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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hepatitis B virus &#40;HBV&#41; infection has decreased in frequency in kidney transplant recipients &#40;KTR&#41; due to the reinforcement of vaccination policies in the Chronic Kidney Disease &#40;CKD&#41; population and increased precautions to prevent transmission of the HBV among dialysis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a> Reactivation of HBV infection in KTR is associated with important morbidity and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">2</span></a> Immunosuppressive &#40;IS&#41; drugs used to prevent graft rejection blunt B and T cell functions and that permits HBV replication and viral protein expression on the surface of the infected hepatocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> Reactivation is more frequent in patients who are HBsAg-positive&#44; but it can also occur in patients with resolved HBV infection &#40;HBsAg-negative and anti-HBc-positive&#41;&#44; since the virus can still replicate within the hepatocytes&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">4&#44;5</span></a> Data are scarce and conflicting regarding the risk of HBV reactivation in this subset of patients&#46; Reported rates of reactivation are variable&#59; while some authors claim that the risk is negligible regardless of anti-HBs status&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">6</span></a> others have published rates ranging from 1 to 6&#46;5&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">7&#44;8</span></a> It has been suggested that in these patients the presence of anti-HBs antibodies may provide protection against HBV reactivation<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">8&#8211;10</span></a> but there are too few data about the proportion of renal transplant patients with resolved HBV infection and with positive anti-HBs titers that lose immunity during follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> Thus&#44; it remains unclear regarding what kind of monitoring is needed and whether these patients would benefit from antiviral prophylaxis during the post-transplant period&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In this study we aim to retrospectively evaluate the risk of HBV reactivation in KTR with previously resolved infection in a Portuguese Kidney Transplant Centre&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study population</span><p id="par0015" class="elsevierStylePara elsevierViewall">We designed a retrospective cohort study enrolling all consecutive patients who underwent a kidney transplant at our center in the period between January 1994 and December 2014 who had serological evidence of resolved HBV infection at the time of transplantation&#46; Patients were followed until September 30<span class="elsevierStyleSup">th</span>&#44; 2015&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Resolved HBV infection was defined as seropositivity for anti-HBc without detectable HBsAg&#44; and normal liver enzymes &#40;ALT&#44; AST&#41;&#44; with or without anti-HBs positive titers&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Cutoff for positive anti-HBs was defined as &#62;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml and loss of immunity was defined by fall of anti-HBs to levels bellow 10<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml and reactivation was defined according to current guidelines by a viral load &#62;2000<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Exclusion criteria were&#58; no information regarding viral status at the time of transplant&#44; if they had a positive HBsAg&#44; primary non-functioning allograft&#44; and allograft survival less than 30 days&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Acute rejection &#40;BPAR&#41; was defined by biopsy-proven histological changes compatible with either cellular or antibody-mediated rejection according to the latest Banff classification update available at the time of diagnosis&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Analyzed data</span><p id="par0040" class="elsevierStylePara elsevierViewall">Data were collected from the patients&#8217; medical records&#46; Demographic data included age&#44; sex&#44; time on dialysis&#44; cause of CKD and number of previous transplants&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Data regarding HBV serological status&#44; IS regimen&#44; use of antiviral prophylaxis&#44; and occurrence of acute rejection were collected&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In the evaluation of kidney transplant candidates and upon admission for renal transplant&#44; liver enzymes &#40;ALT&#44; AST&#41; and routine HBV serological markers were obtained from all transplant candidates&#46; Our transplant center did not test HBV viral load in KTR with resolved HBV infection&#44; and post-transplant serological HBV testing did not follow a systematic protocol&#44; thus&#44; the frequency of monitoring was left at the discretion of the attending Nephrologist&#46; All patients&#8217; post-transplant serological markers were recorded during the follow-up monitoring&#59; the date of reactivation or the date of the last serological testing&#44; whichever came first&#44; was considered the end of follow-up&#46; The follow-up appointments were scheduled according to our Institution&#39;s protocol but could be adjusted by the Nephrologist according to the patient&#39;s clinical status&#46; Serological markers were obtained using hemi luminescent methods &#40;Prism HBsAg<span class="elsevierStyleSup">&#174;</span> and Prism HBcore<span class="elsevierStyleSup">&#174;</span>&#44; Abbott&#59; Architect Anti-HBs<span class="elsevierStyleSup">&#174;</span>&#44; Abbott&#41;&#44; and HBV DNA was obtained using multiplex nucleic acid test&#44; COBAS<span class="elsevierStyleSup">&#174;</span> TaqScreen MPX Test&#44; version 2&#46;0&#44; Roche&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">Descriptive statistics were recorded as median and interquartile range &#40;IQR&#41; intervals&#46; Univariate analysis was performed using Cox regression analysis&#59; covariates with <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1 were tested in a gender-adjusted multivariate model&#46; Cox multiple regression analysis using the forward conditional method was performed to assess independent risk factors for loss of anti-HBs&#44; and significance was considered if <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; Statistical analysis was performed using IBM SPSS version 23 &#40;IBM Corp&#46; Released 2016&#46; Armonk&#44; NY&#58; IBM Corp&#41;&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Patient data</span><p id="par0060" class="elsevierStylePara elsevierViewall">From the 1151 kidney transplant recipients performed during the study period the following were excluded&#58; 137 without record of HBV serological status&#44; 7 HBsAg-positive patients&#44; 28 with primary graft failure and 13 patients with graft survival &#60;30 days&#46; From the remaining 966 patients&#44; 867 were anti-HBc negative and the remaining 99 patients had evidence of resolved infection at the time of surgery&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Four of the 99 patients had no information regarding post-transplant serological data and thus were excluded from the analysis&#46; Of the remaining ninety-five patients&#44; nine had anti-HBs &#60;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Baseline characteristics of the study population are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Patient and graft survival</span><p id="par0075" class="elsevierStylePara elsevierViewall">Patients were followed at our Outpatient Clinic for a median time of 93 months &#40;IQR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>58&#8211;146&#41;&#46; Follow-up time did not differ significantly between patients who lost anti-HBs compared to those who did not &#40;median follow-up time 68 vs 73 months&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;789&#41;&#46; In patients who lost anti-HBs compared to those who did not 5 and 10 year patient survival rates were 93&#46;9&#37; and 89&#46;9&#37;&#44; while 5 and 10 year allograft survival rates were 95&#46;95&#37; and 90&#46;9&#37;&#44; respectively&#46; During the study period&#44; 13 patients died with a functioning allograft and 14 lost graft function&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Seventeen cases of BPAR were recorded&#44; nine of which were treated with pulses of metilprednisolone &#40;MPD&#41;&#59; 1 with MPD plus intravenous immunoglobulin&#44; 5 with anti-thymocyte globulin &#40;ATG&#41; and 1 with MPD plus ATG&#46; Treatment was not known in the remaining case&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Immunosuppression</span><p id="par0085" class="elsevierStylePara elsevierViewall">IS regimens used at the time of transplantation and at the date of the last follow-up are presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; Most patients were treated with a triple drug regimen&#59; additionally&#44; induction imunosuppression consisted of basiliximab in 30 patients &#40;31&#46;6&#37;&#41;&#44; ATG in 17 &#40;17&#46;9&#37;&#41; and daclizumab in 2 &#40;2&#46;1&#37;&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Twenty-one patients received ATG as induction therapy or as part of acute rejection treatment&#46; At the end of follow-up all patients were on a low-dose steroid regimen consisting of 5<span class="elsevierStyleHsp" style=""></span>mg of prednisolone or equivalent per day&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">From the initial cohort of 99 patients&#44; we were able to collect data regarding previous antiviral treatment on 88 patients &#40;88&#46;9&#37;&#41;&#44; confirming that none of those had been treated for HBV&#44; having had spontaneous negativation of HBsAg&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">None of the patients had a history of HBV antiviral prophylaxis or use of rituximab&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Loss of immunity and reactivation</span><p id="par0105" class="elsevierStylePara elsevierViewall">During the time of follow-up 95 patients had 339 HBV serological tests&#44; which corresponded to a median of 3 tests per patient &#40;IQR 1&#8211;5&#41;&#44; or 0&#46;44 tests per patient-year&#46; Twelve patients &#40;13&#46;9&#37;&#41; lost immunity and two patients &#40;2&#37;&#41; showed evidence of reactivation&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The first case was a 67 year-old male who had received a cadaveric allograft in 2007&#59; at the time of transplantation anti-HBc and anti-HBs were positive &#40;7&#46;74 and 986<span class="elsevierStyleHsp" style=""></span>mUI&#47;ml&#44; respectively&#41;&#46; Immunosuppression consisted of a triple regimen of cyclosporine&#44; MMF &#40;mycophenolate mofetil&#41; and prednisolone&#46; No major complications occurred until 2013&#44; when he was admitted with a history of cough and weight loss&#46; <span class="elsevierStyleItalic">Aspergilus fumigatus</span> was isolated in a Bronchoalveolar sample and itraconazol was started&#46; Two weeks later&#44; liver enzymes levels increased&#59; itraconazol toxicity was suspected and the drug was stopped&#46; HBV serological markers were compatible with reverse seroconversion with reappearance of HBsAg&#44; and reactivation was diagnosed as the patient had a viral load of 1&#46;7<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">8</span><span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#46; Anti-HBs titer was 50&#46;7<span class="elsevierStyleHsp" style=""></span>mUI&#47;ml&#46; Liver biopsy showed mild cholestasis&#44; inflammatory infiltrate&#44; ground-glass hepatocytes&#44; nuclear expression of HBcAg and absence of HBsAg&#46; The patient was started on entecavir&#44; but expired a week later due to acute liver failure&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The second patient was a 42 year-old male who had received its 3<span class="elsevierStyleSup">rd</span> transplant from a deceased donor in 2006&#59; at the time of transplantation anti-HBc was 10&#46;7<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml and anti-HBs was 2&#46;67<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml&#46; Induction immunosuppression included ATG and maintenance imunosuppression consisted of tacrolimus&#44; MMF and prednisolone&#59; baseline creatinine was 3&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46; He was admitted with Pneumonia in 2014&#46; Upon admission&#44; liver enzymes were increased&#46; HBV serological markers showed evidence of reverse seroconversion with reappearance of HBsAg&#44; and reactivation was diagnosed as the patient had a viral load of 1&#46;6<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">4</span><span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#46; Anti-HBs was 1&#46;6<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml&#46; Entecavir was started with disappearance of HBsAg and viremia&#44; which became undetectable&#46; At the time of discharge serum creatinine was 4<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46; The patient lost his graft 10 months later due to chronic allograft nephropathy and restarted hemodialysis&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Of the 12 patients who lost immunity during follow-up&#44; the choice of IS drug did not seem to have any impact&#46; Particularly&#44; the use of MMF and use of ATG were not associated with loss of immunity &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;241 and 0&#46;524&#44; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">table 3</a>&#41;&#46; In the multivariate model adjusted for gender&#44; older age &#40;&#62;60 years-old&#41; was associated with loss of immunity &#40;HR 4&#46;853&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#44; CI &#91;1&#46;235&#59; 19&#46;071&#91;&#41; as was the presence of BPAR &#40;HR 5&#46;921&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;015&#44; CI &#91;1&#46;416&#59; 24&#46;759&#91;&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0125" class="elsevierStylePara elsevierViewall">HBV reactivation is a potentially fatal condition with mortality rates reported as high as 25&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">4</span></a> In our study the rate of HBV reactivation in patients with previously resolved infection was approximately 2&#37;&#44; resulting in death in one patient&#46; This highlights the importance of assessing potential risk factors for reactivation since prophylaxis can prevent its occurrence&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Only 4 retrospective studies addressed the risk of reactivation in HBsAg-negative and anti-HBc-positive KTR&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">7&#8211;9&#44;13</span></a> The number of patients was small and reactivation rates varied from 0 to 6&#46;5&#37;&#46; Risk factors for reactivation included older age&#44; presence of rejection&#44; use of rituximab and loss&#47;absence of anti-HBs&#44; but findings were not consistent among the 4 studies possibly due to the small number of cases in each study&#46; We found that 13&#46;9&#37; of the patients with resolved HBV infection and positive anti-HBs titers lost immunity&#46; In our series&#44; older age and presence of BPAR were independent risk factors for loss of anti-HBs&#44; which in its turn might increase the risk of reactivation&#46; Age can be a risk factor since older patients tend to produce weaker immunological response and tend to have lower levels of anti-HBs&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">8</span></a> Acute rejection is thought to be a risk factor through an increase of immunosuppression used for its treatment and this has been confirmed in other solid-organ transplants &#40;SOT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">8</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">It is postulated that IS agents such as B-Cell depleting drugs like rituximab are associated with a high risk of HBV reactivation even in patients with resolved HBV infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">4&#44;13&#44;14</span></a> In our study&#44; none of our patients had received rituximab&#46; Relationship between other drugs used in kidney transplantation and reactivation is less consistent&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">8&#44;15</span></a> We found no association between the type of IS drug used and loss of anti-HBs&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Our study is limited by its retrospective nature&#44; and we are unaware of when the patients included in our study acquired HBV infection and the timing of their acquisition of positive anti-HBs titers after the infection&#46; We were also unable to assess previous HBV vaccination history&#46; Both could influence anti-HBs titers and the risk of HBV reactivation after renal transplantation&#44; although there are no studies addressing this issue&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The retrospective nature of our study and the absence of HBV genotype testing in our reactivation cases do not allow us to completely rule out the possibility of re-infection instead of reactivation&#46; However&#44; both patients were diagnosed in an inpatient setting and none had recent history of high risk behavior or contact with blood products&#46; Besides&#44; both were highly immunosuppressed &#8211; one of the patients had a severe opportunistic infection and the other a high cumulative IS load given the history of 3 transplants&#44; which favors the hypothesis of reactivation&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Our transplant center did not test HBV viral load in KTR with resolved HBV infection&#44; and serological HBV testing did not follow a systematic protocol&#46; This way&#44; we cannot assure that asymptomatic reactivations might have been missed during the follow-up period&#44; and this way we might have underestimated the reactivation rates in our population&#46; At last&#44; the small number of reactivation cases did not allow us to infer about potential risk factors for reactivation&#46; Our study however has some specific strengths&#59; in an era of declining HBV incidence in the Western Countries&#44; we have managed to retrieve a fairly high number of patients and a long term follow-up&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The American Association for the Study of Liver Diseases recommends routine use of appropriate antiviral prophylaxis in all patients who are HBsAg-positive prior to or at the initiation of chemotherapy&#44; immunosuppressive therapy&#44; hematopoietic stem cell transplantation&#44; or solid organ transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a> When B-cell depleting agents like rituximab are used in patients with resolved infection &#40;HBsAg-negative&#44; anti-HBc-positive&#41; antiviral prophylaxis can be anticipated to result in similar risk reduction of HBV reactivation as described for HBsAg-positive patients&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">14</span></a> otherwise recommendations regarding antiviral prophylaxis in KTR with resolved HBV infection are lacking&#46; Current guidelines do not recommend using anti-HBs titer to guide initiation of prophylaxis since there is no threshold level that universally prevents HBV reactivation&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">10&#44;12&#44;14</span></a> However&#44; anti-HBs titer is still believed to confer protection against reactivation&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">8&#44;13&#44;16</span></a> Considering that loss of anti-HBs increases the risk of reactivation&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">7&#44;8&#44;17&#44;18</span></a> patients who are at increased risk of anti-HBs loss&#44; such as older patients and those with BPAR as found in our study&#44; might benefit from closer surveillance of HBV DNA levels<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">4&#44;10&#44;19</span></a> or even antiviral prophylaxis&#46; Although evidence is scarce regarding HBV DNA monitoring in patients with resolved HBV infection we suggest&#44; as a cost-effective measure&#44; a baseline measurement of HBV DNA levels for all candidates to kidney transplantation with resolved HBV infection &#40;anti-HBc positive&#44; HBsAg negative&#41; to exclude occult viral replication&#46; For those with positive HBV DNA we suggest antiviral prophylaxis starting from the time of transplantation and follow-up with periodical assessment of aminotransferases and HBV DNA levels&#46; If the initial baseline HBV DNA is negative&#44; we suggest serological HBV follow-up &#40;HBsAg and anti-HBs&#41; and close monitoring of aminotransferases levels&#46; In case of HBsAg seroreversion or elevated aminotransferases&#44; we suggest HBV DNA assessment&#46; However&#44; even with negative baseline negative HBV DNA&#59; we acknowledge that some of these patients&#44; especially if they are at higher risk of reactivation&#44; might benefit from HBV DNA surveillance from the time of transplantation&#46; In our study the small number of cases of HBV reactivation precludes any conclusion&#44; and further studies are needed&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conclusions</span><p id="par0160" class="elsevierStylePara elsevierViewall">In conclusion&#44; the risk of HBV reactivation in KTR with previous clinically resolved infection is not negligible at 2&#37;&#46; Older age and acute rejection were associated with loss of anti-HBs&#44; and these patients might benefit from closer surveillance of HBV DNA level&#46; Routine serological and&#47;or HBV viral load monitoring in HBsAg-negative&#44; anti-HBc-positive patients is recommended and should be emphasized in these patients&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Author contributions</span><p id="par0165" class="elsevierStylePara elsevierViewall">Meng C&#58; design of study&#44; data collection&#44; drafting article&#46; Belino C&#44; Pereira L&#44; Sampaio S&#44; Tavares&#58; data analysis&#44; drafting article&#46; Pinho A&#58; critical revision and statistical analysis&#46; Bustorff M&#58; design of study&#44; drafting and critical revision&#46; Sarmento A and Pestana M&#58; critical revision&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conflict of interest</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2017-09-07"
    "fechaAceptado" => "2018-02-08"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1046360"
          "palabras" => array:5 [
            0 => "Hepatitis B"
            1 => "Kidney transplantation"
            2 => "Infection"
            3 => "Reactivation"
            4 => "Risk factors"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1046359"
          "palabras" => array:5 [
            0 => "Hepatitis B"
            1 => "Trasplante renal"
            2 => "Infecci&#243;n"
            3 => "Reactivaci&#243;n"
            4 => "Factores de riesgo"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hepatitis B virus &#40;HBV&#41; reactivation in kidney transplant recipients &#40;KTR&#41; involves important morbidity and mortality&#46; Despite being more common in patients who are HBsAg-positive&#44; it may occur in patients with clinically resolved infection &#40;HBsAg-negative and anti-HBc-positive&#41;&#44; in whom the presence of the protective anti-HB antibody is thought to decrease the risk of reactivation&#46; Data regarding reactivation rates in this population are scarce&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To retrospectively evaluate the risk of HBV reactivation in KTR with previously resolved infection&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Material and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Retrospective cohort study including patients who underwent a kidney transplant between January 1994 and December 2014 with resolved HBV infection at the time of transplantation &#40;anti-HBc seropositivity without detectable HBsAg&#44; with or without anti-HB-positive antibodies and normal liver enzymes&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Out of 966 patients&#44; 95 patients with evidence of resolved HBV infection were analyzed&#44; of which 86 had a titer of anti-HBs &#62;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml&#46; Mean follow-up time was 93 months&#59; 12 patients had lost anti-HBs&#46; Two patients showed evidence of reactivation&#46; Risk factors associated with loss of anti-HBs were elderly age &#40;&#62;60&#41; and occurrence of acute graft rejection &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The risk of HBV reactivation in KTR with previously resolved infection is not negligible at 2&#37;&#46; Elderly age and acute rejection were associated with loss of anti-HBs&#44; and these patients may benefit from closer monitoring of HBV DNA levels&#46; Routine serology and&#47;or HBV viral load monitoring in HBsAg-negative&#44; anti-HBc-positive patients is recommended and should be emphasized in these patients&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objective"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Material and methods"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Conclusion"
          ]
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      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La reactivaci&#243;n del virus de la hepatitis B &#40;VHB&#41; en receptores de trasplante renal &#40;RTR&#41; supone una importante morbilidad y mortalidad&#46; A pesar de ser m&#225;s frecuente en pacientes con HBsAg positivo&#44; puede suceder en pacientes con infecci&#243;n cl&#237;nicamente resuelta &#40;HBsAg-negativo y anti-HBc-positivo&#41;&#46; En estos casos&#44; la presencia del anticuerpo protector anti-HBs parece disminuir el riesgo de reactivaci&#243;n&#46; Existen escasos datos relativos a las tasas de reactivaci&#243;n en esta poblaci&#243;n&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Evaluaci&#243;n retrospectiva del riesgo de reactivaci&#243;n del VHB en RTR con infecci&#243;n previa resuelta&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material y m&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio de cohorte retrospectivo&#44; incluyendo RTR entre enero de 1994 y diciembre de 2014&#44; con infecci&#243;n VHB resuelta en el momento del trasplante &#40;anti-HBc seropositivo&#44; HBsAg indetectable&#44; con o sin anticuerpo anti-HBs e enzimas hep&#225;ticas normales&#41;&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">De un total de 966&#44; 95 pacientes con evidencia de infecci&#243;n VHB resuelta fueron analizados&#59; 86 ten&#237;an un t&#237;tulo de anti-HBs<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml&#46; El tiempo medio de seguimiento fue de 93 meses&#44; 12 pacientes hab&#237;an perdido anti-HBs&#46; Dos pacientes tuvieron evidencia de reactivaci&#243;n&#46; Los factores de riesgo asociados a la p&#233;rdida de anti-HBs fueron la edad avanzada &#40;&#62;60&#41; y la evidencia de rechazo agudo del injerto &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusi&#243;n</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">El riesgo de reactivaci&#243;n del VHB en RTR con infecci&#243;n previamente resuelta &#40;2&#37;&#41; no es despreciable&#46; La edad avanzada y el rechazo agudo est&#225;n asociados a la p&#233;rdida de anti-HBs&#44; y estos pacientes podr&#237;an beneficiarse de una vigilancia de los niveles de DNA del VHB&#46; Las serolog&#237;as de rutina y&#47;o la monitorizaci&#243;n de la carga viral en pacientes HBsAg-negativo&#44; anti-HBc-positivo est&#225; recomendado y deber&#237;a ser enfatizado en estos pacientes&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Objetivos"
          ]
          2 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Material y m&#233;todos"
          ]
          3 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0050"
            "titulo" => "Conclusi&#243;n"
          ]
        ]
      ]
    ]
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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                  <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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recipient age &#40;years&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50 &#91;42&#8211;59&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recipient sex&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33 &#40;34&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62 &#40;65&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Cause of chronic kidney disease&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Glomerulonehpritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15 &#40;15&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Polycystic kidney disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;14&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diabetic nephropathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11 &#40;11&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Nephroangiosclerosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;8&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>IgA nephropathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;8&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;10&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Unknown&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29 &#40;30&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Graft rank&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>First transplantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">84 &#40;88&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Retransplantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11 &#40;11&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Donor type&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Deceased&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">93 &#40;97&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Living&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Time on dialysis &#40;months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&#46;5 &#91;23&#46;8&#8211;83&#46;3&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Type of dialysis&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hemodialysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">86 &#40;90&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Peritoneal dialysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9 &#40;9&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of the study population&#46; Values are medians and interquartil ranges unless indicated otherwise&#46;</p>"
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">CsA&#58; ciclosporin A&#44; TAC&#58; tacrolimus&#44; AZA&#58; azathioprine&#44; MMF&#58; mofetil mycophenolate&#46; During the follow-up period&#44; 13 patients died and 14 lost their allograft and were therefore excluded&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IS regimen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">At the time of transplantation&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">At the end of follow-up&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TAC<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>MMF<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>prednisolone&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34 &#40;35&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33 &#40;48&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CsA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>MMF<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>prednisolone&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46 &#40;48&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26 &#40;38&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CsA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Aza<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>prednisolone&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14 &#40;14&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;2&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sirolimus<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>MMF<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>prednisolone&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Everolimus <span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>prednisolone&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;5&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;4&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">HR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">95&#37; CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">All patients</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Male gender</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;299&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;493&#8211;10&#46;710&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;289&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Age &#62;60</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;943&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;904&#8211;25&#46;310&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Number of previous transplants &#62;0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;037&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;00&#8211;109&#46;989&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Cause of CKD</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Diabetes</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="3" align="left" valign="top">Reference</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Hypertension</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;761&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;069&#8211;8&#46;431&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;824&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Policystic kidney disease</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;276&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;226&#8211;7&#46;214&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;783&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">IgA Nephropathy</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;678&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;61&#8211;7&#46;486&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;751&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Glomerulonephritis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;459&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;61&#8211;3&#46;449&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;451&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Other&#47;Unknown</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Induction imunossupression</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ATG vs none&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;636&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;075&#8211;5&#46;392&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;468&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Basiliximab vs none&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;975&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;960&#8211;16&#46;461&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;057&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Use of ATG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;549&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;403&#8211;5&#46;949&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;524&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Use of MMF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;690&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;417&#8211;32&#46;279&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;241&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Biopsy-proven acute rejection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;944&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;223&#8211;28&#46;389&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Risk factors associated with loss of immunity &#40;univariate analysis&#41;&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
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            0 => array:3 [
              "identificador" => "bib0100"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Virus infection&#58; epidemiology and vaccination"
                      "autores" => array:1 [
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Original article
Reactivation of Hepatitis B virus in kidney transplant recipients with previous clinically resolved infection: A single-center experience
Reactivación del virus de la hepatitis B en receptores de trasplante renal con infección previa resuelta clínicamente: una experiencia de un solo centro
Catarina Menga,b,
Corresponding author
catarinameng@gmail.com

Corresponding author.
, Carolina Belinoc, Luciano Pereiraa,b, Ana Pinhoa,b, Susana Sampaioa,b, Isabel Tavaresa,b, Manuela Bustorffa,b, António Sarmentob,d,e, Manuel Pestanaa,b,e
a Nephrology Department, Centro Hospitalar de São João, Porto, Portugal
b Nephrology and Infecciology Group, INEB/I3S, Porto, Portugal
c Nephrology Department, Centro Hospitalar de Vila Nova de Gaia-Espinho, Vila Nova de Gaia, Portugal
d Infectious Diseases Department, Centro Hospitalar de São João, Porto, Portugal
e Faculty of Medicine of University of Porto, Porto, Portugal
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          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>&#46;"
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    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Reactivaci&#243;n del virus de la hepatitis B en receptores de trasplante renal con infecci&#243;n previa resuelta cl&#237;nicamente&#58; una experiencia de un solo centro"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hepatitis B virus &#40;HBV&#41; infection has decreased in frequency in kidney transplant recipients &#40;KTR&#41; due to the reinforcement of vaccination policies in the Chronic Kidney Disease &#40;CKD&#41; population and increased precautions to prevent transmission of the HBV among dialysis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a> Reactivation of HBV infection in KTR is associated with important morbidity and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">2</span></a> Immunosuppressive &#40;IS&#41; drugs used to prevent graft rejection blunt B and T cell functions and that permits HBV replication and viral protein expression on the surface of the infected hepatocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> Reactivation is more frequent in patients who are HBsAg-positive&#44; but it can also occur in patients with resolved HBV infection &#40;HBsAg-negative and anti-HBc-positive&#41;&#44; since the virus can still replicate within the hepatocytes&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">4&#44;5</span></a> Data are scarce and conflicting regarding the risk of HBV reactivation in this subset of patients&#46; Reported rates of reactivation are variable&#59; while some authors claim that the risk is negligible regardless of anti-HBs status&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">6</span></a> others have published rates ranging from 1 to 6&#46;5&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">7&#44;8</span></a> It has been suggested that in these patients the presence of anti-HBs antibodies may provide protection against HBV reactivation<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">8&#8211;10</span></a> but there are too few data about the proportion of renal transplant patients with resolved HBV infection and with positive anti-HBs titers that lose immunity during follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> Thus&#44; it remains unclear regarding what kind of monitoring is needed and whether these patients would benefit from antiviral prophylaxis during the post-transplant period&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In this study we aim to retrospectively evaluate the risk of HBV reactivation in KTR with previously resolved infection in a Portuguese Kidney Transplant Centre&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study population</span><p id="par0015" class="elsevierStylePara elsevierViewall">We designed a retrospective cohort study enrolling all consecutive patients who underwent a kidney transplant at our center in the period between January 1994 and December 2014 who had serological evidence of resolved HBV infection at the time of transplantation&#46; Patients were followed until September 30<span class="elsevierStyleSup">th</span>&#44; 2015&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Resolved HBV infection was defined as seropositivity for anti-HBc without detectable HBsAg&#44; and normal liver enzymes &#40;ALT&#44; AST&#41;&#44; with or without anti-HBs positive titers&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Cutoff for positive anti-HBs was defined as &#62;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml and loss of immunity was defined by fall of anti-HBs to levels bellow 10<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml and reactivation was defined according to current guidelines by a viral load &#62;2000<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Exclusion criteria were&#58; no information regarding viral status at the time of transplant&#44; if they had a positive HBsAg&#44; primary non-functioning allograft&#44; and allograft survival less than 30 days&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Acute rejection &#40;BPAR&#41; was defined by biopsy-proven histological changes compatible with either cellular or antibody-mediated rejection according to the latest Banff classification update available at the time of diagnosis&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Analyzed data</span><p id="par0040" class="elsevierStylePara elsevierViewall">Data were collected from the patients&#8217; medical records&#46; Demographic data included age&#44; sex&#44; time on dialysis&#44; cause of CKD and number of previous transplants&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Data regarding HBV serological status&#44; IS regimen&#44; use of antiviral prophylaxis&#44; and occurrence of acute rejection were collected&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In the evaluation of kidney transplant candidates and upon admission for renal transplant&#44; liver enzymes &#40;ALT&#44; AST&#41; and routine HBV serological markers were obtained from all transplant candidates&#46; Our transplant center did not test HBV viral load in KTR with resolved HBV infection&#44; and post-transplant serological HBV testing did not follow a systematic protocol&#44; thus&#44; the frequency of monitoring was left at the discretion of the attending Nephrologist&#46; All patients&#8217; post-transplant serological markers were recorded during the follow-up monitoring&#59; the date of reactivation or the date of the last serological testing&#44; whichever came first&#44; was considered the end of follow-up&#46; The follow-up appointments were scheduled according to our Institution&#39;s protocol but could be adjusted by the Nephrologist according to the patient&#39;s clinical status&#46; Serological markers were obtained using hemi luminescent methods &#40;Prism HBsAg<span class="elsevierStyleSup">&#174;</span> and Prism HBcore<span class="elsevierStyleSup">&#174;</span>&#44; Abbott&#59; Architect Anti-HBs<span class="elsevierStyleSup">&#174;</span>&#44; Abbott&#41;&#44; and HBV DNA was obtained using multiplex nucleic acid test&#44; COBAS<span class="elsevierStyleSup">&#174;</span> TaqScreen MPX Test&#44; version 2&#46;0&#44; Roche&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">Descriptive statistics were recorded as median and interquartile range &#40;IQR&#41; intervals&#46; Univariate analysis was performed using Cox regression analysis&#59; covariates with <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1 were tested in a gender-adjusted multivariate model&#46; Cox multiple regression analysis using the forward conditional method was performed to assess independent risk factors for loss of anti-HBs&#44; and significance was considered if <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; Statistical analysis was performed using IBM SPSS version 23 &#40;IBM Corp&#46; Released 2016&#46; Armonk&#44; NY&#58; IBM Corp&#41;&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Patient data</span><p id="par0060" class="elsevierStylePara elsevierViewall">From the 1151 kidney transplant recipients performed during the study period the following were excluded&#58; 137 without record of HBV serological status&#44; 7 HBsAg-positive patients&#44; 28 with primary graft failure and 13 patients with graft survival &#60;30 days&#46; From the remaining 966 patients&#44; 867 were anti-HBc negative and the remaining 99 patients had evidence of resolved infection at the time of surgery&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Four of the 99 patients had no information regarding post-transplant serological data and thus were excluded from the analysis&#46; Of the remaining ninety-five patients&#44; nine had anti-HBs &#60;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Baseline characteristics of the study population are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Patient and graft survival</span><p id="par0075" class="elsevierStylePara elsevierViewall">Patients were followed at our Outpatient Clinic for a median time of 93 months &#40;IQR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>58&#8211;146&#41;&#46; Follow-up time did not differ significantly between patients who lost anti-HBs compared to those who did not &#40;median follow-up time 68 vs 73 months&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;789&#41;&#46; In patients who lost anti-HBs compared to those who did not 5 and 10 year patient survival rates were 93&#46;9&#37; and 89&#46;9&#37;&#44; while 5 and 10 year allograft survival rates were 95&#46;95&#37; and 90&#46;9&#37;&#44; respectively&#46; During the study period&#44; 13 patients died with a functioning allograft and 14 lost graft function&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Seventeen cases of BPAR were recorded&#44; nine of which were treated with pulses of metilprednisolone &#40;MPD&#41;&#59; 1 with MPD plus intravenous immunoglobulin&#44; 5 with anti-thymocyte globulin &#40;ATG&#41; and 1 with MPD plus ATG&#46; Treatment was not known in the remaining case&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Immunosuppression</span><p id="par0085" class="elsevierStylePara elsevierViewall">IS regimens used at the time of transplantation and at the date of the last follow-up are presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; Most patients were treated with a triple drug regimen&#59; additionally&#44; induction imunosuppression consisted of basiliximab in 30 patients &#40;31&#46;6&#37;&#41;&#44; ATG in 17 &#40;17&#46;9&#37;&#41; and daclizumab in 2 &#40;2&#46;1&#37;&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Twenty-one patients received ATG as induction therapy or as part of acute rejection treatment&#46; At the end of follow-up all patients were on a low-dose steroid regimen consisting of 5<span class="elsevierStyleHsp" style=""></span>mg of prednisolone or equivalent per day&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">From the initial cohort of 99 patients&#44; we were able to collect data regarding previous antiviral treatment on 88 patients &#40;88&#46;9&#37;&#41;&#44; confirming that none of those had been treated for HBV&#44; having had spontaneous negativation of HBsAg&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">None of the patients had a history of HBV antiviral prophylaxis or use of rituximab&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Loss of immunity and reactivation</span><p id="par0105" class="elsevierStylePara elsevierViewall">During the time of follow-up 95 patients had 339 HBV serological tests&#44; which corresponded to a median of 3 tests per patient &#40;IQR 1&#8211;5&#41;&#44; or 0&#46;44 tests per patient-year&#46; Twelve patients &#40;13&#46;9&#37;&#41; lost immunity and two patients &#40;2&#37;&#41; showed evidence of reactivation&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The first case was a 67 year-old male who had received a cadaveric allograft in 2007&#59; at the time of transplantation anti-HBc and anti-HBs were positive &#40;7&#46;74 and 986<span class="elsevierStyleHsp" style=""></span>mUI&#47;ml&#44; respectively&#41;&#46; Immunosuppression consisted of a triple regimen of cyclosporine&#44; MMF &#40;mycophenolate mofetil&#41; and prednisolone&#46; No major complications occurred until 2013&#44; when he was admitted with a history of cough and weight loss&#46; <span class="elsevierStyleItalic">Aspergilus fumigatus</span> was isolated in a Bronchoalveolar sample and itraconazol was started&#46; Two weeks later&#44; liver enzymes levels increased&#59; itraconazol toxicity was suspected and the drug was stopped&#46; HBV serological markers were compatible with reverse seroconversion with reappearance of HBsAg&#44; and reactivation was diagnosed as the patient had a viral load of 1&#46;7<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">8</span><span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#46; Anti-HBs titer was 50&#46;7<span class="elsevierStyleHsp" style=""></span>mUI&#47;ml&#46; Liver biopsy showed mild cholestasis&#44; inflammatory infiltrate&#44; ground-glass hepatocytes&#44; nuclear expression of HBcAg and absence of HBsAg&#46; The patient was started on entecavir&#44; but expired a week later due to acute liver failure&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The second patient was a 42 year-old male who had received its 3<span class="elsevierStyleSup">rd</span> transplant from a deceased donor in 2006&#59; at the time of transplantation anti-HBc was 10&#46;7<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml and anti-HBs was 2&#46;67<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml&#46; Induction immunosuppression included ATG and maintenance imunosuppression consisted of tacrolimus&#44; MMF and prednisolone&#59; baseline creatinine was 3&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46; He was admitted with Pneumonia in 2014&#46; Upon admission&#44; liver enzymes were increased&#46; HBV serological markers showed evidence of reverse seroconversion with reappearance of HBsAg&#44; and reactivation was diagnosed as the patient had a viral load of 1&#46;6<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">4</span><span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#46; Anti-HBs was 1&#46;6<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml&#46; Entecavir was started with disappearance of HBsAg and viremia&#44; which became undetectable&#46; At the time of discharge serum creatinine was 4<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#46; The patient lost his graft 10 months later due to chronic allograft nephropathy and restarted hemodialysis&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Of the 12 patients who lost immunity during follow-up&#44; the choice of IS drug did not seem to have any impact&#46; Particularly&#44; the use of MMF and use of ATG were not associated with loss of immunity &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;241 and 0&#46;524&#44; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">table 3</a>&#41;&#46; In the multivariate model adjusted for gender&#44; older age &#40;&#62;60 years-old&#41; was associated with loss of immunity &#40;HR 4&#46;853&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#44; CI &#91;1&#46;235&#59; 19&#46;071&#91;&#41; as was the presence of BPAR &#40;HR 5&#46;921&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;015&#44; CI &#91;1&#46;416&#59; 24&#46;759&#91;&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0125" class="elsevierStylePara elsevierViewall">HBV reactivation is a potentially fatal condition with mortality rates reported as high as 25&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">4</span></a> In our study the rate of HBV reactivation in patients with previously resolved infection was approximately 2&#37;&#44; resulting in death in one patient&#46; This highlights the importance of assessing potential risk factors for reactivation since prophylaxis can prevent its occurrence&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Only 4 retrospective studies addressed the risk of reactivation in HBsAg-negative and anti-HBc-positive KTR&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">7&#8211;9&#44;13</span></a> The number of patients was small and reactivation rates varied from 0 to 6&#46;5&#37;&#46; Risk factors for reactivation included older age&#44; presence of rejection&#44; use of rituximab and loss&#47;absence of anti-HBs&#44; but findings were not consistent among the 4 studies possibly due to the small number of cases in each study&#46; We found that 13&#46;9&#37; of the patients with resolved HBV infection and positive anti-HBs titers lost immunity&#46; In our series&#44; older age and presence of BPAR were independent risk factors for loss of anti-HBs&#44; which in its turn might increase the risk of reactivation&#46; Age can be a risk factor since older patients tend to produce weaker immunological response and tend to have lower levels of anti-HBs&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">8</span></a> Acute rejection is thought to be a risk factor through an increase of immunosuppression used for its treatment and this has been confirmed in other solid-organ transplants &#40;SOT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">8</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">It is postulated that IS agents such as B-Cell depleting drugs like rituximab are associated with a high risk of HBV reactivation even in patients with resolved HBV infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">4&#44;13&#44;14</span></a> In our study&#44; none of our patients had received rituximab&#46; Relationship between other drugs used in kidney transplantation and reactivation is less consistent&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">8&#44;15</span></a> We found no association between the type of IS drug used and loss of anti-HBs&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Our study is limited by its retrospective nature&#44; and we are unaware of when the patients included in our study acquired HBV infection and the timing of their acquisition of positive anti-HBs titers after the infection&#46; We were also unable to assess previous HBV vaccination history&#46; Both could influence anti-HBs titers and the risk of HBV reactivation after renal transplantation&#44; although there are no studies addressing this issue&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The retrospective nature of our study and the absence of HBV genotype testing in our reactivation cases do not allow us to completely rule out the possibility of re-infection instead of reactivation&#46; However&#44; both patients were diagnosed in an inpatient setting and none had recent history of high risk behavior or contact with blood products&#46; Besides&#44; both were highly immunosuppressed &#8211; one of the patients had a severe opportunistic infection and the other a high cumulative IS load given the history of 3 transplants&#44; which favors the hypothesis of reactivation&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Our transplant center did not test HBV viral load in KTR with resolved HBV infection&#44; and serological HBV testing did not follow a systematic protocol&#46; This way&#44; we cannot assure that asymptomatic reactivations might have been missed during the follow-up period&#44; and this way we might have underestimated the reactivation rates in our population&#46; At last&#44; the small number of reactivation cases did not allow us to infer about potential risk factors for reactivation&#46; Our study however has some specific strengths&#59; in an era of declining HBV incidence in the Western Countries&#44; we have managed to retrieve a fairly high number of patients and a long term follow-up&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The American Association for the Study of Liver Diseases recommends routine use of appropriate antiviral prophylaxis in all patients who are HBsAg-positive prior to or at the initiation of chemotherapy&#44; immunosuppressive therapy&#44; hematopoietic stem cell transplantation&#44; or solid organ transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a> When B-cell depleting agents like rituximab are used in patients with resolved infection &#40;HBsAg-negative&#44; anti-HBc-positive&#41; antiviral prophylaxis can be anticipated to result in similar risk reduction of HBV reactivation as described for HBsAg-positive patients&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">14</span></a> otherwise recommendations regarding antiviral prophylaxis in KTR with resolved HBV infection are lacking&#46; Current guidelines do not recommend using anti-HBs titer to guide initiation of prophylaxis since there is no threshold level that universally prevents HBV reactivation&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">10&#44;12&#44;14</span></a> However&#44; anti-HBs titer is still believed to confer protection against reactivation&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">8&#44;13&#44;16</span></a> Considering that loss of anti-HBs increases the risk of reactivation&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">7&#44;8&#44;17&#44;18</span></a> patients who are at increased risk of anti-HBs loss&#44; such as older patients and those with BPAR as found in our study&#44; might benefit from closer surveillance of HBV DNA levels<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">4&#44;10&#44;19</span></a> or even antiviral prophylaxis&#46; Although evidence is scarce regarding HBV DNA monitoring in patients with resolved HBV infection we suggest&#44; as a cost-effective measure&#44; a baseline measurement of HBV DNA levels for all candidates to kidney transplantation with resolved HBV infection &#40;anti-HBc positive&#44; HBsAg negative&#41; to exclude occult viral replication&#46; For those with positive HBV DNA we suggest antiviral prophylaxis starting from the time of transplantation and follow-up with periodical assessment of aminotransferases and HBV DNA levels&#46; If the initial baseline HBV DNA is negative&#44; we suggest serological HBV follow-up &#40;HBsAg and anti-HBs&#41; and close monitoring of aminotransferases levels&#46; In case of HBsAg seroreversion or elevated aminotransferases&#44; we suggest HBV DNA assessment&#46; However&#44; even with negative baseline negative HBV DNA&#59; we acknowledge that some of these patients&#44; especially if they are at higher risk of reactivation&#44; might benefit from HBV DNA surveillance from the time of transplantation&#46; In our study the small number of cases of HBV reactivation precludes any conclusion&#44; and further studies are needed&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conclusions</span><p id="par0160" class="elsevierStylePara elsevierViewall">In conclusion&#44; the risk of HBV reactivation in KTR with previous clinically resolved infection is not negligible at 2&#37;&#46; Older age and acute rejection were associated with loss of anti-HBs&#44; and these patients might benefit from closer surveillance of HBV DNA level&#46; Routine serological and&#47;or HBV viral load monitoring in HBsAg-negative&#44; anti-HBc-positive patients is recommended and should be emphasized in these patients&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Author contributions</span><p id="par0165" class="elsevierStylePara elsevierViewall">Meng C&#58; design of study&#44; data collection&#44; drafting article&#46; Belino C&#44; Pereira L&#44; Sampaio S&#44; Tavares&#58; data analysis&#44; drafting article&#46; Pinho A&#58; critical revision and statistical analysis&#46; Bustorff M&#58; design of study&#44; drafting and critical revision&#46; Sarmento A and Pestana M&#58; critical revision&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conflict of interest</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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              "identificador" => "sec0050"
              "titulo" => "Loss of immunity and reactivation"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Conclusions"
        ]
        9 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Author contributions"
        ]
        10 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Conflict of interest"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2017-09-07"
    "fechaAceptado" => "2018-02-08"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1046360"
          "palabras" => array:5 [
            0 => "Hepatitis B"
            1 => "Kidney transplantation"
            2 => "Infection"
            3 => "Reactivation"
            4 => "Risk factors"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1046359"
          "palabras" => array:5 [
            0 => "Hepatitis B"
            1 => "Trasplante renal"
            2 => "Infecci&#243;n"
            3 => "Reactivaci&#243;n"
            4 => "Factores de riesgo"
          ]
        ]
      ]
    ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hepatitis B virus &#40;HBV&#41; reactivation in kidney transplant recipients &#40;KTR&#41; involves important morbidity and mortality&#46; Despite being more common in patients who are HBsAg-positive&#44; it may occur in patients with clinically resolved infection &#40;HBsAg-negative and anti-HBc-positive&#41;&#44; in whom the presence of the protective anti-HB antibody is thought to decrease the risk of reactivation&#46; Data regarding reactivation rates in this population are scarce&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To retrospectively evaluate the risk of HBV reactivation in KTR with previously resolved infection&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Material and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Retrospective cohort study including patients who underwent a kidney transplant between January 1994 and December 2014 with resolved HBV infection at the time of transplantation &#40;anti-HBc seropositivity without detectable HBsAg&#44; with or without anti-HB-positive antibodies and normal liver enzymes&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Out of 966 patients&#44; 95 patients with evidence of resolved HBV infection were analyzed&#44; of which 86 had a titer of anti-HBs &#62;10<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml&#46; Mean follow-up time was 93 months&#59; 12 patients had lost anti-HBs&#46; Two patients showed evidence of reactivation&#46; Risk factors associated with loss of anti-HBs were elderly age &#40;&#62;60&#41; and occurrence of acute graft rejection &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The risk of HBV reactivation in KTR with previously resolved infection is not negligible at 2&#37;&#46; Elderly age and acute rejection were associated with loss of anti-HBs&#44; and these patients may benefit from closer monitoring of HBV DNA levels&#46; Routine serology and&#47;or HBV viral load monitoring in HBsAg-negative&#44; anti-HBc-positive patients is recommended and should be emphasized in these patients&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objective"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Material and methods"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Conclusion"
          ]
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      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La reactivaci&#243;n del virus de la hepatitis B &#40;VHB&#41; en receptores de trasplante renal &#40;RTR&#41; supone una importante morbilidad y mortalidad&#46; A pesar de ser m&#225;s frecuente en pacientes con HBsAg positivo&#44; puede suceder en pacientes con infecci&#243;n cl&#237;nicamente resuelta &#40;HBsAg-negativo y anti-HBc-positivo&#41;&#46; En estos casos&#44; la presencia del anticuerpo protector anti-HBs parece disminuir el riesgo de reactivaci&#243;n&#46; Existen escasos datos relativos a las tasas de reactivaci&#243;n en esta poblaci&#243;n&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Evaluaci&#243;n retrospectiva del riesgo de reactivaci&#243;n del VHB en RTR con infecci&#243;n previa resuelta&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material y m&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio de cohorte retrospectivo&#44; incluyendo RTR entre enero de 1994 y diciembre de 2014&#44; con infecci&#243;n VHB resuelta en el momento del trasplante &#40;anti-HBc seropositivo&#44; HBsAg indetectable&#44; con o sin anticuerpo anti-HBs e enzimas hep&#225;ticas normales&#41;&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">De un total de 966&#44; 95 pacientes con evidencia de infecci&#243;n VHB resuelta fueron analizados&#59; 86 ten&#237;an un t&#237;tulo de anti-HBs<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mIU&#47;ml&#46; El tiempo medio de seguimiento fue de 93 meses&#44; 12 pacientes hab&#237;an perdido anti-HBs&#46; Dos pacientes tuvieron evidencia de reactivaci&#243;n&#46; Los factores de riesgo asociados a la p&#233;rdida de anti-HBs fueron la edad avanzada &#40;&#62;60&#41; y la evidencia de rechazo agudo del injerto &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusi&#243;n</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">El riesgo de reactivaci&#243;n del VHB en RTR con infecci&#243;n previamente resuelta &#40;2&#37;&#41; no es despreciable&#46; La edad avanzada y el rechazo agudo est&#225;n asociados a la p&#233;rdida de anti-HBs&#44; y estos pacientes podr&#237;an beneficiarse de una vigilancia de los niveles de DNA del VHB&#46; Las serolog&#237;as de rutina y&#47;o la monitorizaci&#243;n de la carga viral en pacientes HBsAg-negativo&#44; anti-HBc-positivo est&#225; recomendado y deber&#237;a ser enfatizado en estos pacientes&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Objetivos"
          ]
          2 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Material y m&#233;todos"
          ]
          3 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0050"
            "titulo" => "Conclusi&#243;n"
          ]
        ]
      ]
    ]
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        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
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          ]
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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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recipient age &#40;years&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50 &#91;42&#8211;59&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Recipient sex&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33 &#40;34&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62 &#40;65&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Cause of chronic kidney disease&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Glomerulonehpritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15 &#40;15&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Polycystic kidney disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;14&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diabetic nephropathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11 &#40;11&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Nephroangiosclerosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;8&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>IgA nephropathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;8&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;10&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Unknown&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29 &#40;30&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Graft rank&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>First transplantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">84 &#40;88&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Retransplantation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11 &#40;11&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Donor type&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Deceased&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">93 &#40;97&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Living&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Time on dialysis &#40;months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&#46;5 &#91;23&#46;8&#8211;83&#46;3&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Type of dialysis&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hemodialysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">86 &#40;90&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Peritoneal dialysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9 &#40;9&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of the study population&#46; Values are medians and interquartil ranges unless indicated otherwise&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
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        "tipo" => "MULTIMEDIATABLA"
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        "mostrarDisplay" => false
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            "identificador" => "at2"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">CsA&#58; ciclosporin A&#44; TAC&#58; tacrolimus&#44; AZA&#58; azathioprine&#44; MMF&#58; mofetil mycophenolate&#46; During the follow-up period&#44; 13 patients died and 14 lost their allograft and were therefore excluded&#46;</p>"
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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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IS regimen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">At the time of transplantation&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">At the end of follow-up&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TAC<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>MMF<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>prednisolone&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34 &#40;35&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33 &#40;48&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CsA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>MMF<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>prednisolone&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46 &#40;48&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26 &#40;38&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CsA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Aza<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>prednisolone&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14 &#40;14&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;2&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sirolimus<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>MMF<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>prednisolone&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Everolimus <span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>prednisolone&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;5&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;4&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Immunosuppressive regimens upon transplantation and at the end of follow-up&#46;</p>"
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      ]
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            "detalle" => "Table "
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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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">HR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">95&#37; CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">All patients</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Male gender</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;299&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;493&#8211;10&#46;710&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;289&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Age &#62;60</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;943&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;904&#8211;25&#46;310&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Number of previous transplants &#62;0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;037&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;00&#8211;109&#46;989&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Cause of CKD</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Diabetes</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="3" align="left" valign="top">Reference</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Hypertension</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;761&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;069&#8211;8&#46;431&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;824&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Policystic kidney disease</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;276&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;226&#8211;7&#46;214&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;783&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">IgA Nephropathy</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;678&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;61&#8211;7&#46;486&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;751&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Glomerulonephritis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;459&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;61&#8211;3&#46;449&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;451&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Other&#47;Unknown</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Induction imunossupression</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ATG vs none&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;636&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;075&#8211;5&#46;392&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;468&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Basiliximab vs none&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;975&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;960&#8211;16&#46;461&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;057&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Use of ATG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;549&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;403&#8211;5&#46;949&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;524&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Use of MMF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;690&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;417&#8211;32&#46;279&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;241&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Biopsy-proven acute rejection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;944&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;223&#8211;28&#46;389&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Risk factors associated with loss of immunity &#40;univariate analysis&#41;&#46;</p>"
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Article information
ISSN: 20132514
Original language: English
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