantly more frequent in patients with PBC recurrence after liver transplantation but also in those PBC patients that developed recurrence before OLT &#40;&#42; p &#60; 0&#46;01&#41;&#46; <span class="elsevierStyleBold">B&#46;</span> Recurrence-free survival curves after liver transplantation for PCA positive and negative patients with PBC&#58; While all patients with PCA develop PBC recurrence within 15 years after OLT&#44; none of the PCA negative patients showed clinical signs of PBC recurrence&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Primary biliary cirrhosis &#40;PBC&#41; is a chronic cholestatic liver disease characterized by the destruction of interlobular and septal bile ducts&#44; leading to the development of fibrosis and cirrhosis&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Genetic susceptibility as a predisposing factor for PBC has been suggested and involves MHC and non-MHC genes&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In addition environmental factors have been suggested to include infectious and environmental etiologies&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The diagnosis is based on a combination of clinical features&#44; abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies &#40;AMA&#41; in serum directed against PHD-E2 antigen&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Orthotopic liver transplantation &#40;OLT&#41; remains the definitive treatment for decompensated liver disease secondary to PBC&#46; OLT for primary biliary cirrhosis is characterized by disease recurrence with typical clinical&#44; biochemical&#44; and histologic changes in up to one third of pa-tients&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Although the presence of recurrent PBC does not appear to affect either graft or patient survival rates as severely as in HCV and PSC&#44; the diagnosis of recurrence requires a cholestatic profile and a typical histology representing a challenge for transplant hepatologists&#46; Previous studies identified donor and recipient age and warm&#47;cold ischemic time as a risk factor for PBC recurrence&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> While the initial diagnosis is based on antimitochondrial antibodies &#40;AMA&#41;&#44; which persist after OLT<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> they are thus of limited value for the diagnosis of PBC re-currence&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Aim of this study was to identify autoimmune serological parameters associated with recurrent PBC&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Patients and Methods</span><p id="p0010" class="elsevierStylePara elsevierViewall">All patients who previously had undergone liver transplantation at the Hannover Medical School between 1992 and 2006 were evaluated&#46; Of those&#44; 72 patients underwent liver transplantation with histologically confirmed PBC&#46; Post-transplantation immunosuppressive therapy included cyclosporine A or tacrolimus&#44; corticosteroids and&#47;or mycophenolate mofetil&#46; Cyclosporine A doses were adjusted to maintenance blood levels between 100-200 ng&#47;mL&#46; Tacrolimus doses were adjusted to maintenance blood levels between 5-15 ng&#47;mL&#46; Methylprednisolone was given as a bolus injection of 500 mg at the time of reperfu-sion&#44; and 250 mg were administered six hours post-operatively&#46; Prednisolone was started at 100 mg orally on day 1 after OLT and then individually tapered down to 5-7&#46;5 mg&#46; In addition&#44; some patients also received azathioprin&#44; mycophenolate mofetil or monoclonal anti-interleukin-2 receptor antibodies&#46;</p><p id="p0015" class="elsevierStylePara elsevierViewall">All 72 patients with histologically confirmed PBC were analysed for the following autoimmune serolo-gical parameters&#58; antimitochondrial antibodies &#40;AMA&#41;&#44; antinuclear antibodies &#40;ANA&#41;&#44; anti parietal cell antibodies &#40;anti PCA&#41;&#44; anti-soluble liver antigen &#40;SLA&#41;&#44; anti liver-kidney-microsome antibody &#40;LKM&#41; and anti-pyruvate dehydrogenase-E2 &#40;anti PHD-E2&#41; before and after OLT&#46; Indirect immunofluorescence was used for the detection of AMA&#44; anti PHD-E2&#44; ANA&#44; PCA&#44; SLA&#44; anti-LKM antibodies as previously described&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Titers above 1&#58;80 were considered to be significantly positive&#46; Additionally&#44; we studied im-munosuppressive therapy and outcome of these patients&#46;</p><p id="p0020" class="elsevierStylePara elsevierViewall">Gold standard for the diagnosis of recurrent PBC was a liver biopsy demonstrating the characteristic histologic features&#46; Patients did not receive routine biopsies&#44; but the indication for liver histology was indication-based&#46; Recurrent PBC was based on the presence of epitheloid granulomas&#44; florid bile duct lesions&#44; bile duct injury&#44; and lymphoid aggregates in liver specimens&#44; and biochemical cholestasis&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Other pathology or disorders such as acute and chronic rejection&#44; graft versus host disease&#44; biliary obstruction&#44; cholangitis and other infections&#44; viral hepatitis or drug toxicity were excluded&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">Furthermore during pre OLT diagnostic work-up all patients received an upper intestinal endoscopy&#44; which included a histological assessment of gastric mucosa in all 72 patients and therefore the opportunity to detect <span class="elsevierStyleItalic">H&#46; pylori</span> infection&#46; <span class="elsevierStyleItalic">H&#46; pylori</span> was identified following standard microbiology and biochemical techniques&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Patient and graft survival</span><p id="p0030" class="elsevierStylePara elsevierViewall">Between 1992 and 2006 72 patients &#40;68 female&#44; 4 male&#41; underwent OLT with histologically confirmed PBC&#46; Median follow up was 123 months&#46; Five patients died because of sepsis &#40;2&#41;&#44; cerebral vascular attack &#40;1&#41;&#44; or cholestatic liver failure &#40;2&#41; within 11 years after OLT&#44; 2 patients required re-transplantation because of bile duct necrosis and thrombosis of the hepatic artery &#40;11 months and 1 month after liver transplantation&#41;&#46; Overall patient survival was 85&#46;67&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Autoantibodies after liver transplantation</span><p id="p0035" class="elsevierStylePara elsevierViewall">Nearly all patients &#40;94&#37;&#41; were AMA positive before liver transplantation&#44; while only 6&#37; were negative before OLT&#46; Interestingly&#44; AMA persisted in 55 &#40;76&#37;&#41; patients after OLT <a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>&#44; <a class="elsevierStyleCrossRef" href="#t0005">Table 1A</a>&#41;&#46; Anti-PDH-E2 directed AMA was positive in 26 out of 66 &#40;39&#37;&#41; patients before and in 27 out of 64 patients &#40;42&#37;&#41; after OLT&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0040" class="elsevierStylePara elsevierViewall">ANA were detectable in 17 out of 72 patients before and in 21 patients after OLT &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1A</a>&#41;&#46; 28 out of 68 patients had anti-parietal cell antibodies &#40;PCA&#44; 41&#37;&#41; before and 34 out of 72 patients &#40;47&#37;&#41; had PCA after OLT&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Recurrence of primary biliary cirrhosis after liver transplantation</span><p id="p0045" class="elsevierStylePara elsevierViewall">Liver biopsies were obtained in 34 patients post OLT upon clinical suspicion&#44; and recurrent PBC diagnosed in 20&#47;72 &#40;28&#37;&#41; after a mean of 71 months &#40;range 13-161&#41; &#40;<a class="elsevierStyleCrossRef" href="#t0010">Table 1B</a>&#41;&#46; Interestingly&#44; anti-PCA were detected in 100&#37; of patients with recurrence before and following transplantation &#40;<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>&#41;&#46; Furthermore 15 out of 28 patients with anti-PCA before OLT &#40;54&#37;&#41; developed recurrence during follow-up&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="f0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Immunosuppression</span><p id="p0050" class="elsevierStylePara elsevierViewall">51 patients &#40;71&#37;&#41; received cyclosporine A and 21 patients &#40;29&#37;&#41; tacrolimus as primary immunosu-ppressive agents&#46; From the 20 patients with PBC recurrence after orthotopic liver transplantation&#44; 12 patients had an immunosuppressive regime with ci-closporine &#40;60&#37;&#41; and 8 patients received tacrolimus&#46; There was no significant difference between initial immunosuppression of patients who developed PBC recurrence compared to the patients who did not develop PBC recurrence&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Incidence of <span class="elsevierStyleItalic">Helicobacter pylori</span></span><p id="p0055" class="elsevierStylePara elsevierViewall">Twenty-eight &#40;38&#46;8&#37;&#41; of the 72 patients were positive for <span class="elsevierStyleItalic">H&#46; pylori&#46;</span> The prevalence of <span class="elsevierStyleItalic">H&#46; pylori</span> was not significantly different in the 20 patients&#44; who suffered from PBC recurrence after OLT &#40;40&#37; <span class="elsevierStyleItalic">H&#46; pylori</span> positive before OLT&#44; <a class="elsevierStyleCrossRef" href="#t0005">Table 1A</a> and <a class="elsevierStyleCrossRef" href="#t0010">B</a>&#41;&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Discussion</span><p id="p0060" class="elsevierStylePara elsevierViewall">Although overall survival in a long-term study with a follow-up of approximately II years of patients with primary biliary cirrhosis after OLT is very good &#40;85&#46;6&#37;&#41;&#44; recurrent PBC was diagnosed in 28&#37; of all patients&#46; These data are in line with several other studies&#44; which described PBC recurrence after orthotopic liver transplantation in up to one-third of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="p0065" class="elsevierStylePara elsevierViewall">To predict recurrent disease&#44; a number of putative risk factors such as donor and recipient age&#44; cold and warm ischaemic time&#44; and tacrolimus-based immuno-suppression&#44; have been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However&#44; the diagnosis remains a challenge to transplant hepatologists&#46; In this study cohort no difference between tacroli-mus-based immunosuppression compared to immuno-suppression with cyclosporine A was observed regarding the prevalence of recurrent PBC&#46;</p><p id="p0070" class="elsevierStylePara elsevierViewall">The analysis of the autoantibody profiles led to an interesting association not previously reported&#46; Anti-PCA antibodies detected prior to transplantation were found to be significantly associated with PBC recurrence after OLT&#46; While antimitochon-drial antibodies have a high specificity for PBC and serve as serological confirmation of the diagnosis&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> they did not have a predictive function for the recurrence of PBC in this study&#44; which is in line with several other studies which demonstrate that AMA had no influence of PBC recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Additional autoantibodies such as ANA and anti-PCA are detectable in a subgroup of PBC patients&#44; but to date have limited diagnostic relevance other than in AMA-negative PBC&#44; in which specific ANA exhibit a high specificity for the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Consistent with these findings&#44; we did not observe any significant differences in the number of ANA&#44; anti-PDH-E2 or anti-PCA positive patients before and after OLT&#46; Although unspecific for the diagnosis of PBC&#44; anti-PCA prevalence increased slightly after OLT&#44; and was present in all patients who suffered from recurrent PBC&#46; Recurrent PBC developed in 54&#37; of patients with anti-PCA before OLT&#46; This observation should be approved in a future prospective trial in order to find out if these autoantibodies may represent a simple and cost effective diagnostic marker for the likelihood of PBC recurrences after OLT&#46; Importantly&#44; we could not detect any correlation between disease recurrence after OLT and PCA antibodies in 14 patients with autoimmune hepatitis &#40;AIH&#41;&#58; out of 5 patients with AIH recurrence after OLT only one had detectable PCA antibodies &#40;data not shown&#41;&#46;</p><p id="p0075" class="elsevierStylePara elsevierViewall">PCA have been primarily described in autoimmune atrophic gastritis and in atrophic gastritis following helicobacter infection&#46; PCA autoantibodies have been associated with the severity of gastritis&#44; gastric mucosa atrophy as well as with apoptosis of the mucosa of the gastric corpus&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Human PCA sera react with recombinant H&#43;&#44; K&#43; ATPase&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> and may indicate an autoimmune reaction suggestive of the presence of H &#43;&#44;K&#43; ATPase specific T helper cells found in autoimmune gastritis&#91;18&#93;&#46; From a clinical point of view PCA are classical markers associated with pernicious anemia and gastric atrophy&#46; Since they have a high frequency of up to over 50&#37; in H&#46; pylori infected individuals an etiological link has been suggested&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> However&#44; the role of <span class="elsevierStyleItalic">H&#46; pylori</span> as a cause of autoimmune atrophic gastritis is controversially discussed&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In many features atrophic gastritis after prolonged persistent <span class="elsevierStyleItalic">H&#46; pylori</span> infection resembles autoimmune atrophic gastritis without <span class="elsevierStyleItalic">H&#46; pylori</span> infection&#46; In addition&#44; PCA are detected in patients with atrophic gastritis and appear to correlate with disease activity and stage but are also detected in asymptomatic individuals with <span class="elsevierStyleItalic">H&#46; pylori</span> infection&#46; The relationship of PCA and PBC is unclear&#46; T cell-mediated au-toreacitivity against transporter protein&#44; which is also expressed in biliary epithelium may represent a link of these autoantibodies to PBC&#44; which is primarily mediated by autoreactive T cells&#46; In order to analyze the findings in respect to <span class="elsevierStyleItalic">Helicobacter</span> we evaluated&#44; whether our cohort of PBC Helicobacter infection&#46; None of the 72 patients had signs of atro-phic gastritis upon pre OLT gastroscopy&#46; Interestingly&#44; in this study&#44; we also failed to detect significant differences of <span class="elsevierStyleItalic">H&#46; pylori</span> prevalence between the PBC cohort with recurrence compared to all PBC patients after OLT&#44; which is consistend with other studies&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> It is a diagnostically significant observation that PCA autoantibodies occurred in 41&#37; of PBC patients before OLT and therefore appear to be associated with PBC&#44; but in the group of recurrent PBC after OLT this marker was present in all patients&#46;</p><p id="p0080" class="elsevierStylePara elsevierViewall">Our data suggest that PCA autoantibodies&#44; which are not specific for PBC&#44; appear to indicate a higher probability of PBC recurrence after OLT&#46; If PCA may really represent a facile marker of risk stratification&#44; should be evaluated in future prospective studies&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:7 [
        0 => array:3 [
          "identificador" => "xres1217533"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abs0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1132914"
          "titulo" => "Key words"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        3 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Patients and Methods"
        ]
        4 => array:3 [
          "identificador" => "sec0015"
          "titulo" => "Results"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Patient and graft survival"
            ]
            1 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Autoantibodies after liver transplantation"
            ]
            2 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Recurrence of primary biliary cirrhosis after liver transplantation"
            ]
            3 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Immunosuppression"
            ]
            4 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Incidence of Helicobacter pylori"
            ]
          ]
        ]
        5 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Discussion"
        ]
        6 => array:1 [
          "titulo" => "Reference"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Key words"
          "identificador" => "xpalclavsec1132914"
          "palabras" => array:5 [
            0 => "Primary biliary cirrhosis"
            1 => "Autoantibodies"
            2 => "PCA"
            3 => "Orthotopic liver transplantation"
            4 => "Anti-parietal cell autoantibodies"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abs0005" class="elsevierStyleSection elsevierViewall"><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Introduction&#46;</span> Liver transplantation &#40;OLT&#41; for primary biliary cirrhosis &#40;PBC&#41; is characterized by disease recurrence of up to one third of patients&#46; The diagnosis of recurrence requires a cholestatic profile and a typical histology representing a challenge for transplant hepatologists&#46; Antimitochondrial antibodies &#40;AMA&#41; establish the initial diagnosis&#44; persist after OLT&#44; and are thus of limited value for the diagnosis of recurrence&#46; Aim of this analysis was to identify serological parameters associated with recurrent PBC&#46;</p><p id="sp1025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Patients and methods&#46;</span> OLT performed between 1992 and 2006 at Hannover Medical School were evaluated retrospectively including histology before and after OLT&#44; autoimmune serological parameters and clinical characteristics&#46;</p><p id="sp2025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Results&#46;</span> Between 1992 and 2006 72 patients underwent OLT with histologically confirmed PBC&#46; Median follow up was 123 months&#46; AMA persisted in 55 &#40;767&#41; patients&#46; Anti-parietal cell antibodies &#40;PCA&#41; were detectable in 41&#37; of the patients before and 47&#37; after OLT&#46; Liver biopsies were obtained in 34 patients post OLT upon clinical suspicion&#44; and recurrent PBC diagnosed in 28&#37; after a mean of 71 months &#40;range 13-161&#41;&#46; Anti-PCA were detected in 100&#37; of patients with recurrence before and following transplantation&#44; 54&#37; of patients with anti-PCA before OLT developed recurrence during follow-up&#46; There were no differences in immunosuppressive regimen&#46;</p><p id="sp3025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Discussion&#46;</span> Although unspecific for the diagnosis of PBC&#44; anti-PCA prevalence increased after OLT&#44; and was 100&#37; in patients with recurrent PBC&#46; Recurrent PBC developed in 54&#37; of patients with anti-PCA before OLT suggesting a diagnostic role of anti-PCA as a simple and cost effective marker of recurrence&#46;</p></span>"
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "f0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Detection of antibodies before and after orthotopic liver transplantation in patients with PBC&#46; Indirect immunofluorescence was used for the detection of AMA&#44; anti PHD-E2&#44; PCA&#44; antibodies as previously described&#46;<span class="elsevierStyleSup">7</span> There was no significant difference in detection of AMA&#44; anti PHD-E2 or PCA&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "f0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A&#46;</span> Detection of &#945;nti-PCA&#58; Anti-PCA was significantly more frequent in patients with PBC recurrence after liver transplantation but also in those PBC patients that developed recurrence before OLT &#40;&#42; p &#60; 0&#46;01&#41;&#46; <span class="elsevierStyleBold">B&#46;</span> Recurrence-free survival curves after liver transplantation for PCA positive and negative patients with PBC&#58; While all patients with PCA develop PBC recurrence within 15 years after OLT&#44; none of the PCA negative patients showed clinical signs of PBC recurrence&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "t0005"
        "etiqueta" => "Table 1A"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:1 [
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                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="center" valign="middle" scope="col"><span class="elsevierStyleBold">Age &#40;in years&#41;&#58;</span> SI &#40;range 25-67&#41;&nbsp;\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="center" valign="middle" scope="col">&nbsp;\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="center" valign="middle" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col"><span class="elsevierStyleBold">Sex&#58;</span> 68 female&#47;4 male&nbsp;\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="center" valign="middle" scope="col">&nbsp;\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="center" valign="middle" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col"><span class="elsevierStyleBold">Median follow up &#40;in moths&#41;&#58;</span> 123&nbsp;\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="center" valign="middle" scope="col">&nbsp;\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="center" valign="middle" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">&nbsp;\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="center" valign="middle" scope="col">pre&nbsp;\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="center" valign="middle" scope="col">post&nbsp;\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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">AMA positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">68&#47;72 &#40;94&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">55&#47;72 &#40;76&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">ANA positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">17&#47;72 24&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">21&#47;72 &#40;29&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">AntiPDHE2 positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">17&#47;72 &#40;24&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">21&#47;72 &#40;29&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">antiPCA positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">28&#47;68 &#40;41&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">34&#47;72 &#40;47&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">bilirubine &#40;mg&#40;dl&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">5&#46;2 &#40;1-52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">1&#46;8 &#40;0&#46;1-33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">biopsy available&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">72&#47;72 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">34&#47;72 &#40;47&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle"><span class="elsevierStyleItalic">H&#46; pylori</span> positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">28&#47;72 &#40;38&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">n&#46;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Characteristics and antibody profile of 72 patients with PBC who underwent liver transplantation&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "t0010"
        "etiqueta" => "Table 1B"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
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              "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="center" valign="middle" scope="col"><span class="elsevierStyleBold">Age &#40;in years&#41;&#58;</span> 52 &#40;range 25-63&#41;&nbsp;\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="center" valign="middle" scope="col">&nbsp;\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="center" valign="middle" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col"><span class="elsevierStyleBold">Sex&#58;</span> 19 female&#47;4 male&nbsp;\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="center" valign="middle" scope="col">&nbsp;\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="center" valign="middle" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col"><span class="elsevierStyleBold">Median follow up &#40;in moths&#41;&#58;</span> 71 &#40;13-161&#41;&nbsp;\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="center" valign="middle" scope="col">&nbsp;\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="center" valign="middle" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="middle" scope="col">&nbsp;\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="center" valign="middle" scope="col">pre&nbsp;\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="center" valign="middle" scope="col">post&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="middle">AMA positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">18&#47;20 &#40;90&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">16&#47;20 &#40;80&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">5&#47;20 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">6&#47;20 &#40;33&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle"><span class="elsevierStyleBold">20&#47;20 &#40;100&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">9&#46;8 &#40;5&#46;6-33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">20&#47;20 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">20&#47;20 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="center" valign="middle">8&#47;20 &#40;40&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="middle">n&#46;d&nbsp;\t\t\t\t\t\t\n
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Article information
ISSN: 16652681
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