Plasma cytokine levels imbalance in cirrhotic patients with impaired glucose tolerance and diabetes mellitus. A prospective study

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On the basis of the inclusion and exclusion criteria, 588 HCC patients were generated for baseline-adjusted analyses." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Lei Jianyong, Zhong Jinjing, Wang Wentao, Yan Lunan, Zhou Qiao, Li Bo, Wen Tianfu, Xu Minqing, Yang Jiaying, Wei Yongang" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Lei" "apellidos" => "Jianyong" ] 1 => array:2 [ "nombre" => "Zhong" "apellidos" => "Jinjing" ] 2 => array:3 [ "preGrado" => "M.D., Ph.D." "nombre" => "Wang" "apellidos" => "Wentao" ] 3 => array:2 [ "nombre" => "Yan" "apellidos" => "Lunan" ] 4 => array:2 [ "nombre" => "Zhou" "apellidos" => "Qiao" ] 5 => array:2 [ "nombre" => "Li" "apellidos" => "Bo" ] 6 => array:2 [ "nombre" => "Wen" "apellidos" => "Tianfu" ] 7 => array:2 [ "nombre" => "Xu" "apellidos" => "Minqing" ] 8 => array:2 [ "nombre" => "Yang" "apellidos" => "Jiaying" ] 9 => array:2 [ "nombre" => "Wei" "apellidos" => "Yongang" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119308464?idApp=UINPBA00004N" "url" => "/16652681/0000001300000004/v1_201906020859/S1665268119308464/v1_201906020859/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "titulo" => "Plasma cytokine levels imbalance in cirrhotic patients with impaired glucose tolerance and diabetes mellitus. A prospective study" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "403" "paginaFinal" => "410" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Diego García-Compeán, Joel O. Jáquez-Quintana, Fernando J. Lavalle-González, José A. González-González, Héctor J. Maldonado-Garza, Jesús Z. Villarreal-Pérez" "autores" => array:6 [ 0 => array:5 [ "preGrado" => "M.D., M.MSc." "nombre" => "Diego" "apellidos" => "García-Compeán" "email" => array:1 [ 0 => "digarciacompean@prodigy.net.mx" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Joel O." "apellidos" => "Jáquez-Quintana" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Fernando J." 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"tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 424 "Ancho" => 1045 "Tamanyo" => 31251 ] ] "descripcion" => array:1 [ "en" => "Box-whisker plots (medians, interquartil ranges and upper and lower ranges) showing significantly elevated plasma levels of sTNF-R1 (A) and TGF-β1 (B) in patients with impaired glucose tolerance (IGT) and DM compared with controls." ] ] ] "textoCompleto" => "IntroductionPatients with LC have a prevalence of overt DM of 30%. However, in cirrhotic patients with normal fasting plasma glucose (FPG) impaired glucose tolerance (IGT) or DM may be detected in 38 and 14% of cases respectively by using an oral glucose tolerance test (OGTT).<a class="elsevierStyleCrossRefs" href="#bib0005">1</a>–<a class="elsevierStyleCrossRef" href="#bib0020">4</a>Prospective studies have shown that DM (either overt or subclinical) is associated with an increase risk of complications and reduction of survival.<a class="elsevierStyleCrossRefs" href="#bib0025">5</a>–<a class="elsevierStyleCrossRef" href="#bib0040">8</a> The causes of death were mostly due to liver disease complications.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>,<a class="elsevierStyleCrossRef" href="#bib0030">6</a> Since DM is frequently observed in patients with severe liver dysfunction, it has led to suggest that DM may aggravate liver disease.<a class="elsevierStyleCrossRefs" href="#bib0045">9</a>–<a class="elsevierStyleCrossRef" href="#bib0055">11</a>The type 2 DM and metabolic syndrome are causes of non alcoholic fatty liver disease. Conversely, liver cirrhosis may give rise to DM. It has been demonstrated that hormonal polypeptides called cytokines are involved in the pathophysiology of liver disease induced by type 2 DM. Cytokines act as chemical mediators in the processes of insulin resistance (IR), liver inflammation, and liver fibrosis. Those produced by adipose tissue are called “adipokynes”.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> Some of them have pro-inflammatory and anti-inflammatory activity and others stimulate liver fibrosis, particularly TGF-β1.<a class="elsevierStyleCrossRef" href="#bib0065">13</a>,<a class="elsevierStyleCrossRef" href="#bib0070">14</a>TNF-α mediates its biological responses by binding to two cell surface receptors: TNF-R1 and TNF-R2. TNF-R1 is the main inductor of cytotoxicity through induction of a number of biological responses ranging from NF-κβ activation to cell death.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> Soluble forms of both receptors are present in serum as a result of receptor shedding after cellular activation by stimuli of free TNF-α.<a class="elsevierStyleCrossRefs" href="#bib0080">16</a>–<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Furthermore, TNF-α can induce IR through phophorylation of serine residue of insulin receptor substrate (IRS-1-2).<a class="elsevierStyleCrossRef" href="#bib0095">19</a>Leptin is produced predominantly by adipose tissue. A relationship between leptin and liver fibrosis has been identified in animals<a class="elsevierStyleCrossRef" href="#bib0100">20</a>,<a class="elsevierStyleCrossRef" href="#bib0105">21</a> by up-regulation of the expression of TGF-β1.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Leptin has a direct action on hepatic stellate cells (HSC) which express functionally active leptin receptors.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>,<a class="elsevierStyleCrossRef" href="#bib0120">24</a>TGF-β is a pro-fibrotic cytokine found in liver and other organs.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> β1 isoform is the most abundant in the liver.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> TGF-β1 stimulates cell proliferation and synthesis and deposition of type I collagen and extracellular matrix proteins in the injured liver.<a class="elsevierStyleCrossRef" href="#bib0130">26</a>HGF has antifibrotic activity through inhibition of platelet growth factor and TGF-β1.<a class="elsevierStyleCrossRef" href="#bib0070">14</a>The aims of this study were: to determine if there is an impairment of plasma levels of TNF-α, sTN-R1, leptin, TGF-β1, and HGF in patients with IGT or DM and compensated LC. At the same time to observe if there exists a relationship among these cytokines with other parameters such as Child Pugh score, insulin resistance (IR) and body mass index (BMI).Material and MethodsPatientsWe studied patients with LC who were seen at our hospital from June 2007 to June 2012. Cirrhosis was diagnosed by liver biopsy and/or a combination of clinical data and imaging studies, particularly percutaneous abdominal ultrasound. All patients were adults without a previous diagnosis of DM and with normal FPG (< 100 mg/dL). Patients with: hepatocellular carcinoma, acute alcoholic hepatitis, gastrointestinal bleeding, clinically evident hepatic encephalopathy, chronic renal failure, hepatorenal syndrome, severe infections, and spontaneous bacterial peritonitis were excluded.One hundred out of 293 assessed patients fulfilled the inclusion criteria. They underwent OGTT using a 75 g load for 180 min according to the provisions of the American Diabetes Association.<a class="elsevierStyleCrossRef" href="#bib0135">27</a> Three study groups, with previously established number of patients, were formed in base of OGTT results: eighteen patients with normal glucose tolerance (NGT), 18 with IGT and 18 with DM were randomly selected for the study.The protocol was executed in accordance with the ethical guidelines of the 1975 Declaration of Helsinki and it was approved by the Ethics Committee of the Faculty of Medicine of the Universidad Autónoma de Nuevo León. Written consent for participation into the study was obtained from all patients.AssessmentsComplete clinical examination was conducted inquiring about family history of diabetes and alcohol consumption habits. The following laboratory tests were performed: plasma hemoglobin, platelets blood count, INR, plasma albumin, bilirubin, ALT and γGT. The body mass index (BMI) was calculated, and construed as follows: normal if < 24.9, overweight between 25 and 29.9, and obesity if ≥ 30.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> Liver function was estimated using Child-Pugh and MELD (Model for End-Stage Liver Disease) classifications.<a class="elsevierStyleCrossRef" href="#bib0145">29</a>,<a class="elsevierStyleCrossRef" href="#bib0150">30</a>FPI and HOMA2-IRFPI levels were measure by electrochemiluminescence method (Normal values: 2.6-24.9 μIU/mL). In order to calculate IR, the Homeostasis Model Assessment index was calculated using the HOMA2-IR calculator software (<a href="http://www.dtu.ox.ac.uk/homa-calculator/index.php">http://www.dtu.ox.ac.uk/homa-calculator/index.php</a>).<a class="elsevierStyleCrossRef" href="#bib0155">31</a> IR was arbitrarily defined as a value >2.Measurement of cytokinesVenous blood samples were obtained from fasting patients. They were centrifuged for 10 min at 5 oC, aliquots were made and samples were stored at -70 oC until they were processed. We used commercially available specific immunoassays for the measurement in duplicate of TNF-α, sTNF R1, leptin, TGF-β1 and HGF (MILLIPLEX MAP kits, Millipore, St. Charles, MO, USA). Luminex 200 was used for the essay. After hydration using buffer, standard curve, in-house quality controls, and sera were added. A mixture of microspheres labeled with the antibody specific for the biomarker were added to each pore. After incubating the plate, detection antibody was added to each pore. The plate was incubated and streptavidin-phycoerythrin was added to each pore. After other incubation, 100 of system liquid was added and stirred for 10 min to suspend the microspheres and ensure a homogeneous distribution. The flow cytometer counted the first 50 microspheres that passed through the reader in 60 sec. The calibration curves were used to convert the mean fluorescent intensity readings for each concentration sample (pg/mL) using a five parameter logistic model. The intra- and inter-assay variation coefficient was less than 5% for all cytokines.Plasma cytokine levels in the cirrhotic patients were compared with those of a control group containing 18 individuals without LC and DM matched by age, gender, and BMI.Statistical analysisAll variables were expressed as medians and interquartile ranges (IQR) and categorical variables were expressed as relative proportions. The inter-group comparison was performed by using nonparametric tests: median test, Mann-Whitney U test and Kruskal-Wallis test for independent samples. Correlation analysis was done by using non parametric Spearman rank test. A P-value < 0.05 was considered statistically significant. All statistical analyzes were performed using SPSS v17.0 Statistical Package (Chicago, Illinois, USA).ResultsPatientsDemographic and clinical characteristics of the 54 patients with LC according to the results of the OGTT (NGT, IGT or DM) are shown in <a class="elsevierStyleCrossRef" href="#t0005">table 1</a>. Overall, patients had a median age of 55.5 years (IQR: 38.25-72.75) and 30 were males (55.6%). Median BMI value was 26.6 (IQR: 20.5-32.6). Liver biopsy was performed in 23 (42.5%) patients. The etiology of cirrhosis was alcoholic in 25 (46.3%) and cryptogenic in 11 (20.4%) patients. The Child-Pugh classification score was 6 (IQR: 5.2-9) and the MELD score was 8 (IQR: 6.1-15.25). IR was detected in 74% of the patients.<elsevierMultimedia ident="t0005"></elsevierMultimedia>The patients having NGT, IGT, and DM were demographically and clinically similar. Those with DM and IGT showed significantly less blood platelet counts than those with NGT (p = 0.038 and 0.042 respectively) while those with IGT had increased INR values compared to those with NGT (p = 0.039). On the other hand, compared to NGT patients, those with DM showed significant higher FPI levels (26 μU/mL, IQR: 15.7-36.3 vs. 11.9 μU/mL, IQR: 6.1-17.7, p = 0.03), higher HOMA2-IR values (2.95, IQR: 1.6-4.25 vs. 1.78, IQR: 0.64-2.84, p = 0.017) and greater IR frequency (88.8 vs. 55.5%, p = 0.025) (<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>).Plasma levels of cytokinesPlasma cytokines values are shown in <a class="elsevierStyleCrossRef" href="#t0010">table 2</a>. Compared to controls, patients with DM and IGT showed significantly higher plasma sTNF-R1 levels (DM: 1872.7 pg/mL, IQR: 735.2-3,010.1, IGT: 1,931.8 pg/mL, IQR: 1147-3935.7 and controls: 1404.6 pg/mL, IQR: 864.3-1,944.9) (IGT vs. controls, p = 0.0043 and DM vs. controls p = 0.0045) (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>A). Non significant differences were observed between control group patients compared to cirrhotic patients with NGT. By contrast, compared to controls, serum TGF-β1 levels were significantly lower in patients with DM and IGT (DM: 9,037, pg/mL IQR: 3,074-15,001, IGT: 7,768 pg/mL, IQR: 2,004-20,297 and controls 23,102 pg/mL, IQR: 12,676-33,528) (DM vs. controls and IGT vs. controls p = 0.0001) (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>B). Again, non significant differences were observed between control group patients compared to cirrhotic patients with NGT. On the other hand non statistically significant differences were found in TNF-α, leptin and HGF among all study groups.<elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="f0005"></elsevierMultimedia>Cytokines and Child-Pugh scorePlasma cytokine values according the groups A, B and C of Child-Pugh classification are shown in <a class="elsevierStyleCrossRef" href="#t0015">table 3</a>. Serum TNFa levels were increased in patients from groups B and C, however only significant differences were observed in group C compared to Group A (p = 0.040). Serum sTNF-R1 levels were also increased in patients from groups B and C, but only significant differences were found comparing group B vs. A (p = 0.033). Serum TGF β1 levels were reduced in groups B and C but significant differences were seen in group B compared to A (p = 0.038). Significant differences of HGF levels were found between Child-Pugh group C compared to A (p = 0.029) and finally plasma leptin levels were significantly lower in group C compared to A (p = 0.029).<elsevierMultimedia ident="t0015"></elsevierMultimedia>Cytokines and IRA correlation between sTNF-R1 and HOMA2-IR values (r = 0.32, p = 0.043 and between leptin and HOMA2-IR (r = 0.057, p = 0.001) were observed in cirrhotic patients. No correlation was shown between the other cytokines and HOMA2-IR.Cytokines and BMI<a class="elsevierStyleCrossRef" href="#t0020">Table 4</a> shows cytokines values in cirrhotic patients and controls with normal or abnormal BMI. Only plasma levels of leptin showed a significant increment in patients with BMI > 25 (p = 0.001).<elsevierMultimedia ident="t0020"></elsevierMultimedia>DiscussionIn this selected cohort of cirrhotic patients without overt DM, it was found that plasma sTNF-R1 and TGF-ß1 levels were significantly impaired in those with IGT and DM as compared to controls. Soluble forms of TNF-R1 (sTNF-R1) are present in serum as a result of receptor shedding after cellular activation by stimuli of TNF-α,<a class="elsevierStyleCrossRef" href="#bib0080">16</a> therefore, high serum sTNF-R1 levels are reliable indicators of TNF-system activation.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> An increase of sTNF-R1 levels has been observed in patients with acute alcoholic hepatitis and cirrhosis.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> In addition, high sTNF-R1 levels were predictive of death at 3 months.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> In our study, increased sTNF-R1 observed in patients with IGT and DM may reflect liver inflammation.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> Significant elevations of TNF α and sTNF R1 were also found in Child-Pugh C and B groups of patients. Clinical DM and IGT are more frequently observed in patients with advanced liver cirrhosis.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> In our study patients with DM had significantly lower levels of serum platelets and higher values of INR compared to NGT patients, abnormalities that reflect liver dysfunction (<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>).Our findings suggest that DM and IGT may induce progressive liver failure through liver inflammation. The correlation between sTNF-R1 and HOMA2-IR suggests a link between this cytokine and DM. The possibility that DM and IGT may emerge as a result of liver function deterioration has to be also considered. Nevertheless, the appearance of IR and subclinical forms of DM since early stages of chronic liver disease does not support this theory.It has to be taken into account that, in diverse conditions frequently associated to DM such as en-dotoxemia<a class="elsevierStyleCrossRef" href="#bib0165">33</a> and bacterial infections,<a class="elsevierStyleCrossRef" href="#bib0170">34</a> increments of serum sTNF-R1 have been observed.The significant reduction of TGF-β1 observed in our patients with IGT and DM is difficult to explain. This cytokine has been known for many years for its fibrogenic effect. However, it also has anti-inflammatory and immunosuppressive effects. The TGF-β1 is the most abundant isoform of this cytokine family.<a class="elsevierStyleCrossRef" href="#bib0125">25</a>–<a class="elsevierStyleCrossRef" href="#bib0130">26</a> It is readily expressed in Kupffer cells, HSC and endothelial cells in normal and cirrhotic liver, activating HSC with an increased production of collagen type I and III, fibronectin, and other extracellular matrix proteins.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> Several studies carried out in cirrhotic patients have described increase in serum TGF-β1 levels. A correlation between TGF-β1 levels and Child-Pugh classification groups has also been described, being this correlation higher in group C.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> However, other studies made in cirrhotic patients have yielded conflicting results. For example, it was reported that serum TGF-β1 levels were significantly higher in patients with fatty liver and NASH than in those with chronic hepatitis C virus who had a higher degree of fibrosis.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> Similarly higher TGF-β1 levels were observed in patients with nonalcoholic steatohepatitis (NASH) compared to healthy controls. In this study, plasma insulin was the most important factor affecting TGF-β1 as determined by multiple regression analysis.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> In our study, the significant reduction in serum TGF-β1 levels observed in cirrhotic patients with IGT and DM may be the effect of HGF-mediated down-regulation or it may be the result of other factors linked to liver failure. In this context, TGF-β1 levels were low and HGF levels were high in our patients from Child-Pugh groups B and C compared to those from group A. In summary, TGF-β1 might be higher in pre fibrotic inflammatory liver injury (such as NASH, acute inflammatory processes of viral or alcoholic etiology and early stages of cirrhosis) than in advanced liver cirrhosis.We did not observe differences of leptin levels among cirrhotic patients and controls. Nevertheless some studies have shown that leptin may be affected in patients with liver cirrhosis depending on the etiology and metabolic states. It was observed that leptin is elevated in patients with alcoholic cirrhosis regardless of BMI.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> However, no correlation of leptin with alcoholic cirrhosis was observed in other studies when BMI was adjusted.<a class="elsevierStyleCrossRef" href="#bib0190">38</a> Others studies have shown a decrease of leptin in viral cirrhosis compared with alcoholic one.<a class="elsevierStyleCrossRef" href="#bib0195">39</a> Regardless of the etiology of cirrhosis of our patients, we observed a significant reduction of leptin in Child-Pugh group C patients compared to group A. We also found a correlation between leptin and HOMA2-IR and an association of leptin with BMI > 25. Leptin may be in free form in plasma or forming binding complexes with one of its specific receptors (ObRe).<a class="elsevierStyleCrossRef" href="#bib0200">40</a> Similar serum free leptin levels were observed in patients with and without cirrhosis in a study measuring both forms of leptin. Free leptin was positively correlated with metabolic parameters (BMI and IR), while receptor bound leptin was correlated with inflammatory conditions.<a class="elsevierStyleCrossRef" href="#bib0205">41</a>The HGF is a cytokine involved in liver regeneration.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> It has antifibrosing effect which appears to be due to suppression of the TGF-β1 expression.<a class="elsevierStyleCrossRef" href="#bib0210">42</a> In our study plasma levels of HGF did not show significant differences among patients with IGT or DM compared to NGT. Nevertheless our patients from Child-Pugh C showed significant increase of this cytokine compared to group A. This finding is in accordance with some published studies which have shown a positive correlation of serum HGF levels with the degree of fibrosis and the degree of liver failure in patients with HCV cirrhosis.<a class="elsevierStyleCrossRef" href="#bib0215">43</a>This study has some limitations: the sample size of patients is low, additionally we did not measure the degree of hepatic fibrosis which would have been useful for TGF-β1 correlations (nevertheless, the most important aim of our study was correlation of cytokines with IGT or DM), and finally we did not search for subclinical bacterial infections which may impair cytokines plasma levels.In conclusion, this study showed that in cirrhotic patients, both IGT and DM were associated with significant changes in plasma sTNF-R1 and TGF-β1 levels compared to non cirrhotic, non-diabetic patients. Those in Child-Pugh B and C groups showed significant increases of TNFα, sTNF-R1 and HGF while they had a significant reduction of TGF-β1 and leptin compared to group A. Correlation between sTNF-R1 and leptin with IR and a correlation of leptin with BMI were also observed. These findings suggest that IGT and DM may be causally implicated in liver inflammation process and progressive liver dysfunction." "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:3 [ "identificador" => "xres1199022" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0010" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1117462" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "s0010" "titulo" => "Material and Methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "s0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "s0020" "titulo" => "Assessments" ] 2 => array:2 [ "identificador" => "s0025" "titulo" => "FPI and HOMA2-IR" ] 3 => array:2 [ "identificador" => "s0030" "titulo" => "Measurement of cytokines" ] 4 => array:2 [ "identificador" => "s0035" "titulo" => "Statistical analysis" ] ] ] 4 => array:3 [ "identificador" => "s0040" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "s0045" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "s0050" "titulo" => "Plasma levels of cytokines" ] 2 => array:2 [ "identificador" => "s0055" "titulo" => "Cytokines and Child-Pugh score" ] 3 => array:2 [ "identificador" => "s0060" "titulo" => "Cytokines and IR" ] 4 => array:2 [ "identificador" => "s0065" "titulo" => "Cytokines and BMI" ] ] ] 5 => array:2 [ "identificador" => "s0070" "titulo" => "Discussion" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-12-18" "fechaAceptado" => "2013-12-18" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1117462" "palabras" => array:3 [ 0 => "Liver cirrhosis" 1 => "Oral glucose tolerance test" 2 => "sTNF-R1 and TGF-β1" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Aims. To define if there is an imbalance in plasma levels of proinflammatory, fibrogenic and antifibrogenic cytokines in patients with liver cirrhosis (LC) and impaired glucose tolerance (IGT) or diabetes mellitus (DM).Material and methods. We randomly selected 54 out of 100 patients with LC who had normal fasting plasma glucose (FPG) levels. Three groups were formed based on an oral glucose tolerance test (OGTT) results: 18 patients were normal, 18 had IGT, and 18 had DM. Plasma levels of cytokines were measured: TNF-α, soluble tumor necrosis factor receptor 1 (sTNF-R1), leptin, TGF-β1, and hepatocyte growth factor (HGF). Also, fasting plasma insulin (FPI) levels were determined and HOMa2-IR was calculated. Results were compared with those of a control group of 18 patients without liver disease nor DM. Intergroup comparison was performed using non parametric tests.Results. Significantly higher sTNF-R1 and lower TGF-β1 were found in patients with IGT and DM compared to controls. Leptin, HGF, and TNF-α levels showed no significant differences. According to Child-Pugh classification all cytokines levels were impaired in groups B or C as compared to group A. Positive correlations between sTNF-R1 and HOMA2-IR and between leptin and HOMA2-IR were found.Conclusions. IGT and DM were associated with abnormalities of sTNF-R1 and TGF-β1 compared to non cirrhotic controls. Among cirrhotic patients impairment of all cytokines were more marked in advanced liver disease. Finally, sTNF-R1and leptin correlated with IR. These findings suggest that IGT and DM may be causally implicated with liver inflammation process." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1." "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 424 "Ancho" => 1045 "Tamanyo" => 31251 ] ] "descripcion" => array:1 [ "en" => "Box-whisker plots (medians, interquartil ranges and upper and lower ranges) showing significantly elevated plasma levels of sTNF-R1 (A) and TGF-β1 (B) in patients with impaired glucose tolerance (IGT) and DM compared with controls." ] ] 1 => array:7 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "NGT: normal glucose tolerance. IGT: impaired glucose tolerance. DM: diabetes mellitus. BMI: body mass index. HOMA: homeostatic model assessment. IQR: interquartile range." "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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Total n = 54 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">NGT n =18 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">IGT n =18 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">DM n =18 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age, years, median (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55.5 (38.25-72.75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48.5 (22.5-74.5) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.5 (46.5-72.5) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57 (42-72) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.135 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Males, η (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 (55.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (42.1) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (61.1) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (61.1) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.509 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI, median (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26.6 (20.55-32.65) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26.2 (17.9- 34.5) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25.9 (21.3-30.5) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (20-36) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.513 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Etiology of cirrhosis, η (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" 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="" 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="" 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="" 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="" 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alcohol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (46.3) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (47.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (33,3) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (55.5) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.38 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (3.7) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.125 \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="left" 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (18.5) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (27.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (22.2) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.203 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autoimmunity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (15.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (5.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.57 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cryptogenic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (26.3) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (22.2) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (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="left" 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Child-Pugh \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" 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="" 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="" 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="" 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="" 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A, 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (53.7) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (52.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (61.1) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (44.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.594 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Β, 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (31.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (33.3) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.728 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">C, 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (9.3) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (10.5) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (5.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.802 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Child Pugh score, median (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.0 (5.2-9) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.0 (5.2-8.25) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.5 (5.18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (5.9-10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.594 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MELD score, median (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.0 (6-15.25) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.0 (6.2-14.7) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.22 (6.3-14.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (6.1-16.7) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.132 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Laboratory, median (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="" 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="" 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="" 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="" 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="" 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hemoglobin, g/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.8 (9.23-14.37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.5 (8.8-14.2) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (9.6-14.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.9 (8-15.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.929 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Platelets, χ mm3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">106000 (28,400-135,200) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">156000 (10,250-301,750) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77800 (28,400-223,550) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">92,650 (32,400-152,900) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.015<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">INR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.29 (0.77-1.81) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.15 (0.84-1.46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.5 (1.0-1.9) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.3 (0.8-1.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.039<a class="elsevierStyleCrossRef" href="#tblfn0010">**</a> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Creatinine, mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.80 (0.57-1.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.80 (0.59-1.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.83 (0.48-1.18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.85 (0.53-1.17) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.742 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Albumin, g/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.27 (1.1-2.14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.45 (1.98-4.92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.4 (2.47-4.33) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.95 (2.0-3.9) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.801 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT, UI /L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38.5 (18.5-70) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25.5 (9.0-57) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42.5 (10-96.75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48 (11.7-64.2) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.068 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total bilirubin, mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.41 (0.31-2.51) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.36 (0.26-2.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.26 (0.42-2.55) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.75 (0.7-2.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.277 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FPI, μU/mL, median (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.30 (4.7- 25.9) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.9 (6.1-17.7) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19.4 (8.2-30.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 (15.7-36.3) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.03<a class="elsevierStyleCrossRef" href="#tblfn0015">†</a> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HOMA2-IR, median (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.3 (1.1-3.5) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.78 (0.64-2.84) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.41 (1.0-3.73) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.95 (1.6-4.25) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.017<a class="elsevierStyleCrossRef" href="#tblfn0020">¶</a> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HOMA >2, η (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 (74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (55.5) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (77.7) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (88.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.025<a class="elsevierStyleCrossRef" href="#tblfn0025">§</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047810.png" ] ] ] "notaPie" => array:5 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "DM and IGT vs. N." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "**" "nota" => "IGT vs. N." ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "†" "nota" => "DM vs. N." ] 3 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "¶" "nota" => "DM vs. N." ] 4 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "§" "nota" => "DM vs. N." ] ] ] "descripcion" => array:1 [ "en" => "Clinical and biochemical characteristics of cirrhotic patients with NGT, IGT and DM." ] ] 2 => array:7 [ "identificador" => "t0010" "etiqueta" => "Table 2." "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "NGT: normal glucose tolerance. IGT: impaired glucose tolerance. DM: diabetes mellitus. CG: control group. TNF-α: tumor necrosis factor alpha. sTNF-R1: soluble tumor necrosis factor receptor type 1. TGF-β1 : transforming growth factor-β1. HG F: hepatocyte growth factor." "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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Total \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">NGT n = 18 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">IGT n = 18 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">DM n = 18 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">CG n = 18 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TNF-α, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.36 (2-6.72) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.00 (1.02-6.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.21 (2.83-8.92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.62(1.64-7.6) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">sTNF- R1, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1,654.9 (507.8-2,802) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1,931.8 (1,147-3,935.7) <a class="elsevierStyleCrossRef" href="#tblfn0035">a</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1,872.7 (735.2-3,010.1) <a class="elsevierStyleCrossRef" href="#tblfn0040">b</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1404.6 (864.3-1,944.9) <a class="elsevierStyleCrossRef" href="#tblfn0030">a,b</a> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TGF-β1, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14,357.1 (3,683.6-25,030.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7,768 (2,004-20,297) <a class="elsevierStyleCrossRef" href="#tblfn0035">a</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9,037 (3,074-15,001) <a class="elsevierStyleCrossRef" href="#tblfn0040">b</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23102 (12,676-33,528) <a class="elsevierStyleCrossRef" href="#tblfn0030">a,b</a> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HGF, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">819.8 (279.9-1,359.7) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">568.6 (283.1-1,172.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">735.0 (601.1-868.9) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">825.9 (46.2-1,605.6) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leptin, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6,214.5 (1,018.1-18,315.5) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3,723.6 (83.8-14,322.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10,107.6 (1,059.1-26,410.1) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18,593 (462.1-51,995) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047808.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0030" "etiqueta" => "a,b" "nota" => "p < 0.05." ] 1 => array:3 [ "identificador" => "tblfn0035" "etiqueta" => "a" "nota" => "IGT vs. CG." ] 2 => array:3 [ "identificador" => "tblfn0040" "etiqueta" => "b" "nota" => "DM vs. CG." ] ] ] "descripcion" => array:1 [ "en" => "Plasma cytokines levels of cirrhotic patients with NGT, IGT and DM and controls (median and interquartile range)." ] ] 3 => array:7 [ "identificador" => "t0015" "etiqueta" => "Table 3." "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "TNF-a: tumor necrosis factor alpha. sTNF-R1: soluble tumor necrosis factor receptor type 1. TGF-ß1: transforming growth factor-ß1. HGF: hepatocyte growth factor.a,bp < 0.05." "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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Total \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Child-Pugh A n = 29 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Child-Pugh B n = 20 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Child Pugh C n = 5 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TNF-a, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.47 (1.3-8.83)<a class="elsevierStyleCrossRef" href="#tblfn0050">b</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.1 (1.92-12.5) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.13 (3.2-10.4)<a class="elsevierStyleCrossRef" href="#tblfn0050">b</a> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">sTNF-R1, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1,786 (276-3,609)<a class="elsevierStyleCrossRef" href="#tblfn0045">a</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3,439 (895-15,880)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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3,011 (1,961-6,482) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TGF-ß1, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12,836 (2,004-34,072)<a class="elsevierStyleCrossRef" href="#tblfn0045">a</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9,315 (2,003-22,942)<a class="elsevierStyleCrossRef" href="#tblfn0045">a</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11,945 (3,503-21,371) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HGF, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">750 (175-1,629)<a class="elsevierStyleCrossRef" href="#tblfn0050">b</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">998 (96-2,941) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2,711 (123.6-6,034)<a class="elsevierStyleCrossRef" href="#tblfn0050">b</a> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leptin, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9,869 (1,132-34,582)<a class="elsevierStyleCrossRef" href="#tblfn0050">b</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11,995 (83-45,991) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4,270 (1,059-12,914)<a class="elsevierStyleCrossRef" href="#tblfn0050">b</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047807.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0045" "etiqueta" => "a" "nota" => "CPA vs. CPB." ] 1 => array:3 [ "identificador" => "tblfn0050" "etiqueta" => "b" "nota" => "CPA vs. CPC." ] ] ] "descripcion" => array:1 [ "en" => "Plasma cytokines levels of cirrhotic patients according to Child-Pugh classification (median and interquartile range)." ] ] 4 => array:7 [ "identificador" => "t0020" "etiqueta" => "Table 4." "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Total \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">BMI < 25 n = 26 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">BMI > 25 n = 46 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">P values \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TNF-α, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.38 (1.72-7.04) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.48 (0.77-8.19) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.967 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">sTNF-R1, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1,627.0 (788.9-2,465.1) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1,797.5 (849-2,746) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.088 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TGF-β1, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15,623.3 (1,933.7-29,312.9) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13,265.8 (2,003.4-28,067.7) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.787 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HGF, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">594.62 (100.7-1,088.5) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">841.98 (123.6-1,839.9) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.058 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leptin, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4,084.08 (380.0-10,189) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11,379.7 (83.82-36,502.3) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2047809.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Plasma cytokine levels of cirrhotic patients with normal and abnormal BMI (median and interquartile range)." ] ] ] "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" => "Spectrum of liver disease in type 2 diabetes and management of patients with diabetes and liver disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Tolman K.G." 1 => "Fonseca V." 2 => "Dalpiaz A." 3 => "Tan M.H." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Diab Care" "fecha" => "2007" "volumen" => "30" "paginaInicial" => "734" "paginaFinal" => "743" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diabetes in chronic liver disease: from old concepts to new evidence" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Picardi A." 1 => "D’Avola D." 2 => "Gentilucci U.V." 3 => "Galati G." 4 => "Fiori E." 5 => "Spataro S." 6 => "Afeltra A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/dmrr.636" "Revista" => array:6 [ "tituloSerie" => "Diabetes Metab Res Rev" "fecha" => "2006" "volumen" => "22" "paginaInicial" => "274" "paginaFinal" => "283" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16506276" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3." 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Diego García-Compeán

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digarciacompean@prodigy.net.mx

Correspondence and reprint request:

, Joel O. Jáquez-Quintana*, Fernando J. Lavalle-González**, José A. González-González*, Héctor J. Maldonado-Garza*, Jesús Z. Villarreal-Pérez**

* Gastroenterology Service and, Department of Internal Medicine, University Hospital “Dr. José E. González” and Medical School. Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico

** Endocrinology Service, Department of Internal Medicine, University Hospital “Dr. José E. González” and Medical School. Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico

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          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Box-whisker plots &#40;medians&#44; interquartil ranges and upper and lower ranges&#41; showing significantly elevated plasma levels of sTNF-R1 &#40;A&#41; and TGF-&#946;1 &#40;B&#41; in patients with impaired glucose tolerance &#40;IGT&#41; and DM compared with controls&#46;</p>"
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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">Patients with LC have a prevalence of overt DM of 30&#37;&#46; However&#44; in cirrhotic patients with normal fasting plasma glucose &#40;FPG&#41; impaired glucose tolerance &#40;IGT&#41; or DM may be detected in 38 and 14&#37; of cases respectively by using an oral glucose tolerance test &#40;OGTT&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#8211;</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">Prospective studies have shown that DM &#40;either overt or subclinical&#41; is associated with an increase risk of complications and reduction of survival&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#8211;</span><a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The causes of death were mostly due to liver disease complications&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Since DM is frequently observed in patients with severe liver dysfunction&#44; it has led to suggest that DM may aggravate liver disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#8211;</span><a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">The type 2 DM and metabolic syndrome are causes of non alcoholic fatty liver disease&#46; Conversely&#44; liver cirrhosis may give rise to DM&#46; It has been demonstrated that hormonal polypeptides called cytokines are involved in the pathophysiology of liver disease induced by type 2 DM&#46; Cytokines act as chemical mediators in the processes of insulin resistance &#40;IR&#41;&#44; liver inflammation&#44; and liver fibrosis&#46; Those produced by adipose tissue are called &#8220;adipokynes&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Some of them have pro-inflammatory and anti-inflammatory activity and others stimulate liver fibrosis&#44; particularly TGF-&#946;1&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="p0020" class="elsevierStylePara elsevierViewall">TNF-&#945; mediates its biological responses by binding to two cell surface receptors&#58; TNF-R1 and TNF-R2&#46; TNF-R1 is the main inductor of cytotoxicity through induction of a number of biological responses ranging from NF-&#954;&#946; activation to cell death&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Soluble forms of both receptors are present in serum as a result of receptor shedding after cellular activation by stimuli of free TNF-&#945;&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">&#8211;</span><a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Furthermore&#44; TNF-&#945; can induce IR through phophorylation of serine residue of insulin receptor substrate &#40;IRS-1-2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="p0025" class="elsevierStylePara elsevierViewall">Leptin is produced predominantly by adipose tissue&#46; A relationship between leptin and liver fibrosis has been identified in animals<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> by up-regulation of the expression of TGF-&#946;1&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Leptin has a direct action on hepatic stellate cells &#40;HSC&#41; which express functionally active leptin receptors&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="p0030" class="elsevierStylePara elsevierViewall">TGF-&#946; is a pro-fibrotic cytokine found in liver and other organs&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> &#946;1 isoform is the most abundant in the liver&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> TGF-&#946;1 stimulates cell proliferation and synthesis and deposition of type I collagen and extracellular matrix proteins in the injured liver&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="p0035" class="elsevierStylePara elsevierViewall">HGF has antifibrotic activity through inhibition of platelet growth factor and TGF-&#946;1&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="p0040" class="elsevierStylePara elsevierViewall">The aims of this study were&#58; to determine if there is an impairment of plasma levels of TNF-&#945;&#44; sTN-R1&#44; leptin&#44; TGF-&#946;1&#44; and HGF in patients with IGT or DM and compensated LC&#46; At the same time to observe if there exists a relationship among these cytokines with other parameters such as Child Pugh score&#44; insulin resistance &#40;IR&#41; and body mass index &#40;BMI&#41;&#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="p0045" class="elsevierStylePara elsevierViewall">We studied patients with LC who were seen at our hospital from June 2007 to June 2012&#46; Cirrhosis was diagnosed by liver biopsy and&#47;or a combination of clinical data and imaging studies&#44; particularly percutaneous abdominal ultrasound&#46; All patients were adults without a previous diagnosis of DM and with normal FPG &#40;&#60; 100 mg&#47;dL&#41;&#46; Patients with&#58; hepatocellular carcinoma&#44; acute alcoholic hepatitis&#44; gastrointestinal bleeding&#44; clinically evident hepatic encephalopathy&#44; chronic renal failure&#44; hepatorenal syndrome&#44; severe infections&#44; and spontaneous bacterial peritonitis were excluded&#46;</p><p id="p0050" class="elsevierStylePara elsevierViewall">One hundred out of 293 assessed patients fulfilled the inclusion criteria&#46; They underwent OGTT using a 75 g load for 180 min according to the provisions of the American Diabetes Association&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Three study groups&#44; with previously established number of patients&#44; were formed in base of OGTT results&#58; eighteen patients with normal glucose tolerance &#40;NGT&#41;&#44; 18 with IGT and 18 with DM were randomly selected for the study&#46;</p><p id="p0055" class="elsevierStylePara elsevierViewall">The protocol was executed in accordance with the ethical guidelines of the 1975 Declaration of Helsinki and it was approved by the Ethics Committee of the Faculty of Medicine of the Universidad Aut&#243;noma de Nuevo Le&#243;n&#46; Written consent for participation into the study was obtained from all patients&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Assessments</span><p id="p0060" class="elsevierStylePara elsevierViewall">Complete clinical examination was conducted inquiring about family history of diabetes and alcohol consumption habits&#46; The following laboratory tests were performed&#58; plasma hemoglobin&#44; platelets blood count&#44; INR&#44; plasma albumin&#44; bilirubin&#44; ALT and &#947;GT&#46; The body mass index &#40;BMI&#41; was calculated&#44; and construed as follows&#58; normal if &#60; 24&#46;9&#44; overweight between 25 and 29&#46;9&#44; and obesity if &#8805; 30&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Liver function was estimated using Child-Pugh and MELD &#40;Model for End-Stage Liver Disease&#41; classifications&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">FPI and HOMA2-IR</span><p id="p0065" class="elsevierStylePara elsevierViewall">FPI levels were measure by electrochemiluminescence method &#40;Normal values&#58; 2&#46;6-24&#46;9 <span class="elsevierStyleItalic">&#956;</span>IU&#47;mL&#41;&#46; In order to calculate IR&#44; the Homeostasis Model Assessment index was calculated using the HOMA2-IR calculator software &#40;<a href="http://www.dtu.ox.ac.uk/homa-calculator/index.php">http&#58;&#47;&#47;www&#46;dtu&#46;ox&#46;ac&#46;uk&#47;homa-calculator&#47;index&#46;php</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> IR was arbitrarily defined as a value &#62;2&#46;</p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Measurement of cytokines</span><p id="p0070" class="elsevierStylePara elsevierViewall">Venous blood samples were obtained from fasting patients&#46; They were centrifuged for 10 min at 5 <span class="elsevierStyleSup">o</span>C&#44; aliquots were made and samples were stored at -70 <span class="elsevierStyleSup">o</span>C until they were processed&#46; We used commercially available specific immunoassays for the measurement in duplicate of TNF-&#945;&#44; sTNF R1&#44; leptin&#44; TGF-&#946;1 and HGF &#40;MILLIPLEX MAP kits&#44; Millipore&#44; St&#46; Charles&#44; MO&#44; USA&#41;&#46; Luminex 200 was used for the essay&#46; After hydration using buffer&#44; standard curve&#44; in-house quality controls&#44; and sera were added&#46; A mixture of microspheres labeled with the antibody specific for the biomarker were added to each pore&#46; After incubating the plate&#44; detection antibody was added to each pore&#46; The plate was incubated and streptavidin-phycoerythrin was added to each pore&#46; After other incubation&#44; 100 of system liquid was added and stirred for 10 min to suspend the microspheres and ensure a homogeneous distribution&#46; The flow cytometer counted the first 50 microspheres that passed through the reader in 60 sec&#46; The calibration curves were used to convert the mean fluorescent intensity readings for each concentration sample &#40;pg&#47;mL&#41; using a five parameter logistic model&#46; The intra- and inter-assay variation coefficient was less than 5&#37; for all cytokines&#46;</p><p id="p0075" class="elsevierStylePara elsevierViewall">Plasma cytokine levels in the cirrhotic patients were compared with those of a control group containing 18 individuals without LC and DM matched by age&#44; gender&#44; and BMI&#46;</p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Statistical analysis</span><p id="p0080" class="elsevierStylePara elsevierViewall">All variables were expressed as medians and interquartile ranges &#40;IQR&#41; and categorical variables were expressed as relative proportions&#46; The inter-group comparison was performed by using nonparametric tests&#58; median test&#44; Mann-Whitney U test and Kruskal-Wallis test for independent samples&#46; Correlation analysis was done by using non parametric Spearman rank test&#46; A P-value &#60; 0&#46;05 was considered statistically significant&#46; All statistical analyzes were performed using SPSS v17&#46;0 Statistical Package &#40;Chicago&#44; Illinois&#44; USA&#41;&#46;</p></span></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Results</span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Patients</span><p id="p0085" class="elsevierStylePara elsevierViewall">Demographic and clinical characteristics of the 54 patients with LC according to the results of the OGTT &#40;NGT&#44; IGT or DM&#41; are shown in <a class="elsevierStyleCrossRef" href="#t0005">table 1</a>&#46; Overall&#44; patients had a median age of 55&#46;5 years &#40;IQR&#58; 38&#46;25-72&#46;75&#41; and 30 were males &#40;55&#46;6&#37;&#41;&#46; Median BMI value was 26&#46;6 &#40;IQR&#58; 20&#46;5-32&#46;6&#41;&#46; Liver biopsy was performed in 23 &#40;42&#46;5&#37;&#41; patients&#46; The etiology of cirrhosis was alcoholic in 25 &#40;46&#46;3&#37;&#41; and cryptogenic in 11 &#40;20&#46;4&#37;&#41; patients&#46; The Child-Pugh classification score was 6 &#40;IQR&#58; 5&#46;2-9&#41; and the MELD score was 8 &#40;IQR&#58; 6&#46;1-15&#46;25&#41;&#46; IR was detected in 74&#37; of the patients&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0090" class="elsevierStylePara elsevierViewall">The patients having NGT&#44; IGT&#44; and DM were demographically and clinically similar&#46; Those with DM and IGT showed significantly less blood platelet counts than those with NGT &#40;p &#61; 0&#46;038 and 0&#46;042 respectively&#41; while those with IGT had increased INR values compared to those with NGT &#40;p &#61; 0&#46;039&#41;&#46; On the other hand&#44; compared to NGT patients&#44; those with DM showed significant higher FPI levels &#40;26 &#956;U&#47;mL&#44; IQR&#58; 15&#46;7-36&#46;3 <span class="elsevierStyleItalic">vs&#46;</span> 11&#46;9 <span class="elsevierStyleItalic">&#956;</span>U&#47;mL&#44; IQR&#58; 6&#46;1-17&#46;7&#44; p &#61; 0&#46;03&#41;&#44; higher HOMA2-IR values &#40;2&#46;95&#44; IQR&#58; 1&#46;6-4&#46;25 <span class="elsevierStyleItalic">vs&#46;</span> 1&#46;78&#44; IQR&#58; 0&#46;64-2&#46;84&#44; p &#61; 0&#46;017&#41; and greater IR frequency &#40;88&#46;8 <span class="elsevierStyleItalic">vs&#46;</span> 55&#46;5&#37;&#44; p &#61; 0&#46;025&#41; &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46;</p></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Plasma levels of cytokines</span><p id="p0095" class="elsevierStylePara elsevierViewall">Plasma cytokines values are shown in <a class="elsevierStyleCrossRef" href="#t0010">table 2</a>&#46; Compared to controls&#44; patients with DM and IGT showed significantly higher plasma sTNF-R1 levels &#40;DM&#58; 1872&#46;7 pg&#47;mL&#44; IQR&#58; 735&#46;2-3&#44;010&#46;1&#44; IGT&#58; 1&#44;931&#46;8 pg&#47;mL&#44; IQR&#58; 1147-3935&#46;7 and controls&#58; 1404&#46;6 pg&#47;mL&#44; IQR&#58; 864&#46;3-1&#44;944&#46;9&#41; &#40;IGT <span class="elsevierStyleItalic">vs&#46;</span> controls&#44; p &#61; 0&#46;0043 and DM <span class="elsevierStyleItalic">vs&#46;</span> controls p &#61; 0&#46;0045&#41; &#40;<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>A&#41;&#46; Non significant differences were observed between control group patients compared to cirrhotic patients with NGT&#46; By contrast&#44; compared to controls&#44; serum TGF-&#946;1 levels were significantly lower in patients with DM and IGT &#40;DM&#58; 9&#44;037&#44; pg&#47;mL IQR&#58; 3&#44;074-15&#44;001&#44; IGT&#58; 7&#44;768 pg&#47;mL&#44; IQR&#58; 2&#44;004-20&#44;297 and controls 23&#44;102 pg&#47;mL&#44; IQR&#58; 12&#44;676-33&#44;528&#41; &#40;DM <span class="elsevierStyleItalic">vs&#46;</span> controls and IGT <span class="elsevierStyleItalic">vs&#46;</span> controls p &#61; 0&#46;0001&#41; &#40;<a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>B&#41;&#46; Again&#44; non significant differences were observed between control group patients compared to cirrhotic patients with NGT&#46; On the other hand non statistically significant differences were found in TNF-&#945;&#44; leptin and HGF among all study groups&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="f0005"></elsevierMultimedia></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Cytokines and Child-Pugh score</span><p id="p0100" class="elsevierStylePara elsevierViewall">Plasma cytokine values according the groups A&#44; B and C of Child-Pugh classification are shown in <a class="elsevierStyleCrossRef" href="#t0015">table 3</a>&#46; Serum TNFa levels were increased in patients from groups B and C&#44; however only significant differences were observed in group C compared to Group A &#40;p &#61; 0&#46;040&#41;&#46; Serum sTNF-R1 levels were also increased in patients from groups B and C&#44; but only significant differences were found comparing group B <span class="elsevierStyleItalic">vs&#46;</span> A &#40;p &#61; 0&#46;033&#41;&#46; Serum TGF &#946;1 levels were reduced in groups B and C but significant differences were seen in group B compared to A &#40;p &#61; 0&#46;038&#41;&#46; Significant differences of HGF levels were found between Child-Pugh group C compared to A &#40;p &#61; 0&#46;029&#41; and finally plasma leptin levels were significantly lower in group C compared to A &#40;p &#61; 0&#46;029&#41;&#46;</p><elsevierMultimedia ident="t0015"></elsevierMultimedia></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Cytokines and IR</span><p id="p0105" class="elsevierStylePara elsevierViewall">A correlation between sTNF-R1 and HOMA2-IR values &#40;r &#61; 0&#46;32&#44; p &#61; 0&#46;043 and between leptin and HOMA2-IR &#40;r &#61; 0&#46;057&#44; p &#61; 0&#46;001&#41; were observed in cirrhotic patients&#46; No correlation was shown between the other cytokines and HOMA2-IR&#46;</p></span><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Cytokines and BMI</span><p id="p0110" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#t0020">Table 4</a> shows cytokines values in cirrhotic patients and controls with normal or abnormal BMI&#46; Only plasma levels of leptin showed a significant increment in patients with BMI &#62; 25 &#40;p &#61; 0&#46;001&#41;&#46;</p><elsevierMultimedia ident="t0020"></elsevierMultimedia></span></span><span id="s0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Discussion</span><p id="p0115" class="elsevierStylePara elsevierViewall">In this selected cohort of cirrhotic patients without overt DM&#44; it was found that plasma sTNF-R1 and TGF-&#223;1 levels were significantly impaired in those with IGT and DM as compared to controls&#46; Soluble forms of TNF-R1 &#40;sTNF-R1&#41; are present in serum as a result of receptor shedding after cellular activation by stimuli of TNF-&#945;&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> therefore&#44; high serum sTNF-R1 levels are reliable indicators of TNF-system activation&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> An increase of sTNF-R1 levels has been observed in patients with acute alcoholic hepatitis and cirrhosis&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In addition&#44; high sTNF-R1 levels were predictive of death at 3 months&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In our study&#44; increased sTNF-R1 observed in patients with IGT and DM may reflect liver inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Significant elevations of TNF &#945; and sTNF R1 were also found in Child-Pugh C and B groups of patients&#46; Clinical DM and IGT are more frequently observed in patients with advanced liver cirrhosis&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> In our study patients with DM had significantly lower levels of serum platelets and higher values of INR compared to NGT patients&#44; abnormalities that reflect liver dysfunction &#40;<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#41;&#46;</p><p id="p0120" class="elsevierStylePara elsevierViewall">Our findings suggest that DM and IGT may induce progressive liver failure through liver inflammation&#46; The correlation between sTNF-R1 and HOMA2-IR suggests a link between this cytokine and DM&#46; The possibility that DM and IGT may emerge as a result of liver function deterioration has to be also considered&#46; Nevertheless&#44; the appearance of IR and subclinical forms of DM since early stages of chronic liver disease does not support this theory&#46;</p><p id="p0125" class="elsevierStylePara elsevierViewall">It has to be taken into account that&#44; in diverse conditions frequently associated to DM such as en-dotoxemia<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> and bacterial infections&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> increments of serum sTNF-R1 have been observed&#46;</p><p id="p0130" class="elsevierStylePara elsevierViewall">The significant reduction of TGF-&#946;1 observed in our patients with IGT and DM is difficult to explain&#46; This cytokine has been known for many years for its fibrogenic effect&#46; However&#44; it also has anti-inflammatory and immunosuppressive effects&#46; The TGF-&#946;1 is the most abundant isoform of this cytokine family&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#8211;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> It is readily expressed in Kupffer cells&#44; HSC and endothelial cells in normal and cirrhotic liver&#44; activating HSC with an increased production of collagen type I and III&#44; fibronectin&#44; and other extracellular matrix proteins&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Several studies carried out in cirrhotic patients have described increase in serum TGF-&#946;1 levels&#46; A correlation between TGF-&#946;1 levels and Child-Pugh classification groups has also been described&#44; being this correlation higher in group C&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> However&#44; other studies made in cirrhotic patients have yielded conflicting results&#46; For example&#44; it was reported that serum TGF-&#946;1 levels were significantly higher in patients with fatty liver and NASH than in those with chronic hepatitis C virus who had a higher degree of fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Similarly higher TGF-&#946;1 levels were observed in patients with nonalcoholic steatohepatitis &#40;NASH&#41; compared to healthy controls&#46; In this study&#44; plasma insulin was the most important factor affecting TGF-&#946;1 as determined by multiple regression analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> In our study&#44; the significant reduction in serum TGF-&#946;1 levels observed in cirrhotic patients with IGT and DM may be the effect of HGF-mediated down-regulation or it may be the result of other factors linked to liver failure&#46; In this context&#44; TGF-&#946;1 levels were low and HGF levels were high in our patients from Child-Pugh groups B and C compared to those from group A&#46; In summary&#44; TGF-&#946;1 might be higher in pre fibrotic inflammatory liver injury &#40;such as NASH&#44; acute inflammatory processes of viral or alcoholic etiology and early stages of cirrhosis&#41; than in advanced liver cirrhosis&#46;</p><p id="p0135" class="elsevierStylePara elsevierViewall">We did not observe differences of leptin levels among cirrhotic patients and controls&#46; Nevertheless some studies have shown that leptin may be affected in patients with liver cirrhosis depending on the etiology and metabolic states&#46; It was observed that leptin is elevated in patients with alcoholic cirrhosis regardless of BMI&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> However&#44; no correlation of leptin with alcoholic cirrhosis was observed in other studies when BMI was adjusted&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> Others studies have shown a decrease of leptin in viral cirrhosis compared with alcoholic one&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> Regardless of the etiology of cirrhosis of our patients&#44; we observed a significant reduction of leptin in Child-Pugh group C patients compared to group A&#46; We also found a correlation between leptin and HOMA2-IR and an association of leptin with BMI &#62; 25&#46; Leptin may be in free form in plasma or forming binding complexes with one of its specific receptors &#40;ObRe&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> Similar serum free leptin levels were observed in patients with and without cirrhosis in a study measuring both forms of leptin&#46; Free leptin was positively correlated with metabolic parameters &#40;BMI and IR&#41;&#44; while receptor bound leptin was correlated with inflammatory conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p><p id="p0140" class="elsevierStylePara elsevierViewall">The HGF is a cytokine involved in liver regeneration&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> It has antifibrosing effect which appears to be due to suppression of the TGF-&#946;1 expression&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> In our study plasma levels of HGF did not show significant differences among patients with IGT or DM compared to NGT&#46; Nevertheless our patients from Child-Pugh C showed significant increase of this cytokine compared to group A&#46; This finding is in accordance with some published studies which have shown a positive correlation of serum HGF levels with the degree of fibrosis and the degree of liver failure in patients with HCV cirrhosis&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a></p><p id="p0145" class="elsevierStylePara elsevierViewall">This study has some limitations&#58; the sample size of patients is low&#44; additionally we did not measure the degree of hepatic fibrosis which would have been useful for TGF-&#946;1 correlations &#40;nevertheless&#44; the most important aim of our study was correlation of cytokines with IGT or DM&#41;&#44; and finally we did not search for subclinical bacterial infections which may impair cytokines plasma levels&#46;</p><p id="p0150" class="elsevierStylePara elsevierViewall">In conclusion&#44; this study showed that in cirrhotic patients&#44; both IGT and DM were associated with significant changes in plasma sTNF-R1 and TGF-&#946;1 levels compared to non cirrhotic&#44; non-diabetic patients&#46; Those in Child-Pugh B and C groups showed significant increases of TNF&#945;&#44; sTNF-R1 and HGF while they had a significant reduction of TGF-&#946;1 and leptin compared to group A&#46; Correlation between sTNF-R1 and leptin with IR and a correlation of leptin with BMI were also observed&#46; These findings suggest that IGT and DM may be causally implicated in liver inflammation process and progressive liver dysfunction&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:7 [
        0 => array:3 [
          "identificador" => "xres1199022"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abs0010"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1117462"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "s0005"
          "titulo" => "Introduction"
        ]
        3 => array:3 [
          "identificador" => "s0010"
          "titulo" => "Material and Methods"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "s0015"
              "titulo" => "Patients"
            ]
            1 => array:2 [
              "identificador" => "s0020"
              "titulo" => "Assessments"
            ]
            2 => array:2 [
              "identificador" => "s0025"
              "titulo" => "FPI and HOMA2-IR"
            ]
            3 => array:2 [
              "identificador" => "s0030"
              "titulo" => "Measurement of cytokines"
            ]
            4 => array:2 [
              "identificador" => "s0035"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        4 => array:3 [
          "identificador" => "s0040"
          "titulo" => "Results"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "s0045"
              "titulo" => "Patients"
            ]
            1 => array:2 [
              "identificador" => "s0050"
              "titulo" => "Plasma levels of cytokines"
            ]
            2 => array:2 [
              "identificador" => "s0055"
              "titulo" => "Cytokines and Child-Pugh score"
            ]
            3 => array:2 [
              "identificador" => "s0060"
              "titulo" => "Cytokines and IR"
            ]
            4 => array:2 [
              "identificador" => "s0065"
              "titulo" => "Cytokines and BMI"
            ]
          ]
        ]
        5 => array:2 [
          "identificador" => "s0070"
          "titulo" => "Discussion"
        ]
        6 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-12-18"
    "fechaAceptado" => "2013-12-18"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1117462"
          "palabras" => array:3 [
            0 => "Liver cirrhosis"
            1 => "Oral glucose tolerance test"
            2 => "sTNF-R1 and TGF-&#946;1"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><p id="sp0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Aims&#46;</span> To define if there is an imbalance in plasma levels of proinflammatory&#44; fibrogenic and antifibrogenic cytokines in patients with liver cirrhosis &#40;LC&#41; and impaired glucose tolerance &#40;IGT&#41; or diabetes mellitus &#40;DM&#41;&#46;</p><p id="sp1030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Material and methods&#46;</span> We randomly selected 54 out of 100 patients with LC who had normal fasting plasma glucose &#40;FPG&#41; levels&#46; Three groups were formed based on an oral glucose tolerance test &#40;OGTT&#41; results&#58; 18 patients were normal&#44; 18 had IGT&#44; and 18 had DM&#46; Plasma levels of cytokines were measured&#58; TNF-&#945;&#44; soluble tumor necrosis factor receptor 1 &#40;sTNF-R1&#41;&#44; leptin&#44; TGF-&#946;1&#44; and hepatocyte growth factor &#40;HGF&#41;&#46; Also&#44; fasting plasma insulin &#40;FPI&#41; levels were determined and HOMa2-IR was calculated&#46; Results were compared with those of a control group of 18 patients without liver disease nor DM&#46; Intergroup comparison was performed using non parametric tests&#46;</p><p id="sp2030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Results&#46;</span> Significantly higher sTNF-R1 and lower TGF-&#946;1 were found in patients with IGT and DM compared to controls&#46; Leptin&#44; HGF&#44; and TNF-&#945; levels showed no significant differences&#46; According to Child-Pugh classification all cytokines levels were impaired in groups B or C as compared to group A&#46; Positive correlations between sTNF-R1 and HOMA2-IR and between leptin and HOMA2-IR were found&#46;</p><p id="sp3030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Conclusions&#46;</span> IGT and DM were associated with abnormalities of sTNF-R1 and TGF-&#946;1 compared to non cirrhotic controls&#46; Among cirrhotic patients impairment of all cytokines were more marked in advanced liver disease&#46; Finally&#44; sTNF-R1and leptin correlated with IR&#46; These findings suggest that IGT and DM may be causally implicated with liver inflammation process&#46;</p></span>"
      ]
    ]
    "multimedia" => array:5 [
      0 => array:7 [
        "identificador" => "f0005"
        "etiqueta" => "Figure 1&#46;"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 424
            "Ancho" => 1045
            "Tamanyo" => 31251
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        "descripcion" => array:1 [
          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Box-whisker plots &#40;medians&#44; interquartil ranges and upper and lower ranges&#41; showing significantly elevated plasma levels of sTNF-R1 &#40;A&#41; and TGF-&#946;1 &#40;B&#41; in patients with impaired glucose tolerance &#40;IGT&#41; and DM compared with controls&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "t0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="np0005" class="elsevierStyleSimplePara elsevierViewall">NGT&#58; normal glucose tolerance&#46; IGT&#58; impaired glucose tolerance&#46; DM&#58; diabetes mellitus&#46; BMI&#58; body mass index&#46; HOMA&#58; homeostatic model assessment&#46; IQR&#58; interquartile range&#46;</p>"
          "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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Total n &#61; 54&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">NGT n &#61;18&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">IGT n &#61;18&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">DM n &#61;18&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&#44; years&#44; median &#40;IQR&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;5 &#40;38&#46;25-72&#46;75&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;5 &#40;22&#46;5-74&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#46;5 &#40;46&#46;5-72&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57 &#40;42-72&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;135&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Males&#44; &#951; &#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;55&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;42&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;61&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;61&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;509&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BMI&#44; median &#40;IQR&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#46;6 &#40;20&#46;55-32&#46;65&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#46;2 &#40;17&#46;9- 34&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#46;9 &#40;21&#46;3-30&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;20-36&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;513&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etiology of cirrhosis&#44; &#951; &#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="" 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="" 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="" 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="" 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="" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alcohol&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;46&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;47&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;33&#44;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;55&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;38&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HB&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;3&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;11&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;125&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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;18&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;5&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;27&#46;8&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;22&#46;2&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;203&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Autoimmunity&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;11&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;15&#46;8&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;5&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;11&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;57&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cryptogenic&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;20&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;26&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;22&#46;2&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;11&#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="left" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Child-Pugh&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="" 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="" valign="\n
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                  \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="" 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="" 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="" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29 &#40;53&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;52&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;61&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;44&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;594&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#914;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;31&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;33&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;44&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;728&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;9&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;10&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;5&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;11&#44;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;802&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Child Pugh score&#44; median &#40;IQR&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;0 &#40;5&#46;2-9&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;0 &#40;5&#46;2-8&#46;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;5 &#40;5&#46;18&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;5&#46;9-10&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;594&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MELD score&#44; median &#40;IQR&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;0 &#40;6-15&#46;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;0 &#40;6&#46;2-14&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;22 &#40;6&#46;3-14&#46;0&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;6&#46;1-16&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;132&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Laboratory&#44; median &#40;IQR&#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="" 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="" 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="" valign="\n
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                  \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="" 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="" 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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hemoglobin&#44; g&#47;dL&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;8 &#40;9&#46;23-14&#46;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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;5 &#40;8&#46;8-14&#46;2&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;9&#46;6-14&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;9 &#40;8-15&#46;8&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;929&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Platelets&#44; &#967; mm<span class="elsevierStyleSup">3</span>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">106000 &#40;28&#44;400-135&#44;200&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">156000 &#40;10&#44;250-301&#44;750&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77800 &#40;28&#44;400-223&#44;550&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92&#44;650 &#40;32&#44;400-152&#44;900&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;015<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">sTNF- R1&#44; pg&#47;mL&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;654&#46;9 &#40;507&#46;8-2&#44;802&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;931&#46;8 &#40;1&#44;147-3&#44;935&#46;7&#41; <a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">a</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;872&#46;7 &#40;735&#46;2-3&#44;010&#46;1&#41; <a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">b</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1404&#46;6 &#40;864&#46;3-1&#44;944&#46;9&#41; <a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a&#44;b</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TGF-&#946;1&#44; pg&#47;mL&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;357&#46;1 &#40;3&#44;683&#46;6-25&#44;030&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;768 &#40;2&#44;004-20&#44;297&#41; <a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">a</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;037 &#40;3&#44;074-15&#44;001&#41; <a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">b</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23102 &#40;12&#44;676-33&#44;528&#41; <a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">a&#44;b</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HGF&#44; pg&#47;mL&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">819&#46;8 &#40;279&#46;9-1&#44;359&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">568&#46;6 &#40;283&#46;1-1&#44;172&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">735&#46;0 &#40;601&#46;1-868&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">825&#46;9 &#40;46&#46;2-1&#44;605&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leptin&#44; pg&#47;mL&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;214&#46;5 &#40;1&#44;018&#46;1-18&#44;315&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;723&#46;6 &#40;83&#46;8-14&#44;322&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;107&#46;6 &#40;1&#44;059&#46;1-26&#44;410&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#44;593 &#40;462&#46;1-51&#44;995&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="np0015" class="elsevierStyleSimplePara elsevierViewall">TNF-a&#58; tumor necrosis factor alpha&#46; sTNF-R1&#58; soluble tumor necrosis factor receptor type 1&#46; TGF-&#223;1&#58; transforming growth factor-&#223;1&#46; HGF&#58; hepatocyte growth factor&#46;</p><p id="np1015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a&#44;b</span>p &#60; 0&#46;05&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Total&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Child-Pugh A n &#61; 29&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
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                  \t\t\t\t" scope="col">Child-Pugh B n &#61; 20&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Child Pugh C n &#61; 5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TNF-a&#44; pg&#47;mL&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;47 &#40;1&#46;3-8&#46;83&#41;<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">b</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;1 &#40;1&#46;92-12&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;13 &#40;3&#46;2-10&#46;4&#41;<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">b</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">sTNF-R1&#44; pg&#47;mL&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;786 &#40;276-3&#44;609&#41;<a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">a</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;439 &#40;895-15&#44;880&#41;<span class="elsevierStyleInf">a</span>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;011 &#40;1&#44;961-6&#44;482&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TGF-&#223;1&#44; pg&#47;mL&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;836 &#40;2&#44;004-34&#44;072&#41;<a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">a</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;315 &#40;2&#44;003-22&#44;942&#41;<a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">a</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#44;945 &#40;3&#44;503-21&#44;371&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HGF&#44; pg&#47;mL&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">750 &#40;175-1&#44;629&#41;<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">b</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">998 &#40;96-2&#44;941&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;711 &#40;123&#46;6-6&#44;034&#41;<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">b</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leptin&#44; pg&#47;mL&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;869 &#40;1&#44;132-34&#44;582&#41;<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">b</span></a>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#44;995 &#40;83-45&#44;991&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;270 &#40;1&#44;059-12&#44;914&#41;<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Total&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">BMI &#60; 25 n &#61; 26&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">BMI &#62; 25 n &#61; 46&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">P values&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TNF-&#945;&#44; pg&#47;mL&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;38 &#40;1&#46;72-7&#46;04&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;48 &#40;0&#46;77-8&#46;19&#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="left" valign="\n
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                  \t\t\t\t">0&#46;967&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 16652681
Original language: English

DOI:10.1016/S1665-2681(19)30847-6

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Year/Month	Html	Pdf	Total

2024 November	2	0	2
2024 October	17	6	23
2024 September	25	9	34
2024 August	21	5	26
2024 July	20	5	25
2024 June	27	3	30
2024 May	20	4	24
2024 April	35	6	41
2024 March	29	3	32
2024 February	13	9	22
2024 January	15	4	19
2023 December	6	5	11
2023 November	9	8	17
2023 October	8	3	11
2023 September	8	1	9
2023 August	10	4	14
2023 July	10	3	13
2023 June	14	1	15
2023 May	37	2	39
2023 April	38	2	40
2023 March	32	2	34
2023 February	13	1	14
2023 January	6	3	9
2022 December	8	2	10
2022 November	5	5	10
2022 October	12	5	17
2022 September	6	6	12
2022 August	7	7	14
2022 July	9	7	16
2022 June	7	5	12
2022 May	8	4	12
2022 April	9	10	19
2022 March	14	6	20
2022 February	10	5	15
2022 January	17	5	22
2021 December	6	12	18
2021 November	11	5	16
2021 October	9	5	14
2021 September	10	11	21
2021 August	4	6	10
2021 July	7	6	13
2021 June	9	4	13
2021 May	6	10	16
2021 April	14	10	24
2021 March	4	4	8
2021 February	8	4	12
2021 January	2	6	8
2020 December	5	7	12
2020 November	2	5	7
2020 October	4	3	7
2020 September	4	7	11
2020 August	4	3	7
2020 July	4	0	4
2020 June	3	2	5
2020 May	2	4	6
2020 April	1	3	4
2020 March	2	1	3
2020 February	3	2	5
2020 January	1	1	2
2019 December	5	7	12
2019 November	3	1	4
2019 October	1	1	2
2019 September	0	1	1
2019 August	1	1	2
2019 July	1	4	5
2019 June	3	6	9

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