Conversion to Mycophenolate Mofetil Monotherapy in Liver Recipients: Calcineurin Inhibitor Levels are Key

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In blue, non sarcopenic patients survival curve. In red, sarcopenic patients survival curve." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Paola Begini, Elia Gigante, Giulio Antonelli, Francesco Carbonetti, Elsa Iannicelli, Giulia Anania, Barbara Imperatrice, Adriano Maria Pellicelli, Gianfranco Delle Fave, Massimo Marignani" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Paola" "apellidos" => "Begini" ] 1 => array:2 [ "nombre" => "Elia" "apellidos" => "Gigante" ] 2 => array:2 [ "nombre" => "Giulio" "apellidos" => "Antonelli" ] 3 => array:2 [ "nombre" => "Francesco" "apellidos" => "Carbonetti" ] 4 => array:2 [ "nombre" => "Elsa" "apellidos" => "Iannicelli" ] 5 => array:2 [ "nombre" => "Giulia" "apellidos" => "Anania" ] 6 => array:2 [ "nombre" => "Barbara" "apellidos" => "Imperatrice" ] 7 => array:2 [ "nombre" => "Adriano" "apellidos" => "Maria Pellicelli" ] 8 => array:2 [ "nombre" => "Gianfranco" "apellidos" => "Delle Fave" ] 9 => array:2 [ "nombre" => "Massimo" "apellidos" => "Marignani" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119303679?idApp=UINPBA00004N" "url" => "/16652681/0000001600000001/v1_201905311015/S1665268119303679/v1_201905311015/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119303655" "issn" => "16652681" "doi" => "10.5604/16652681.1226819" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "70187" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2017;16:86-93" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 103 "formatos" => array:3 [ "EPUB" => 15 "HTML" => 47 "PDF" => 41 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Sofosbuvir and Daclatasvir in Mono- and HIV-coinfected Patients with Recurrent Hepatitis C After Liver Transplant" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "86" "paginaFinal" => "93" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1394 "Ancho" => 2067 "Tamanyo" => 179589 ] ] "descripcion" => array:1 [ "en" => "Selected laboratory tests and scores over time. Variables are depicted as median and IQR. EOT: end of treatment. FU: follow-up. IQR: intercuarti-le range." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Lluís Castells, Jordi Llaneras, Isabel Campos-Varela, Itxarone Bilbao, Manel Crespo, Oscar Len, Francisco Rodríguez-Frías, Ramon Charco, Teresa Salcedo, Juan Ignacio Esteban, Rafael Esteban-Mur" "autores" => array:11 [ 0 => array:2 [ "nombre" => "Lluís" "apellidos" => "Castells" ] 1 => array:2 [ "nombre" => "Jordi" "apellidos" => "Llaneras" ] 2 => array:2 [ "nombre" => "Isabel" "apellidos" => "Campos-Varela" ] 3 => array:2 [ "nombre" => "Itxarone" "apellidos" => "Bilbao" ] 4 => array:2 [ "nombre" => "Manel" "apellidos" => "Crespo" ] 5 => array:2 [ "nombre" => "Oscar" "apellidos" => "Len" ] 6 => array:2 [ "nombre" => "Francisco" "apellidos" => "Rodríguez-Frías" ] 7 => array:2 [ "nombre" => "Ramon" "apellidos" => "Charco" ] 8 => array:2 [ "nombre" => "Teresa" "apellidos" => "Salcedo" ] 9 => array:2 [ "nombre" => "Juan" "apellidos" => "Ignacio Esteban" ] 10 => array:2 [ "nombre" => "Rafael" "apellidos" => "Esteban-Mur" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119303655?idApp=UINPBA00004N" "url" => "/16652681/0000001600000001/v1_201905311015/S1665268119303655/v1_201905311015/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "titulo" => "Conversion to Mycophenolate Mofetil Monotherapy in Liver Recipients: Calcineurin Inhibitor Levels are Key" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "94" "paginaFinal" => "106" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Blanca Norero, Carolina A. Serrano, Alberto Sanchez-Fueyo, Ignacio Duarte, Javiera Torres, Mauricio Ocquetau, Francisco Barrera, Marco Arrese, Alejandro Soza, Carlos Benítez" "autores" => array:10 [ 0 => array:3 [ "nombre" => "Blanca" "apellidos" => "Norero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] ] ] 1 => array:3 [ "nombre" => "Carolina A." "apellidos" => "Serrano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "†" "identificador" => "aff2" ] ] ] 2 => array:3 [ "nombre" => "Alberto" "apellidos" => "Sanchez-Fueyo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "‡" "identificador" => "aff5" ] ] ] 3 => array:3 [ "nombre" => "Ignacio" "apellidos" => "Duarte" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "§" "identificador" => "aff3" ] ] ] 4 => array:3 [ "nombre" => "Javiera" "apellidos" => "Torres" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "§" "identificador" => "aff3" ] ] ] 5 => array:3 [ "nombre" => "Mauricio" "apellidos" => "Ocquetau" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "||" "identificador" => "aff4" ] ] ] 6 => array:3 [ "nombre" => "Francisco" "apellidos" => "Barrera" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] ] ] 7 => array:3 [ "nombre" => "Marco" "apellidos" => "Arrese" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] ] ] 8 => array:3 [ "nombre" => "Alejandro" "apellidos" => "Soza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] ] ] 9 => array:4 [ "nombre" => "Carlos" "apellidos" => "Benítez" "email" => array:1 [ 0 => "cbenitez@med.puc.cl" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Departamentos de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile" "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Departamentos de Gastroenterología y Nutrición Pediátrica, Escuela de Medicina, Pontificia Universidad Católica de Chile" "etiqueta" => "†" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Departamentos de Patología y Escuela de Medicina, Pontificia Universidad Católica de Chile" "etiqueta" => "§" "identificador" => "aff3" ] 3 => array:3 [ "entidad" => "Departamentos de Hemato-Oncología, Escuela de Medicina, Pontificia Universidad Católica de Chile" "etiqueta" => "||" "identificador" => "aff4" ] 4 => array:3 [ "entidad" => "Institute of Liver Studies, MRC Centre for Transplantation, King’s College London, London SE5 9RS, United Kingdom" "etiqueta" => "‡" "identificador" => "aff5" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 797 "Ancho" => 1381 "Tamanyo" => 83543 ] ] "descripcion" => array:1 [ "en" => "Description of the study methodology and follow-up: Calcineurin inhibitors were gradually reduced until their total withdrawal during the first four weeks, followed by a 48-week follow-up. Medical evaluations were conducted on the indicated dates and whenever necessary." ] ] ] "textoCompleto" => "IntroductionImprovements in immunosuppressive drugs (ISD) have significantly increased survival rates of liver transplant recipients. Thus, one-year survival after liver transplantation (LT) currently reaches 85-90%, and 50% after ten years (http://www.eltr.org/, http://www.unos.org/). However, ISDs are toxic and commonly have severe side effects, affecting survival and quality of life of liver recipients,<a class="elsevierStyleCrossRefs" href="#bib0005">1-3</a> with infections acting as the main cause of mortality during the first year after LT (85%).<a class="elsevierStyleCrossRef" href="#bib0020">4</a> In the long-term, most cases of morbidity and mortality of LT recipients are related to side effects of ISD, mostly calcineurin inhibitors (CNI), although steroids, antimetabolites and mTOR inhibitors are also related to significant side effects.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> In a recent study, two thirds of the deaths that occurred one year after LT were unrelated to graft failure. In fact, most deaths were attributable to ISD side effects such as infections, renal failure, cancer and cardiovascular diseases.<a class="elsevierStyleCrossRefs" href="#bib0025">5-8</a> Renal failure is a common cause of morbidity after LT. The incidence of a glomerular filtration rate (GFR) of 30 mL/min or less is 18.1% five years after LT.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> Importantly, renal failure seems to be independently related to mortality among liver recipients.<a class="elsevierStyleCrossRefs" href="#bib0025">5,6</a> Indeed, the relation between renal failure and mortality after LT seems to be even more important when renal failure occurs late after LT.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> Considering these facts, several strategies have been developed to minimize the nephrotoxicity related to CNI,<a class="elsevierStyleCrossRefs" href="#bib0045">9-17</a> delaying, reducing or eliminating recipient’s exposure to them. Some of these strategies consider introducing mycophenolate mofetyl (MMF) in order to minimize the CNI dose.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> Compared to CNI, MMF is a weaker ISD, with a better side-effect profile and specifically, no reported nephrotoxicity. MMF use allows to reduce CNI (or its complete withdrawal), in order to preserve or improve renal function after liver transplantation as has recently been shown by a systematic review that included eight high quality randomized trials.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Nonetheless, CNI reduction or withdrawal carries a risk of allograft dysfunction. The goal then, is to establish a balance between the potential improvement of renal function and the risk of graft rejection before minimizing CNI. The available data show that although conversion to MMF monotherapy (CMM) implies a relative risk of graft rejection of 4.96, CMM is not associated with increased risk of graft loss or death, suggesting that with proper monitoring, adequate recipient selection and a prompt initiation of rejection treatment (if it develops), the risks involved in CNI minimization by employing MMF are reasonable.<a class="elsevierStyleCrossRef" href="#bib0090">18</a>Presently, most studies are designed to demonstrate the advantages of CMM to preserve renal function, but not specifically to identify variables associated with successful CMM. A recent study by Benítez, et al. identified clinical variables associated with successful withdrawal of ISD at baseline.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> Moreover, Bohne, et al. studied the same cohort and identified transcriptional variables and changes in lymphocyte subpopulations associated with successful ISD withdrawal.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> Identifying these variables will allow for determining which recipients will develop rejection. There is little information about predictors of a successful CNI conversion to MMF. Thus, the aim of this study was to identify patient characteristics or laboratory tests associated with successful conversion from CNI to MMF monotherapy in a group of liver transplant recipients.Material and MethodsPatientsPatients were registered at the Clinical Hospital of the Pontificia Universidad Católica de Chile. The immuno-suppression scheme employed immediately after LT was CNI plus steroids and MMF and basiliximab following the attendance indication. All recipients were screened in their outpatient clinics for potential inclusion. Inclusion criteria were:<ul class="elsevierStyleList" id="l0010"><li class="elsevierStyleListItem" id="u0005">•Adult recipients.</li><li class="elsevierStyleListItem" id="u0010">•Single liver recipients.</li><li class="elsevierStyleListItem" id="u0015">•Stable liver function (ALT less than three times x ULN during the last year).</li><li class="elsevierStyleListItem" id="u0020">•CNI monotherapy as ISD scheme.</li><li class="elsevierStyleListItem" id="u0025">•Absence of steroid use.</li><li class="elsevierStyleListItem" id="u0030">•Absence of a rejection episode in the last twelve months.</li><li class="elsevierStyleListItem" id="u0035">•At least twelve months after LT.</li><li class="elsevierStyleListItem" id="u0040">•Had signed an informed consent form.</li><li class="elsevierStyleListItem" id="u0045">•Baseline liver biopsy excluding rejection.</li></ul>Exclusion criteria were:<ul class="elsevierStyleList" id="l0015"><li class="elsevierStyleListItem" id="u0050">•Age under 18 yrs.</li><li class="elsevierStyleListItem" id="u0055">•Presence of rejection at baseline liver biopsy.</li><li class="elsevierStyleListItem" id="u0060">•Non-compliance to medical prescriptions.</li><li class="elsevierStyleListItem" id="u0065">•Total white cell count ≤ 2 x 10<a class="elsevierStyleCrossRef" href="#bib0045">9</a>/L.</li><li class="elsevierStyleListItem" id="u0070">•Hemoglobin ≤ 7.5 g/L.</li><li class="elsevierStyleListItem" id="u0075">•Platelet count ≤ 70 x 10<a class="elsevierStyleCrossRef" href="#bib0045">9</a>/L.</li><li class="elsevierStyleListItem" id="u0080">•Retransplantation.</li><li class="elsevierStyleListItem" id="u0085">•Pregnancy.</li></ul>The study protocol was conducted in accordance with the Helsinki Declaration and approved by the Ethics Committee of the University. Clinicaltrials.gov identification: NCT01321112.Study designThe current study was designed as a prospective cohort study of conversion from CNI monotherapy to MMF monotherapy in stable liver transplant recipients. The primary end point was successful conversion to MMF mon-otherapy defined as the absence of biopsy proven rejection after a 12 months follow up.Conversion procedure<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a> schematically depicts the interventions made with the group of patients under study. During the first four weeks, MMF was introduced in the ISD scheme and its dose was gradually increased, first at 500 mgs bid. Two weeks later the dose was increased again to achieve the target dose (1,000 mgs bid).<a class="elsevierStyleCrossRef" href="#bib0075">15</a> Simultaneously, the CNI dose was maintained for the first two weeks, then reduced by 50% and finally completely withdrawn by week four, so the complete conversion took 4 weeks.<elsevierMultimedia ident="f0005"></elsevierMultimedia>Patient follow-upPatients were followed up for 12 months. Before the start of the conversion procedure, liver chemistry and a complete blood cell count were determined, and serum levels of glucose, uric acid, creatinine, glomerular filtration rate (IDMS-traceable MDRD-4), sodium, potassium, lipids, hemoglobin A1C (HbA1C) and tacrolimus or cyclosporine C2 were measured. Chronic renal failure was defined as the presence of stage 2 or more as has been established by the National Kidney Foundation.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> The proportion of patients that increased its GFR at the end the study (5 mL/min or more) was evaluated. Patients were evaluated every month during the first 3 months after conversion and then every 3 months until the end of the follow-up. The lipid profile was determined every 3 months and HbA1C every 6 months. The remaining tests were repeated every visit, as well determining arterial blood pressure and BMI.Definition of allograft dysfunctionDuring follow up, increases of > 2-fold (the upper limit of normal or baseline value if they were not normal) in serum aminotransferases (alanine-aminotransferase [ALT], aspartate-aminotransferase [AST]) or alkaline phosphatase (AP) were considered an indication of acute cellular rejection and a liver biopsy was performed. In cases of < 2-fold increases in ALT, AST or AP, liver chemistry was repeated 2 weeks later. Unexplained persistence of allograft dysfunction was considered an indication for liver biopsy. Isolated elevation of GGT was not considered as an indication for liver biopsy.Definition of rejectionAllograft dysfunction, in combination with histologic findings suggestive of rejection (mononuclear portal infiltrate, biliary damage by mononuclear infiltrate and en-dothelitis), were considered diagnostic criteria for acute cellular rejection. Rejection severity was graded according to the Banff criteria.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Viral infections, autoimmune diseases, drug-induced liver injury, and biliary complications were ruled out when histological evaluation was borderline for rejection diagnosis (BANFF score = 3). All the recipients that developed rejection during the follow up period were classified as failed conversion (FC), those that did not were classified as successful conversion (SC) (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>). All the samples were evaluated by two independent pathologist.Peripheral blood cell immunophenotypingMultiparameter flow cytometry was performed on peripheral blood mononuclear cells (PBMC) obtained by fi-coll gradient centrifugation in all patients during weeks -4 and 48 of the protocol. Isolated cells were stored in liquid nitrogen until phenotyping. Monoclonal antibodies directed against the following targets were used: CD3, CD4, CD19, CD25, CD56, TCRa(3, TCRy§ (from BD Bio-sciences; San Jose, CA, USA); V81 TCR (from Thermo-Scientific; Waltham, MA, USA); and V82 TCR (from Immunotech; Marseille, France); and Foxp3 (eBio-science, San Diego, CA, USA). Surface phenotyping was performed by staining 2-5 x 10<a class="elsevierStyleCrossRef" href="#bib0025">5</a> cells with specific fluorescence conjugated mAbs for 20 minutes at 4°C after blocking with PBS containing 0.1% BSA and 10% heat inactivated human AB serum. Cells were washed twice with PBS containing 0.1% BSA and fixed with 4% paraformaldehyde or BD fixing solution. Intracellular staining was performed in a similar fashion after permeabilizing cells with BD fix and perm solution. Flow cytometry data was acquired using a BDFacs Canto II flow cytometer (BD Biosciences) and data was analyzed with FlowJo Software (Tree Star, Inc., Ashland, OR, USA).Statistical analysisClinical variables were analyzed using SPSS 20.0 software. Categorical variables were analyzed using the %<a class="elsevierStyleCrossRef" href="#bib0010">2</a> test and the Student’s t-test was used for continuous variables following a normal distribution. The Mann-Whitney U test was employed for variables without a normal distribution. We employed ROC curves and evaluated different points in order to identify the best cut off values of CNI levels (and categorize it low or high levels) in order to predict a successful conversion Multivariate analyses used binary logistic regressions adjusted employing Hosmer Lemeshow test.Sample sizeTo discriminate variables with at least 30% difference between the SC vs. FC groups with a power of 80% and considering a 50% rate of successful conversion, we defined a minimum sample size of 40 liver recipients for one tailed test. P values of < 0.05 were considered significant. For this estimation we employed the program Ene 2.0.ResultsPatient recruitmentFrom March 2011 to November 2013, 124 liver recipients were screened for study eligibility. Forty recipients fulfilled the inclusion criteria and accepted to be included in the study (<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>). Subclinical rejection was ruled out from the baseline liver biopsy of all recruited recipients. <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a> shows the baseline characteristics. Mean age was 59.8 ± 10.58 years. Most of the recipients were male (70%) and the time from transplantation to inclusion in the study was 50 ± 49.5 months (median ± IQR). The most common etiologies were alcoholic liver disease (27.5%), NASH (25%), chronic hepatitis C virus infection (17.5%), acute liver failure (7.5%) and others (22.5%). Sixty percent of the recipients were using tacrolimus. Mean creatinine and median MDRD-4 were 1.17 ± 0.27 mg/dL and 60.5 ± 19 mL/min, respectively. As expected, although 13 of the liver recipients included in the study had normal creati-nine levels, 69.2% of them had chronic renal failure when GFR was estimated (stage 2 or more).<elsevierMultimedia ident="f0010"></elsevierMultimedia><elsevierMultimedia ident="t0005"></elsevierMultimedia>Forty percent of the recipients had hyperlipidemia, 30% diabetes and 47.5% hypertension. As expected, this was a cohort with high cardiovascular risk.Conversion outcomeDuring the follow-up period after conversion, 12 liver recipients (30%) developed rejection and were classified as failed conversion (FC). In this group, the median time to rejection was 8 weeks, quartile 25-75% were 5-11 weeks respectively. The diagnosis of the rejections involved biopsies with all but in one recipient that was receiving anticoagulants at the time. In this case diagnosis was based on liver chemistry, ruling out other causes of allograft dysfunction and steroid response. One recipient required two biopsies to diagnose the rejection (the first was normal and the second showed mild rejection). The median and interquartile range of the Banff score for FC recipients was 4 and 2 respectively, quartiles 25%-75%: 3-5. Most of the rejections were mild, and only one was moderate. Only one rejection episode required steroid bolus treatment. The others were treated with oral steroids and resumption of CNI. There was significant variability in the time required to resolve the rejections (<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>). However, in most cases complete withdrawal from steroids took fourteen weeks or less. In only one patient the attending physician dediced to slowly taper off steroid use over 32 weeks, even after liver chemistry was normal. <a class="elsevierStyleCrossRef" href="#f0015">Figure 3</a>A shows the percentage of subjects that remained rejection-free during the follow-up period. Interestingly, most of the rejection episodes (91.6%) occurred during the first 3 months after complete conversion, and only one rejection episode was diagnosed 24 weeks after complete conversion. All the rejections were resolved and no grafts were lost. Liver enzyme evolutions were consistent with the response of rejection episodes to steroids (Figures <a class="elsevierStyleCrossRef" href="#f0015">3B</a> and <a class="elsevierStyleCrossRef" href="#f0015">3C</a>). There were no adverse effects associated with rejection treatment. On the other hand, 28 liver recipients (70%) completed the follow-up period without rejection and were classified as Successful Conversions (SC). MMF administration was well tolerated. There was only one case of diarrhea that disappeared spontaneously after 3 weeks.<elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="f0015"></elsevierMultimedia>Impact of conversion on renal functionThere was a significant improvement in renal function among SC liver recipients. There was progressive improvement in GFR from week 12 after conversion until the end of the study (<a class="elsevierStyleCrossRef" href="#f0015">Figure 3</a>D). By the end of the follow-up (48 weeks), the proportion of recipients that improved its GFR (increase of 5 ml/min or more) was 82.14% and 25.0% (p = 0.001) on the SC and FC groups respectively. The patients with improved GFR had a significantly lower baseline GFR (54.5 ± 18.25 vs. 63.5 ± 32.25 [median ± IQR], p = 0.05).Baseline clinical differences between the SC and FC groups<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a> shows the main baseline clinical differences between SC and FC recipients with. Notably, SC recipients had a longer post transplantation period than FC recipients (54.5 ± 47.0 vs. 30.6 ± 35.0 [median ± IQR] months, p = 0.008). Cyclosporine and tacrolimus levels were also lower among SC recipients. We used ROC curve analysis and evaluated different points to identify the best CNI levels cutoff values to predict successful conversion. Thus, we classified CNI levels as low when tacrolimus levels were < 6.5 ng/mL or cyclosporine C2 levels were < 635 ng/mL. At baseline, low CNI levels were significantly more common among SC recipients than FC counterparts (78.6 vs. 25%, p = 0.001). Considering that a longer post transplantation time is frequently related to lower CNI levels, we performed a binary logistic regression only including low CNI levels and time since LT. In this analysis, low CNI levels was related to successful conversion independently to the time elapsed since LT: p = 0.02, OR: 6.93, 95% CI: 1.3-29.7.Peripheral blood mononuclear cell immunophenotypingTo establish which lymphocytic cell types are related to SC and how they change after the follow-up we determined the frequency of CD3-CD19+B cells, CD3-CD56+ NK cells, TCRαβ and γδ CD3+ T cells, CD3+Vδ1+ and Vδ2+ γδ T cell subpopulations and CD4+CD25+Foxp3+ Treg cells. At baseline we found no differences between SC and FC recipients in the frequency of B, TCRαβ and γδ T cells (Supplementary figures). SC group recipients showed a higher frequency of NK cells and a lower frequency of Vδ2 TCR γδ cells (<a class="elsevierStyleCrossRef" href="#f0020">Figure 4</a>A, 4B respectively) than FC recipients. Although CD4+CD25+Foxp3+ Treg cells showed a non-significant decrease at baseline among FC recipients (Supplementary figures), remarkably, mean fluorescent intensity (MFI) for FoxP3 in CD4+CD25+ T cells was higher among SC recipients (<a class="elsevierStyleCrossRef" href="#f0020">Figure 4</a>C), suggesting a role of regulatory cells in the development of successful conversion. Interestingly, FoxP3 MFI was significantly higher at baseline among recipients with low CNI levels (<a class="elsevierStyleCrossRef" href="#f0020">Figure 4</a>D), which was a condition highly related to successful conversion. To evaluate changes in the levels of lymphocytic populations from baseline to the end of the follow-up, we calculated delta between baseline and the end of follow up (48 weeks) among the analyzed populations. At the end of follow up, there were no differences on NK cells frequency and Vδ2 TCR γδ (Supplementary figures). While at baseline Vδ1 TCRγδ cell frequency was similar in the SC and FC groups, a slight reduction was observed in the FC group at the end of follow up (<a class="elsevierStyleCrossRef" href="#f0025">Figure 5</a>A). In addition, Foxp3 MFI in CD4+CD25+ T cells was slightly lower in the SC group than the FC group (<a class="elsevierStyleCrossRef" href="#f0025">Figure 5</a>B).<elsevierMultimedia ident="f0020"></elsevierMultimedia><elsevierMultimedia ident="f0025"></elsevierMultimedia>DiscussionCalcineurin inhibitor minimization or conversion to MMF has been proposed as an alternative to preserve renal function and decrease cardiovascular risk by employing a drug with a safe side-effect profile.<a class="elsevierStyleCrossRefs" href="#bib0090">18,23</a> At this point, there are no available data to identify predictors of successful conversion to MMF to discriminate recipients with a higher probability of rejection.The present study suggests that CNI conversion to MMF monotherapy is safe and clinically feasible. The rate of rejection was significant (30%) but due to close patient monitoring all rejection episodes were resolved by the end of the follow-up. In addition, we report no significant consequences for the graft or the recipient. This finding is consistent with the recently published experience of Benítez, et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> They conducted an immunosuppression withdrawal trial with 102 liver recipients, 57 of which developed late rejection during the withdrawal. Most of these episodes were mild and all the rejections were resolved. These findings suggest that proper monitoring minimizes the risk of late acute cellular rejection. In our study, there was clear benefit in renal function for the SC group. The variables associated with improved renal function were lower baseline GFR and C2 cyclosporine levels. The latter finding could be related to the fact that CNI exposure is highly related to renal arteriolar hyaliniza-tion,<a class="elsevierStyleCrossRef" href="#bib0120">24</a> and suggest that a higher and prolonged exposure to CNI increases the risk of structural changes that do not reverse after CNI withdrawal.Considering that CMM preserves GFR, this strategy seems reasonable, at least with patients with the highest probability of success. At this respect, we found that the only clinical variable independently related to successful conversion was a low CNI level at baseline (defined as tacrolimus levels ≤ 6.5 ng/mL or cyclosporine C2 levels ≤ 635 ng/mL).This finding is consistent with the fact that MMF, at the administered doses of two grams per day, adequately suppresses alloresponse at a similar level to that of the previous immunosuppressive scheme to avoid rejection. Thus, the ICN levels considered as “low” have similar or less effect on immune response than a dose of 2 grams of MMF. For some patients with low CNI levels, conversion to MMF monotherapy at the doses employed in this study imply higher immunosuppressive potency. This is probably the case for recipients with successful conversion and low baseline tacrolimus or cyclosporine levels. Identifying a clear threshold based on ISD levels could guide the clinical practice of transplant physicians, optimizing the selection of liver recipients with higher probability of successful CMM and all the benefits this implies.We also found an association between successful conversion and some lymphocyte subpopulations. Expression of the lineage-specific transcription factor FoxP3 CD4+CD25T cells was higher in recipients with successful conversion, suggesting a role for immune regulatory processes in this phenomenon. However, it is also true that CNI has negative effects on Treg proliferation and function, which several studies have confirmed, including a recent systematic review.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> In fact, at baseline, FoxP3 MFI was higher in the CD4+CD25 T cells of recipients with less exposure to CNI (<a class="elsevierStyleCrossRef" href="#f0020">Figure 4</a>), expressed by low CNI levels at baseline. This suggests that higher FOXP3 MFI in T cells in the SC group is at least partially explained by less CNI exposure at baseline, however, a confounding effect of the time elapsed since LT over CNI exposure cannot be excluded. Interestingly, there was a slight reduction of FOXP3 MFI at the end of follow-up, which could be explained by the deleterious effect that MMF appears to have on Tregs (<a class="elsevierStyleCrossRef" href="#f0025">Figure 5</a>B).<a class="elsevierStyleCrossRefs" href="#bib0130">26-29</a> This effect appears to be dose dependent,<a class="elsevierStyleCrossRef" href="#bib0135">27</a> and is not observed with low MMF doses. In the study of Demirkiran, et al., liver recipients swichted to MMF monotherapy were compared to recipients on CNI-based immunosuppres-sion. The authors showed a relative increase (compared to the baseline) of CD4+CD25+FOXP3+ T cells after conversion to MMF monotherapy. All recipients received a single dose of daclizumab, which binds to CD25, the alpha subunit of the IL-2 receptor of T cells<a class="elsevierStyleCrossRef" href="#bib0150">30</a> that has been found to have significant negative effects on Treg frequency in most studies.<a class="elsevierStyleCrossRefs" href="#bib0155">31-34</a> Therefore, a marked reduction in CD4+CD25+FOXP3+ T cell frequency after administering daclizumab, and its recovery in the following months are expected.The SC group also had a higher number of NK cells. NK cells have traditionally been associated with pro-inflammatory immunity, resulting in allograft injury. More recently the regulatory function of NK cells has been identified.<a class="elsevierStyleCrossRef" href="#bib0175">35</a>,<a class="elsevierStyleCrossRef" href="#bib0180">36</a> One of the mechanisms is the release of anti-inflammatory cytokines such as TGF-(3 and IL-10,<a class="elsevierStyleCrossRef" href="#bib0185">37</a>,<a class="elsevierStyleCrossRef" href="#bib0190">38</a> but also, and very interestingly, several studies have indicated that cytotoxic activity against activated T cells is an important regulatory mechanism employed by NK cells.<a class="elsevierStyleCrossRef" href="#bib0195">39</a> The effect of immunosuppressive drugs (specifically ICNs) on NK cells has not been totally elucidated. Several studies indicate a negative effect on NK cell proliferation, while others do not.<a class="elsevierStyleCrossRef" href="#bib0200">40</a>,<a class="elsevierStyleCrossRef" href="#bib0205">41</a> In our study, NK cell frequency was not related to ICN serum levels (data not shown). Thus, although it is not possible to rule out an effect of ICN on NK cell frequency, it is plausible that higher NK cell frequency has a causal effect on the outcome of conversion.Although Y§TCR+ cell frequency did not differ between the two groups, V§2TCR+ cell frequency was significantly higher in the FC group. Like NK cells, Y§TCR+ cells are part of the innate immune system and V§2TCR+ cells are the most common y§ subpopulation in peripheral blood, displaying effector functions against infectious stimulus and acting as antigen presenting cells.<a class="elsevierStyleCrossRef" href="#bib0210">42</a> There is no information about the effect of immunosuppressive drugs on §2TCR+ cell biology or the successful conversion to MMF monotherapy. The lower frequency of 82TCR+ cells at baseline in the SC group deserves further investigation as it could be related to lower alloimmune response against the graft.We registered a slight reduction in the frequency of V81TCR+ in the FC group at the end of the follow-up. The cause of this change is not clear and we speculate that it could be a consequence of the ISD employed to treat rejection among FC group recipients.This is the first study to identify clinical variables related to successful conversion to MMF. All previous conversion studies have sought to demonstrate the feasibility and benefits of CNI minimization/withdrawal and not to identify the subset of liver recipients with the highest chance of successful conversion. This could be an interesting advance in evaluating the potential benefits of conversion to MMF monotherapy. Interestingly, some of the variables associated with successful conversion are also related to the development of operational tolerance, such as the time since transplantation, lower exposure to CNI, higher frequency of NK cells, lower frequency of §2TCR+ cells and higher expression of FoxP3.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>,<a class="elsevierStyleCrossRef" href="#bib0100">20</a>,<a class="elsevierStyleCrossRef" href="#bib0215">43</a> This raises the question of whether the SC group has a higher chance of developing operational tolerance in the future.The fact that we recruited only 40 of 124 recipients in our cohort suggests that this strategy is suitable for a minority of recipients. The authors excluded 29 steroid-dependent recipients in order to administer immunosup-pression of similar intensity to all recipients. However, in real life steroid dependency does not preclude CNI minimization/withdrawal. Thirty-one recipients were on a non-CNI-based immunosuppressive regime. Twenty-five of them were already receiving MMF, with minimization or complete withdrawal of CNI. Considering these recipients, in relation to those that were recruited, it can be said that this strategy could be employed with at least 75.8% of the total cohort.The small size of this study limits us to suggesting that low CNI levels can predict successful conversion. Further studies are needed to demonstrate the usefulness of this indicator and to establish the best cutoff for defining low CNI levels. However, our findings can guide future studies to determine predictors of successful conversion.In conclusion, conversion to MMF monotherapy in liver recipients with a steroid free immunosuppressive scheme based on CNIs, compliant and in the absence of recently diagnosed rejection, seems to be plausible and safe. A significant benefit can be obtained in terms of preserving renal function, especially with patients with lower GFR or CNI levels. The most important finding in this study is probably the identification of a CNI level threshold to select liver recipients with a higher probability of successful CMM. A higher FoxP3 MFI, an increased frequency of NK cells and a lower number δ2TCR+ cells at baseline were also associated with successful conversion. These findings could allow an improved selection of candidates for MMF monotherapy conversion.Abbreviations<ul class="elsevierStyleList" id="l0020"><li class="elsevierStyleListItem" id="u0090">•ALT: Alanine aminotransferase.</li><li class="elsevierStyleListItem" id="u0095">•AST: Aspartate aminotransferase.</li><li class="elsevierStyleListItem" id="u0100">•AP: Alkaline phosphatase.</li><li class="elsevierStyleListItem" id="u0105">•CMM: Conversion to mycophenolate mofetil mono-therapy.</li><li class="elsevierStyleListItem" id="u0110">•CNI: Calcineurin inhibitors.</li><li class="elsevierStyleListItem" id="u0115">•DBP: Diastolic blood pressure.</li><li class="elsevierStyleListItem" id="u0120">•DM: Diabetes mellitus.</li><li class="elsevierStyleListItem" id="u0125">•FC: Failed conversion.</li><li class="elsevierStyleListItem" id="u0130">•GFR: Glomerular filtration rate.</li><li class="elsevierStyleListItem" id="u0135">•GGT: γ-glutamil transferase.</li><li class="elsevierStyleListItem" id="u0140">•HTN: Arterial hypertension.</li><li class="elsevierStyleListItem" id="u0145">•ISD: Immunosuppressive drugs.</li><li class="elsevierStyleListItem" id="u0150">•LT: Liver transplantation.</li><li class="elsevierStyleListItem" id="u0155">•MMF: Mycophenolate mofetil.</li><li class="elsevierStyleListItem" id="u0160">•PBMC: Peripheral blood mononuclear cell.</li><li class="elsevierStyleListItem" id="u0165">•SBP: Systolic blood pressure.</li><li class="elsevierStyleListItem" id="u0170">•SC: Successful conversion.</li></ul>Funding SourcesFondecyt iniciacion # 11100113.Conflict of InterestAll authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1198052" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0010" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1116696" "titulo" => "Key words" ] 2 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "s0010" "titulo" => "Material and Methods" "secciones" => array:9 [ 0 => array:2 [ "identificador" => "s0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "s0020" "titulo" => "Study design" ] 2 => array:2 [ "identificador" => "s0025" "titulo" => "Conversion procedure" ] 3 => array:2 [ "identificador" => "s0030" "titulo" => "Patient follow-up" ] 4 => array:2 [ "identificador" => "s0035" "titulo" => "Definition of allograft dysfunction" ] 5 => array:2 [ "identificador" => "s0040" "titulo" => "Definition of rejection" ] 6 => array:2 [ "identificador" => "s0045" "titulo" => "Peripheral blood cell immunophenotyping" ] 7 => array:2 [ "identificador" => "s0050" "titulo" => "Statistical analysis" ] 8 => array:2 [ "identificador" => "s0055" "titulo" => "Sample size" ] ] ] 4 => array:3 [ "identificador" => "s0060" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "s0065" "titulo" => "Patient recruitment" ] 1 => array:2 [ "identificador" => "s0070" "titulo" => "Conversion outcome" ] 2 => array:2 [ "identificador" => "s0075" "titulo" => "Impact of conversion on renal function" ] 3 => array:2 [ "identificador" => "s0080" "titulo" => "Baseline clinical differences between the SC and FC groups" ] 4 => array:2 [ "identificador" => "s0085" "titulo" => "Peripheral blood mononuclear cell immunophenotyping" ] ] ] 5 => array:2 [ "identificador" => "s0090" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "s0095" "titulo" => "Abbreviations" ] 7 => array:2 [ "identificador" => "s0100" "titulo" => "Funding Sources" ] 8 => array:2 [ "identificador" => "s0105" "titulo" => "Conflict of Interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-05-12" "fechaAceptado" => "2016-07-05" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec1116696" "palabras" => array:6 [ 0 => "Calcineurin inhibitors" 1 => "Minimization" 2 => "Mycophenolate mofetil" 3 => "Conversion" 4 => "Liver transplantation" 5 => "Renal function" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to myc-ophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow-up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112." ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 797 "Ancho" => 1381 "Tamanyo" => 83543 ] ] "descripcion" => array:1 [ "en" => "Description of the study methodology and follow-up: Calcineurin inhibitors were gradually reduced until their total withdrawal during the first four weeks, followed by a 48-week follow-up. Medical evaluations were conducted on the indicated dates and whenever necessary." ] ] 1 => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1118 "Ancho" => 1000 "Tamanyo" => 122295 ] ] "descripcion" => array:1 [ "en" => "Patient enrollment." ] ] 2 => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1245 "Ancho" => 2023 "Tamanyo" => 201938 ] ] "descripcion" => array:1 [ "en" => "Evolution of clinical parameters in SC and FC groups. A. Kaplan-Meir curve showing follow-up time free of rejection. B. Evolution of ALT levels during follow-up. Differences were calculated between SC and FC groups on each time point. * p = 0.01. C. Evolution of AP levels during follow-up. Differences were calculated between SC and FC groups on each time point. * p = 0.01. D. Change of GFR (calculated as MDRD) expressed in mL/min. Differences were calculated between SC and FC groups on each time point. * p = 0.01." ] ] 3 => array:7 [ "identificador" => "f0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1283 "Ancho" => 2077 "Tamanyo" => 183025 ] ] "descripcion" => array:1 [ "en" => "Baseline of lymphocytic populations determined by flow cytometry studies of the SC and FC groups. A. Frequency of natural killer cells. B. Frequency of CD3+Vδ2 cells. C. Mean FoxP3 fluorescent intensity in CD4+CD25+ T cells. D. Mean FoxP3 fluorescent intensity in CD4+CD25+ T cells of recipients with low and high CNI levels." ] ] 4 => array:7 [ "identificador" => "f0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 613 "Ancho" => 2072 "Tamanyo" => 78914 ] ] "descripcion" => array:1 [ "en" => "Changes between baseline and end of the follow up in lymphocytic populations of the SC and FC groups. A. Change in the frequency of CD3+Vδ1 cells. B. Change in FoxP3 MFI in CD4+CD25+ T cells." ] ] 5 => array:8 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "* TTE: Time from transplantation to enrollment. TAC: Tacrolimus. LT: liver transplantation. SBP: systolic blood pressure. DPB: diastolic blood pressure. † Data expressed as median ± IQR." "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SC, n = 28 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FC, n = 12 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Overall recipients, n = 40 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 ± 11.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.3 ± 9.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.8 ± 10.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.83 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male gender, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (64.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (83.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TTE*,† (months) ± IQR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.5 ± 44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.5 ± 32.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 ± 49.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.009 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TAC use*; n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (83.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.049 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Indication for LT* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alcoholic liver disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (27.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NASH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (17.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (41.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HCV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (21.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (8.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (17.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute liver failure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (7.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (8.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (7.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (28.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (22.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Liver and Kidney function \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.7 ± 16.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40.3 ± 47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35 ± 28.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.45 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.9 ± 19.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.9 ± 84.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39.7 ± 49.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.26 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GGT ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70.7 ± 97.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72.6 ± 89.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71.3 ± 93.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.95 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AP ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">130.6 ± 60.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">127.2 ± 72.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">129.5 ± 63.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.88 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TB ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.8 ± 0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.9 ± 0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.8± 0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.82 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protrombine time ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94.8 ± 13.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87.6 ± 12.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">92.6 ± 13.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Creatinine ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.2 ± 0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.19 ± 0.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.17± 0.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MDRD-4†± IQR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57.5 ± 16.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62.5 ± 32.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60.5 ± 19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Uric acid ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.4 ± 1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.2 ± 1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.3 ± 1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.98 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glucose ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">105.1 ± 28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">129.5 ± 75.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">112.5 ± 47.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glicated haemoglobin ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.7 ± 0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.8 ± 1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.7 ± 1.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.88 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HOMA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.3 ± 5.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.3 ± 3.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.3 ± 5.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.95 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SBP ±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">138.2 ± 20.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">131.7 ± 18.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">136 ± 19.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.35 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DBP ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85 ± 9.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80.8 ± 14.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83.7 ± 11.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.28 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Colesterol level ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">174.9 ± 43.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">152.2 ± 33.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">168.1 ± 41.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Triglicerides ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">144 ± 100.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">146.2 ± 75.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">144.6 ± 92.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.94 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HDL ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.3 ± 17.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.3 ± 12.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48.1 ± 16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.48 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LDL ± SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">96.8 ± 31.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75.1 ± 32.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90.3 ± 32.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.054 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HTN; n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (53.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (47.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.09 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DM; n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (21.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (41.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.19 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hiperlipidemia; n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (46.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (16.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.07 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2046071.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Trial participants clinical characteristics." ] ] 6 => array:8 [ "identificador" => "t0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "* Rejection was not biopsy proven because the patient was on anticoagulant treatment. † Rejection resolution was defined as the moment of complete steroids withdrawal." "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Recipient No. \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Banff score at rejection \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rejection treament \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Time for rejection resolution (weeks)† \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNI reinstitution plus oral steroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNI reinstitution plus oral steroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">N/A* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNI reinstitution plus oral steroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNI reinstitution plus oral steroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNI reinstitution plus metilprednisole boluses \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNI reinstitution plus oral steroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNI reinstitution plus oral steroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNI reinstitution plus oral steroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNI reinstitution plus oral steroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNI reinstitution plus oral steroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNI reinstitution plus oral steroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNI reinstitution plus oral steroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2046072.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical characteristics of non-succesful conversion patients at the time of liver rejection." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0010" "bibliografiaReferencia" => array:43 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Calcineurin inhibitor-free mycophe-nolate mofetil/sirolimus maintenance in liver transplantation: the randomized spare-the-nephron trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Teperman L." 1 => "Moonka D." 2 => "Sebastian A." 3 => "Sher L." 4 => "Marotta P." 5 => "Marsh C." 6 => "Koneru B." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/lt.23658" "Revista" => array:6 [ "tituloSerie" => "Liver Transpl" "fecha" => "2013" "volumen" => "19" "paginaInicial" => "675" "paginaFinal" => "689" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23775875" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." 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Blanca Norero*, Carolina A. Serrano†, Alberto Sanchez-Fueyo‡, Ignacio Duarte§, Javiera Torres§, Mauricio Ocquetau||, Francisco Barrera*, Marco Arrese*, Alejandro Soza*, Carlos Benítez

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cbenitez@med.puc.cl

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* Departamentos de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile

† Departamentos de Gastroenterología y Nutrición Pediátrica, Escuela de Medicina, Pontificia Universidad Católica de Chile

§ Departamentos de Patología y Escuela de Medicina, Pontificia Universidad Católica de Chile

|| Departamentos de Hemato-Oncología, Escuela de Medicina, Pontificia Universidad Católica de Chile

‡ Institute of Liver Studies, MRC Centre for Transplantation, King’s College London, London SE5 9RS, United Kingdom

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Improvements in immunosuppressive drugs &#40;ISD&#41; have significantly increased survival rates of liver transplant recipients&#46; Thus&#44; one-year survival after liver transplantation &#40;LT&#41; currently reaches 85-90&#37;&#44; and 50&#37; after ten years &#40;http&#58;&#47;&#47;www&#46;eltr&#46;org&#47;&#44; http&#58;&#47;&#47;www&#46;unos&#46;org&#47;&#41;&#46; However&#44; ISDs are toxic and commonly have severe side effects&#44; affecting survival and quality of life of liver recipients&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1-3</span></a> with infections acting as the main cause of mortality during the first year after LT &#40;85&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In the long-term&#44; most cases of morbidity and mortality of LT recipients are related to side effects of ISD&#44; mostly calcineurin inhibitors &#40;CNI&#41;&#44; although steroids&#44; antimetabolites and mTOR inhibitors are also related to significant side effects&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> In a recent study&#44; two thirds of the deaths that occurred one year after LT were unrelated to graft failure&#46; In fact&#44; most deaths were attributable to ISD side effects such as infections&#44; renal failure&#44; cancer and cardiovascular diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5-8</span></a> Renal failure is a common cause of morbidity after LT&#46; The incidence of a glomerular filtration rate &#40;GFR&#41; of 30 mL&#47;min or less is 18&#46;1&#37; five years after LT&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Importantly&#44; renal failure seems to be independently related to mortality among liver recipients&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Indeed&#44; the relation between renal failure and mortality after LT seems to be even more important when renal failure occurs late after LT&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Considering these facts&#44; several strategies have been developed to minimize the nephrotoxicity related to CNI&#44;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9-17</span></a> delaying&#44; reducing or eliminating recipient&#8217;s exposure to them&#46; Some of these strategies consider introducing mycophenolate mofetyl &#40;MMF&#41; in order to minimize the CNI dose&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Compared to CNI&#44; MMF is a weaker ISD&#44; with a better side-effect profile and specifically&#44; no reported nephrotoxicity&#46; MMF use allows to reduce CNI &#40;or its complete withdrawal&#41;&#44; in order to preserve or improve renal function after liver transplantation as has recently been shown by a systematic review that included eight high quality randomized trials&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Nonetheless&#44; CNI reduction or withdrawal carries a risk of allograft dysfunction&#46; The goal then&#44; is to establish a balance between the potential improvement of renal function and the risk of graft rejection before minimizing CNI&#46; The available data show that although conversion to MMF monotherapy &#40;CMM&#41; implies a relative risk of graft rejection of 4&#46;96&#44; CMM is not associated with increased risk of graft loss or death&#44; suggesting that with proper monitoring&#44; adequate recipient selection and a prompt initiation of rejection treatment &#40;if it develops&#41;&#44; the risks involved in CNI minimization by employing MMF are reasonable&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">Presently&#44; most studies are designed to demonstrate the advantages of CMM to preserve renal function&#44; but not specifically to identify variables associated with successful CMM&#46; A recent study by Ben&#237;tez&#44; <span class="elsevierStyleItalic">et al&#46;</span> identified clinical variables associated with successful withdrawal of ISD at baseline&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Moreover&#44; Bohne&#44; <span class="elsevierStyleItalic">et al&#46;</span> studied the same cohort and identified transcriptional variables and changes in lymphocyte subpopulations associated with successful ISD withdrawal&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Identifying these variables will allow for determining which recipients will develop rejection&#46; There is little information about predictors of a successful CNI conversion to MMF&#46; Thus&#44; the aim of this study was to identify patient characteristics or laboratory tests associated with successful conversion from CNI to MMF monotherapy in a group of liver transplant recipients&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Material and Methods</span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Patients</span><p id="p0015" class="elsevierStylePara elsevierViewall">Patients were registered at the Clinical Hospital of the Pontificia Universidad Cat&#243;lica de Chile&#46; The immuno-suppression scheme employed immediately after LT was CNI plus steroids and MMF and basiliximab following the attendance indication&#46; All recipients were screened in their outpatient clinics for potential inclusion&#46; Inclusion criteria were&#58;<ul class="elsevierStyleList" id="l0010"><li class="elsevierStyleListItem" id="u0005"><span class="elsevierStyleLabel">&#8226;</span><p id="p0020" class="elsevierStylePara elsevierViewall">Adult recipients&#46;</p></li><li class="elsevierStyleListItem" id="u0010"><span class="elsevierStyleLabel">&#8226;</span><p id="p0025" class="elsevierStylePara elsevierViewall">Single liver recipients&#46;</p></li><li class="elsevierStyleListItem" id="u0015"><span class="elsevierStyleLabel">&#8226;</span><p id="p0030" class="elsevierStylePara elsevierViewall">Stable liver function &#40;ALT less than three times x ULN during the last year&#41;&#46;</p></li><li class="elsevierStyleListItem" id="u0020"><span class="elsevierStyleLabel">&#8226;</span><p id="p0035" class="elsevierStylePara elsevierViewall">CNI monotherapy as ISD scheme&#46;</p></li><li class="elsevierStyleListItem" id="u0025"><span class="elsevierStyleLabel">&#8226;</span><p id="p0040" class="elsevierStylePara elsevierViewall">Absence of steroid use&#46;</p></li><li class="elsevierStyleListItem" id="u0030"><span class="elsevierStyleLabel">&#8226;</span><p id="p0045" class="elsevierStylePara elsevierViewall">Absence of a rejection episode in the last twelve months&#46;</p></li><li class="elsevierStyleListItem" id="u0035"><span class="elsevierStyleLabel">&#8226;</span><p id="p0050" class="elsevierStylePara elsevierViewall">At least twelve months after LT&#46;</p></li><li class="elsevierStyleListItem" id="u0040"><span class="elsevierStyleLabel">&#8226;</span><p id="p0055" class="elsevierStylePara elsevierViewall">Had signed an informed consent form&#46;</p></li><li class="elsevierStyleListItem" id="u0045"><span class="elsevierStyleLabel">&#8226;</span><p id="p0060" class="elsevierStylePara elsevierViewall">Baseline liver biopsy excluding rejection&#46;</p></li></ul></p><p id="p0065" class="elsevierStylePara elsevierViewall">Exclusion criteria were&#58;<ul class="elsevierStyleList" id="l0015"><li class="elsevierStyleListItem" id="u0050"><span class="elsevierStyleLabel">&#8226;</span><p id="p0070" class="elsevierStylePara elsevierViewall">Age under 18 yrs&#46;</p></li><li class="elsevierStyleListItem" id="u0055"><span class="elsevierStyleLabel">&#8226;</span><p id="p0075" class="elsevierStylePara elsevierViewall">Presence of rejection at baseline liver biopsy&#46;</p></li><li class="elsevierStyleListItem" id="u0060"><span class="elsevierStyleLabel">&#8226;</span><p id="p0080" class="elsevierStylePara elsevierViewall">Non-compliance to medical prescriptions&#46;</p></li><li class="elsevierStyleListItem" id="u0065"><span class="elsevierStyleLabel">&#8226;</span><p id="p0085" class="elsevierStylePara elsevierViewall">Total white cell count &#8804; 2 x 10<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#47;L&#46;</p></li><li class="elsevierStyleListItem" id="u0070"><span class="elsevierStyleLabel">&#8226;</span><p id="p0090" class="elsevierStylePara elsevierViewall">Hemoglobin &#8804; 7&#46;5 g&#47;L&#46;</p></li><li class="elsevierStyleListItem" id="u0075"><span class="elsevierStyleLabel">&#8226;</span><p id="p0095" class="elsevierStylePara elsevierViewall">Platelet count &#8804; 70 x 10<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#47;L&#46;</p></li><li class="elsevierStyleListItem" id="u0080"><span class="elsevierStyleLabel">&#8226;</span><p id="p0100" class="elsevierStylePara elsevierViewall">Retransplantation&#46;</p></li><li class="elsevierStyleListItem" id="u0085"><span class="elsevierStyleLabel">&#8226;</span><p id="p0105" class="elsevierStylePara elsevierViewall">Pregnancy&#46;</p></li></ul></p><p id="p0110" class="elsevierStylePara elsevierViewall">The study protocol was conducted in accordance with the Helsinki Declaration and approved by the Ethics Committee of the University&#46; Clinicaltrials&#46;gov identification&#58; NCT01321112&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Study design</span><p id="p0115" class="elsevierStylePara elsevierViewall">The current study was designed as a prospective cohort study of conversion from CNI monotherapy to MMF monotherapy in stable liver transplant recipients&#46; The primary end point was successful conversion to MMF mon-otherapy defined as the absence of biopsy proven rejection after a 12 months follow up&#46;</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Conversion procedure</span><p id="p0120" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a> schematically depicts the interventions made with the group of patients under study&#46; During the first four weeks&#44; MMF was introduced in the ISD scheme and its dose was gradually increased&#44; first at 500 mgs bid&#46; Two weeks later the dose was increased again to achieve the target dose &#40;1&#44;000 mgs bid&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Simultaneously&#44; the CNI dose was maintained for the first two weeks&#44; then reduced by 50&#37; and finally completely withdrawn by week four&#44; so the complete conversion took 4 weeks&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Patient follow-up</span><p id="p0125" class="elsevierStylePara elsevierViewall">Patients were followed up for 12 months&#46; Before the start of the conversion procedure&#44; liver chemistry and a complete blood cell count were determined&#44; and serum levels of glucose&#44; uric acid&#44; creatinine&#44; glomerular filtration rate &#40;IDMS-traceable MDRD-4&#41;&#44; sodium&#44; potassium&#44; lipids&#44; hemoglobin A1C &#40;HbA1C&#41; and tacrolimus or cyclosporine C2 were measured&#46; Chronic renal failure was defined as the presence of stage 2 or more as has been established by the National Kidney Foundation&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The proportion of patients that increased its GFR at the end the study &#40;5 mL&#47;min or more&#41; was evaluated&#46; Patients were evaluated every month during the first 3 months after conversion and then every 3 months until the end of the follow-up&#46; The lipid profile was determined every 3 months and HbA1C every 6 months&#46; The remaining tests were repeated every visit&#44; as well determining arterial blood pressure and BMI&#46;</p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Definition of allograft dysfunction</span><p id="p0130" class="elsevierStylePara elsevierViewall">During follow up&#44; increases of &#62; 2-fold &#40;the upper limit of normal or baseline value if they were not normal&#41; in serum aminotransferases &#40;alanine-aminotransferase &#91;ALT&#93;&#44; aspartate-aminotransferase &#91;AST&#93;&#41; or alkaline phosphatase &#40;AP&#41; were considered an indication of acute cellular rejection and a liver biopsy was performed&#46; In cases of &#60; 2-fold increases in ALT&#44; AST or AP&#44; liver chemistry was repeated 2 weeks later&#46; Unexplained persistence of allograft dysfunction was considered an indication for liver biopsy&#46; Isolated elevation of GGT was not considered as an indication for liver biopsy&#46;</p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Definition of rejection</span><p id="p0135" class="elsevierStylePara elsevierViewall">Allograft dysfunction&#44; in combination with histologic findings suggestive of rejection &#40;mononuclear portal infiltrate&#44; biliary damage by mononuclear infiltrate and en-dothelitis&#41;&#44; were considered diagnostic criteria for acute cellular rejection&#46; Rejection severity was graded according to the Banff criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Viral infections&#44; autoimmune diseases&#44; drug-induced liver injury&#44; and biliary complications were ruled out when histological evaluation was borderline for rejection diagnosis &#40;BANFF score &#61; 3&#41;&#46; All the recipients that developed rejection during the follow up period were classified as failed conversion &#40;FC&#41;&#44; those that did not were classified as successful conversion &#40;SC&#41; &#40;<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>&#41;&#46; All the samples were evaluated by two independent pathologist&#46;</p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Peripheral blood cell immunophenotyping</span><p id="p0140" class="elsevierStylePara elsevierViewall">Multiparameter flow cytometry was performed on peripheral blood mononuclear cells &#40;PBMC&#41; obtained by fi-coll gradient centrifugation in all patients during weeks -4 and 48 of the protocol&#46; Isolated cells were stored in liquid nitrogen until phenotyping&#46; Monoclonal antibodies directed against the following targets were used&#58; CD3&#44; CD4&#44; CD19&#44; CD25&#44; CD56&#44; TCRa&#40;3&#44; TCRy&#167; &#40;from BD Bio-sciences&#59; San Jose&#44; CA&#44; USA&#41;&#59; V81 TCR &#40;from Thermo-Scientific&#59; Waltham&#44; MA&#44; USA&#41;&#59; and V82 TCR &#40;from Immunotech&#59; Marseille&#44; France&#41;&#59; and Foxp3 &#40;eBio-science&#44; San Diego&#44; CA&#44; USA&#41;&#46; Surface phenotyping was performed by staining 2-5 x 10<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> cells with specific fluorescence conjugated mAbs for 20 minutes at 4&#176;C after blocking with PBS containing 0&#46;1&#37; BSA and 10&#37; heat inactivated human AB serum&#46; Cells were washed twice with PBS containing 0&#46;1&#37; BSA and fixed with 4&#37; paraformaldehyde or BD fixing solution&#46; Intracellular staining was performed in a similar fashion after permeabilizing cells with BD fix and perm solution&#46; Flow cytometry data was acquired using a BDFacs Canto II flow cytometer &#40;BD Biosciences&#41; and data was analyzed with FlowJo Software &#40;Tree Star&#44; Inc&#46;&#44; Ashland&#44; OR&#44; USA&#41;&#46;</p></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Statistical analysis</span><p id="p0145" class="elsevierStylePara elsevierViewall">Clinical variables were analyzed using SPSS 20&#46;0 software&#46; Categorical variables were analyzed using the <span class="elsevierStyleItalic"><span class="elsevierStyleBold">&#37;</span></span><a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> test and the Student&#8217;s <span class="elsevierStyleItalic">t</span>-test was used for continuous variables following a normal distribution&#46; The Mann-Whitney <span class="elsevierStyleItalic">U</span> test was employed for variables without a normal distribution&#46; We employed ROC curves and evaluated different points in order to identify the best cut off values of CNI levels &#40;and categorize it low or high levels&#41; in order to predict a successful conversion Multivariate analyses used binary logistic regressions adjusted employing Hosmer Lemeshow test&#46;</p></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Sample size</span><p id="p0150" class="elsevierStylePara elsevierViewall">To discriminate variables with at least 30&#37; difference between the SC <span class="elsevierStyleItalic">vs&#46;</span> FC groups with a power of 80&#37; and considering a 50&#37; rate of successful conversion&#44; we defined a minimum sample size of 40 liver recipients for one tailed test&#46; P values of &#60; 0&#46;05 were considered significant&#46; For this estimation we employed the program Ene 2&#46;0&#46;</p></span></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Results</span><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Patient recruitment</span><p id="p0155" class="elsevierStylePara elsevierViewall">From March 2011 to November 2013&#44; 124 liver recipients were screened for study eligibility&#46; Forty recipients fulfilled the inclusion criteria and accepted to be included in the study &#40;<a class="elsevierStyleCrossRef" href="#f0010">Figure 2</a>&#41;&#46; Subclinical rejection was ruled out from the baseline liver biopsy of all recruited recipients&#46; <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a> shows the baseline characteristics&#46; Mean age was 59&#46;8 &#177; 10&#46;58 years&#46; Most of the recipients were male &#40;70&#37;&#41; and the time from transplantation to inclusion in the study was 50 &#177; 49&#46;5 months &#40;median &#177; IQR&#41;&#46; The most common etiologies were alcoholic liver disease &#40;27&#46;5&#37;&#41;&#44; NASH &#40;25&#37;&#41;&#44; chronic hepatitis C virus infection &#40;17&#46;5&#37;&#41;&#44; acute liver failure &#40;7&#46;5&#37;&#41; and others &#40;22&#46;5&#37;&#41;&#46; Sixty percent of the recipients were using tacrolimus&#46; Mean creatinine and median MDRD-4 were 1&#46;17 &#177; 0&#46;27 mg&#47;dL and 60&#46;5 &#177; 19 mL&#47;min&#44; respectively&#46; As expected&#44; although 13 of the liver recipients included in the study had normal creati-nine levels&#44; 69&#46;2&#37; of them had chronic renal failure when GFR was estimated &#40;stage 2 or more&#41;&#46;</p><elsevierMultimedia ident="f0010"></elsevierMultimedia><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0160" class="elsevierStylePara elsevierViewall">Forty percent of the recipients had hyperlipidemia&#44; 30&#37; diabetes and 47&#46;5&#37; hypertension&#46; As expected&#44; this was a cohort with high cardiovascular risk&#46;</p></span><span id="s0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Conversion outcome</span><p id="p0165" class="elsevierStylePara elsevierViewall">During the follow-up period after conversion&#44; 12 liver recipients &#40;30&#37;&#41; developed rejection and were classified as failed conversion &#40;FC&#41;&#46; In this group&#44; the median time to rejection was 8 weeks&#44; quartile 25-75&#37; were 5-11 weeks respectively&#46; The diagnosis of the rejections involved biopsies with all but in one recipient that was receiving anticoagulants at the time&#46; In this case diagnosis was based on liver chemistry&#44; ruling out other causes of allograft dysfunction and steroid response&#46; One recipient required two biopsies to diagnose the rejection &#40;the first was normal and the second showed mild rejection&#41;&#46; The median and interquartile range of the Banff score for FC recipients was 4 and 2 respectively&#44; quartiles 25&#37;-75&#37;&#58; 3-5&#46; Most of the rejections were mild&#44; and only one was moderate&#46; Only one rejection episode required steroid bolus treatment&#46; The others were treated with oral steroids and resumption of CNI&#46; There was significant variability in the time required to resolve the rejections &#40;<a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>&#41;&#46; However&#44; in most cases complete withdrawal from steroids took fourteen weeks or less&#46; In only one patient the attending physician dediced to slowly taper off steroid use over 32 weeks&#44; even after liver chemistry was normal&#46; <a class="elsevierStyleCrossRef" href="#f0015">Figure 3</a>A shows the percentage of subjects that remained rejection-free during the follow-up period&#46; Interestingly&#44; most of the rejection episodes &#40;91&#46;6&#37;&#41; occurred during the first 3 months after complete conversion&#44; and only one rejection episode was diagnosed 24 weeks after complete conversion&#46; All the rejections were resolved and no grafts were lost&#46; Liver enzyme evolutions were consistent with the response of rejection episodes to steroids &#40;Figures <a class="elsevierStyleCrossRef" href="#f0015">3B</a> and <a class="elsevierStyleCrossRef" href="#f0015">3C</a>&#41;&#46; There were no adverse effects associated with rejection treatment&#46; On the other hand&#44; 28 liver recipients &#40;70&#37;&#41; completed the follow-up period without rejection and were classified as Successful Conversions &#40;SC&#41;&#46; MMF administration was well tolerated&#46; There was only one case of diarrhea that disappeared spontaneously after 3 weeks&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="f0015"></elsevierMultimedia></span><span id="s0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Impact of conversion on renal function</span><p id="p0170" class="elsevierStylePara elsevierViewall">There was a significant improvement in renal function among SC liver recipients&#46; There was progressive improvement in GFR from week 12 after conversion until the end of the study &#40;<a class="elsevierStyleCrossRef" href="#f0015">Figure 3</a>D&#41;&#46; By the end of the follow-up &#40;48 weeks&#41;&#44; the proportion of recipients that improved its GFR &#40;increase of 5 ml&#47;min or more&#41; was 82&#46;14&#37; and 25&#46;0&#37; &#40;p &#61; 0&#46;001&#41; on the SC and FC groups respectively&#46; The patients with improved GFR had a significantly lower baseline GFR &#40;54&#46;5 &#177; 18&#46;25 <span class="elsevierStyleItalic">vs&#46;</span> 63&#46;5 &#177; 32&#46;25 &#91;median &#177; IQR&#93;&#44; p &#61; 0&#46;05&#41;&#46;</p></span><span id="s0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">Baseline clinical differences between the SC and FC groups</span><p id="p0175" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#t0005">Table 1</a> shows the main baseline clinical differences between SC and FC recipients with&#46; Notably&#44; SC recipients had a longer post transplantation period than FC recipients &#40;54&#46;5 &#177; 47&#46;0 <span class="elsevierStyleItalic">vs&#46;</span> 30&#46;6 &#177; 35&#46;0 &#91;median &#177; IQR&#93; months&#44; p &#61; 0&#46;008&#41;&#46; Cyclosporine and tacrolimus levels were also lower among SC recipients&#46; We used ROC curve analysis and evaluated different points to identify the best CNI levels cutoff values to predict successful conversion&#46; Thus&#44; we classified CNI levels as low when tacrolimus levels were &#60; 6&#46;5 ng&#47;mL or cyclosporine C2 levels were &#60; 635 ng&#47;mL&#46; At baseline&#44; low CNI levels were significantly more common among SC recipients than FC counterparts &#40;78&#46;6 <span class="elsevierStyleItalic">vs&#46;</span> 25&#37;&#44; p &#61; 0&#46;001&#41;&#46; Considering that a longer post transplantation time is frequently related to lower CNI levels&#44; we performed a binary logistic regression only including low CNI levels and time since LT&#46; In this analysis&#44; low CNI levels was related to successful conversion independently to the time elapsed since LT&#58; p &#61; 0&#46;02&#44; OR&#58; 6&#46;93&#44; 95&#37; CI&#58; 1&#46;3-29&#46;7&#46;</p></span><span id="s0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Peripheral blood mononuclear cell immunophenotyping</span><p id="p0180" class="elsevierStylePara elsevierViewall">To establish which lymphocytic cell types are related to SC and how they change after the follow-up we determined the frequency of CD3-CD19<span class="elsevierStyleSup">&#43;</span>B cells&#44; CD3-CD56<span class="elsevierStyleSup">&#43;</span> NK cells&#44; TCR&#945;&#946; and &#947;&#948; CD3<span class="elsevierStyleSup">&#43;</span> T cells&#44; CD3<span class="elsevierStyleSup">&#43;</span>V&#948;1<span class="elsevierStyleSup">&#43;</span> and V&#948;2<span class="elsevierStyleSup">&#43;</span> &#947;&#948; T cell subpopulations and CD4<span class="elsevierStyleSup">&#43;</span>CD25<span class="elsevierStyleSup">&#43;</span>Foxp3<span class="elsevierStyleSup">&#43;</span> Treg cells&#46; At baseline we found no differences between SC and FC recipients in the frequency of B&#44; TCR&#945;&#946; and &#947;&#948; T cells &#40;Supplementary figures&#41;&#46; SC group recipients showed a higher frequency of NK cells and a lower frequency of V&#948;2 TCR &#947;&#948; cells &#40;<a class="elsevierStyleCrossRef" href="#f0020">Figure 4</a>A&#44; 4B respectively&#41; than FC recipients&#46; Although CD4<span class="elsevierStyleSup">&#43;</span>CD25<span class="elsevierStyleSup">&#43;</span>Foxp3<span class="elsevierStyleSup">&#43;</span> Treg cells showed a non-significant decrease at baseline among FC recipients &#40;Supplementary figures&#41;&#44; remarkably&#44; mean fluorescent intensity &#40;MFI&#41; for FoxP3 in CD4<span class="elsevierStyleSup">&#43;</span>CD25<span class="elsevierStyleSup">&#43;</span> T cells was higher among SC recipients &#40;<a class="elsevierStyleCrossRef" href="#f0020">Figure 4</a>C&#41;&#44; suggesting a role of regulatory cells in the development of successful conversion&#46; Interestingly&#44; FoxP3 MFI was significantly higher at baseline among recipients with low CNI levels &#40;<a class="elsevierStyleCrossRef" href="#f0020">Figure 4</a>D&#41;&#44; which was a condition highly related to successful conversion&#46; To evaluate changes in the levels of lymphocytic populations from baseline to the end of the follow-up&#44; we calculated delta between baseline and the end of follow up &#40;48 weeks&#41; among the analyzed populations&#46; At the end of follow up&#44; there were no differences on NK cells frequency and V&#948;2 TCR &#947;&#948; &#40;Supplementary figures&#41;&#46; While at baseline V&#948;1 TCR&#947;&#948; cell frequency was similar in the SC and FC groups&#44; a slight reduction was observed in the FC group at the end of follow up &#40;<a class="elsevierStyleCrossRef" href="#f0025">Figure 5</a>A&#41;&#46; In addition&#44; Foxp3 MFI in CD4<span class="elsevierStyleSup">&#43;</span>CD25<span class="elsevierStyleSup">&#43;</span> T cells was slightly lower in the SC group than the FC group &#40;<a class="elsevierStyleCrossRef" href="#f0025">Figure 5</a>B&#41;&#46;</p><elsevierMultimedia ident="f0020"></elsevierMultimedia><elsevierMultimedia ident="f0025"></elsevierMultimedia></span></span><span id="s0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">Discussion</span><p id="p0185" class="elsevierStylePara elsevierViewall">Calcineurin inhibitor minimization or conversion to MMF has been proposed as an alternative to preserve renal function and decrease cardiovascular risk by employing a drug with a safe side-effect profile&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;23</span></a> At this point&#44; there are no available data to identify predictors of successful conversion to MMF to discriminate recipients with a higher probability of rejection&#46;</p><p id="p0190" class="elsevierStylePara elsevierViewall">The present study suggests that CNI conversion to MMF monotherapy is safe and clinically feasible&#46; The rate of rejection was significant &#40;30&#37;&#41; but due to close patient monitoring all rejection episodes were resolved by the end of the follow-up&#46; In addition&#44; we report no significant consequences for the graft or the recipient&#46; This finding is consistent with the recently published experience of Ben&#237;tez&#44; <span class="elsevierStyleItalic">et al&#46;</span><a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> They conducted an immunosuppression withdrawal trial with 102 liver recipients&#44; 57 of which developed late rejection during the withdrawal&#46; Most of these episodes were mild and all the rejections were resolved&#46; These findings suggest that proper monitoring minimizes the risk of late acute cellular rejection&#46; In our study&#44; there was clear benefit in renal function for the SC group&#46; The variables associated with improved renal function were lower baseline GFR and C2 cyclosporine levels&#46; The latter finding could be related to the fact that CNI exposure is highly related to renal arteriolar hyaliniza-tion&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> and suggest that a higher and prolonged exposure to CNI increases the risk of structural changes that do not reverse after CNI withdrawal&#46;</p><p id="p0195" class="elsevierStylePara elsevierViewall">Considering that CMM preserves GFR&#44; this strategy seems reasonable&#44; at least with patients with the highest probability of success&#46; At this respect&#44; we found that the only clinical variable independently related to successful conversion was a low CNI level at baseline &#40;defined as tacrolimus levels &#8804; 6&#46;5 ng&#47;mL or cyclosporine C2 levels &#8804; 635 ng&#47;mL&#41;&#46;</p><p id="p0200" class="elsevierStylePara elsevierViewall">This finding is consistent with the fact that MMF&#44; at the administered doses of two grams per day&#44; adequately suppresses alloresponse at a similar level to that of the previous immunosuppressive scheme to avoid rejection&#46; Thus&#44; the ICN levels considered as &#8220;low&#8221; have similar or less effect on immune response than a dose of 2 grams of MMF&#46; For some patients with low CNI levels&#44; conversion to MMF monotherapy at the doses employed in this study imply higher immunosuppressive potency&#46; This is probably the case for recipients with successful conversion and low baseline tacrolimus or cyclosporine levels&#46; Identifying a clear threshold based on ISD levels could guide the clinical practice of transplant physicians&#44; optimizing the selection of liver recipients with higher probability of successful CMM and all the benefits this implies&#46;</p><p id="p0205" class="elsevierStylePara elsevierViewall">We also found an association between successful conversion and some lymphocyte subpopulations&#46; Expression of the lineage-specific transcription factor FoxP3 CD4<span class="elsevierStyleSup">&#43;</span>CD25T cells was higher in recipients with successful conversion&#44; suggesting a role for immune regulatory processes in this phenomenon&#46; However&#44; it is also true that CNI has negative effects on Treg proliferation and function&#44; which several studies have confirmed&#44; including a recent systematic review&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> In fact&#44; at baseline&#44; FoxP3 MFI was higher in the CD4<span class="elsevierStyleSup">&#43;</span>CD25 T cells of recipients with less exposure to CNI &#40;<a class="elsevierStyleCrossRef" href="#f0020">Figure 4</a>&#41;&#44; expressed by low CNI levels at baseline&#46; This suggests that higher FOXP3 MFI in T cells in the SC group is at least partially explained by less CNI exposure at baseline&#44; however&#44; a confounding effect of the time elapsed since LT over CNI exposure cannot be excluded&#46; Interestingly&#44; there was a slight reduction of FOXP3 MFI at the end of follow-up&#44; which could be explained by the deleterious effect that MMF appears to have on Tregs &#40;<a class="elsevierStyleCrossRef" href="#f0025">Figure 5</a>B&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26-29</span></a> This effect appears to be dose dependent&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> and is not observed with low MMF doses&#46; In the study of Demirkiran&#44; <span class="elsevierStyleItalic">et al&#46;&#44;</span> liver recipients swichted to MMF monotherapy were compared to recipients on CNI-based immunosuppres-sion&#46; The authors showed a relative increase &#40;compared to the baseline&#41; of CD4<span class="elsevierStyleSup">&#43;</span>CD25<span class="elsevierStyleSup">&#43;</span>FOXP3<span class="elsevierStyleSup">&#43;</span> T cells after conversion to MMF monotherapy&#46; All recipients received a single dose of daclizumab&#44; which binds to CD25&#44; the alpha subunit of the IL-2 receptor of T cells<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> that has been found to have significant negative effects on Treg frequency in most studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31-34</span></a> Therefore&#44; a marked reduction in CD4<span class="elsevierStyleSup">&#43;</span>CD25<span class="elsevierStyleSup">&#43;</span>FOXP3<span class="elsevierStyleSup">&#43;</span> T cell frequency after administering daclizumab&#44; and its recovery in the following months are expected&#46;</p><p id="p0210" class="elsevierStylePara elsevierViewall">The SC group also had a higher number of NK cells&#46; NK cells have traditionally been associated with pro-inflammatory immunity&#44; resulting in allograft injury&#46; More recently the regulatory function of NK cells has been identified&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> One of the mechanisms is the release of anti-inflammatory cytokines such as TGF-&#40;3 and IL-10&#44;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> but also&#44; and very interestingly&#44; several studies have indicated that cytotoxic activity against activated T cells is an important regulatory mechanism employed by NK cells&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> The effect of immunosuppressive drugs &#40;specifically ICNs&#41; on NK cells has not been totally elucidated&#46; Several studies indicate a negative effect on NK cell proliferation&#44; while others do not&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> In our study&#44; NK cell frequency was not related to ICN serum levels &#40;data not shown&#41;&#46; Thus&#44; although it is not possible to rule out an effect of ICN on NK cell frequency&#44; it is plausible that higher NK cell frequency has a causal effect on the outcome of conversion&#46;</p><p id="p0215" class="elsevierStylePara elsevierViewall">Although Y&#167;TCR&#43; cell frequency did not differ between the two groups&#44; V&#167;<span class="elsevierStyleInf">2</span>TCR&#43; cell frequency was significantly higher in the FC group&#46; Like NK cells&#44; Y&#167;TCR&#43; cells are part of the innate immune system and V&#167;<span class="elsevierStyleInf">2</span>TCR&#43; cells are the most common <span class="elsevierStyleBold">y&#167;</span> subpopulation in peripheral blood&#44; displaying effector functions against infectious stimulus and acting as antigen presenting cells&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> There is no information about the effect of immunosuppressive drugs on &#167;<span class="elsevierStyleInf">2</span>TCR&#43; cell biology or the successful conversion to MMF monotherapy&#46; The lower frequency of 8<span class="elsevierStyleInf">2</span>TCR&#43; cells at baseline in the SC group deserves further investigation as it could be related to lower alloimmune response against the graft&#46;</p><p id="p0220" class="elsevierStylePara elsevierViewall">We registered a slight reduction in the frequency of V81TCR&#43; in the FC group at the end of the follow-up&#46; The cause of this change is not clear and we speculate that it could be a consequence of the ISD employed to treat rejection among FC group recipients&#46;</p><p id="p0225" class="elsevierStylePara elsevierViewall">This is the first study to identify clinical variables related to successful conversion to MMF&#46; All previous conversion studies have sought to demonstrate the feasibility and benefits of CNI minimization&#47;withdrawal and not to identify the subset of liver recipients with the highest chance of successful conversion&#46; This could be an interesting advance in evaluating the potential benefits of conversion to MMF monotherapy&#46; Interestingly&#44; some of the variables associated with successful conversion are also related to the development of operational tolerance&#44; such as the time since transplantation&#44; lower exposure to CNI&#44; higher frequency of NK cells&#44; lower frequency of &#167;<span class="elsevierStyleInf">2</span>TCR&#43; cells and higher expression of FoxP3&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> This raises the question of whether the SC group has a higher chance of developing operational tolerance in the future&#46;</p><p id="p0230" class="elsevierStylePara elsevierViewall">The fact that we recruited only 40 of 124 recipients in our cohort suggests that this strategy is suitable for a minority of recipients&#46; The authors excluded 29 steroid-dependent recipients in order to administer immunosup-pression of similar intensity to all recipients&#46; However&#44; in real life steroid dependency does not preclude CNI minimization&#47;withdrawal&#46; Thirty-one recipients were on a non-CNI-based immunosuppressive regime&#46; Twenty-five of them were already receiving MMF&#44; with minimization or complete withdrawal of CNI&#46; Considering these recipients&#44; in relation to those that were recruited&#44; it can be said that this strategy could be employed with at least 75&#46;8&#37; of the total cohort&#46;</p><p id="p0235" class="elsevierStylePara elsevierViewall">The small size of this study limits us to suggesting that low CNI levels can predict successful conversion&#46; Further studies are needed to demonstrate the usefulness of this indicator and to establish the best cutoff for defining low CNI levels&#46; However&#44; our findings can guide future studies to determine predictors of successful conversion&#46;</p><p id="p0240" class="elsevierStylePara elsevierViewall">In conclusion&#44; conversion to MMF monotherapy in liver recipients with a steroid free immunosuppressive scheme based on CNIs&#44; compliant and in the absence of recently diagnosed rejection&#44; seems to be plausible and safe&#46; A significant benefit can be obtained in terms of preserving renal function&#44; especially with patients with lower GFR or CNI levels&#46; The most important finding in this study is probably the identification of a CNI level threshold to select liver recipients with a higher probability of successful CMM&#46; A higher FoxP3 MFI&#44; an increased frequency of NK cells and a lower number &#948;<span class="elsevierStyleInf">2</span>TCR&#43; cells at baseline were also associated with successful conversion&#46; These findings could allow an improved selection of candidates for MMF monotherapy conversion&#46;</p></span><span id="s0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0105">Abbreviations</span><p id="p0245" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="l0020"><li class="elsevierStyleListItem" id="u0090"><span class="elsevierStyleLabel">&#8226;</span><p id="p0250" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">ALT&#58;</span> Alanine aminotransferase&#46;</p></li><li class="elsevierStyleListItem" id="u0095"><span class="elsevierStyleLabel">&#8226;</span><p id="p0255" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">AST&#58;</span> Aspartate aminotransferase&#46;</p></li><li class="elsevierStyleListItem" id="u0100"><span class="elsevierStyleLabel">&#8226;</span><p id="p0260" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">AP&#58;</span> Alkaline phosphatase&#46;</p></li><li class="elsevierStyleListItem" id="u0105"><span class="elsevierStyleLabel">&#8226;</span><p id="p0265" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">CMM&#58;</span> Conversion to mycophenolate mofetil mono-therapy&#46;</p></li><li class="elsevierStyleListItem" id="u0110"><span class="elsevierStyleLabel">&#8226;</span><p id="p0270" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">CNI&#58;</span> Calcineurin inhibitors&#46;</p></li><li class="elsevierStyleListItem" id="u0115"><span class="elsevierStyleLabel">&#8226;</span><p id="p0275" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">DBP&#58;</span> Diastolic blood pressure&#46;</p></li><li class="elsevierStyleListItem" id="u0120"><span class="elsevierStyleLabel">&#8226;</span><p id="p0280" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">DM&#58;</span> Diabetes mellitus&#46;</p></li><li class="elsevierStyleListItem" id="u0125"><span class="elsevierStyleLabel">&#8226;</span><p id="p0285" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">FC&#58;</span> Failed conversion&#46;</p></li><li class="elsevierStyleListItem" id="u0130"><span class="elsevierStyleLabel">&#8226;</span><p id="p0290" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">GFR&#58;</span> Glomerular filtration rate&#46;</p></li><li class="elsevierStyleListItem" id="u0135"><span class="elsevierStyleLabel">&#8226;</span><p id="p0295" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">GGT&#58;</span> &#947;-glutamil transferase&#46;</p></li><li class="elsevierStyleListItem" id="u0140"><span class="elsevierStyleLabel">&#8226;</span><p id="p0300" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HTN&#58;</span> Arterial hypertension&#46;</p></li><li class="elsevierStyleListItem" id="u0145"><span class="elsevierStyleLabel">&#8226;</span><p id="p0305" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">ISD&#58;</span> Immunosuppressive drugs&#46;</p></li><li class="elsevierStyleListItem" id="u0150"><span class="elsevierStyleLabel">&#8226;</span><p id="p0310" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">LT&#58;</span> Liver transplantation&#46;</p></li><li class="elsevierStyleListItem" id="u0155"><span class="elsevierStyleLabel">&#8226;</span><p id="p0315" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">MMF&#58;</span> Mycophenolate mofetil&#46;</p></li><li class="elsevierStyleListItem" id="u0160"><span class="elsevierStyleLabel">&#8226;</span><p id="p0320" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">PBMC&#58;</span> Peripheral blood mononuclear cell&#46;</p></li><li class="elsevierStyleListItem" id="u0165"><span class="elsevierStyleLabel">&#8226;</span><p id="p0325" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">SBP&#58;</span> Systolic blood pressure&#46;</p></li><li class="elsevierStyleListItem" id="u0170"><span class="elsevierStyleLabel">&#8226;</span><p id="p0330" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">SC&#58;</span> Successful conversion&#46;</p></li></ul></p></span><span id="s0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0110">Funding Sources</span><p id="p0335" class="elsevierStylePara elsevierViewall">Fondecyt iniciacion &#35; 11100113&#46;</p></span><span id="s0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0115">Conflict of Interest</span><p id="p0340" class="elsevierStylePara elsevierViewall">All authors declare no conflict of interest&#46;</p></span></span>"
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        0 => array:3 [
          "identificador" => "xres1198052"
          "titulo" => "Abstract"
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              "identificador" => "abs0010"
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          ]
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        1 => array:2 [
          "identificador" => "xpalclavsec1116696"
          "titulo" => "Key words"
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        2 => array:2 [
          "identificador" => "s0005"
          "titulo" => "Introduction"
        ]
        3 => array:3 [
          "identificador" => "s0010"
          "titulo" => "Material and Methods"
          "secciones" => array:9 [
            0 => array:2 [
              "identificador" => "s0015"
              "titulo" => "Patients"
            ]
            1 => array:2 [
              "identificador" => "s0020"
              "titulo" => "Study design"
            ]
            2 => array:2 [
              "identificador" => "s0025"
              "titulo" => "Conversion procedure"
            ]
            3 => array:2 [
              "identificador" => "s0030"
              "titulo" => "Patient follow-up"
            ]
            4 => array:2 [
              "identificador" => "s0035"
              "titulo" => "Definition of allograft dysfunction"
            ]
            5 => array:2 [
              "identificador" => "s0040"
              "titulo" => "Definition of rejection"
            ]
            6 => array:2 [
              "identificador" => "s0045"
              "titulo" => "Peripheral blood cell immunophenotyping"
            ]
            7 => array:2 [
              "identificador" => "s0050"
              "titulo" => "Statistical analysis"
            ]
            8 => array:2 [
              "identificador" => "s0055"
              "titulo" => "Sample size"
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          ]
        ]
        4 => array:3 [
          "identificador" => "s0060"
          "titulo" => "Results"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "s0065"
              "titulo" => "Patient recruitment"
            ]
            1 => array:2 [
              "identificador" => "s0070"
              "titulo" => "Conversion outcome"
            ]
            2 => array:2 [
              "identificador" => "s0075"
              "titulo" => "Impact of conversion on renal function"
            ]
            3 => array:2 [
              "identificador" => "s0080"
              "titulo" => "Baseline clinical differences between the SC and FC groups"
            ]
            4 => array:2 [
              "identificador" => "s0085"
              "titulo" => "Peripheral blood mononuclear cell immunophenotyping"
            ]
          ]
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        5 => array:2 [
          "identificador" => "s0090"
          "titulo" => "Discussion"
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        6 => array:2 [
          "identificador" => "s0095"
          "titulo" => "Abbreviations"
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          "identificador" => "s0100"
          "titulo" => "Funding Sources"
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          "identificador" => "s0105"
          "titulo" => "Conflict of Interest"
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        9 => array:1 [
          "titulo" => "References"
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      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-05-12"
    "fechaAceptado" => "2016-07-05"
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      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Key words"
          "identificador" => "xpalclavsec1116696"
          "palabras" => array:6 [
            0 => "Calcineurin inhibitors"
            1 => "Minimization"
            2 => "Mycophenolate mofetil"
            3 => "Conversion"
            4 => "Liver transplantation"
            5 => "Renal function"
          ]
        ]
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    "resumen" => array:1 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">The use of calcineurin inhibitors &#40;CNI&#41; after liver transplantation is associated with post-transplant nephrotoxicity&#46; Conversion to myc-ophenolate mofetil &#40;MMF&#41; monotherapy improves renal function&#44; but is related to graft rejection in some recipients&#46; Our aim was to identify variables associated with rejection after conversion to MMF monotherapy&#46; Conversion was attempted in 40 liver transplant recipients&#46; Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow-up&#46; Conversion was classified as successful &#40;SC&#41; if rejection did not occur during the follow-up&#46; MMF conversion was successful with 28 patients &#40;70&#37;&#41; and was associated with higher glomerular filtration rates at the end of study&#46; It also correlated with increased time elapsed since transplantation&#44; low baseline CNI levels &#40;Tacrolimus &#8804; 6&#46;5 ng&#47;mL or Cyclosporine &#8804; 635 ng&#47;mL&#41; and lower frequency of tacrolimus use&#46; The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels &#40;p &#61; 0&#46;02&#44; OR&#58; 6&#46;93&#44; 95&#37;&#44; CI&#58; 1&#46;3-29&#46;7&#41;&#46; Mean baseline fluorescent intensity of FOXP3&#43; T cells was significantly higher among recipients with SC&#46; In conclusion&#44; this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy&#46; Clinicaltrials&#46;gov identification&#58; NCT01321112&#46;</p></span>"
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    ]
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        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
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        "descripcion" => array:1 [
          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Description of the study methodology and follow-up&#58; Calcineurin inhibitors were gradually reduced until their total withdrawal during the first four weeks&#44; followed by a 48-week follow-up&#46; Medical evaluations were conducted on the indicated dates and whenever necessary&#46;</p>"
        ]
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        "identificador" => "f0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Patient enrollment&#46;</p>"
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      ]
      2 => array:7 [
        "identificador" => "f0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1245
            "Ancho" => 2023
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Evolution of clinical parameters in SC and FC groups&#46; <span class="elsevierStyleBold">A&#46;</span> Kaplan-Meir curve showing follow-up time free of rejection&#46; <span class="elsevierStyleBold">B&#46;</span> Evolution of ALT levels during follow-up&#46; Differences were calculated between SC and FC groups on each time point&#46; &#42; p &#61; 0&#46;01&#46; <span class="elsevierStyleBold">C&#46;</span> Evolution of AP levels during follow-up&#46; Differences were calculated between SC and FC groups on each time point&#46; &#42; p &#61; 0&#46;01&#46; <span class="elsevierStyleBold">D&#46;</span> Change of GFR &#40;calculated as MDRD&#41; expressed in mL&#47;min&#46; Differences were calculated between SC and FC groups on each time point&#46; &#42; p &#61; 0&#46;01&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "f0020"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Baseline of lymphocytic populations determined by flow cytometry studies of the SC and FC groups&#46; <span class="elsevierStyleBold">A&#46;</span> Frequency of natural killer cells&#46; <span class="elsevierStyleBold">B&#46;</span> Frequency of CD3&#43;V&#948;<span class="elsevierStyleInf">2</span> cells&#46; <span class="elsevierStyleBold">C&#46;</span> Mean FoxP3 fluorescent intensity in CD4<span class="elsevierStyleSup">&#43;</span>CD25<span class="elsevierStyleSup">&#43;</span> T cells&#46; <span class="elsevierStyleBold">D&#46;</span> Mean FoxP3 fluorescent intensity in CD4<span class="elsevierStyleSup">&#43;</span>CD25<span class="elsevierStyleSup">&#43;</span> T cells of recipients with low and high CNI levels&#46;</p>"
        ]
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        "etiqueta" => "Figure 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Changes between baseline and end of the follow up in lymphocytic populations of the SC and FC groups&#46; <span class="elsevierStyleBold">A&#46;</span> Change in the frequency of CD3<span class="elsevierStyleSup">&#43;</span>V&#948;<span class="elsevierStyleInf">1</span> cells&#46; <span class="elsevierStyleBold">B&#46;</span> Change in FoxP3 MFI in CD4<span class="elsevierStyleSup">&#43;</span>CD25<span class="elsevierStyleSup">&#43;</span> T cells&#46;</p>"
        ]
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "fuente" => "&#42; TTE&#58; Time from transplantation to enrollment&#46; TAC&#58; Tacrolimus&#46; LT&#58; liver transplantation&#46; SBP&#58; systolic blood pressure&#46; DPB&#58; diastolic blood pressure&#46; <span class="elsevierStyleSup">&#8224;</span> Data expressed as median &#177; IQR&#46;"
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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="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">SC&#44; n &#61; 28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FC&#44; n &#61; 12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Overall recipients&#44; n &#61; 40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60 &#177; 11&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#46;3 &#177; 9&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#46;8 &#177; 10&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male gender&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;64&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;83&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TTE&#42;&#44;&#8224; &#40;months&#41; &#177; IQR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#46;5 &#177; 44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;5 &#177; 32&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#177; 49&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TAC use&#42;&#59; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;83&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;049&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Indication for LT&#42;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alcoholic liver disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;27&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NASH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;17&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;41&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HCV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;21&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;17&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acute liver failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;7&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;7&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Others&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;28&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;16&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;22&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liver and Kidney function&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AST &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;7 &#177; 16&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#46;3 &#177; 47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35 &#177; 28&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ALT &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;9 &#177; 19&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#46;9 &#177; 84&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#46;7 &#177; 49&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GGT &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#46;7 &#177; 97&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#46;6 &#177; 89&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#46;3 &#177; 93&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AP &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130&#46;6 &#177; 60&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">127&#46;2 &#177; 72&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">129&#46;5 &#177; 63&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TB &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;8 &#177; 0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;9 &#177; 0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;8&#177; 0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Protrombine time &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">94&#46;8 &#177; 13&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87&#46;6 &#177; 12&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92&#46;6 &#177; 13&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Creatinine &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;2 &#177; 0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;19 &#177; 0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;17&#177; 0&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MDRD-4&#8224;&#177; IQR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&#46;5 &#177; 16&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#46;5 &#177; 32&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#46;5 &#177; 19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Uric acid &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;4 &#177; 1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;2 &#177; 1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;3 &#177; 1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glucose &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">105&#46;1 &#177; 28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">129&#46;5 &#177; 75&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">112&#46;5 &#177; 47&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glicated haemoglobin &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;7 &#177; 0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;8 &#177; 1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;7 &#177; 1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HOMA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;3 &#177; 5&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;3 &#177; 3&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;3 &#177; 5&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SBP &#177;SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">138&#46;2 &#177; 20&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">131&#46;7 &#177; 18&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">136 &#177; 19&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DBP &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85 &#177; 9&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80&#46;8 &#177; 14&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&#46;7 &#177; 11&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Colesterol level &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">174&#46;9 &#177; 43&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">152&#46;2 &#177; 33&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">168&#46;1 &#177; 41&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Triglicerides &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">144 &#177; 100&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">146&#46;2 &#177; 75&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">144&#46;6 &#177; 92&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HDL &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#46;3 &#177; 17&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#46;3 &#177; 12&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;1 &#177; 16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LDL &#177; SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96&#46;8 &#177; 31&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&#46;1 &#177; 32&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&#46;3 &#177; 32&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;054&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HTN&#59; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;53&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;47&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DM&#59; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;21&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;41&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hiperlipidemia&#59; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;46&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                      "titulo" => "Complete weaning off immunosup-pression in HCV liver transplant recipients is feasible and favourably impacts on the progression of disease recurrence"
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                          "etal" => true
                          "autores" => array:7 [
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                            3 => "Palmieri G&#46;"
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                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2005.11.047"
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                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2006"
                        "volumen" => "44"
                        "paginaInicial" => "702"
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                        "link" => array:1 [
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                      "titulo" => "The Tor Vergata weaning off immunosuppression protocol in stable HCV liver transplant patients&#58; the updated follow up at 78 months"
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                          "autores" => array:6 [
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                            4 => "Angelico M&#46;"
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                      "doi" => "10.1016/j.trim.2008.08.007"
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Article information

ISSN: 16652681
Original language: English

DOI:10.5604/16652681.1226820

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	1	0	1
2024 October	21	1	22
2024 September	17	1	18
2024 August	19	4	23
2024 July	11	1	12
2024 June	13	1	14
2024 May	9	2	11
2024 April	12	6	18
2024 March	19	8	27
2024 February	28	4	32
2024 January	27	4	31
2023 December	24	2	26
2023 November	24	7	31
2023 October	19	4	23
2023 September	14	1	15
2023 August	7	8	15
2023 July	11	4	15
2023 June	25	8	33
2023 May	51	7	58
2023 April	43	4	47
2023 March	36	4	40
2023 February	13	10	23
2023 January	20	1	21
2022 December	12	4	16
2022 November	7	8	15
2022 October	13	6	19
2022 September	13	9	22
2022 August	8	7	15
2022 July	9	7	16
2022 June	9	7	16
2022 May	8	6	14
2022 April	6	10	16
2022 March	9	7	16
2022 February	7	6	13
2022 January	18	6	24
2021 December	9	7	16
2021 November	11	13	24
2021 October	14	8	22
2021 September	8	9	17
2021 August	10	11	21
2021 July	7	12	19
2021 June	8	10	18
2021 May	27	7	34
2021 April	58	15	73
2021 March	13	4	17
2021 February	9	8	17
2021 January	9	12	21
2020 December	8	7	15
2020 November	20	8	28
2020 October	10	5	15
2020 September	17	7	24
2020 August	12	6	18
2020 July	9	7	16
2020 June	7	8	15
2020 May	10	6	16
2020 April	8	6	14
2020 March	7	1	8
2020 February	12	3	15
2020 January	10	6	16
2019 December	6	3	9
2019 November	3	3	6
2019 October	2	0	2
2019 September	3	5	8
2019 August	1	1	2
2019 July	1	8	9
2019 June	8	3	11
2019 May	1	4	5

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