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Serum Mac-2-binding protein glycosylation isomer predicts esophagogastric varices in cirrhotic patients with chronic hepatitis C virus infection treated with IFN-free direct-acting antiviral agent: M2BPGi levels predict varices in SVR patients
Kanako Kikukawaa, Sawako Uchida-Kobayashia, Akihiro Tamoria,d,
Corresponding author
atamori@med.osaka-cu.ac.jp

Corresponding author at: Department of Hepatology, Osaka City University Graduate School of Medicine and Department of Bool Transfusion, Osaka City University Hospital, 1-4-3, Asahi-machi, Abenoku, Osaka 545-8585, Japan.
, Kanako Yoshidaa, Kohei Kotania, Hiroyuki Motoyamaa, Ritsuzo Kozukaa, Atsushi Hagiharaa, Hideki Fujiib,c, Hiroyasu Morikawaa, Masaru Enomotoa, Yoshiki Murakamia, Norifumi Kawadaa,b
a Department of Hepatology, Endowed Department of Liver Cirrhosis Therapeutics, Japan
b Department of Premier Preventive Medicine, Japan
c Osaka City University Graduate School of Medicine, Japan
d Department of Bool Transfusion, Osaka City University Hospital, Japan
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic hepatitis C virus &#40;HCV&#41; infection is associated with significant morbidity and mortality due to liver cirrhosis and hepatocellular carcinoma &#40;HCC&#41;&#46; Current therapies with direct-acting antiviral agents &#40;DAAs&#41; result in high rates of sustained virological response &#40;SVR&#41;&#44; generally exceeding 90&#37; <a class="elsevierStyleCrossRefs" href="#bib0220">&#91;1&#44;2&#93;</a>&#46; In addition&#44; DAAs improve liver function even in advanced cirrhotic patients <a class="elsevierStyleCrossRefs" href="#bib0230">&#91;3&#8211;7&#93;</a>&#46; However&#44; it has been reported that HCC develops in cirrhotic patients even if SVR is achieved <a class="elsevierStyleCrossRefs" href="#bib0255">&#91;8&#44;9&#93;</a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Another important issue in cirrhotic patients is portal hypertension&#46; A recent study showed that hepatic wedge pressure decreased in SVR patients compared with before treatment <a class="elsevierStyleCrossRefs" href="#bib0265">&#91;10&#8211;12&#93;</a>&#46; However&#44; esophagogastric varices &#40;EGV&#41;&#44; a potentially fatal complication&#44; has not been sufficiently evaluated in SVR patients&#46; Among SVR patients treated with interferon &#40;IFN&#41;-based therapies&#44; the incidence of de novo EGV decreases and portal hypertension improves <a class="elsevierStyleCrossRefs" href="#bib0280">&#91;13&#44;14&#93;</a>&#46; However&#44; few studies have evaluated patients after achieving SVR using IFN-free DAA treatment <a class="elsevierStyleCrossRefs" href="#bib0270">&#91;11&#44;15&#93;</a>&#46; Clinically&#44; after DAA treatment&#44; there have been reports of persistent portal hypertension and EGV <a class="elsevierStyleCrossRef" href="#bib0270">&#91;11&#93;</a>&#46; Thus&#44; it is important for cirrhotic patients to undergo EGV monitoring even after achieving SVR&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Esophagogastroduodenoscopy &#40;EGD&#41; is the most reliable tool for evaluating EGV and should be performed periodically in cirrhotic patients after achieving SVR <a class="elsevierStyleCrossRefs" href="#bib0300">&#91;17&#8211;19&#93;</a>&#46; However&#44; EGD poses a physical and economic burden on patients&#46; Some patients refuse EGD despite understanding the importance of the procedure&#46; Therefore&#44; a noninvasive examination that can replace EGD is required&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Several reports have identified noninvasive variables that could predict the presence of EGV&#44; such as platelet count&#44; albumin concentration&#44; spleen&#44; and liver stiffness measured by elastography&#44; as well as ultrasonographic parameters including splenomegaly and portal vein diameter <a class="elsevierStyleCrossRefs" href="#bib0295">&#91;16&#44;20&#8211;25&#93;</a>&#46; However&#44; elastography and ultrasonographic techniques are not as useful in patients with obesity due to decreased reproducibility <a class="elsevierStyleCrossRef" href="#bib0345">&#91;26&#93;</a>&#46; Platelet count and albumin in nonalcoholic fatty liver disease &#40;NAFLD&#41; patients are higher than in HCV patients with advanced fibrosis <a class="elsevierStyleCrossRefs" href="#bib0350">&#91;27&#44;28&#93;</a>&#46; Since the number of obese and NAFLD patients is increasing&#44; a novel reliable marker is required to predict EGV&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Serum Mac-2-binding protein glycosylation isomer &#40;M2BPGi&#41; has been reported as a novel serum marker for assessing liver fibrosis in chronic viral hepatitis C patients <a class="elsevierStyleCrossRefs" href="#bib0260">&#91;9&#44;29&#8211;32&#93;</a>&#46; However&#44; the association between M2BPGi and EGV has not been explored&#46; The aim of this study was to evaluate M2BPGi as a serum marker of EGV in cirrhotic patients receiving IFN-free DAA treatment&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2</span><span class="elsevierStyleSectionTitle" id="sect0040">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0045">Patients</span><p id="par0030" class="elsevierStylePara elsevierViewall">This is a retrospective study of 180 cirrhotic patients&#44; among 843 patients with chronic HCV infection receiving antiviral therapy with an IFN-free DAA treatment in Osaka City University Hospital from September 2014 to March 2017&#46; The cirrhosis was clinically diagnosed by each attending physician based on platelet counts of under 100<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">3</span>&#47;&#956;l or liver stiffness of 16&#46;0<span class="elsevierStyleHsp" style=""></span>kPa&#44; as measured by transient elastography &#40;FibroScan&#174;&#41; <a class="elsevierStyleCrossRef" href="#bib0380">&#91;33&#93;</a>&#46; Among 180 patients&#44; 102 patients underwent EGD for screening EGV before or after DAA treatment&#46; This study was conducted according to the guidelines of the Declaration of Helsinki&#46; Written informed consent was obtained from all patients prior to treatment&#46; The study protocol was approved by the Ethics Committee of Osaka City University Hospital &#40;No&#46; 3685&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;2</span><span class="elsevierStyleSectionTitle" id="sect0050">Laboratory and ultrasonographic examinations</span><p id="par0035" class="elsevierStylePara elsevierViewall">Liver stiffness&#44; spleen index calculated as &#91;&#40;maximum width&#41;<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>&#40;maximum length&#41;&#93; of the spleen <a class="elsevierStyleCrossRef" href="#bib0385">&#91;34&#93;</a> aspartate aminotransferase &#40;AST&#41;&#44; alanine aminotransferase &#40;ALT&#41;&#44; platelet count&#44; albumin&#44; bilirubin&#44; prothrombin time &#40;PT&#41;&#44; M2BPGi&#44; ammonia &#40;NH3&#41;&#44; fibrosis-4 &#40;FIB-4&#41; index&#44; and AST-to-platelet ratio index &#40;APRI&#41; could discriminate patients at the start and end of IFN-free DAA treatment&#46; The FIB-4 index and APRI were also calculated <a class="elsevierStyleCrossRefs" href="#bib0390">&#91;35&#44;36&#93;</a>&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;3</span><span class="elsevierStyleSectionTitle" id="sect0055">Esophagogastric varices evaluation</span><p id="par0040" class="elsevierStylePara elsevierViewall">EGV was evaluated using EGD in 84 patients &#40;82&#37;&#41; before treatment in Cohort A&#44; in 66 &#40;65&#37;&#41; after treatment in Cohort B&#44; and in 48 &#40;47&#37;&#41; at both time points in Cohort C &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; All EGD procedures were performed by well-trained endoscopists within 1 year before the start and end of DAA treatment&#46; EGV were described according to the JGES classification&#59; F0&#44; no varicose appearance&#59; F1&#44; straight&#44; small-caliber varies&#59; F2&#44; moderately enlarged&#44; beady varies&#59; and F3&#44; markedly enlarged&#44; nodular&#44; or tumor-shaped varices <a class="elsevierStyleCrossRefs" href="#bib0400">&#91;37&#44;38&#93;</a>&#46; We divided patients into two groups&#58; an EGV-positive group &#40;F1&#47;F2&#47;F3&#44; red-color sign positive&#44; or history of treatment for varices&#41; and an EGV-negative group &#40;F0&#41;&#46; Furthermore&#44; in Cohort C we compared the F factor of EGV before and after DAA treatment and divided patients into three groups&#58; EGV-improvement&#44; EGV-invariant&#44; and EGV exacerbation groups&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;4</span><span class="elsevierStyleSectionTitle" id="sect0060">Measurement of serum Wisteria floribunda agglutinin positive M2BPGi levels</span><p id="par0045" class="elsevierStylePara elsevierViewall">M2BPGi was measured by sandwich immunoassay with anti-WFA and anti-M2BP antibodies using the fully automatic immunoanalyzer&#44; HISCL-2000i &#40;Sysmex Co&#46;&#44; Tokyo&#44; Japan&#41;&#44; as described previously <a class="elsevierStyleCrossRef" href="#bib0365">&#91;30&#93;</a>&#46; M2BPGi values conjugated to WFA were indexed with scored values using the following equation&#58; Cutoff index &#40;C&#46;O&#46;I&#41;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#40;&#91;M2BPGi&#93; sample<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>&#91;M2BPGi&#93; NC&#41;&#47;&#40;&#91;M2BPGi&#93; PC<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>&#91;M2BPGi&#93; NC&#41;&#44; where &#91;M2BPGi&#93; sample is the M2BPGi level in the serum sample&#44; PC is the positive control&#44; and NC is negative control&#46; The positive control was supplied as a calibration solution preliminarily standardized to yield a cutoff value of 1&#46;0 <a class="elsevierStyleCrossRef" href="#bib0375">&#91;32&#93;</a>&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;5</span><span class="elsevierStyleSectionTitle" id="sect0065">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Statistical analysis was performed with EZR software &#40;ver&#46; 1&#46;37&#59; Saitama Medical Center&#44; Jichi Medical University&#44; Saitama&#44; Japan&#41;&#46; Data are expressed as the mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;SD&#41; or as numbers&#46; Patient characteristics were evaluated using the Wilcoxon signed-rank test&#46; The characteristics of patients before and after treatment&#44; and the factors associated with EGV&#44; were compared using a Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test&#46; Details of EGV were evaluated using the Fisher test&#46; To compare the reduction in M2BPGi&#44; the Kruskal&#8211;Wallis test was used&#46; The utility of M2BPGi levels for diagnosing EGV was assessed using time-dependent receiver operating characteristic &#40;ROC&#41; curves&#46; Values of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 were considered statistically significant&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3</span><span class="elsevierStyleSectionTitle" id="sect0070">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0075">Baseline patient characteristics</span><p id="par0055" class="elsevierStylePara elsevierViewall">Patient characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The subjects consisted of 46 males and 56 females&#44; aged 46&#8211;88 years &#40;median age&#44; 69 years&#41;&#46; SVR was achieved in 97 &#40;95&#46;1&#37;&#41; of 102 patients&#46; Treatment regimens of IFN-free DAA were as follows&#58; 38 patients received 24 weeks of asunaprevir &#40;ASV&#41; and daclatasvir &#40;DCV&#41;&#59; 44 patients received 12 weeks of sofosbuvir &#40;SOF&#41; and ledipasvir &#40;LDV&#41;&#59; 2 patients received 12 weeks of ombitasvir &#40;OBV&#41; and paritaprevir &#40;PTV&#41; in combination with ritonavir&#59; 13 patients received 12 weeks of SOF and ribavirin &#40;RBV&#41;&#59; and 5 patients received 12 weeks of elbasvir &#40;EBR&#41; and grazoprevir &#40;GZR&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;2</span><span class="elsevierStyleSectionTitle" id="sect0080">Comparison of patient characteristics before and after DAA treatment</span><p id="par0060" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows patient characteristics before and after DAA treatment&#46; There were significant improvements in the spleen index &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41;&#44; AST &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; ALT &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; platelet count &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; albumin &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; M2BPGi &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; NH3 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;044&#41;&#44; FIB-4 index &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; and APRI &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; after treatment compared to before treatment&#46; There was a trend toward an improvement in liver stiffness&#44; and was no significant change in PT &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;054 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;28&#44; respectively&#41;&#46; Although Total-bilirubin levels increased after DAA treatment&#44; it was a change within the normal range &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;3</span><span class="elsevierStyleSectionTitle" id="sect0085">Factors associated with EGV before DAA treatment</span><p id="par0065" class="elsevierStylePara elsevierViewall">In Cohort A&#44; 84 patients underwent EGD before DAA treatment&#46; The EGV-positive group consisted of 41 patients and the EGV-negative group had 43 patients&#46; In the EGV-positive group&#44; 32 patients had esophageal varices &#40;EV&#41; &#40;F1&#47;F2&#47;F3&#44; 27&#47;5&#47;0&#41;&#44; 12 had gastric varices &#40;GV&#41; &#40;F1&#47;F2&#47;F3&#44; 9&#47;3&#47;0&#41;&#44; and 20 had a history of EGV treatment before DAA treatment&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows factors associated with EGV before DAA treatment&#46; Liver stiffness &#40;28&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;3 vs 20&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;9<span class="elsevierStyleHsp" style=""></span>kPa&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;042&#41; and M2BPGi levels &#40;7&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;2 vs 5&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;2<span class="elsevierStyleHsp" style=""></span>C&#46;O&#46;I&#46;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;034&#41; in the EGV-positive group were significantly higher than in the EGV-negative group&#46; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A shows an association between M2BPGi levels and EGV before DAA treatment&#46; To investigate the before-treatment level of M2BPGi to predict EGV&#44; ROC analysis was performed&#46; The area under the ROC curve &#40;AUROC&#41; for M2BPGi levels was 0&#46;63&#46; The cut-off value for before-treatment levels of M2BPGi was 7&#46;3 C&#46;O&#46;I&#46; Among patients with before-treatment levels of M2BPGi &#8807; 7&#46;3 C&#46;O&#46;I&#46;&#44; the proportion of those with EGV was significantly higher than in those with levels of M2BPGi<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>7&#46;3 C&#46;O&#46;I&#46; &#40;21&#47;32 and 19&#47;50&#44; respectively&#59; sensitivity&#44; 52&#37;&#59; specificity&#44; 74&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;015&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;4</span><span class="elsevierStyleSectionTitle" id="sect0090">Factors associated with EGV after DAA treatment</span><p id="par0075" class="elsevierStylePara elsevierViewall">In Cohort B&#44; 66 patients underwent EGD after DAA treatment&#46; The EGV-positive group consisted of 42 patients and the EGV-negative group had 24 patients&#46; In the EGV-positive group&#44; 31 patients had EV &#40;F1&#47;F2&#47;F3&#44; 29&#47;2&#47;0&#41;&#44; 8 had GV &#40;F1&#47;F2&#47;F3&#44; 6&#47;2&#47;0&#41;&#44; and 14 had a history of EGV treatment before DAA treatment&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows the factors associated with EGV after DAA treatment&#46; M2BPGi in the EGV-positive group was significantly higher than in the EGV-negative group after treatment &#40;5&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;6 and 2&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;2 C&#46;O&#46;I&#46;&#44; respectively&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B shows an association between M2BPGi levels and EGV after DAA treatment&#46; The AUROC for M2BPGi levels was 0&#46;76 and the cut-off for after-treatment levels of M2BPGi for prediction of EGV was 3&#46;4<span class="elsevierStyleHsp" style=""></span>C&#46;O&#46;I&#46; In patients with after-treatment levels of M2BPGi &#8807; 3&#46;4<span class="elsevierStyleHsp" style=""></span>C&#46;O&#46;I&#46;&#44; the proportion of those with EGV was significantly higher than that without EGV&#44; among patients with levels of M2BPGi<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>3&#46;4 C&#46;O&#46;I&#46; &#40;21&#47;25 and 9&#47;23&#44; respectively&#59; sensitivity&#44; 70&#37;&#59; specificity&#44; 78&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;5</span><span class="elsevierStyleSectionTitle" id="sect0095">Reduction of M2BPGi during DAA treatment in morphological change of EGV</span><p id="par0085" class="elsevierStylePara elsevierViewall">In Cohort C&#44; 48 patients evaluated for EGV by EGD before and after DAA treatment were divided into three groups according to the morphological change of EGV&#44; i&#46;e&#46;&#44; the change of F factor&#58; EGV improvement group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41;&#44; EGV invariant group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>32&#41;&#44; and EGV exacerbation group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41;&#46; We excluded eight patients with a history of EGV treatment during DAA treatment&#46; Among the 40 patients&#44; 29 had M2BPGi data at both times&#44; and the others did not have the data because paired serum was not left&#46; In all three groups&#44; namely&#44; the improvement group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#44; invariant group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#41;&#44; and exacerbation group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#44; after-treatment levels of M2BPGi were lower than before-treatment levels&#46; We analyzed the decrease in M2BPGi during DAA treatment in the improvement&#44; invariant and exacerbation groups to explore the association with EGV changes&#44; and found no significant difference among them &#40;&#8722;3&#46;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;92&#44; &#8722;2&#46;99<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;36&#44; and &#8722;2&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;30<span class="elsevierStyleHsp" style=""></span>C&#46;O&#46;I&#46;&#44; respectively&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;659&#41;&#46;</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">4</span><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">Our study showed that M2BPGi levels could serve as a noninvasive serum marker for the presence of EGV&#46; This is the first report showing the association between EGV and M2BPGi levels in cirrhotic patients treated with DAA&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">M2BPGi was associated with the stage of hepatic fibrosis in patients with chronic viral hepatitis&#44; NAFLD&#44; and primary biliary cholangitis&#44; and in particular with chronic hepatitis C <a class="elsevierStyleCrossRef" href="#bib0360">&#91;29&#93;</a>&#46; In addition&#44; M2BPGi was a marker for HCC in patients with chronic hepatitis C <a class="elsevierStyleCrossRef" href="#bib0410">&#91;39&#93;</a>&#44; and HCC in patients who have achieved SVR with DAAs <a class="elsevierStyleCrossRef" href="#bib0260">&#91;9&#93;</a>&#46; In our study&#44; we observed associations between M2BPGi and liver stiffness&#44; the FIB-4 index&#44; APRI before treatments&#44; and the FIB-4 index&#44; APRI after treatment &#40;data not shown&#41;&#46; Our results confirmed that M2BPGi was associated with hepatic fibrosis markers in cirrhotic patients&#44; and with EGV&#46; It was reported that FIB-4 index is reliable liver fibrosis marker&#46; However&#44; FIB-4 index was reported to be useful marker for distinguishing low fibrosis from fibrosis stage F0-F1 to F2 <a class="elsevierStyleCrossRef" href="#bib0415">&#91;40&#93;</a>&#46; EGV are observed in patients with more advanced fibrosis stage&#46; Therefore&#44; it was considered that FIB-4 index was not related to EGV in this study&#46; In addition&#44; it was reported that M2BPGi levels were associated with atherosclerosis <a class="elsevierStyleCrossRef" href="#bib0420">&#91;41&#93;</a> or pulmonary fibrosis <a class="elsevierStyleCrossRef" href="#bib0425">&#91;42&#93;</a>&#46; Although we did not examine atherosclerosis or pulmonary hypertension in this study&#44; EGV might be associated not only with liver fibrosis but also in conditions causing them&#46; Therefore&#44; we consider that only M2BPGi&#44; but not other fibrosis markers such as FIB-4 index and APRI&#44; was associated with EGV&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Previous studies have reported that laboratory tests&#44; such as platelet count and albumin&#44; were predictive serum markers of EGV <a class="elsevierStyleCrossRefs" href="#bib0315">&#91;20&#44;21&#93;</a>&#46; However&#44; we did not observe a significant association between these laboratory tests and EGV before or after treatment&#46; These results suggest that M2BPGi was a more reliable serum marker for screening of early stage EGV than the platelet count and albumin&#46; In general&#44; platelet count and albumin do not decrease in compensated cirrhotic patients&#46; Patients with decompensated cirrhosis were not enrolled in the previous study&#46; In the study&#44; patients with EV showed a median platelet count of 8&#46;5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">4</span>&#47;&#956;l and median albumin of 3&#46;3<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#46; A total of 71 patients had small EV &#40;F1&#41; and 47 had a large EV &#40;F2&#47;F3&#41; <a class="elsevierStyleCrossRef" href="#bib0330">&#91;23&#93;</a>&#46; Compared to the report&#44; platelet count and albumin levels were higher in our study&#46; In addition&#44; only 15&#46;6&#37; &#40;5&#47;32&#41; and 6&#46;5&#37; &#40;2&#47;31&#41; of patients showed F2 or F3 of EV before and after treatment&#44; respectively&#44; which was associated with severe portal hypertension in our patients&#46; Therefore&#44; it is possible that only M2BPGi was associated with EGV&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Several non-invasive imaging tests have been proposed for EGV screening&#46; Elastography has been reported to be a useful tool for EGV <a class="elsevierStyleCrossRefs" href="#bib0325">&#91;22&#8211;24&#93;</a>&#46; In the present study&#44; liver stiffness by elastography was associated with EGV before DAA therapy&#46; However&#44; it was difficult to evaluate this relationship after DAA therapy because of the small number of patients&#46; Spleen stiffness by transient elastography <a class="elsevierStyleCrossRef" href="#bib0335">&#91;24&#93;</a> and portal vein diameter measurements by ultrasonography <a class="elsevierStyleCrossRef" href="#bib0320">&#91;21&#93;</a> are also reported to be useful to evaluate EGV&#46; However&#44; in patients with ascites&#44; obesity&#44; or gastrointestinal gas&#44; it is difficult to obtain consistent results <a class="elsevierStyleCrossRefs" href="#bib0320">&#91;21&#44;24&#93;</a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Next&#44; we compared EGV between pre-DAA and post-DAA&#46; Some patients showed improved EGV after DAA therapy&#46; Previous IFN-based studies showed that EGV was not improved in patients who achieved SVR <a class="elsevierStyleCrossRefs" href="#bib0275">&#91;12&#44;43&#93;</a>&#46; Overall&#44; EGD was checked once every 2&#8211;3 years in patients with EGV after IFN-based treatments&#44; and EGV persisted in 32&#47;41 patients for a median 7&#46;6 years <a class="elsevierStyleCrossRef" href="#bib0430">&#91;43&#93;</a>&#46; Although some cirrhotic patients achieved SVR after IFN-based therapy&#44; DAA could increase the proportion of patients achieving SVR&#46; In Cohort C&#44; the decrease in M2BPGi was lower according to the morphological exacerbation of EGV &#40;EGV exacerbation group<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>EGV invariant group<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>EGV improvement group&#41;&#46; There was no significant relationship between changes in M2BPGi and EGV exacerbation or improvement&#46; The follow-up period of our study was within 1 year before treatment to 1 year after treatment&#44; and was not long enough to evaluate changes in EGV&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Our study had several limitations&#46; First&#44; the number of enrolled patients in our cohort was small&#46; Because DAA therapy was only approved in July 2014 and the observation period of cirrhotic patients treated with DAAs &#40;within 1 year before treatment to 1 year after treatment&#41; is relatively short&#44; some cirrhotic patients are not undergoing EGV screening&#46; Second&#44; in Japan&#44; DAA regimens were not permitted for cirrhotic patients with Child&#8211;Pugh stage B and C until February 2019&#46; Thus&#44; we could not evaluate-EGV in decompensated cirrhotic patients&#46; Third&#44; the dates of EGV screening&#44; liver stiffness and spleen index measurements&#44; and laboratory examinations differed because the physical and mental burden of patients was high if all examinations are performed on the same day&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In conclusion&#44; the M2BPGi level could be a new serum marker for the presence of EGV development before and after DAA treatment&#46; This novel surrogate marker for EGV can identify patients that require EGD&#46;<span class="elsevierStyleDefList"><span class="elsevierStyleSectionTitle" id="sect0105">Abbreviations</span><span class="elsevierStyleDefTerm">M2BPGi</span><span class="elsevierStyleDefDescription"><p id="par0125" class="elsevierStylePara elsevierViewall">Mac-2-binding protein glycosylation isomer</p></span><span class="elsevierStyleDefTerm">EGV</span><span class="elsevierStyleDefDescription"><p id="par0130" class="elsevierStylePara elsevierViewall">esophagogastric varices</p></span><span class="elsevierStyleDefTerm">HCV</span><span class="elsevierStyleDefDescription"><p id="par0135" class="elsevierStylePara elsevierViewall">hepatitis C virus</p></span><span class="elsevierStyleDefTerm">DAAs</span><span class="elsevierStyleDefDescription"><p id="par0140" class="elsevierStylePara elsevierViewall">direct-acting antiviral agents</p></span><span class="elsevierStyleDefTerm">SVR</span><span class="elsevierStyleDefDescription"><p id="par0145" class="elsevierStylePara elsevierViewall">sustained virologic response</p></span><span class="elsevierStyleDefTerm">HCC</span><span class="elsevierStyleDefDescription"><p id="par0150" class="elsevierStylePara elsevierViewall">hepatocellular carcinoma</p></span><span class="elsevierStyleDefTerm">IFN</span><span class="elsevierStyleDefDescription"><p id="par0155" class="elsevierStylePara elsevierViewall">interferon</p></span><span class="elsevierStyleDefTerm">EGD</span><span class="elsevierStyleDefDescription"><p id="par0160" class="elsevierStylePara elsevierViewall">esophagogastroduodenoscopy</p></span><span class="elsevierStyleDefTerm">NAFLD</span><span class="elsevierStyleDefDescription"><p id="par0165" class="elsevierStylePara elsevierViewall">nonalcoholic fatty liver disease</p></span><span class="elsevierStyleDefTerm">AST</span><span class="elsevierStyleDefDescription"><p id="par0170" class="elsevierStylePara elsevierViewall">aspartate aminotransferase</p></span><span class="elsevierStyleDefTerm">ALT</span><span class="elsevierStyleDefDescription"><p id="par0175" class="elsevierStylePara elsevierViewall">alanine aminotransferase</p></span><span class="elsevierStyleDefTerm">PT</span><span class="elsevierStyleDefDescription"><p id="par0180" class="elsevierStylePara elsevierViewall">prothrombin time</p></span><span class="elsevierStyleDefTerm">NH3</span><span class="elsevierStyleDefDescription"><p id="par0185" class="elsevierStylePara elsevierViewall">ammonia</p></span><span class="elsevierStyleDefTerm">FIB-4 index</span><span class="elsevierStyleDefDescription"><p id="par0190" class="elsevierStylePara elsevierViewall">fibrosis-4 index</p></span><span class="elsevierStyleDefTerm">APRI</span><span class="elsevierStyleDefDescription"><p id="par0195" class="elsevierStylePara elsevierViewall">AST-to-platelet ratio index</p></span><span class="elsevierStyleDefTerm">SD</span><span class="elsevierStyleDefDescription"><p id="par0200" class="elsevierStylePara elsevierViewall">standard deviation</p></span><span class="elsevierStyleDefTerm">ASV</span><span class="elsevierStyleDefDescription"><p id="par0205" class="elsevierStylePara elsevierViewall">asunaprevir</p></span><span class="elsevierStyleDefTerm">DCV</span><span class="elsevierStyleDefDescription"><p id="par0210" class="elsevierStylePara elsevierViewall">daclatasvir</p></span><span class="elsevierStyleDefTerm">SOF</span><span class="elsevierStyleDefDescription"><p id="par0215" class="elsevierStylePara elsevierViewall">sofosbuvir</p></span><span class="elsevierStyleDefTerm">LDV</span><span class="elsevierStyleDefDescription"><p id="par0220" class="elsevierStylePara elsevierViewall">ledipasvir</p></span><span class="elsevierStyleDefTerm">OBV</span><span class="elsevierStyleDefDescription"><p id="par0225" class="elsevierStylePara elsevierViewall">ombitasvir</p></span><span class="elsevierStyleDefTerm">PTV</span><span class="elsevierStyleDefDescription"><p id="par0230" class="elsevierStylePara elsevierViewall">paritaprevir</p></span><span class="elsevierStyleDefTerm">RBV</span><span class="elsevierStyleDefDescription"><p id="par0235" class="elsevierStylePara elsevierViewall">ribavirin</p></span><span class="elsevierStyleDefTerm">EBR</span><span class="elsevierStyleDefDescription"><p id="par0240" class="elsevierStylePara elsevierViewall">elbasvir</p></span><span class="elsevierStyleDefTerm">GZR</span><span class="elsevierStyleDefDescription"><p id="par0245" class="elsevierStylePara elsevierViewall">grazoprevir</p></span><span class="elsevierStyleDefTerm">EV</span><span class="elsevierStyleDefDescription"><p id="par0250" class="elsevierStylePara elsevierViewall">esophageal varices</p></span><span class="elsevierStyleDefTerm">GV</span><span class="elsevierStyleDefDescription"><p id="par0255" class="elsevierStylePara elsevierViewall">gastric varices</p></span><span class="elsevierStyleDefTerm">AUROC</span><span class="elsevierStyleDefDescription"><p id="par0260" class="elsevierStylePara elsevierViewall">area under the ROC curve</p></span></span></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interest</span><p id="par0265" class="elsevierStylePara elsevierViewall">Akihiro Tamori received lecture&#39;s fee from MSD&#46; Norifumi Kawada received research funding from Abbvie Inc&#46; and Gilead Sciences&#44; and lecture&#39;s fee from Abbvie Inc&#46;&#44; Gilead Sciences and MSD&#46; Dr&#46; Hideki Fujii belongs to the Endowed Department of Liver Cirrhosis Therapeutics donated by Gilead&#46; The other authors declare that they do not have anything to disclose regarding funding or conflict of interest with respect to this study&#46;</p></span></span>"
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              "titulo" => "Patients"
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              "titulo" => "Laboratory and ultrasonographic examinations"
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              "identificador" => "sec0025"
              "titulo" => "Esophagogastric varices evaluation"
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              "titulo" => "Measurement of serum Wisteria floribunda agglutinin positive M2BPGi levels"
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              "titulo" => "Statistical analysis"
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              "titulo" => "Baseline patient characteristics"
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            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Comparison of patient characteristics before and after DAA treatment"
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            2 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Factors associated with EGV before DAA treatment"
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            3 => array:2 [
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              "titulo" => "Factors associated with EGV after DAA treatment"
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              "identificador" => "sec0065"
              "titulo" => "Reduction of M2BPGi during DAA treatment in morphological change of EGV"
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          "titulo" => "Discussion"
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    "fechaRecibido" => "2020-02-15"
    "fechaAceptado" => "2020-04-23"
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            0 => "M2BPGi"
            1 => "Esophagogastric varices"
            2 => "Direct-acting antiviral agent"
            3 => "Liver cirrhosis"
            4 => "Hepatitis C virus"
            5 => "Sustained virological response"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">We examined whether Mac-2-binding protein glycosylation isomer &#40;M2BPGi&#41; levels could be a predictive marker for the presence of esophagogastric varices &#40;EGV&#41; in cirrhotic patients after hepatitis C virus &#40;HCV&#41; eradication with direct-acting antivirals &#40;DAAs&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A total of 102 cirrhotic patients with HCV infection treated with DAAs were enrolled&#46; Esophagogastroduodenoscopy was performed in 84 of the patients before treatment &#40;Cohort A&#41;&#44; in 66 after treatment &#40;Cohort B&#41;&#44; and in 48 at both time points &#40;Cohort C&#41;&#46; We examined factors associated with EGV before and after DAA treatment&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In Cohort A&#44; M2BPGi levels and liver stiffness were significantly higher in the EGV-positive group than the EGV-negative group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;034&#44; and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;042&#44; respectively&#41;&#46; The proportion of EGV-positive patients with before-treatment levels of M2BPGi &#8807; 7&#46;3 C&#46;O&#46;I&#46; was significantly higher than in patients with M2BPGi levels<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>7&#46;3 C&#46;O&#46;I&#46; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;015&#41;&#46; In Cohort B&#44; M2BPGi levels were significantly higher in the EGV-positive group than EGV-negative group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#46; The proportion of EGV-positive patients with after-treatment levels of M2BPGi &#8807; 3&#46;4 C&#46;O&#46;I&#46; was significantly higher than in patients with M2BPGi levels<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>3&#46;4<span class="elsevierStyleHsp" style=""></span>C&#46;O&#46;I&#46; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; In Cohort C&#44; M2BPGi levels decreased during DAA treatment regardless of EGV development&#44; but there was no significant difference in the reduction of M2BPGi among the EGV-improvement&#44; EGV-invariant&#44; and EGV-exacerbation groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;659&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">M2BPGi levels may be a novel serum marker for the presence of EGV before and after DAA treatment&#46;</p></span>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Serum M2BPGi values associated with EGV before and after treatment&#46; The Box and whisker charts of Serum Mac-2-binding protein glycosylation isomer &#40;M2BPGi&#41; values in the patients before &#40;A&#41; and after &#40;B&#41; treatment&#46; Box areas indicate interquartile range&#44; and horizontal bars in the interquartile range indicate median value&#46; Whiskers represent the minimum and maximum values&#46; M2BPGi levels were higher in the EGV-positive group than in the EGV-negative group before and after treatment &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;034&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#46; &#42;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; BMI&#44; body mass index&#59; SVR&#44; sustained virological response&#59; AST&#44; aspartate aminotransferase&#59; ALT&#44; alanine aminotransferase&#59; PT&#44; prothrombin time&#59; M2BPGi&#59; Wisteria floribunda agglutinin positive MAC-2-binding protein&#44; NH<span class="elsevierStyleInf">3</span>&#44; ammonia&#59; FIB-4 index&#44; fibrosis-4 index&#59; APRI&#44; AST-to-platelet ratio index&#59; ASV&#44; asunaprevir&#59; DCV&#44; daclatasvir&#59; SOF&#44; sofosbuvir&#59; LDV&#44; ledipasvir&#59; OBV&#44; ombitasvir&#59; PTV&#44; paritaprevir&#59; RBV&#44; ribavirin&#59; EBV&#44; elbasvir&#59; GZR&#44; grazoprevir&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Data are shown as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD &#40;range&#41;&#46;</p>"
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">BMI &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#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">23&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;249&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">Age &#40;years&#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">70<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>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">70<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;740&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">HCV genotype 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#47;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#47;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;291&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">Liver stiffness &#40;kPa&#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&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;042<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&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">Spleen index &#40;cm<span class="elsevierStyleSup">2</span>&#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">75&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>28&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;085&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">AST &#40;IU&#47;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">62<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>33&nbsp;\t\t\t\t\t\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;897&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">ALT &#40;IU&#47;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">52<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>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">56<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&nbsp;\t\t\t\t\t\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;897&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">Platelets &#40;10<span class="elsevierStyleSup">4</span>&#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">9&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;160&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">Albumin &#40;g&#47;dL&#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&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;985&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">Total-bilirubin &#40;mg&#47;dL&#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;91<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;40&nbsp;\t\t\t\t\t\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;226&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">PT &#40;&#37; of normal&#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">79&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;3&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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">82&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;219&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">M<span class="elsevierStyleInf">2</span>BPGi &#40;C&#46;O&#46;I&#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
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                  \t\t\t\t">7&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;2&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&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;2&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">0&#46;034<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;</a>&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">NH<span class="elsevierStyleInf">3</span> &#40;&#956;g&#47;dl&#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  " align="left" valign="\n
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                  \t\t\t\t">42<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&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  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;768&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">FIB-4 index&nbsp;\t\t\t\t\t\t\n
                  \t\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">7&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;9&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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;4&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  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;277&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">APRI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&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">2&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;318&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        ]
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        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
            "identificador" => "at4"
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">AST &#40;U&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">47<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>68&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;669&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">ALT &#40;U&#47;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
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>108&nbsp;\t\t\t\t\t\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;566&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</td><td class="td" title="\n
                  \t\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&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;4&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;238&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">Albumin &#40;g&#47;dL&#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">3&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;4&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  " align="char" valign="\n
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                  \t\t\t\t">0&#46;196&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">Total-bilirubin &#40;mg&#47;dL&#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;91<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;40&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  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;808&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">PT &#40;&#37; of normal&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">79&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\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">83&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;3&nbsp;\t\t\t\t\t\t\n
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                  \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;242&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">M<span class="elsevierStyleInf">2</span>BPGi &#40;C&#46;O&#46;I&#46;&#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">5&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;003<a class="elsevierStyleCrossRef" href="#tblfn0015">&#42;</a>&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">NH<span class="elsevierStyleInf">3</span> &#40;&#956;g&#47;dl&#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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&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">0&#46;825&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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Article information
ISSN: 16652681
Original language: English
DOI:10.1016/j.aohep.2020.04.002
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