Sensitivity and Specificity of Biochemical Tests for Diagnosis of Intrahepatic Cholestasis of Pregnancy

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Mahmoud" "autores" => array:9 [ 0 => array:2 [ "nombre" => "Mona A." "apellidos" => "Abu El-Makarem" ] 1 => array:2 [ "nombre" => "Atef F." "apellidos" => "El-Akad" ] 2 => array:2 [ "nombre" => "Moustafa M." "apellidos" => "Elian" ] 3 => array:2 [ "nombre" => "Tahra M." "apellidos" => "Sherif" ] 4 => array:2 [ "nombre" => "Ragaa A." "apellidos" => "El-shaheed" ] 5 => array:2 [ "nombre" => "Aliaa S." "apellidos" => "Abd EL Fatah" ] 6 => array:2 [ "nombre" => "Douaa M." "apellidos" => "Sayed" ] 7 => array:2 [ "nombre" => "Rania M." "apellidos" => "Bakry" ] 8 => array:2 [ "nombre" => "Aisha M." "apellidos" => "Mahmoud" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119310956?idApp=UINPBA00004N" "url" => "/16652681/0000001600000004/v1_201906150930/S1665268119310956/v1_201906150930/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119310932" "issn" => "16652681" "doi" => "10.5604/01.3001.0010.0293" "estado" => "S300" "fechaPublicacion" => "2017-07-01" "aid" => "70848" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2017;16:565-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 91 "formatos" => array:3 [ "EPUB" => 10 "HTML" => 34 "PDF" => 47 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Prevalence, Risk Factors, and Survival of Patients with Intrahepatic Cholangiocarcinoma" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "565" "paginaFinal" => "568" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 721 "Ancho" => 1000 "Tamanyo" => 42613 ] ] "descripcion" => array:1 [ "en" => "Survival curves (Kaplan-Meier) for 16 patients with intrahepatic cholangiocarcinomas TNM stage IV. The median survival time was 286 days (25th-75th interquartile range, 174-645 days)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Paulina Chinchilla-López, Nancy E. Aguilar-Olivos, Jaime García-Gómez, Karen K. Hernández-Alejandro, Fredy Chablé-Montero, Daniel Motola-Kuba, Tushar Patel, Nahum Méndez-Sánchez" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Paulina" "apellidos" => "Chinchilla-López" ] 1 => array:2 [ "nombre" => "Nancy E." "apellidos" => "Aguilar-Olivos" ] 2 => array:2 [ "nombre" => "Jaime" "apellidos" => "García-Gómez" ] 3 => array:2 [ "nombre" => "Karen K." "apellidos" => "Hernández-Alejandro" ] 4 => array:2 [ "nombre" => "Fredy" "apellidos" => "Chablé-Montero" ] 5 => array:2 [ "nombre" => "Daniel" "apellidos" => "Motola-Kuba" ] 6 => array:2 [ "nombre" => "Tushar" "apellidos" => "Patel" ] 7 => array:2 [ "nombre" => "Nahum" "apellidos" => "Méndez-Sánchez" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119310932?idApp=UINPBA00004N" "url" => "/16652681/0000001600000004/v1_201906150930/S1665268119310932/v1_201906150930/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "titulo" => "Sensitivity and Specificity of Biochemical Tests for Diagnosis of Intrahepatic Cholestasis of Pregnancy" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "569" "paginaFinal" => "573" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Kondrackiene Jurate, Zalinkevicius Rimantas, Sumskiene Jolanta, Gintautas Vladas, Kupcinskas Limas" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Kondrackiene" "apellidos" => "Jurate" "email" => array:1 [ 0 => "kondrackiene@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] 1 => array:3 [ "nombre" => "Zalinkevicius" "apellidos" => "Rimantas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "**" "identificador" => "aff2" ] ] ] 2 => array:3 [ "nombre" => "Sumskiene" "apellidos" => "Jolanta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] ] ] 3 => array:3 [ "nombre" => "Gintautas" "apellidos" => "Vladas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "***" "identificador" => "aff3" ] ] ] 4 => array:3 [ "nombre" => "Kupcinskas" "apellidos" => "Limas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "****" "identificador" => "aff4" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Gastroenterology. Lithuanian University of Health Sciences, Kaunas, Lithuania" "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Institute of Endocrinology. Lithuanian University of Health Sciences, Kaunas, Lithuania" "etiqueta" => "**" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Department of Obstetrics and Gynecology. Lithuanian University of Health Sciences, Kaunas, Lithuania" "etiqueta" => "***" "identificador" => "aff3" ] 3 => array:3 [ "entidad" => "Institute for Digestive Research. Lithuanian University of Health Sciences, Kaunas, Lithuania" "etiqueta" => "****" "identificador" => "aff4" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "textoCompleto" => "IntroductionIntrahepatic cholestasis of pregnancy (ICP) is a liver disorder unique to pregnancy. Pruritus with abnormal serum liver tests is the classical presentation of this disease.ICP predominantly occurs during the third trimester of pregnancy and disappears after delivery.<a class="elsevierStyleCrossRefs" href="#bib0010">1</a>-<a class="elsevierStyleCrossRef" href="#bib0020">3</a> The cause of ICP remains unknown. Current research on the pathogenesis of ICP focuses on genetic and hormonal factors.<a class="elsevierStyleCrossRef" href="#bib0025">4</a>,<a class="elsevierStyleCrossRef" href="#bib0030">5</a> While maternal prognosis is benign, there is a clear association between ICP and higher frequency of fetal distress, preterm delivery, and sudden intrauterine fetal death.<a class="elsevierStyleCrossRefs" href="#bib0035">6</a>-<a class="elsevierStyleCrossRef" href="#bib0065">12</a> An accurate test is needed to make timely diagnosis of this high-risk disorder. Serum bile acid measurement is considered the most sensitive laboratory abnormality in ICP; however, the levels of bile acids can fluctuate depending on the fasting state or gestational age.<a class="elsevierStyleCrossRefs" href="#bib0040">7</a>-<a class="elsevierStyleCrossRef" href="#bib0080">15</a> In addition, the turnaround time for receiving the laboratory results may be 1 or 2 weeks, making it difficult to await the results when deciding on induction of labour to reduce potential fetal complications. Serum liver enzymes are an important component for diagnosis but they may be normal in up to one third of cases. The upper normal limit of transaminases normal range was recently challenged, because possible modulators are often ignored in determining normal range.<a class="elsevierStyleCrossRef" href="#bib0085">16</a> Reference ranges for transaminases also require re-evaluation in pregnancy. No single reliable test can currently unequivocally distinguish all cases of ICP and other liver diseases or dermatoses of pregnancy. New diagnostic autotaxin test with high specificity and sensitivity was recently suggested; however, it may be hardly accessible in clinical practice.<a class="elsevierStyleCrossRef" href="#bib0090">17</a>,<a class="elsevierStyleCrossRef" href="#bib0095">18</a>The aim of our study was to estimate sensitivity and specificity of total and individual bile acids and to determine a more reliable cut-off value of transaminases activity for diagnosing ICP.Material and MethodsWe conducted a retrospective analysis of 61 pregnancies complicated by ICP. Inclusion criteria were: skin pruritus starting in the second or third trimester of pregnancy, and elevation of fasting serum total bile acids (TBA) > 10 μmol/L. Exclusion criteria were: chronic liver disease, hepatic viral infections (HAV, HBV, HCV, cytomegalovirus, Herpes simplex virus, Epstein-Barr virus), skin disease, allergic disease, symptomatic cholelithiasis. Patients with ICP were compared with 29 healthy consecutive pregnant women in the second or third trimester of pregnancy. Serum samples were collected prospectively from healthy pregnant and ICP patients. This patients’ cohort is a subgroup of our previously described cases.<a class="elsevierStyleCrossRef" href="#bib0100">19</a> In contrast to the previous study, in the actual retrospective analysis we include only patients having elevation of fasting serum total bile acids (TBA) > 10 μmol/L and control group of healthy pregnant women.All serum samples were processed in the same laboratory using the same methods and the same reference values: ALT- 5-45 U/L, AST- 5-40 U/L, alkaline phosphatase (AP)- 80- 290 U/L, gamma-glutamyl transpeptidase (γ-GT)- 5-35 U/L, total bilirubin 2.0-22.0- μmol/L, direct bilirubin- 0-6.8 μmol/L. Serum liver tests were determined using routine laboratory techniques. Fasting serum bile acids and cholic acid (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA), ursodeoxycholic (UDCA) were analyzed by gasliquid chromatography as described previously.<a class="elsevierStyleCrossRef" href="#bib0105">20</a> Fasting serum samples were stored at -20 °C until analyzed.Statistical analysisStatistical analysis was performed using the SPSS software version 20.0 (SPSS Inc., Chicago, IL, U.S.A.). Results are presented as median (range) or mean ± SD. The Mann-Whitney test for non-parametric data was used for comparison between groups. Cut-off levels for transaminases were determined. Area under the receiver operating characteristic curves (AUC) of all significant biochemical tests was calculated. The percentage of cases correctly classified by each diagnostic test as well as sensitivity, specificity, and positive and negative predictive values were calculated by discriminant analysis. The likelihood - ratio was calculated according to the formula: positive (LR + ) = sensitivity/1-specificity and negative (LR-) = 1-sensitivity/ specificity. In all cases, tests of significance were two-tailed, with a significance level < 0.05.ResultsThe clinical and biochemical characteristics of all patients are shown in the <a class="elsevierStyleCrossRef" href="#t0010">table 1</a>. There were no differences between groups regarding age, gestational age, total bilirubin, γ-GT, DCA, LCA, UDCA levels. Significantly higher levels of ALT, AST, AP, direct bilirubin, TBA, CA, CDCA were found in ICP patients when compared with healthy pregnant women.<elsevierMultimedia ident="t0010"></elsevierMultimedia>ICP patients had higher TBA levels than healthy women (32 vs. 6; p < 0.0001) due to increase in CA, CDCA. We observed TBA increase over upper normal limit (10 μmol/L) in 3 (10%) healthy women: 24.1, 10.8 and 10.7 μmol/L. CA was more elevated than CDCA in 41 (64%) ICP patients. In all healthy patients CDCA was higher than CA. Cholic/ chenodeoxycholic acid ratio was significantly higher in ICP patients compared to healthy pregnant women: 1.13 vs. 0.68; P < 0.00002. Calculation of the area under the curve (AUC) confirmed diagnostic accuracy of all significant biochemical parameters (<a class="elsevierStyleCrossRef" href="#t0015">Table 2</a>). No significant difference was found between sensitivity and specificity of serum TBA, CA and CDCA (<a class="elsevierStyleCrossRef" href="#t0020">Table 3</a>). CA/CDCA < 0.8 resulted in sensitivity 71.9% and specificity 79.3%.<elsevierMultimedia ident="t0015"></elsevierMultimedia><elsevierMultimedia ident="t0020"></elsevierMultimedia>We intended to establish a more reliable cut-off value of transaminases (<a class="elsevierStyleCrossRef" href="#t0025">Table 4</a>). A cut-off value of ALT 31 U/ L resulted in sensitivity 92.2%, specificity 100% (compared to current range of ALT 45 U/L- sensitivity 90.1%, specificity 100%), and accuracy with -LR of 0.078, a positive predictive value 100%; negative predictive value 85%. When cut-off value of AST 30 U/L was used, sensitivity 92.2%, specificity 100% (current range of AST 40 U/L -sensitivity 90.6%, specificity 100%), accuracy with LR- of 0.078, a positive predictive value 100%; negative predictive value 85%.<elsevierMultimedia ident="t0025"></elsevierMultimedia>DiscussionIntrahepatic cholestasis of pregnancy (ICP) is associated with increased risk of fetal complications. Therefore it is important to determine sensitive biochemical parameters that aid in timely diagnosis of this disorder. The present study did not confirm any single specific and sensitive marker for early diagnosis of ICP despite of significantly higher serum TBA and CA levels in addition with markedly elevated CA/CDCA ratio in ICP patients. We also intended to show that adoption of lower limits for transaminases values might increase the effectiveness of case finding for ICP.The biochemical parameter commonly used in the diagnosis of ICP is determination of the concentration of serum bile acids.<a class="elsevierStyleCrossRef" href="#bib0010">1</a>,<a class="elsevierStyleCrossRef" href="#bib0020">3</a> In the large prospective study of perinatal out-comes in women with severe ICP, significant relationships were found between the maternal serum bile acid level and preterm delivery, spontaneous preterm delivery, stillbirth. In this study, the risk of fetal complications was statistically increased at bile acid levels ≥40 μmol/L.<a class="elsevierStyleCrossRef" href="#bib0040">7</a> However, an unexplainable fetal death was reported at 39 weeks despite treatment with UDCA and low bile acid values.<a class="elsevierStyleCrossRef" href="#bib0110">21</a> On the other hand, a study from Argentina showed that asymptomatic hypercholanemia of pregnancy does not necessarily lead to ICP.<a class="elsevierStyleCrossRef" href="#bib0115">22</a> Recently, it has been reported that elevated autotaxin activity is a highly sensitive and specific diagnostic biomarker.<a class="elsevierStyleCrossRef" href="#bib0090">17</a>,<a class="elsevierStyleCrossRef" href="#bib0095">18</a> In contrast to the current gold standard for diagnosis total fasting serum bile salt levels, autotaxin is not influenced by food intake.<a class="elsevierStyleCrossRef" href="#bib0095">18</a>In our retrospective analysis we showed that TBA levels alone cannot serve as sensitive and specific marker of the disease. In agreement with other reports we found that the cholic acid level and cholic/chenodeoxycholic acid ratio were significantly higher in ICP patients compared to healthy pregnant women, indicating that CA and CA/ CDCA are more relevant in diagnosis of ICP. Huang, et al. assessed the addition of bile acid CA/CDCA ratio information in diagnosing ICP and found similar results that CA/CDCA ratio contributed little to the diagnosis of ICP. The use of total bile acid and transaminases without bile acid ratios decreased positive tests by less than 2%.<a class="elsevierStyleCrossRef" href="#bib0075">14</a>It is difficult to diagnose ICP only by routine biochemical tests, however, activity of transaminases and direct bilirubin concentration were considerably higher in ICP patients.Significant increase of AP also was noticed in ICP group compared to healthy patients, but AP is of poor diagnostic value due to placental and bone production. No difference was found in activity of γ-GT in both groups. Genes, et al. found that ALT has a significant, although weaker than level of serum bile acids, positive correlation with preterm delivery.<a class="elsevierStyleCrossRef" href="#bib0045">8</a>The level of transaminases elevation that is considered abnormal varies widely and has recently been brought into question.<a class="elsevierStyleCrossRef" href="#bib0085">16</a> The determination of a more reliable cut-off value for liver tests is very important for diagnosing liver disease. There is also a debate as to whether or not different cutoff's are indicated for normal ranges of liver enzymes. Recently, it has been suggested that the upper normal limit for ALT should be decreased to 30 IU/L for men and 19 IU/L for women.<a class="elsevierStyleCrossRef" href="#bib0120">23</a> Liver function tests can be lower in normal pregnancy than the reference ranges currently used. Girling, et al. in a prospective, cross-sectional study determines reference ranges for liver function tests that allow more precise identification of abnormal liver function in women with pre-eclampsia. Using the new ranges, the prevalence of elevated liver function tests was significantly higher in the pre-eclampsia group (54%) than in those with pregnancy induced hypertension (14%) (P < 0.01).<a class="elsevierStyleCrossRef" href="#bib0125">24</a> We evaluated significance of lower cut-off values for ALT (31 U/L) and AST (30 U/L) in our ICP patients. Decreasing the ULN values for transaminases levels only minimally increased the ability to diagnose ICP. There are some limitations to our retrospective analysis. Relatively small number of healthy controls was included into study and specificity of the test was likely to be lower if a larger control set was used. ICP is a diagnosis of exclusion. In our study we excluded patients with other hepatobiliary and skin diseases. However, in a real world situation there may be coexisting latent hepatobiliary diseases during pregnancy that could also affect the specificity of the tests.<a class="elsevierStyleCrossRef" href="#bib0130">25</a>,<a class="elsevierStyleCrossRef" href="#bib0135">26</a>ConclusionThe present study did not reveal any single specific and sensitive marker for reliable diagnosis of ICP despite of significantly higher serum TBA and CA levels and CA:CDCA ratio in ICP patients in comparison to healthy pregnant woman. Establishment of lower cut-off values for transaminases activity might only minimally increase the accuracy of diagnosing ICP.Abbreviations<ul class="elsevierStyleList" id="l0010"><li class="elsevierStyleListItem" id="u0010">•ALT: alanine aminotransferase.</li><li class="elsevierStyleListItem" id="u0015">•AP: alkaline phosphatase.</li><li class="elsevierStyleListItem" id="u0020">•AST: aspartate aminotransferase.</li><li class="elsevierStyleListItem" id="u0025">•CDCA: chenodeoxycholic acid.</li><li class="elsevierStyleListItem" id="u0030">•CA: cholic acid.</li><li class="elsevierStyleListItem" id="u0035">•DCA: deoxycholic acid.</li><li class="elsevierStyleListItem" id="u0040">•γ-GT: gamma-glutamyl transpeptidase.</li><li class="elsevierStyleListItem" id="u0045">•ICP: intrahepatic cholestasis of pregnancy.</li><li class="elsevierStyleListItem" id="u0050">•LCA: lithocholic acid.</li><li class="elsevierStyleListItem" id="u0055">•TBA: total bile acids.</li><li class="elsevierStyleListItem" id="u0060">•UDCA: ursodeoxycholic acid.</li></ul>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1207265" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abs0010" "titulo" => "Background and aim" ] 1 => array:2 [ "identificador" => "abs0015" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abs0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abs0025" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1124311" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "s0010" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "s0015" "titulo" => "Material and Methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "s0020" "titulo" => "Statistical analysis" ] ] ] 4 => array:2 [ "identificador" => "s0025" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "s0030" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "s0035" "titulo" => "Conclusion" ] 7 => array:2 [ "identificador" => "s0040" "titulo" => "Abbreviations" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-09-18" "fechaAceptado" => "2016-12-22" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1124311" "palabras" => array:5 [ 0 => "Intrahepatic cholestasis" 1 => "Pregnancy" 2 => "Diagnostics" 3 => "Serum bile acids" 4 => "Transaminases" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Background and aimIntrahepatic cholestasis of pregnancy (ICP) is linked with increased risk of fetal complications. An accurate diagnostic test is needed to diagnose this disorder on time. We aimed to assess sensitivity and specificity of laboratory tests used for diagnosis of intrahepatic cholestasis of pregnancy and determine more reliable cut-off values of transaminases. Material and methodsSixty one symptomatic patients with ICP and 29 healthy pregnant women were included in the retrospective analysis. ResultsICP patients had higher total bile acids (TBA) levels than healthy women (32 vs. 6; P < 0.0001) due to increase in cholic acid (CA) and chenodeoxycholic acid (CDCA). CA/CDCA ratio was significantly higher in ICP patients compared to healthy pregnant women (1.13 vs. 0.68; P < 0.00002). TBA, CA, CDCA and CA/CDCA ratio demonstrate the following sensitivity (94%, 96%, 89%, 71.9%) and specificity (63%, 63%, 59%, 79.3%, respectively) for ICP diagnosis. Lowering cut-off values for ALT (31 U/ L) and AST (30 U/L) resulted only in minimal increase of sensitivity to 92.2% vs. 90.1% for ALT and to 92.2%, vs. 90.6% for AST. ConclusionThe present study did not reveal any single specific and sensitive marker for reliable diagnosis of ICP. Establishment of lower cut-off values for transaminases activity might only minimally increase the accuracy of diagnosing ICP." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abs0010" "titulo" => "Background and aim" ] 1 => array:2 [ "identificador" => "abs0015" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abs0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abs0025" "titulo" => "Conclusion" ] ] ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "t0010" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Values are median (range) or mean ± SD. ALT: alanine aminotransferase. AST: aspartate aminotransferase. AP: alkaline phosphatase. γ-GT: gammaglutamyl transpeptidase. TBA: total bile acid. CA: cholic acid. CDCA: chenodeoxycholic acid. DCA: deoxycholic acid. UDCA: ursodeoxycholic acid. LCA: lithocholic acid. ICP: cholestasis of pregnancy." "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient characteristics Age \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">28.59 ± 5.71 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Healthy pregnant women (n = 29) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p value 0.723 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gestational age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38.98 ± 2.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34.07± 4.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.367 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">158 (15-7014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (11-31) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">113 (18-554) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (10-30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AP U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">356 (150-900) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">210 (156-245) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">γ-GT U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (8-89) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (19-30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.490 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bilirubin μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (4-94) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (9-16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.483 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Direct bilirubin μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (1-68) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (1-3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TBA μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (11-151) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (3-24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CA μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (0-98) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (1-7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CDCA μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (1-568) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (1-10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DCA μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (0-222) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (1-5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.792 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UDCA μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (0-6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0-1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.982 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LCA μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (0-4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0-1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.135 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CA/CDCA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.13 (0.83-1.60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.68 (0.52- 0.81) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.00002 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2060664.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Clinical, biochemical characteristics of patients with intrahepatic cholestasis of pregnancy and healthy pregnant women." ] ] 1 => array:8 [ "identificador" => "t0015" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "ALT: alanine aminotransferase. AST: aspartate aminotransferase. AP: alkaline phosphatise. TBA: total bile acid. CA: cholic acid. CDCA: chenodeoxycholic acid." "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable(s) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Area \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95% CI \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.916 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.91-1.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.986 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.98-1.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AP U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.976 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.96-0.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Direct bilirubin μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.922 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.77-0.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TBA μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.853 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.78-0.93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CA μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.789 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.61-0.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CDCA μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.692 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.58-0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CA/CDCA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.803 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.69-0.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2060663.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Area under the curve (AUC) of all significant biochemical parameters." ] ] 2 => array:8 [ "identificador" => "t0020" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "PPV: positive predictive value. NPV: negative predictive value. TBA: total bile acid. CA: cholic acid. CDCA: chenodeoxycholic acid." "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sensitivity % \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Specificity % \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Predictive value % \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Likelihood-ratio \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PPV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NPV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TBA μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">76.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.09 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CA μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">96.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62.79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">93.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CDCA μmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">88.89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58.97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.19 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2060666.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Sensitivity, specificity, predictive value and likelihood-ratio of total and individual bile acids for the diagnosis of ICP." ] ] 3 => array:8 [ "identificador" => "t0025" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "ALT: alanine aminotransferase. AST: aspartate aminotransferase." "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ALT U/L \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">New cut-off value 31 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sensitivity 92.2 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95% CI 82.7-97.4 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Specificity 100.0 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95% CI 87.9-100.0 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p < 0.0001 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">92.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82.7-97.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87.9-100.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< 0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2060665.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Validity of new cut- off levels of transaminases for diagnosis of ICP." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0010" "bibliografiaReferencia" => array:26 [ 0 => array:3 [ "identificador" => "bib0010" "etiqueta" => "1." 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Kondrackiene Jurate

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, Zalinkevicius Rimantas**, Sumskiene Jolanta*, Gintautas Vladas***, Kupcinskas Limas****

* Department of Gastroenterology. Lithuanian University of Health Sciences, Kaunas, Lithuania

** Institute of Endocrinology. Lithuanian University of Health Sciences, Kaunas, Lithuania

*** Department of Obstetrics and Gynecology. Lithuanian University of Health Sciences, Kaunas, Lithuania

**** Institute for Digestive Research. Lithuanian University of Health Sciences, Kaunas, Lithuania

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there is a clear association between ICP and higher frequency of fetal distress&#44; preterm delivery&#44; and sudden intrauterine fetal death&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">12</span></a> An accurate test is needed to make timely diagnosis of this high-risk disorder&#46; Serum bile acid measurement is considered the most sensitive laboratory abnormality in ICP&#59; however&#44; the levels of bile acids can fluctuate depending on the fasting state or gestational age&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">7</span></a><span class="elsevierStyleSup">-</span><a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">15</span></a> In addition&#44; the turnaround time for receiving the laboratory results may be 1 or 2 weeks&#44; making it difficult to await the results when deciding on induction of labour to reduce potential fetal complications&#46; Serum liver enzymes are an important component for diagnosis but they may be normal in up to one third of cases&#46; The upper normal limit of transaminases normal range was recently challenged&#44; because possible modulators are often ignored in determining normal range&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">16</span></a> Reference ranges for transaminases also require re-evaluation in pregnancy&#46; No single reliable test can currently unequivocally distinguish all cases of ICP and other liver diseases or dermatoses of pregnancy&#46; New diagnostic autotaxin test with high specificity and sensitivity was recently suggested&#59; however&#44; it may be hardly accessible in clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">18</span></a></p><p id="p0020" class="elsevierStylePara elsevierViewall">The aim of our study was to estimate sensitivity and specificity of total and individual bile acids and to determine a more reliable cut-off value of transaminases activity for diagnosing ICP&#46;</p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Material and Methods</span><p id="p0025" class="elsevierStylePara elsevierViewall">We conducted a retrospective analysis of 61 pregnancies complicated by ICP&#46; Inclusion criteria were&#58; skin pruritus starting in the second or third trimester of pregnancy&#44; and elevation of fasting serum total bile acids &#40;TBA&#41; &#62; 10 &#956;mol&#47;L&#46; Exclusion criteria were&#58; chronic liver disease&#44; hepatic viral infections &#40;HAV&#44; HBV&#44; HCV&#44; cytomegalovirus&#44; Herpes simplex virus&#44; Epstein-Barr virus&#41;&#44; skin disease&#44; allergic disease&#44; symptomatic cholelithiasis&#46; Patients with ICP were compared with 29 healthy consecutive pregnant women in the second or third trimester of pregnancy&#46; Serum samples were collected prospectively from healthy pregnant and ICP patients&#46; This patients&#8217; cohort is a subgroup of our previously described cases&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">19</span></a> In contrast to the previous study&#44; in the actual retrospective analysis we include only patients having elevation of fasting serum total bile acids &#40;TBA&#41; &#62; 10 &#956;mol&#47;L and control group of healthy pregnant women&#46;</p><p id="p0030" class="elsevierStylePara elsevierViewall">All serum samples were processed in the same laboratory using the same methods and the same reference values&#58; ALT- 5-45 U&#47;L&#44; AST- 5-40 U&#47;L&#44; alkaline phosphatase &#40;AP&#41;- 80- 290 U&#47;L&#44; gamma-glutamyl transpeptidase &#40;&#947;-GT&#41;- 5-35 U&#47;L&#44; total bilirubin 2&#46;0-22&#46;0- &#956;mol&#47;L&#44; direct bilirubin- 0-6&#46;8 &#956;mol&#47;L&#46; Serum liver tests were determined using routine laboratory techniques&#46; Fasting serum bile acids and cholic acid &#40;CA&#41;&#44; chenodeoxycholic &#40;CDCA&#41;&#44; deoxycholic &#40;DCA&#41;&#44; lithocholic &#40;LCA&#41;&#44; ursodeoxycholic &#40;UDCA&#41; were analyzed by gasliquid chromatography as described previously&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">20</span></a> Fasting serum samples were stored at -20 &#176;C until analyzed&#46;</p><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Statistical analysis</span><p id="p0035" class="elsevierStylePara elsevierViewall">Statistical analysis was performed using the SPSS software version 20&#46;0 &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#44; U&#46;S&#46;A&#46;&#41;&#46; Results are presented as median &#40;range&#41; or mean &#177; SD&#46; The Mann-Whitney test for non-parametric data was used for comparison between groups&#46; Cut-off levels for transaminases were determined&#46; Area under the receiver operating characteristic curves &#40;AUC&#41; of all significant biochemical tests was calculated&#46; The percentage of cases correctly classified by each diagnostic test as well as sensitivity&#44; specificity&#44; and positive and negative predictive values were calculated by discriminant analysis&#46; The likelihood - ratio was calculated according to the formula&#58; positive &#40;LR &#43; &#41; &#61; sensitivity&#47;1-specificity and negative &#40;LR-&#41; &#61; 1-sensitivity&#47; specificity&#46; In all cases&#44; tests of significance were two-tailed&#44; with a significance level &#60; 0&#46;05&#46;</p></span></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Results</span><p id="p0040" class="elsevierStylePara elsevierViewall">The clinical and biochemical characteristics of all patients are shown in the <a class="elsevierStyleCrossRef" href="#t0010">table 1</a>&#46; There were no differences between groups regarding age&#44; gestational age&#44; total bilirubin&#44; &#947;-GT&#44; DCA&#44; LCA&#44; UDCA levels&#46; Significantly higher levels of ALT&#44; AST&#44; AP&#44; direct bilirubin&#44; TBA&#44; CA&#44; CDCA were found in ICP patients when compared with healthy pregnant women&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><p id="p0045" class="elsevierStylePara elsevierViewall">ICP patients had higher TBA levels than healthy women &#40;32 <span class="elsevierStyleItalic">vs</span>&#46; 6&#59; p &#60; 0&#46;0001&#41; due to increase in CA&#44; CDCA&#46; We observed TBA increase over upper normal limit &#40;10 &#956;mol&#47;L&#41; in 3 &#40;10&#37;&#41; healthy women&#58; 24&#46;1&#44; 10&#46;8 and 10&#46;7 &#956;mol&#47;L&#46; CA was more elevated than CDCA in 41 &#40;64&#37;&#41; ICP patients&#46; In all healthy patients CDCA was higher than CA&#46; Cholic&#47; chenodeoxycholic acid ratio was significantly higher in ICP patients compared to healthy pregnant women&#58; 1&#46;13 <span class="elsevierStyleItalic">vs</span>&#46; 0&#46;68&#59; P &#60; 0&#46;00002&#46; Calculation of the area under the curve &#40;AUC&#41; confirmed diagnostic accuracy of all significant biochemical parameters &#40;<a class="elsevierStyleCrossRef" href="#t0015">Table 2</a>&#41;&#46; No significant difference was found between sensitivity and specificity of serum TBA&#44; CA and CDCA &#40;<a class="elsevierStyleCrossRef" href="#t0020">Table 3</a>&#41;&#46; CA&#47;CDCA &#60; 0&#46;8 resulted in sensitivity 71&#46;9&#37; and specificity 79&#46;3&#37;&#46;</p><elsevierMultimedia ident="t0015"></elsevierMultimedia><elsevierMultimedia ident="t0020"></elsevierMultimedia><p id="p0050" class="elsevierStylePara elsevierViewall">We intended to establish a more reliable cut-off value of transaminases &#40;<a class="elsevierStyleCrossRef" href="#t0025">Table 4</a>&#41;&#46; A cut-off value of ALT 31 U&#47; L resulted in sensitivity 92&#46;2&#37;&#44; specificity 100&#37; &#40;compared to current range of ALT 45 U&#47;L- sensitivity 90&#46;1&#37;&#44; specificity 100&#37;&#41;&#44; and accuracy with -LR of 0&#46;078&#44; a positive predictive value 100&#37;&#59; negative predictive value 85&#37;&#46; When cut-off value of AST 30 U&#47;L was used&#44; sensitivity 92&#46;2&#37;&#44; specificity 100&#37; &#40;current range of AST 40 U&#47;L -sensitivity 90&#46;6&#37;&#44; specificity 100&#37;&#41;&#44; accuracy with LR- of 0&#46;078&#44; a positive predictive value 100&#37;&#59; negative predictive value 85&#37;&#46;</p><elsevierMultimedia ident="t0025"></elsevierMultimedia></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Discussion</span><p id="p0055" class="elsevierStylePara elsevierViewall">Intrahepatic cholestasis of pregnancy &#40;ICP&#41; is associated with increased risk of fetal complications&#46; Therefore it is important to determine sensitive biochemical parameters that aid in timely diagnosis of this disorder&#46; The present study did not confirm any single specific and sensitive marker for early diagnosis of ICP despite of significantly higher serum TBA and CA levels in addition with markedly elevated CA&#47;CDCA ratio in ICP patients&#46; We also intended to show that adoption of lower limits for transaminases values might increase the effectiveness of case finding for ICP&#46;</p><p id="p0060" class="elsevierStylePara elsevierViewall">The biochemical parameter commonly used in the diagnosis of ICP is determination of the concentration of serum bile acids&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">3</span></a> In the large prospective study of perinatal out-comes in women with severe ICP&#44; significant relationships were found between the maternal serum bile acid level and preterm delivery&#44; spontaneous preterm delivery&#44; stillbirth&#46; In this study&#44; the risk of fetal complications was statistically increased at bile acid levels &#8805;40 &#956;mol&#47;L&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">7</span></a> However&#44; an unexplainable fetal death was reported at 39 weeks despite treatment with UDCA and low bile acid values&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">21</span></a> On the other hand&#44; a study from Argentina showed that asymptomatic hypercholanemia of pregnancy does not necessarily lead to ICP&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">22</span></a> Recently&#44; it has been reported that elevated autotaxin activity is a highly sensitive and specific diagnostic biomarker&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">18</span></a> In contrast to the current gold standard for diagnosis total fasting serum bile salt levels&#44; autotaxin is not influenced by food intake&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">18</span></a></p><p id="p0065" class="elsevierStylePara elsevierViewall">In our retrospective analysis we showed that TBA levels alone cannot serve as sensitive and specific marker of the disease&#46; In agreement with other reports we found that the cholic acid level and cholic&#47;chenodeoxycholic acid ratio were significantly higher in ICP patients compared to healthy pregnant women&#44; indicating that CA and CA&#47; CDCA are more relevant in diagnosis of ICP&#46; Huang&#44; <span class="elsevierStyleItalic">et al&#46;</span> assessed the addition of bile acid CA&#47;CDCA ratio information in diagnosing ICP and found similar results that CA&#47;CDCA ratio contributed little to the diagnosis of ICP&#46; The use of total bile acid and transaminases without bile acid ratios decreased positive tests by less than 2&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">14</span></a></p><p id="p0070" class="elsevierStylePara elsevierViewall">It is difficult to diagnose ICP only by routine biochemical tests&#44; however&#44; activity of transaminases and direct bilirubin concentration were considerably higher in ICP patients&#46;</p><p id="p0075" class="elsevierStylePara elsevierViewall">Significant increase of AP also was noticed in ICP group compared to healthy patients&#44; but AP is of poor diagnostic value due to placental and bone production&#46; No difference was found in activity of &#947;-GT in both groups&#46; Genes&#44; et al&#46; found that ALT has a significant&#44; although weaker than level of serum bile acids&#44; positive correlation with preterm delivery&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">8</span></a></p><p id="p0080" class="elsevierStylePara elsevierViewall">The level of transaminases elevation that is considered abnormal varies widely and has recently been brought into question&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">16</span></a> The determination of a more reliable cut-off value for liver tests is very important for diagnosing liver disease&#46; There is also a debate as to whether or not different cutoff&#39;s are indicated for normal ranges of liver enzymes&#46; Recently&#44; it has been suggested that the upper normal limit for ALT should be decreased to 30 IU&#47;L for men and 19 IU&#47;L for women&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">23</span></a> Liver function tests can be lower in normal pregnancy than the reference ranges currently used&#46; Girling&#44; et al&#46; in a prospective&#44; cross-sectional study determines reference ranges for liver function tests that allow more precise identification of abnormal liver function in women with pre-eclampsia&#46; Using the new ranges&#44; the prevalence of elevated liver function tests was significantly higher in the pre-eclampsia group &#40;54&#37;&#41; than in those with pregnancy induced hypertension &#40;14&#37;&#41; &#40;P &#60; 0&#46;01&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">24</span></a> We evaluated significance of lower cut-off values for ALT &#40;31 U&#47;L&#41; and AST &#40;30 U&#47;L&#41; in our ICP patients&#46; Decreasing the ULN values for transaminases levels only minimally increased the ability to diagnose ICP&#46; There are some limitations to our retrospective analysis&#46; Relatively small number of healthy controls was included into study and specificity of the test was likely to be lower if a larger control set was used&#46; ICP is a diagnosis of exclusion&#46; In our study we excluded patients with other hepatobiliary and skin diseases&#46; However&#44; in a real world situation there may be coexisting latent hepatobiliary diseases during pregnancy that could also affect the specificity of the tests&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">26</span></a></p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Conclusion</span><p id="p0085" class="elsevierStylePara elsevierViewall">The present study did not reveal any single specific and sensitive marker for reliable diagnosis of ICP despite of significantly higher serum TBA and CA levels and CA&#58;CDCA ratio in ICP patients in comparison to healthy pregnant woman&#46; Establishment of lower cut-off values for transaminases activity might only minimally increase the accuracy of diagnosing ICP&#46;</p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Abbreviations</span><p id="p0090" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="l0010"><li class="elsevierStyleListItem" id="u0010"><span class="elsevierStyleLabel">&#8226;</span><p id="p0095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">ALT&#58;</span> alanine aminotransferase&#46;</p></li><li class="elsevierStyleListItem" id="u0015"><span class="elsevierStyleLabel">&#8226;</span><p id="p0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">AP&#58;</span> alkaline phosphatase&#46;</p></li><li class="elsevierStyleListItem" id="u0020"><span class="elsevierStyleLabel">&#8226;</span><p id="p0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">AST&#58;</span> aspartate aminotransferase&#46;</p></li><li class="elsevierStyleListItem" id="u0025"><span class="elsevierStyleLabel">&#8226;</span><p id="p0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">CDCA&#58;</span> chenodeoxycholic acid&#46;</p></li><li class="elsevierStyleListItem" id="u0030"><span class="elsevierStyleLabel">&#8226;</span><p id="p0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">CA&#58;</span> cholic acid&#46;</p></li><li class="elsevierStyleListItem" id="u0035"><span class="elsevierStyleLabel">&#8226;</span><p id="p0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">DCA&#58;</span> deoxycholic acid&#46;</p></li><li class="elsevierStyleListItem" id="u0040"><span class="elsevierStyleLabel">&#8226;</span><p id="p0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">&#947;-GT&#58;</span> gamma-glutamyl transpeptidase&#46;</p></li><li class="elsevierStyleListItem" id="u0045"><span class="elsevierStyleLabel">&#8226;</span><p id="p0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">ICP&#58;</span> intrahepatic cholestasis of pregnancy&#46;</p></li><li class="elsevierStyleListItem" id="u0050"><span class="elsevierStyleLabel">&#8226;</span><p id="p0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">LCA&#58;</span> lithocholic acid&#46;</p></li><li class="elsevierStyleListItem" id="u0055"><span class="elsevierStyleLabel">&#8226;</span><p id="p0140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">TBA&#58;</span> total bile acids&#46;</p></li><li class="elsevierStyleListItem" id="u0060"><span class="elsevierStyleLabel">&#8226;</span><p id="p0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">UDCA&#58;</span> ursodeoxycholic acid&#46;</p></li></ul></p></span></span>"
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    "fechaRecibido" => "2016-09-18"
    "fechaAceptado" => "2016-12-22"
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          "palabras" => array:5 [
            0 => "Intrahepatic cholestasis"
            1 => "Pregnancy"
            2 => "Diagnostics"
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    "resumen" => array:1 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015"><span class="elsevierStyleBold">Background and aim</span></span><p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">Intrahepatic cholestasis of pregnancy &#40;ICP&#41; is linked with increased risk of fetal complications&#46; An accurate diagnostic test is needed to diagnose this disorder on time&#46; We aimed to assess sensitivity and specificity of laboratory tests used for diagnosis of intrahepatic cholestasis of pregnancy and determine more reliable cut-off values of transaminases&#46;</p></span> <span id="abs0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020"><span class="elsevierStyleBold">Material and methods</span></span><p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">Sixty one symptomatic patients with ICP and 29 healthy pregnant women were included in the retrospective analysis&#46;</p></span> <span id="abs0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025"><span class="elsevierStyleBold">Results</span></span><p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">ICP patients had higher total bile acids &#40;TBA&#41; levels than healthy women &#40;32 <span class="elsevierStyleItalic">vs</span>&#46; 6&#59; P &#60; 0&#46;0001&#41; due to increase in cholic acid &#40;CA&#41; and chenodeoxycholic acid &#40;CDCA&#41;&#46; CA&#47;CDCA ratio was significantly higher in ICP patients compared to healthy pregnant women &#40;1&#46;13 <span class="elsevierStyleItalic">vs</span>&#46; 0&#46;68&#59; P &#60; 0&#46;00002&#41;&#46; TBA&#44; CA&#44; CDCA and CA&#47;CDCA ratio demonstrate the following sensitivity &#40;94&#37;&#44; 96&#37;&#44; 89&#37;&#44; 71&#46;9&#37;&#41; and specificity &#40;63&#37;&#44; 63&#37;&#44; 59&#37;&#44; 79&#46;3&#37;&#44; respectively&#41; for ICP diagnosis&#46; Lowering cut-off values for ALT &#40;31 U&#47; L&#41; and AST &#40;30 U&#47;L&#41; resulted only in minimal increase of sensitivity to 92&#46;2&#37; <span class="elsevierStyleItalic">vs</span>&#46; 90&#46;1&#37; for ALT and to 92&#46;2&#37;&#44; <span class="elsevierStyleItalic">vs</span>&#46; 90&#46;6&#37; for AST&#46;</p></span> <span id="abs0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030"><span class="elsevierStyleBold">Conclusion</span></span><p id="sp0045" class="elsevierStyleSimplePara elsevierViewall">The present study did not reveal any single specific and sensitive marker for reliable diagnosis of ICP&#46; Establishment of lower cut-off values for transaminases activity might only minimally increase the accuracy of diagnosing ICP&#46;</p></span>"
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        "fuente" => "Values are median &#40;range&#41; or mean &#177; SD&#46; ALT&#58; alanine aminotransferase&#46; AST&#58; aspartate aminotransferase&#46; AP&#58; alkaline phosphatase&#46; &#947;-GT&#58; gammaglutamyl transpeptidase&#46; TBA&#58; total bile acid&#46; CA&#58; cholic acid&#46; CDCA&#58; chenodeoxycholic acid&#46; DCA&#58; deoxycholic acid&#46; UDCA&#58; ursodeoxycholic acid&#46; LCA&#58; lithocholic acid&#46; ICP&#58; cholestasis of pregnancy&#46;"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient characteristics Age&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Healthy pregnant women &#40;n &#61; 29&#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">p value 0&#46;723&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Gestational age&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">38&#46;98 &#177; 2&#46;99&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">Direct bilirubin &#956;mol&#47;L&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">UDCA &#956;mol&#47;L&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">LCA &#956;mol&#47;L&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">CA&#47;CDCA&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;68 &#40;0&#46;52- 0&#46;81&#41;&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;00002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2060664.png"
              ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Clinical&#44; biochemical characteristics of patients with intrahepatic cholestasis of pregnancy and healthy pregnant women&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "t0015"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "ALT&#58; alanine aminotransferase&#46; AST&#58; aspartate aminotransferase&#46; AP&#58; alkaline phosphatise&#46; TBA&#58; total bile acid&#46; CA&#58; cholic acid&#46; CDCA&#58; chenodeoxycholic acid&#46;"
        "tabla" => array:1 [
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            0 => array:2 [
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                0 => """
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;976&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;96-0&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Direct bilirubin &#956;mol&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;922&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;77-0&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TBA &#956;mol&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;853&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;78-0&#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">&#60; 0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CA &#956;mol&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;789&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;61-0&#46;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CDCA &#956;mol&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;692&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;58-0&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CA&#47;CDCA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;803&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;69-0&#46;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2060663.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Area under the curve &#40;AUC&#41; of all significant biochemical parameters&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "t0020"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "PPV&#58; positive predictive value&#46; NPV&#58; negative predictive value&#46; TBA&#58; total bile acid&#46; CA&#58; cholic acid&#46; CDCA&#58; chenodeoxycholic acid&#46;"
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sensitivity &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Specificity &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Predictive value &#37;&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Likelihood-ratio&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PPV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NPV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TBA &#956;mol&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">94&#46;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">63&#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">76&#46;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CA &#956;mol&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&#46;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">93&#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">2&#46;58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CDCA &#956;mol&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&#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">58&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&#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">2&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2060666.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Sensitivity&#44; specificity&#44; predictive value and likelihood-ratio of total and individual bile acids for the diagnosis of ICP&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "t0025"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "ALT&#58; alanine aminotransferase&#46; AST&#58; aspartate aminotransferase&#46;"
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ALT U&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">New cut-off value 31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sensitivity 92&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95&#37; CI 82&#46;7-97&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Specificity 100&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">95&#37; CI 87&#46;9-100&#46;0&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">p &#60; 0&#46;0001&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 16652681
Original language: English

DOI:10.5604/01.3001.0010.0294

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Year/Month	Html	Pdf	Total

2024 November	3	1	4
2024 October	34	18	52
2024 September	24	19	43
2024 August	33	10	43
2024 July	24	11	35
2024 June	24	6	30
2024 May	33	18	51
2024 April	33	2	35
2024 March	26	3	29
2024 February	17	5	22
2024 January	23	6	29
2023 December	31	7	38
2023 November	30	8	38
2023 October	50	9	59
2023 September	27	0	27
2023 August	33	6	39
2023 July	40	6	46
2023 June	36	2	38
2023 May	71	11	82
2023 April	59	3	62
2023 March	58	4	62
2023 February	49	7	56
2023 January	27	8	35
2022 December	61	5	66
2022 November	67	4	71
2022 October	40	14	54
2022 September	77	10	87
2022 August	42	8	50
2022 July	26	6	32
2022 June	22	7	29
2022 May	30	9	39
2022 April	25	12	37
2022 March	30	14	44
2022 February	25	6	31
2022 January	29	5	34
2021 December	15	15	30
2021 November	12	8	20
2021 October	16	14	30
2021 September	5	14	19
2021 August	11	4	15
2021 July	9	12	21
2021 June	8	5	13
2021 May	9	7	16
2021 April	14	6	20
2021 March	7	9	16
2021 February	16	19	35
2021 January	9	13	22
2020 December	14	5	19
2020 November	9	6	15
2020 October	6	5	11
2020 September	8	6	14
2020 August	6	18	24
2020 July	8	10	18
2020 June	10	3	13
2020 May	5	7	12
2020 April	2	2	4
2020 March	6	5	11
2020 February	4	1	5
2020 January	5	5	10
2019 December	6	8	14
2019 November	2	9	11
2019 October	2	9	11
2019 September	2	9	11
2019 August	1	2	3
2019 July	3	16	19
2019 June	1	8	9

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