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Inicio Gastroenterología y Hepatología (English Edition) A model incorporating serum C3 complement levels may be useful for diagnosing bi...
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Original Article
A model incorporating serum C3 complement levels may be useful for diagnosing biliary atresia in infants
Un modelo que incorpore niveles séricos de C3 del complemento podría ser de utilidad para el diagnóstico de atresia biliar en niños
Jiankun Lianga,1, Huixian Lib,1, Jie Fub,1, Qifeng Lianga,1, Tao Liua,1, Fengxia Yangc,1, Bingbing Zhanga,1, Xiaoling Baia,1, Zhe Wena,1,
Corresponding author
wenzhepaper@163.com

Corresponding author.
a Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
b Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
c Isolation Clinic, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Receiver operating characteristic &#40;ROC&#41; curves of &#40;A&#41; Model 1&#59; &#40;B&#41; Model 2&#59; &#40;C&#41; Model 3&#59; and &#40;D&#41; Model 4&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Biliary atresia &#40;BA&#41; is a destructive&#44; inflammatory and obliterative cholangiopathy of neonates that affects the lengths of the intrahepatic and extrahepatic bile ducts&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> BA has a complex pathogenesis&#44; typically manifests as cholestatic jaundice&#44; and progresses rapidly to end-stage cirrhosis if not diagnosed and treated in a timely manner&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> The disease occurs with variable geographical frequency&#44; ranging from 1 in 5000 live births per year in Taiwan to an estimated 1 in 15&#44;000&#8211;19&#44;000 live births per year in the United States and The Netherlands&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#8211;6</span></a> Once diagnosed&#44; BA is managed surgically by removing atretic biliary remnants and creating a Roux-en-Y intestinal conduit for bile drainage&#44; a procedure known as Kasai hepatoportoenterostomy&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> However&#44; the procedure is not effective in around half of patients&#44; and the definitive treatment for BA is liver transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Other conditions can cause cholestatic jaundice&#44; and most will resolve completely with conservative management&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> Thus&#44; it is vitally important to distinguish BA from other conditions that cause chole&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2&#44;7</span></a> Cholangiography and liver biopsy performed laparoscopically or via laparotomy are highly accurate for differentiating BA from other causes of cholestatic jaundice&#44; but they are invasive and associated with risks inherent to invasive surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8&#44;9</span></a> There is no consensus regarding the diagnosis of BA with non-invasive methods&#46; However&#44; studies have suggested that models incorporating levels of circulatory immune markers and other risk factors for BA may be useful for distinguishing BA from other causes of cholestatic jaundice&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">10&#8211;13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Thus&#44; the purpose of this study was to develop a model incorporating lymphocyte subsets&#44; immunoglobulin and complement levels in order to distinguish BA from other causes of cholestatic jaundice&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patients and study design</span><p id="par0020" class="elsevierStylePara elsevierViewall">This was a retrospective study that used patient data and blood and tissue specimens collected in a previous clinical trial &#40;ChiCTR1800015717&#41;&#46; The prior clinical trial enrolled 227 patients who were newly diagnosed with cholestatic jaundice at the Guangzhou Women and Children&#39;s Medical Center in Guangzhou&#44; China&#44; between March 2016 and December 2018&#46; Of the 227 patients&#44; 35 were excluded for reasons including a recent acute febrile illnesses or infection&#44; severe malformation of other organs or choledochal cysts&#46; Thus&#44; 192 patients were included in the trial&#44; and were assigned to a BA group or a cholestasis control &#40;CC&#41; group&#46; The flow chart of patient selection was shown in <a class="elsevierStyleCrossRef" href="#sec0105">Supplemental Fig&#46; 1</a>&#46; Group assignment and BA diagnosis was based on cholangiography and liver biopsy&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The current study was approved by the Ethics Committee of Guangzhou Women and Children&#39;s Medical Center &#40;approval number 2016030304&#41;&#46; Because of the retrospective nature of the study&#44; the requirement of informed patient consent was waived&#46; All patients provided written informed consent for participation in the prior clinical trial and for all procedures performed&#44; and to have their data used for research purposes&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Patient characteristics</span><p id="par0030" class="elsevierStylePara elsevierViewall">The following data were collected in the clinical study and were extracted from the medical records for the current analysis&#46; Demographic and clinical information included the patient sex&#44; age&#44; stool color at hospital admission and age in days at the time of surgery&#46; Stool color was obtained by questioning parents at the time of admission&#46; Hematological studies at the time of admission included total white blood cell &#40;WBC&#41; count&#44; neutrophil count&#44; monocyte count&#44; lymphocyte count&#44; and eosinophil count&#46; Biochemical studies included serum aspartate aminotransferase &#40;AST&#41;&#44; alanine aminotransferase &#40;ALT&#41;&#44; albumin&#44; globulin&#44; total bilirubin&#44; direct bilirubin&#44; and gamma-glutamyl transpeptidase &#40;&#947;-GT&#41; levels&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Flow cytometry</span><p id="par0035" class="elsevierStylePara elsevierViewall">Flow cytometry for identification of lymphocytes was performed with a BD FACS Canto&#174; II flow cytometer using commercially available antibodies &#40;BD Multitest IMK Kit&#41;&#46; Lymphocytes were identified by low side scatter&#44; and moderate&#47;bright CD45 expression&#46; Back-gating on CD3-positive events was performed to avoid contamination by monocytes and other non-lymphocyte subsets&#46; Lymphocyte subsets were counted as an absolute number&#44; and a percentage of the total lymphocytes identified in the lymphocyte gate&#44; according to the kit instructions&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Enzyme-linked immunosorbent assay &#40;ELISA&#41; measurement of immunoglobulin and complement levels</span><p id="par0040" class="elsevierStylePara elsevierViewall">Serum IgG&#44; IgA&#44; IgM&#44; and IgE and C3 and C4 levels were determined using an Immage&#174; 800 instrument &#40;Beckman Coulter&#44; Inc&#46;&#41; with commercially available antibodies&#44; according to the manufacturer&#39;s instructions&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Categorical variables were presented as number &#40;percentage&#41;&#46; Continuous variables were presented as median &#40;interquartile range &#91;IQR&#93;&#41; if normality was not assumed&#59; otherwise as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#46; An assessment of the diagnostic performance of lymphocyte subsets and immunoglobulin and complement levels for diagnosis of BA was performed in 3 steps using &#947;-GT as the reference&#46; First&#44; all of the indices were compared between the BA group and the CC group using the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test or chi-square test&#44; as appropriate&#46; Second&#44; Spearman correlation coefficients were determined and scatter plots were generated to further assess the relations among the parameters and relations with age&#46; Third&#44; univariate and multivariate logistic regression analyses were performed to determine the best combination of indicators for predicting BA&#46; Independent variables with a value of <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;10 in the univariate analysis were entered into the multivariate model&#46; Variables found to be significant in the multivariate analysis were considered to be significantly associated with BA&#46; Receiver operating characteristic &#40;ROC&#41; curve analysis was performed to examine the diagnostic value of different indicator combinations&#46; The diagnostic values of the various combinations was assessed by examining the change &#40;<span class="elsevierStyleItalic">&#916;</span>&#41; of the area under the ROC curve &#40;AUC&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#44;15</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">All statistical analyses were 2-tailed and a value of <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered to indicate statistical significance&#46; All analyses were performed using IBM SPSS version 20 statistical software &#40;SPSS Statistics V20&#44; IBM Corporation&#44; Somers&#44; New York&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Sample size estimation</span><p id="par0055" class="elsevierStylePara elsevierViewall">Sample size was estimated by software G&#42;Power version 3&#46;1 &#40;Heinrich-Heine-Universit&#228;t D&#252;sseldorf&#44; D&#252;sseldorf&#44; German&#41;&#46; The effect size was conservatively set at a medium level of 0&#46;5&#44; type I error &#40;alpha&#41; of 0&#46;05&#44; power of 0&#46;80&#44; and the number of independent groups of 2 &#40;BA and CC&#41;&#46; The ratio of sample size between group &#40;BA&#47;CC&#41; was set at 2&#46; Statistical method was Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test&#46; The estimated minimum required sample size of BA and CC was 50 and 100&#44; respectively&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In post hoc estimation of statistical power by the results of C3 and C4&#44; the estimated statistical powers were 99&#46;86&#37; and 71&#46;17&#37;&#44; respectively&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Considering the prior estimation of sample size and post hoc estimation of statistical power&#44; the final sample sizes of both groups in this study were acceptable&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Patient characteristics</span><p id="par0070" class="elsevierStylePara elsevierViewall">A total of 106 male and 86 female infants with a median age of 2&#46;2 months &#40;IQR&#58; 1&#46;8&#8211;2&#46;7 months&#41; were included in the current analysis&#46; Of the 192 infants&#44; 129 &#40;67&#46;2&#37;&#41; were included in the BA group and 63 cases &#40;32&#46;8&#37;&#41; were included in the CC group&#46; In the CC group&#44; there were 40 cases of neonatal cholestasis&#44; 4 cases of congenital bile duct anomalies&#44; and 19 cases of genetic and metabolic cholestatic diseases&#46; Approximately three-quarters &#40;70&#37;&#41; of the BA group had yellowish-white&#47;clay colored stool on admission&#44; which was significantly higher than that in the CC group &#40;20&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; In the BA group&#44; basophil count and monocyte count were significantly lower&#44; and globulin&#44; direct bilirubin and &#947;-GT levels were significantly higher than in the CC group &#40;all <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; Other demographic and laboratory characteristics were similar between the 2 groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Lymphocyte subsets&#44; immunoglobulin and complement levels in the BA and CC groups</span><p id="par0075" class="elsevierStylePara elsevierViewall">However&#44; the levels of CD3<span class="elsevierStyleSup">&#43;</span> T cells&#44; CD3<span class="elsevierStyleSup">&#43;</span>CD4<span class="elsevierStyleSup">&#43;</span> T cells premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group &#40;all <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Correlations between monocytes&#44; globulin&#44; direct bilirubin&#44; &#947;-GT&#44; CD3<span class="elsevierStyleSup">&#43;</span> T cells&#44; CD3<span class="elsevierStyleSup">&#43;</span>CD4<span class="elsevierStyleSup">&#43;</span> T cells&#44; pT cells&#44; C3 and C4</span><p id="par0080" class="elsevierStylePara elsevierViewall">Analysis indicated that monocytes&#44; globulin&#44; direct bilirubin&#44; &#947;-GT&#44; CD3<span class="elsevierStyleSup">&#43;</span> T cells&#44; CD3<span class="elsevierStyleSup">&#43;</span>CD4<span class="elsevierStyleSup">&#43;</span> T cells&#44; pT cells&#44; C3 and C4 were significantly associated with BA &#40;all <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; However&#44; pair-wise correlation analyses indicated that C3 and C4 had a significant positive correlation with &#947;-GT in the BA group&#44; but not in the CC group &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Trends of monocytes&#44; globulin&#44; direct bilirubin&#44; &#947;-GT&#44; CD3<span class="elsevierStyleSup">&#43;</span> T cells&#44; CD3<span class="elsevierStyleSup">&#43;</span>CD4<span class="elsevierStyleSup">&#43;</span> T cells&#44; pT cells C3 and C4 with age</span><p id="par0085" class="elsevierStylePara elsevierViewall">The &#947;-GT level was correlated with age in the BA group &#40;r<span class="elsevierStyleInf">s</span>BA<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;3&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#44; but not in the CC group&#46; Similarly&#44; globulin level was correlated with age in the BA group &#40;r<span class="elsevierStyleInf">s</span>BA<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;3&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#44; but not in the CC group&#46; The correlation coefficients of all other indices examined with respect to age were not statistically significant&#44; indicating the indices were stable with age &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Investigation of factors associated with BA</span><p id="par0090" class="elsevierStylePara elsevierViewall">Independent variables&#44; which were significantly different between the BA and CC groups&#44; were analyzed by univariate and multivariate logistic regression&#46; As shown in <a class="elsevierStyleCrossRefs" href="#tbl0020">Tables 4 and 5</a>&#44; indices were found to be significantly associated with BA&#58; stool color&#44; globulin&#44; &#947;-GT&#44; C3 and C4&#46; With respect to stool color&#44; light yellow and yellowish-white&#47;clay colored were both associated with a higher risk of BA than yellow&#47;yellow green stool&#46; Of the other indices&#44; higher globulin level and higher C4 level were associated with a lower risk of BA&#44; while higher &#947;-GT level and higher C3 level were associated with a higher risk of BA&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Model comparison and diagnostic value</span><p id="par0095" class="elsevierStylePara elsevierViewall">The 5 aforementioned associated indices were examined in different combinations for their diagnostic value&#46; All of the multivariate logistic regression results and corresponding ROC analysis results of the different models are summarized in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#46; In Model 1 and Model 2&#44; globulin level was not a stable predictor of BA&#44; and after removing globulin level&#44; the value of C3 and C4 became insignificant&#46; Comparison of the different models indicated that stool color and &#947;-GT were stable &#40;significant&#41; indices associated with BA&#46; The AUC of Model 4 was 0&#46;93 &#40;95&#37; confidence interval &#91;CI&#93;&#58; 0&#46;88&#8211;0&#46;97&#41;&#44; with a sensitivity of 87&#37; and a specificity of 87&#37;&#46; Adding C3 and C4 to model 4 did not significantly improve the diagnostic accuracy for determining BA &#40;&#916;AUC<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The ROC curves of the 4 models indicate there are only slight differences among the different models &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Discussion</span><p id="par0105" class="elsevierStylePara elsevierViewall">In this study&#44; we found that serum complement C3 and C4 levels were significantly increased in the BA group compared to CC group&#44; and were positively correlated with &#947;-GT&#44; globulin and stool color in patients with BA&#44; irrespective of age&#46; However&#44; the addition of C3 and C4 to the most useful model did not improve the diagnostic accuracy&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Accurately distinguishing BA from other cholestatic diseases is crucial because most cholestatic diseases will resolve completely with conservative treatment&#44; while BA requires surgery&#46; There is currently no single diagnostic tool that can non-invasively provide a definitive diagnosis of BA&#46; Rather&#44; a number of diagnostic tools are collectively used to establish a diagnosis&#46; Recently&#44; The Childhood Liver Disease Research Network reported an optimized prediction model &#40;AUC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;89&#41; that uses 7 clinical variables&#58; sex&#44; acholic stools&#44; normal facial features&#44; &#947;-GT&#44; weighted <span class="elsevierStyleItalic">Z</span>-score&#44; palpable liver below the costal margin and a sonographically absent gallbladder&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> However&#44; the high precision required to differentiate BA from non-BA was not achieved&#58; a predicted probability of &#62;0&#46;8 yielded an 81&#37; true positive rate for BA and &#60;0&#46;2 yielded an 11&#37; false negative rate&#46; In another study&#44; a nomogram model was developed using a large respective cohort of Chinese patients&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> The model included 5 indices&#58; sex&#44; weight&#44; direct bilirubin&#44; alanine aminotransferase and &#947;-GT&#46; While the model displayed a high sensitivity and positive predictive value &#40;PPV&#41;&#44; the specificity was low&#46; Interestingly&#44; a study showed that including &#947;-GT can improve the accuracy of BA diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">As the aforementioned studies suggest&#44; the existing diagnostic methods are insufficient for establishing a diagnosis of BA&#46; Other studies&#44; however&#44; have suggested that circulatory immune markers&#44; in combination with &#947;-GT&#44; may be valuable in the diagnosis of liver diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">12&#44;13&#44;17&#44;19</span></a> Based on these&#44; studies&#44; we sought to determine the value of immune markers in the diagnosis of BA&#46; Our results suggest that serum C3 level may be useful for distinguishing BA from other causes of cholestasis&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Our results raise the question of why serum C3 level is increased in BA&#46; While the pathogenesis of BA is not completely understood&#44; studies have indicated that abnormal inflammation and autoimmunity play key roles in the disease process&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> Elevations of serum C3 in BA may be responsible for liver inflammation and fibrosis associated with the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> Three large clinical studies have confirmed an association between serum C3 levels and non-alcoholic fatty liver disease &#40;NAFLD&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">21&#8211;23</span></a> However&#44; few studies examining the complement system and BA have been published&#46; In 1983&#44; Larcher et al&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> measured C3 and C4 concentrations in sera from 69 children with liver disease and 39 controls&#44; and reported mean serum C3 and C4 concentrations were not different between children with BA &#40;9 cases&#41; and controls&#46; In another study&#44; 11 potential serum biomarkers&#44; including C3&#44; were identified by 2-dimensional difference gel electrophoresis&#59; however&#44; no single biomarker reliably distinguished BA from neonatal cholestasis&#44; although the sample size of the study was small&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Much research on BA has examined the cell-mediated immune response seen in liver tissue&#46; Histologically examination of liver tissues from patients with BA found that C4d complement was expressed in the endothelium of the portal vein&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> Another study showed an increased concentration of the C3 complement effector protein during the progression of liver regeneration<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> and hence may be an independent protective factor for BA&#46; Other studies of patients with liver cirrhosis indicated that serum concentrations of C3 correlated negatively with Child&#8211;Pugh score&#44; regardless of the cause of cirrhosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">27&#8211;30</span></a> Taken together these data suggest that C3 is involved in the course of BA&#44; and monitoring serum C3 levels may be useful for determining the deterioration of liver function in BA&#46; However&#44; prospective studies are needed to confirm this hypothesis&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">This study is limited in part by its retrospective nature and the statistical power associated with the relatively small number of patients&#46; For the sample of 129 BA cases and 63 CC controls&#44; the statistical power to detect a C3 level difference of 0&#46;1 is approximately 76&#37;&#46; Furthermore&#44; the relatively low number of patients in the control group may have resulted in biased data selection&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conclusions</span><p id="par0135" class="elsevierStylePara elsevierViewall">The results of this study suggest that a model incorporating serum C3 level may be useful for diagnosing BA in infants&#44; and potentially avoid the need for invasive diagnostic procedures&#46; The role of C3 in the pathogenesis of BA is unknown and further in vitro and in vivo studies are needed&#46; Based on the results of this study&#44; further studies incorporating serum C3 level into predictive models for BA are warranted&#46; Accurate&#44; non-invasive methods to diagnosis BA&#44; or rule out BA&#44; may help avoid unnecessary invasive diagnostic procedures&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Funding</span><p id="par0140" class="elsevierStylePara elsevierViewall">This study was supported by funds from the <span class="elsevierStyleGrantSponsor" id="gs1">Guangzhou Women and Children&#39;s Medical Center&#47;Guangzhou Institute of Pediatrics</span> &#91;No&#58; <span class="elsevierStyleGrantNumber" refid="gs1">0160038</span>&#93;&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Conflict of interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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              "identificador" => "sec0025"
              "titulo" => "Flow cytometry"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Enzyme-linked immunosorbent assay &#40;ELISA&#41; measurement of immunoglobulin and complement levels"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        7 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Results"
          "secciones" => array:7 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Sample size estimation"
            ]
            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Patient characteristics"
            ]
            2 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Lymphocyte subsets&#44; immunoglobulin and complement levels in the BA and CC groups"
            ]
            3 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Correlations between monocytes&#44; globulin&#44; direct bilirubin&#44; &#947;-GT&#44; CD3 T cells&#44; CD3CD4 T cells&#44; pT cells&#44; C3 and C4"
            ]
            4 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Trends of monocytes&#44; globulin&#44; direct bilirubin&#44; &#947;-GT&#44; CD3 T cells&#44; CD3CD4 T cells&#44; pT cells C3 and C4 with age"
            ]
            5 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Investigation of factors associated with BA"
            ]
            6 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Model comparison and diagnostic value"
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Discussion"
        ]
        9 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conclusions"
        ]
        10 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Funding"
        ]
        11 => array:2 [
          "identificador" => "sec0095"
          "titulo" => "Conflict of interest"
        ]
        12 => array:2 [
          "identificador" => "xack585179"
          "titulo" => "Acknowledgements"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-11-27"
    "fechaAceptado" => "2021-02-08"
    "PalabrasClave" => array:2 [
      "en" => array:2 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1475395"
          "palabras" => array:4 [
            0 => "Biliary atresia"
            1 => "Complement"
            2 => "Gamma-glutamyl transpeptidase"
            3 => "Diagnosis"
          ]
        ]
        1 => array:4 [
          "clase" => "abr"
          "titulo" => "Abbreviations"
          "identificador" => "xpalclavsec1475394"
          "palabras" => array:10 [
            0 => "BA"
            1 => "CC"
            2 => "WBC"
            3 => "AST"
            4 => "ALT"
            5 => "&#947;-GT"
            6 => "ELISAR"
            7 => "ROC"
            8 => "PPV"
            9 => "NAFLD"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1475396"
          "palabras" => array:4 [
            0 => "Atresia biliar"
            1 => "Complemento"
            2 => "Gamma-glutamil transpeptidasa"
            3 => "Diagn&#243;stico"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Correctly identifying patients with biliary atresia &#40;BA&#41;&#44; while avoiding invasive diagnostic methods is challenging&#46; The purpose of this study was to determine the value of serum immune indicators for distinguishing BA from other causes of cholestasis in infants&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The data of infants with a surgical&#47;histological diagnosis of BA and those with other causes of cholestatic jaundice were retrospectively analyzed&#46; Patients were divided into a BA group and a cholestasis control &#40;CC&#41; group&#46; Biochemical parameters&#44; major lymphocyte subsets&#44; immunoglobin and C3 and C4 complement levels were compared between the groups&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 129 infants with BA and 63 with other causes of cholestasis &#40;CC control group&#41; with a median age of 2&#46;2 months were included in the analysis&#46; The levels of CD3<span class="elsevierStyleSup">&#43;</span> T cells&#44; CD3<span class="elsevierStyleSup">&#43;</span>CD4<span class="elsevierStyleSup">&#43;</span> T cells&#44; and premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group &#40;all <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; Pair-wise correlation analyses indicated that C3 and C4 had a significant positive correlation with &#947;-GT in the BA group&#44; but not in the CC group&#46; Five indices were found to be significantly associated with BA&#58; stool color&#44; globulin&#44; &#947;-GT&#44; C3 and C4&#46; A model incorporating stool color&#44; gamma-glutamyl transpeptidase level&#44; and C3 level exhibited an area under the ROC curve &#40;AUC&#41; of 0&#46;93&#44; and a sensitivity of 93&#37; and specificity of 83&#37; for the diagnosis of BA&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Models incorporating serum C3 levels may be useful for accurately diagnosing BA in infants&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Patients and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Es dif&#237;cil la identificaci&#243;n correcta de los pacientes con atresia biliar &#40;AB&#41;&#44; evitando los m&#233;todos diagn&#243;sticos invasivos&#46; El objetivo de este estudio fue determinar el valor de los indicadores inmunol&#243;gicos s&#233;ricos para distinguir AB de otras causas de colestasis en ni&#241;os&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Se analizaron retrospectivamente los datos de ni&#241;os con diagn&#243;stico quir&#250;rgico&#47;histol&#243;gico de AB y los datos de ni&#241;os con otras causas de ictericia colest&#225;sica&#46; Se dividi&#243; a los pacientes entre el grupo AB y el grupo de control de colestasis &#40;CC&#41;&#46; Se compar&#243; entre los dos grupo los par&#225;metros bioqu&#237;micos&#44; principales subconjuntos linfoc&#237;ticos&#44; inmunoglobina y niveles s&#233;ricos de C3 y C4 del complemento&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Se incluy&#243; en el an&#225;lisis a un total de 129 ni&#241;os con AB y 63 con otras causas de colestasis &#40;grupo control CC&#41; con una edad media de 2&#44;2 meses&#46; Los niveles de c&#233;lulas T CD3&#43;&#44; c&#233;lulas T CD3&#43;CD4&#43;&#44; c&#233;lulas T prematuras y los niveles de C3 y C4 fueron significativamente m&#225;s altos en el grupo AB en comparaci&#243;n con el grupo CC &#40;all P &#60; 0&#44;05&#41;&#46; Los an&#225;lisis de correlaci&#243;n pareada indicaron que C3 y C4 ten&#237;an una correlaci&#243;n positiva significativa con -GT en el grupo AB&#44; pero no en el grupo CC&#46; Se determin&#243; que cinco &#237;ndices estaban significativamente asociados a AB&#58; color de las heces&#44; globulina&#44; -GT&#44; C3 y C4&#46; Un modelo que incorpor&#243; el color de las heces&#44; nivel de gamma-glutamil transpeptidasa&#44; y nivel de C3 reflej&#243; un &#225;rea bajo la curva ROC &#40;AUC&#41; de 0&#44;93&#44; sensibilidad del 93&#37; y especificidad del 83&#37; para el diagn&#243;stico de AB&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Los modelos que incorporan niveles s&#233;ricos de C3 pueden ser de utilidad para diagnosticar AB de manera precisa en ni&#241;os&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Pacientes y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:3 [
        "etiqueta" => "1"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">These authors contributed equally to this work&#46;</p>"
        "identificador" => "fn1"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0160" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article&#58;<elsevierMultimedia ident="fig0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0105"
          ]
        ]
      ]
    ]
    "multimedia" => array:8 [
      0 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 3678
            "Ancho" => 3810
            "Tamanyo" => 674709
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Trends of monocytes&#44; eosinophils&#44; gamma-glutamyl transpeptidase&#44; direct bilirubin&#44; globulin&#44; CD3<span class="elsevierStyleSup">&#43;</span>CD4<span class="elsevierStyleSup">&#43;</span> T cells and C3 and C4 with age&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2006
            "Ancho" => 2175
            "Tamanyo" => 163866
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Receiver operating characteristic &#40;ROC&#41; curves of &#40;A&#41; Model 1&#59; &#40;B&#41; Model 2&#59; &#40;C&#41; Model 3&#59; and &#40;D&#41; Model 4&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">ALT&#44; alanine aminotransferase&#59; AST&#44; aspartate aminotransferase&#59; ALB&#44; albumin&#59; &#947;-GT&#44; gamma-glutamyl transpeptidase&#59; TBA&#59; total bile acids&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Continuous variables were presented as median &#40;IQR&#58; interquartile range&#41;&#44; and compared using the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test as they were non-normally distributed&#46; Categorical variables were presented as number &#40;percentage&#41;&#44; and compared using the chi-square test&#46; Bold values denote statistical significance at the <span class="elsevierStyleItalic">P</span> &#60;0&#46;05&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\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" style="border-bottom: 2px solid black">Indicators&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
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>192&#41;&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" style="border-bottom: 2px solid black">Cholestasis control group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>63&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Biliary atresia group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>129&#41;&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
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span>&#124;<span class="elsevierStyleItalic">Z&#124;</span>&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
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Demographic and clinical characteristics</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Age&#44; months</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;15 &#40;1&#46;81&#44; 2&#46;72&#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
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                  \t\t\t\t">2&#46;14 &#40;1&#46;84&#44; 2&#46;63&#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&#46;17 &#40;1&#46;76&#44; 2&#46;74&#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
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                  \t\t\t\t">0&#46;05&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;957&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Sex</span>&nbsp;\t\t\t\t\t\t\n
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                  \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
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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
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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="left" valign="\n
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                  \t\t\t\t">1&#46;70&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;192&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Male&nbsp;\t\t\t\t\t\t\n
                  \t\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">106 &#40;55&#46;21&#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">39 &#40;61&#46;90&#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">67 &#40;51&#46;94&#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
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                  \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-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Female&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Lymphocytes</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Eosinophils</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Platelets</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">428 &#40;329&#44; 549&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">431 &#40;336&#44; 532&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">204 &#40;144&#44; 299&#46;25&#41;&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Continuous variables were presented as median &#40;IQR&#58; interquartile range&#41;&#44; and compared using the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test as they were non-normally distributed&#46; Bold values denote statistical significance at the <span class="elsevierStyleItalic">P</span> &#60;0&#46;05&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cholestasis control group&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>63&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD3<span class="elsevierStyleSup">&#43;</span> T cells &#40;cells&#47;&#956;L&#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">4402&#46;32 &#40;3284&#46;62&#44; 5727&#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">3754&#46;05 &#40;3021&#46;24&#44; 5660&#46;22&#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">4669&#46;43 &#40;3403&#46;30&#44; 5958&#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">2&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;021</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD3<span class="elsevierStyleSup">&#43;</span>CD45<span class="elsevierStyleSup">&#43;</span>&#47;CD3<span class="elsevierStyleSup">&#43;</span> T cells &#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">68&#46;25 &#40;61&#46;16&#44; 75&#46;11&#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">66&#46;41 &#40;58&#46;83&#44; 74&#46;46&#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">69 &#40;61&#46;66&#44; 75&#46;24&#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;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;352&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD3<span class="elsevierStyleSup">&#43;</span>CD4<span class="elsevierStyleSup">&#43;</span> T cells &#40;cells&#47;&#956;L&#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">2524&#46;75 &#40;1909&#46;43&#44; 3387&#46;79&#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">2153&#46;12 &#40;1764&#46;34&#44; 3182&#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">2756&#46;51 &#40;2026&#46;21&#44; 3477&#46;73&#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&#46;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;011</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD3<span class="elsevierStyleSup">&#43;</span>CD4<span class="elsevierStyleSup">&#43;</span>&#47;CD3<span class="elsevierStyleSup">&#43;</span> T cells &#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">38&#46;95 &#40;33&#46;45&#44; 46&#46;87&#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">38&#46;34 &#40;32&#46;49&#44; 44&#46;28&#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">39&#46;21 &#40;33&#46;63&#44; 48&#46;46&#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&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;265&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD3<span class="elsevierStyleSup">&#43;</span>CD8<span class="elsevierStyleSup">&#43;</span> T cells &#40;cells&#47;&#956;L&#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">1574&#46;63 &#40;1098&#46;77&#44; 2303&#46;42&#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">1306&#46;17 &#40;1016&#46;34&#44; 2158&#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">1720&#46;91 &#40;1161&#46;60&#44; 2311&#46;31&#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&#46;90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;057&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD3<span class="elsevierStyleSup">&#43;</span>CD8<span class="elsevierStyleSup">&#43;</span>&#47;CD3<span class="elsevierStyleSup">&#43;</span> T cells &#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">24&#46;20 &#40;19&#46;40&#44; 30&#46;42&#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">22&#46;48 &#40;18&#46;33&#44; 29&#46;52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#46;05 &#40;20&#46;06&#44; 31&#46;76&#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&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;239&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD19<span class="elsevierStyleSup">&#43;</span> B cells &#40;cells&#47;&#956;L&#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">1177&#46;54 &#40;781&#46;17&#44; 1651&#46;16&#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">1189&#46;19 &#40;809&#46;81&#44; 1576&#46;84&#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">1162&#46;49 &#40;769&#46;82&#44; 1693&#46;78&#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;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;757&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD19<span class="elsevierStyleSup">&#43;</span>&#47;CD3<span class="elsevierStyleSup">&#43;</span> T cells &#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">17&#46;96 &#40;12&#46;76&#44; 25&#46;01&#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&#46;87 &#40;14&#46;21&#44; 26&#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">17&#46;34 &#40;12&#46;62&#44; 23&#46;94&#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&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;272&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD16<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CD56<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>natural killer cells &#40;cells&#47;&#956;L&#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">588&#46;50 &#40;341&#46;16&#44; 1088&#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">569&#46;10 &#40;264&#46;61&#44; 935&#46;34&#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">617&#46;05 &#40;356&#46;85&#44; 1213&#46;06&#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;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;375&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD16<span class="elsevierStyleSup">&#43;</span>CD56<span class="elsevierStyleSup">&#43;&#47;</span>CD3<span class="elsevierStyleSup">&#43;</span> T cells &#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">9&#46;68 &#40;5&#46;83&#44; 14&#46;84&#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&#46;25 &#40;5&#46;74&#44; 14&#46;51&#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&#46;80 &#40;5&#46;89&#44; 14&#46;97&#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;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;877&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>pT &#40;cells&#47;&#956;L&#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">42&#46;39 &#40;24&#46;45&#44; 68&#46;27&#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\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">CD3<span class="elsevierStyleSup">&#43;</span>CD4<span class="elsevierStyleSup">&#43;</span> T cells&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
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">pT cells&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">C3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">C4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Monocytes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Globulin&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Direct bilirubin&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#947;-GT&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8722;0&#46;37<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD3<span class="elsevierStyleSup">&#43;</span> T cells&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD3<span class="elsevierStyleSup">&#43;</span>CD4<span class="elsevierStyleSup">&#43;</span> T cells&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;86<a class="elsevierStyleCrossRef" href="#tblfn0015">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>pT cells&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1796&#46;85 &#40;1&#46;32&#8211;2453118&#46;27&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yellowish-white&#47;clay colored&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#46;33 &#40;11&#46;50&#8211;170&#46;88&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t">22040&#46;43 &#40;10&#46;89&#8211;44625830&#46;07&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Basophil count</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">ref&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ref&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;16 &#40;0&#46;08&#8211;0&#46;31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Monocytes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;42 &#40;0&#46;04&#8211;4&#46;04&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Globulin&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;11 &#40;1&#46;03&#8211;1&#46;19&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Direct bilirubin&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD3<span class="elsevierStyleSup">&#43;</span> T cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&#46;00 &#40;1&#46;00&#8211;1&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;00 &#40;1&#46;00&#8211;1&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;303&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CD3<span class="elsevierStyleSup">&#43;</span>CD4<span class="elsevierStyleSup">&#43;</span> T cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&#46;00 &#40;1&#46;00&#8211;1&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;027&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;00 &#40;1&#46;00&#8211;1&#46;00&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>pT cells&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;01 &#40;1&#46;00&#8211;1&#46;02&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;065&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;02 &#40;1&#46;00&#8211;1&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;114&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>C3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#46;77 &#40;9&#46;31&#8211;383&#46;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">700&#46;87 &#40;9&#46;88&#8211;49699&#46;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>C4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1693&#46;33 &#40;3&#46;97&#8211;722224&#46;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;00 &#40;0&#46;00&#8211;0&#46;07&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;024</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2826387.png"
              ]
            ]
          ]
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Article information
ISSN: 24443824
Original language: English
DOI:10.1016/j.gastre.2021.02.010
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