Study on Etiological Shunting of Neonatal Cholestasis by High-Frequency Ultrasound Combined with Clinical Indicators

Study on Etiological Shunting of Neonatal Cholestasis by High-Frequency Ultrasound Combined with Clinical Indicators | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Study on Etiological Shunting of Neonatal Cholestasis by High-Frequency Ultrasound Combined with Clinical Indicators Yaxuan Xu, Guowei Tao, Xiubin Sun, Qun Liu, Wen Li, Dong Zhou, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2864824/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Retrospectively evaluating the biliary atresia (BA) - related ultrasound (US) and clinical indictors and exploring the feasibility of surgical shunting for neonatal cholestasis (NC) with a simplified two-step strategy: clinical indicators and US evaluation. Methods A total of 152 infants were enrolled and divided into BA group (80 cases) and non-BA group (72 cases). Their detailed US signs, clinical features and laboratory tests were collected, and their diagnostic performances were compared. Results Among physical and routine laboratory indicators: pale stool, hepatomegaly, γ-glutamyl transferase > 117 U/L, direct bilirubin > 87.7 μmol/L, total bilirubin > 131.9 μmol/L appeared significantly different between the two groups. They could act as the early warning indicators for detailed US evaluation. The combination of the following five US signs had better diagnostic efficiency with highest sensitivity (100%): “anterior-wall thickness of the right portal vein >1.6 mm”, “triangular cord sign”, “portal vein diameter > 5.1 mm”, “hepatic subcapsular flow” or “porta hepatic cystic or tubular echoes”. They might act as US shunting signs for surgical exploration. Among the signs of abnormal gallbladder, “irregular gallbladder wall” showed higher efficiency (AUC 0.733), which followed by fasting gallbladder length ≤ 1.8 cm and non-visualization of gallbladder. Moreover, a new laboratory indicator - the matrix metallopeptidase-7 (MMP-7)had an excellent diagnostic value (AUC 0.989) with a cut-off value of 14.04 ng/ml. Conclusions When the early clinical warning indicators appears in NC children, the intensive US evaluation may be helpful in the etiology shunting. And widely use of MMP-7 is promising. Neonatal cholestasis Biliary atresia Ultrasound γ-glutamyl transferase Matrix metallopeptidase-7 Figures Figure 1 Figure 2 Figure 3 Figure 4 What is Known Early etiological screening of NC is a task, and as the most common and severe cause of it, a timely exclusion of BA is the main concern. However, existing diagnostic indicators are numerous, and their performances are controversial. Especailly, the US method is complicated and non-standardized. What is New We evaluated the clinical and US indicators in a large sample study and the most effective indicators were selected out. The scanning of significant US features was optimized. We conclude that the summarized two-step strategy is effective and practical in ruling out BA accurately. Introduction Neonatal cholestasis (NC), characterized by conjugated hyperbilirubinemia in newborn and young infants, is a common sign of over 100 hepatobiliary and/or metabolic disorders, affecting approximately 1 in every 2,500 live births [1]. The guideline for the evaluation of cholestatic jaundice in infants made by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition in 2004 (abbr. the 2004 Guideline) [2] was widely used in clinical practice. Its details were the serum direct bilirubin (DBIL) > 1 mg/dL (17.1 μmol/L) when the total bilirubin (TBIL) 20% while the TBIL > 5 mg/dL. Further, the new guideline made by the NASPGHAN and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition in 2017 (abbr. the 2017 Guideline) [3] emphasized that it could be judged abnormal when the TBIL was elevated (regardless of the degree) and the DBIL > 1 mg/dL. Among its surgical etiologies, biliary atresia (BA) is the most common one. Early etiological screening of NC children is difficult, and a timely, accurate medical and surgical shunting is the main concern in clinics. Meanwhile, reducing unnecessary and invasive examinations is also an unavoidable problem. This study retrospectively analyzed the physical, laboratory, and ultrasound (US) indicators of NC children with difficulties in etiological shunting in our hospital over the past 7 years, aiming to recommend those most effective indicators and simplified schemes by using the most basic and non-invasive methods. Methods Ⅰ . Patients This study was approved by the Ethics Committee of Scientific Research of Shandong University Qilu Hospital. Due to its retrospective design, written informed parental consent was exempted. The NC children younger than 90 days from January 2016 to December 2022 in the Department of Ultrasound, Qilu Hospital of Shandong University were retrospectively analyzed. The clinical diagnostic criteria of NC referred to the 2004 Guideline. The inclusion criteria were undergoing at least once US scan in the Department of Ultrasound within 90 days of age, prolonged jaundice (longer than 2 weeks), the final diagnosis was clear, and the clinical data were complete. The exclusion criteria were very low birth weight or premature infants with total parenteral nutrition, genetic metabolic disorders, severe bacterial infection, or complex congenital anomalies such as polysplenic syndrome. Ⅱ . US scan methods After fasting for 4-6 hours, the liver, gallbladder fossa, portal area, and spleen were systematically scanned by color Doppler US instrument (Philips iU22 with probe L12-5, Philips EPIC 7 with probe e18-4, or Mindray Resona 7S with probe L14-5. We had made a uniform and standard scan strategy for the US signs required to be analyzed, as showed in Table. 1 and Figs. 1-3. Ⅲ . Clinical characteristics and groupings We collected the basic clinical information - age, gender, mode of delivery, feeding pattern, stool color and physical examination results. Meanwhile the results of their first biochemical tests were documented, including serum TBIL, DBIL, D/T (DBIL/TBIL), γ-glutamyl transferase (GGT), and alkaline phosphatase alkaline (AKP), as they were the most widely used indicators in clinics. TORCH screening, quantitative analysis of cytomegalovirus (CMV) copy number test, and matrix metallopeptidase-7 (MMP-7) levels were also be collected if they had performed. Moreover, intraoperative cholangiography (IOC), liver biopsy, and genetic diagnosis were also be collected to gain the final diagnoses. The clinical outcomes of the children were followed up for 6 months to 7 years. According to their final diagnoses, they were divided into the BA group and the non-BA group. Ⅳ . Statistical analysis The Kolmogorov - Smirnov tests were performed to test whether quantitative variables were normally distributed. Quantitative variables were expressed as the mean ± standard deviation if they followed the normal distribution, and the unpaired t test was used for comparisons between groups. Otherwise, they were expressed as median and quartiles (quartile 1 [Q1], quartile 3 [Q3]) and the Mann - Whitney U test was used for comparisons. Chi-Square and Fisher's exact tests were used for qualitative data. We developed receiver operating characteristic (ROC) curves to calculate the cut-off values and area under curves (AUCs) to estimate the probability of predicting BA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to show the diagnostic performances of single or combined parameters. SPSS software (version 26.0, IBM Corp, New York, USA) and MedCalc software (version 19.0.4, MedCalc Software, Ostend, Belgium) were used for data analysis. The differences were considered statistically significant with p value < 0.01. Results Ⅰ. Clinical and laboratory indicators 1.Basic demographic information and physical characteristics A total of 152 children were enrolled at last. The BA group contained 80 cases, which were confirmed by IOC in 66 cases, by liver biopsy in 1 case, and by clinical follow-up in 13 cases (12 cases died at 5-12 months of age, and 1 case had survived to 11 months old with cirrhosis and ascites at the last follow-up visit). Among the 72 cases of the non-BA group, 5 cases showed a patent biliary tree and 7 cases were diagnosed with inspissated bile syndrome by IOC. There were 1 case of Alagille syndrome, 1 case of gallbladder hypoplasia and 2 cases of biliary stones, while the other 28 cases underwent medical treatments and their jaundice completely resolved after medical therapy within 14-day to 5-month follow-up, leading to the final diagnosis of idiopathic neonatal hepatitis. As summarized in Table. 2, the median age at first US scan in our department of the two groups was comparable [49 (39, 70) vs. 55.5 (40, 68.25) days, p = 0.444]. There were 39 male infants (48.8%) in the BA group and 48 male infants (66.7%) in the non-BA group ( p = 0.026). Pale stool (progressive or transient) was more common in BA group than in non-BA group (51.3% vs. 12.5%, p < 0.001), as well as hepatomegaly (32.5% vs. 13.9%, p = 0.007). 2.Routine laboratory indicators GGT, TBIL, DBIL, and CMV infection rate had statistically significant differences between groups ( p 117 U/L, then followed DBIL (AUC 0.699, cut-off value > 87.7μmol/L) and TBIL (AUC 0.668, cut-off value > 131.9 μmol/L) (Table. 3). Concomitant CMV infection showed a higher incidence in non-BA group (BA 11.3% vs. non-BA 29.2%, p = 0.006, Table. 2). 3.MMP-7 A total of 27 cases of NC children in our hospital were tested for serum MMP-7 since 2021. Among them, 15 cases in BA group had a median level of 43.2 (20.51, 59.64) ng/ml, while 12 cases in non-BA group had a median level of 10.99 (9.95, 13.38) ng/ml ( p 14.04 ng/ml, showing an excellent diagnostic value (AUC 0.989, sensitivity 100%, specificity 91.67%, PPV 93.7% and NPV 100%) and being much better than all the other laboratory indicators. Ⅱ. US signs in NC etiological shunting 1. US signs with statistical significances Among all these single US signs, the following nine were statistically significant between groups ( p < 0.001): hepatomegaly, hepatic subcapsular flow (HSF), portal vein (PV) diameter, triangular cord (TC) sign, thickened anterior wall of the right portal vein, reduced length of the gallbladder, non-visualization of gallbladder (NVGB), irregular gallbladder wall, and portal cystic or tubular echoes (PCTE) (Table. 4). 2. Performance assessment of the US signs As listed in Table. 5, the top five signs with the better diagnostic efficiencies (ranked by AUC, high to low) were ATRPV > 1.6 mm, the PV diameter > 5.1 mm, irregular gallbladder wall, TC sign and gallbladder length ≤ 1.8cm. The PPVs of these following signs exceeded 90%: PCTE, TC sign, HSF, and thickened ATRPV. Among all the sign-combinations, the best diagnostic efficiency came from the combinations - “ATRPV > 1.6 mm or TC sign” (AUC 0.919) and “ATRPV > 1.6 mm or PV diameter > 5.1 mm or TC sign or HSF or PCTE” (AUC 0.891), and the latter had better sensitivity (94.4% vs. 100%) and NPV (92.6% vs. 100%) (Table. 5). Abnormal echoes in the portal area included the TC sign in the porta hepatis (the confluence site of left and right portal branches), thickened ATRPV, PCTE and the dilated PV diameter. All of them had great diagnostic performances, the PPV of first three exceeding 90% (Table. 5). In this study, 20 cases (25%, 20/80) of BA children showed PCTE in the portal area, with high specificity and PPV (both 100%), but the diagnostic performance was limited (AUC 0.625) due to its lower sensitivity (25.0%). Multiple cysts were commoner (70%, 14/20), with the mean diameter ranging 0.15-0.8 cm (Fig. 3a). Among the 6 cases with solitary cyst, 3 were in the gallbladder fossae, with the mean diameter ranging 0.5-0.85 cm, and dysplastic gallbladders were proved by laparoscopy later. And the other 3 cases were cystic BA with the diameter ranging 1.1-2.0 cm. Their preoperative USs showed that the cyst was connected with the gallbladder or common bile duct with a suspicious diagnosis of bile duct dilatation, but type I BA was finally confirmed by IOC. The diameters of the tubular echoes (different form the normal bile ducts) ranged 0.1-0.6 cm. In addition, children with TC sign, or ATRPV > 1.6 mm accounted for 80% (16/20) of them. Hilar cysts, combined with multiple irregular tubular-like echoes accounted for 50% (10/20) of them, and combined with a dysplastic or non-visualized gallbladder in 25% (5/20) of cases. Among all the morphological signs of the abnormal gallbladder, the diagnostic accuracy of irregular gallbladder wall was the highest (AUC 0.733). The following two were gallbladder length ≤ 1.8 cm (AUC 0.682) and NVGB (AUC 0.590). Obviously, their diagnostic efficacies as independent indicators were all limited and so did as they combined with other signs (not list). Discussion Ⅰ . Clinical and laboratory indicators in NC etiological shunting 1.Physical characteristics Consistent with previous literatures and guidelines [1,3], our study showed that pathological jaundice with progressive or transient pale stool and hepatomegaly were the most important clinical features related to BA. 2.Routine laboratory indicators As showed in Table. 3, GGT had the relatively better efficacy in the differential diagnosis of BA, and the cut-off value was > 117 U/L, which was lower than previous literatures [4,5]. And our results suggested that NC neonates with whose DBIL exceeding 87.7 μmol/L and TBIL exceeding 131.9 μmol/L should be alert to the possibility of BA. Accordingly, biochemical examinations might be helpful, but it was insufficient to rely on them alone for NC etiological shunting due to the considerable overlap between the BA and non-BA causes. At present, there is insufficient clinical evidence for perinatal CMV infection as a cause or trigger of BA [6,7]. Previous studies had shown that non-white BA children had a higher rate of co-infection with CMV [6]. The jaundice clearance rate after Kasai operation and autologous liver survival rate decreased, and postoperative mortality increased in CMV (+) BA children [8,9]. However, the rate of CMV infection in the BA group was lower than the non-BA group in this study cohort. Therefore, the relationship between CMV infection and NC (especially BA) needs further research. 3.MMP-7 MMP-7 is a protease responsible for tissue remodeling. It was found to be significantly associated with liver fibrosis [10,11]. Its diagnostic application in BA children was described firstly by Bezerra et al. in 2002 [12]. In 2021, a large sample cohort study based on Chinese people by Chen Yaxing et al. had found that the cut-off value of MMP-7 for the diagnosis of BA was 12.8 ng/ml (AUC 0.98, sensitivity 99%, specificity 93.0% and PPV 94.44%) [11]. In this study, the optimal cut-off value for MMP‐7 was 14.04 ng/ml, with the sensitivity, specificity, PPV and NPV of 100%, 91.67%, 93.7% and 100%, demonstrating an excellent predictive accuracy. Therefore, MMP-7 is a quite valuable biomarker for BA diagnosis, which is superior to GGT and other routine laboratory indicators. In consequence, when NC children have any of the following clinical characteristics: pale stool, hepatomegaly, GGT > 117U/L, DBIL > 87.7 μmol/L, TBIL >131.9 μmol/L, they should be alert to the possibility of BA. They may act as the early warning indicators for detailed US scans. The widespread application of MMP-7 in clinics is worth popularizing. Ⅱ. US signs in NC etiological shunting 1. Observation of abnormal echoes in the portal area The typical histopathological features of BA include edema in the portal area, bile duct proliferation, bile plugs, portal or perilobular fibrosis, and inflammatory cell infiltrating around bile ducts [13]. That is the pathological basis for the TC sign, thickened ATRPV and PCTE formation. And another new significant US sign was found in this study – “PV Diameter > 5.1mm”. The TC sign was first discovered by Choi SO et al. in 1996 [14]. Series literatures had showed its high value for the diagnosis of BA [7,15,16]. But there was no clear consensus on where and how to measure the TC, as well as the cut-off value [17,18]. There were two common sites for TC measurement: the maximum anteroposterior diameter of the proliferative fibrous cord in the porta hepatis at a cut-off of > 3-4 mm [14,19], or ATRPV excluding the right HA with a cut-off value as low as 2 mm [5,17,20,21]. In fact, these two parameters all represented the fibrous proliferation in portal area and their measuring sites were very close. In this study, we had lowered the cut-off value of ATRPV down to 1.6 mm by using high-frequency probe and standardizing scan, and it had higher sensitivity than TC sign (90.9% vs. 43.8%) (Table. 5). Combination of them could elevate the sensitivity to 94.4%. The occurrence of PCTE in BA is related to biliary hyperplasia, bile aggregation, or biliary cystic dilation above obstruction. It can be manifested as solitary or multiple cysts or clustered, irregular tubulars (different from normal hepatic bile ducts) within or adjacent to the proliferative fibrous tissue in the porta hepatis (Fig. 3). If the cyst is large and connected with the gallbladder and extrahepatic biliary tract, it can be detected prenatally and misdiagnosed as biliary dilatation, also known as cystic BA. In previous large sample studies, cystic BA could be found in 5-10% of BA children [6,22]. Overall, PCTE had extremely high specificity and PPV (both 100%) for the discrimination of BA. Once appears, it must evoke the strong suspicion of BA. Although not been reported previously, this study found that in NC children younger than 90 days, there was a significant difference in the PV diameter between the two groups - 5.30 (4.40, 5.70) mm in the BA group and 4.30 (3.80, 4.98) mm in the non-BA group, p = 0.007). When the PV diameter > 5.1 mm, the sensitivity for diagnosing BA was 53.3%, the specificity 91.7% and the PPV 80%. The dilated PV in BA children might be related to liver fibrosis and portal hypertension. 2. Abnormal gallbladder morphological signs Before the use of the TC sign and ATRPV, gallbladder abnormalities were the most widely used US signs for BA. However, the diversities and similarities in shape and size of the gallbladder still made it confusing to discriminate BA from NC children according to the existing classification [17,19,20,23]. This study showed that among all the gallbladder morphological signs, the “irregularity” of the gallbladder wall might be relatively better, which referred to the tortuous, uneven, or irregularly thickened wall (Fig. 2). In the analysis process, the use of double contour lines profilometry in controversial cases could help in the judgment of this sign (Fig. 2). The next two were fasting gallbladder length ≤ 1.8 cm and NVGB. But as showed above, the differential performances of all the gallbladder-related signs were not so satisfactory, and they couldn’t improve the diagnostic accuracy for BA when combined with other signs. A normal gallbladder couldn’t rule out BA. Even so, gallbladder morphological signs still seemed easier to be identified and mastered by the beginners, and an abnormal morphology of gallbladder could help raising our vigilance for further inspection. 3.HSF and HA diameter The presence of the HSF had been considered useful in identifying BA, which was associated with subcapsular telangiectatic vessels. We observed a high specificity of it (96.4%), but a lower positive rate (38.9%) than previous literatures. The differences between literatures might be related to the US probe’s sensibility to distinguish slender blood flows with a lower velocity. Furthermore, different from previous literatures [4,24,25], there was no significant difference in the HA diameter between the two groups without definite reasons. 4.Suggestion for US shunting signs and strategies So, based on the above research, any one of the following five US signs: ATRPV > 1.6 mm, PV diameter > 5.1 mm, TC sign, HSF, PCTE could be used as indicators for surgical shunting. Morphological signs of abnormal gallbladder had limited diagnostic efficacy, and they were best to be used combined with the above signs. Conclusion Thorough clinical indicators and intensive US scan may provide an effective etiological shunting scheme for NC children. We have recommended an optimized diagnosis process as shown in Fig. 4. When the clinical early warning indicators appears, the NC children need detailed US scan, especially the US shunting signs. The abnormal gallbladder morphological signs can be used as useful supplements for clinical judgment. Widely use of MMP-7 in NC shunt is promising. Abbreviations NC Neonatal cholestasis DBIL Direct bilirubin TBIL Total bilirubin BA Biliary atresia US Ultrasound GGT γ-glutamyl transferase AKP Alkaline phosphatase alkaline CMV Cytomegalovirus MMP-7 Matrix metallopeptidase-7 IOC Intraoperative cholangiography ROC Operating characteristic AUC Area under curve PPV Positive predictive value NPV Negative predictive value HSF Hepatic subcapsular flow PV Portal vein TC Triangular cord sign NVGB Non-visualization of gallbladder PCTE Portal cystic or tubular echoes Declarations Acknowledgement Thanks to Dr. Edward C. Mignot, Shandong University, for linguistic advice. Data availability Data that support the findings of this study are available and can be provided by the corresponding author, based upon reasonable request. Ethics approval The study protocol was approved by the Ethics Committee of Scientific Research of Shandong University Qilu Hospital. 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Radiology 245 (2): 549–555. https://doi.org/10.1148/radiol.2452061093 Tables Table 1 US signs and scan methods of hepatobiliary system and spleen US signs Scan methods Liver size (cm) measure the maximum subcostal diameter of the right lobe, > 2 cm was hepatomegaly HA diameter (mm) measure along the direction of the main PV PV diameter (mm) measure within 1.5 cm from the bifurcation of the main PV (Fig 1a) HSF under CDFI mode, the velocity scale was ± 3-5 cm/s, the color box was placed within 3 cm deep from the hepatic capsule, and the HA flow extended to the liver surface without grossly visible artifacts (Fig 1b) TC sign a hyperechoic cord in the porta hepatis and its size (long, transverse, and anteroposterior diameters) was measured, those with anteroposterior diameters ≥ 3 mm were positive (Fig 1c) ATRPV (mm) the maximum thickness of the anterior wall of the right PV was measured vertically (Fig 1d) PCTE it could be cystic or tubular echoes, distributing around the porta hepatis or along the PV (Fig 3); measure the size (length*width) of the cystic echo (cm) or the width of the tubular echo (cm); the vascular structures were excluded by CDFI Gallbladder size (cm) measure the length and the width after 4-6 hours fasting and 40-60 minutes later after breastfeeding wall echo with or without “bilateral sign” and “irregularity” (tortuous, uneven wall or irregular thickening) (Fig 2) contraction rate (%) [1- (length*width) after breastfeeding / (length*width) during fasting] *100 Spleen length (cm) measure the maximum length of the spleen, > 7 cm was splenomegaly US ultrasound, HA hepatic artery, PV portal vein, HSF hepatic subcapsular flow, TC sign triangular cord sign, ATRPV anterior wall of the right portal vein, PCTE portal cystic or tubular echoes Table 2 Comparison of clinical and routine laboratory indicators between the BA and non-BA groups BA group (n = 80) non-BA group (n = 72) P Age(d) # 49.0 (39.0, 70.0) 55.5 (40.0, 68.3) 0.444 a Gender male female 39 (48.8%) 41 (51.3%) 48 (66.7%) 24 (33.3%) 0.026 b Mode of delivery cesarean vaginal 51 (63.8%) 29 (36.3%) 38 (52.8%) 34 (47.2%) 0.170 b Feeding pattern exclusive breast formula or mixed 43 (53.8%) 37 (46.3%) 33 (45.8%) 39 (54.2%) 0.330 b Pale stool 41 (51.3%) 9 (12.5%) <0.001 b Hepatomegaly † 26 (32.5%) 10 (13.9%) 0.007 b Splenomegaly † 10 (12.5%) 3 (4.2%) 0.123 b TBIL (μmol/L) # 158.4 (136.7, 188.6) 131.9 (104.6, 166.8) 0.001 a DBIL (μmol/L) # 109.7 (93.6, 128.1) 85.4 (66.2, 113.7) <0.001 a D/T (%) # 71.2 (65.7, 73.8) 71.2 (62.4, 73.6) 0.518 a GGT (U/L) # 372 (176.0, 669.8) 96 (62.0, 182.0) <0.001 a AKP (U/L) # 508.5 (424.8, 696.8) 625.5 (478.5, 875.3) 0.023 a Cytomegalovirus infection 9 (11.3%) 21 (29.2%) 0.006 b BA biliary atresia, TBIL total bilirubin, DBIL direct bilirubin, D/T DBIL/TBIL, GGT γ-glutamyl transferase, AKP alkaline phosphatase alkaline # Abnormal distribution, data were medians with the interquartiles (quartile 1 [Q1], quartile 3 [Q3]). a Mann-Whitney U test, b Chi-Square test, † By physical examination Table 3 Diagnostic performances of routine laboratory indicators for the diagnosis of biliary atresia Cut-off AUC Sensitivity (%) Specificity (%) PPV (%) NPV (%) GGT (U/L) >117.0 0.825 94.9 60.8 78.7 88.6 DBIL (μmol/L) >87.7 0.699 85.9 58.5 75.3 73.8 TBIL (μmol/L) >131.9 0.668 82.1 50.9 71.1 65.9 GGT γ-glutamyl transferase, DBIL direct bilirubin, TBIL total bilirubin, AUC area under curve, PPV positive predictive value, NPV negative predictive value Table 4 Comparison of US signs between the BA and non-BA groups US signs BA group (n=80) Non-BA group (n=72) P Cut-off Liver Hepatomegaly 46 (57.5%) 17 (23.6%) 1.6 PV diameter (mm) # 5.3 (4.40-5.70) 4.3 (3.80-4.98) 0.007 c ≤5.1 TC sign 35 (43.8%) 1 (1.4%) <0.001 a NA ATRPV (mm) # 2.8 (2.15-4.25) 1.0(0.80-1.40) 1.6 PCTE 20 (25.0%) 0 (0%) <0.001 d NA GB Length (cm) * 1.86 ± 0.94 2.36 ± 0.82 0.002 b ≤1.8 Width (cm) # 0.4 (0.3-0.5) 0.5 (0.4-0.8) 0.014 c ≤0.5 Length-to-width ratio # 4.17 (3-5.45) 4.15 (3.07-6) 0.945 c NA NVGB 21 (26.3%) 6 (8.3%) 0.004 a NA Unfilled GB 5 (6.3%) 4 (5.6%) 1.000 a NA Bilateral sign of GB wall 42 (52.5%) 39 (54.2%) 0.837 a NA Irregular GB wall 54 (67.5%) 15 (20.8%) <0.001 a NA GB contraction rate (%) # 3.57 (0-45.83) 61.63 (2.42-79.58) 0.028 c ≤50 Spleen Splenomegaly 10 (12.5%) 6 (8.3%) 0.261 a NA US ultrasound, BA biliary atresia, HSF hepatic subcapsular flow, HA hepatic artery, PV portal vein, TC sign triangular cord sign, ATRPV anterior wall of the right portal vein, PCTE portal cystic or tubular echoes, GB gallbladder, NVGB Non-visualization of GB, NA not available * Normal distribution, data were means ± standards deviation. # Abnormal distribution, data were medians with the interquartiles (quartile 1 [Q1], quartile 3 [Q3]). a Chi-Square test, b T test, c Mann-Whitney U test, d Fisher's exact test . Table 5 Diagnostic performances of single or combined US signs for the diagnosis of biliary atresia US signs AUC Sensitivity (%) Specificity (%) PPV (%) NPV (%) Single signs ATRPV > 1.6 mm A 0.933 90.9 88.5 90.9 88.5 PV diameter > 5.1 mm B 0.760 53.3 91.7 80.0 75.9 irregular GB wall 0.733 67.5 79.2 78.3 68.7 TC sign C 0.712 43.8 98.6 97.2 61.2 GB length ≤ 1.8 cm 0.682 56.3 74.1 65.9 65.6 HSF D 0.677 38.9 96.4 93.3 55.1 hepatomegaly 0.669 57.5 76.4 73.0 61.8 PCTE E 0.625 25.0 100.0 100.0 54.5 NVGB 0.590 26.3 91.7 77.8 52.8 Best sign-combinations (AUC ≥ 0.891) A or C 0.919 94.4 89.3 91.9 92.6 A or B or C or D or E 0.891 100.0 78.3 88.9 100.0 US ultrasound, ATRPV anterior wall of the right portal vein, PV portal vein, GB gallbladder, TC sign triangular cord sign, HSF hepatic subcapsular flow, PCTE portal cystic or tubular echoes, NVGB Non-visualization of GB, AUC area under curve, PPV positive predictive value, NPV negative predictive value Additional Declarations No competing interests reported. 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University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Guowei","middleName":"","lastName":"Tao","suffix":""},{"id":197616982,"identity":"72515c46-02d1-4530-8eb1-4cd530b12179","order_by":2,"name":"Xiubin Sun","email":"","orcid":"","institution":"Shandong University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiubin","middleName":"","lastName":"Sun","suffix":""},{"id":197616983,"identity":"9c2d3a3a-f249-4ef3-80b3-54fbbe892bdc","order_by":3,"name":"Qun Liu","email":"","orcid":"","institution":"The Sixth People’s Hospital of Heze, Qilu Hospital of Shandong University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qun","middleName":"","lastName":"Liu","suffix":""},{"id":197616984,"identity":"81a826e7-400f-4a8a-9e36-025aeebb5d9c","order_by":4,"name":"Wen Li","email":"","orcid":"","institution":"Qilu Hospital of Shandong 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15:29:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2864824/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2864824/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":36744727,"identity":"091e7dc8-5fca-4467-af5b-8d36a52a3b8a","added_by":"auto","created_at":"2023-05-09 14:07:02","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2042994,"visible":true,"origin":"","legend":"\u003cp\u003eImages and measurements of ultrasound (US) signs with diagnostic value. \u003cstrong\u003ea\u003c/strong\u003e: Portal vein diameter (calipers) of 5.4mm in a 46-day-old male infant. \u003cstrong\u003eb\u003c/strong\u003e: The hepatic subcapsular flow extended to the liver surface in a 35-day-old male infant. \u003cstrong\u003ec\u003c/strong\u003e: Triangular cord size (calipers) of 1.1*0.54 cm in a 73-day-old male infant. \u003cstrong\u003ed\u003c/strong\u003e: Anterior wall of the right portal vein thickness (calipers) of 2.2 mm in a 35-day-old male infant.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2864824/v1/0e2d299b323580b2e22ba2e9.jpg"},{"id":36744166,"identity":"f85f7329-057b-4eb3-bfe7-9a64b3c12603","added_by":"auto","created_at":"2023-05-09 13:51:02","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":516820,"visible":true,"origin":"","legend":"\u003cp\u003eIrregularity of the gallbladder (GB) wall in biliary atresia children. The double contour lines profilometry is helpful to identify the irregular GB wall in various forms: the contour line of the inner GB wall is tortuous and uneven, or the wall thickens irregularly (uneven thickness between outer wall and inner wall). The yellow solid line and the green dotted line show the contour lines of the inner and outer walls of GB respectively.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2864824/v1/c6983e4bc527f284779172a3.jpg"},{"id":36744405,"identity":"3db35b3a-e10b-4670-80e4-0fcffc2a1061","added_by":"auto","created_at":"2023-05-09 13:59:02","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":580013,"visible":true,"origin":"","legend":"\u003cp\u003eUltrasound images of portal cystic or tubular echoes in biliary atresia children. \u003cstrong\u003ea\u003c/strong\u003e: Multiple small cysts (arrows) and tubular echoes (arrowhead) in portal area. \u003cstrong\u003eb\u003c/strong\u003e: Multiple tubular echoes (arrowheads) distributed in clusters and running irregularly in portal area. \u003cstrong\u003ec\u003c/strong\u003e: Multiple tubular echoes (arrowheads) were running tortuous, with beaded expansion in portal area. \u003cstrong\u003ed\u003c/strong\u003e: A cystic echo (arrow) of 2.0*1.3 cm at the porta hepatis and connected with the gallbladder.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2864824/v1/c0eed4cfd7c99a585a6141ab.jpg"},{"id":36744169,"identity":"703659c0-45c0-4492-9a2c-92dfe39bd213","added_by":"auto","created_at":"2023-05-09 13:51:02","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":334005,"visible":true,"origin":"","legend":"\u003cp\u003eOptimized process of etiologic shunting for NC children: the two-step strategy\u003c/p\u003e\n\u003cp\u003eNC = neonatal cholestasis; GGT = γ-glutamyl transferase; DBIL = direct bilirubin; TBIL = total bilirubin; ATRPV = anterior wall of the right portal vein; TC sign = triangular cord sign; PV = portal vein; PCTE = portal cystic or tubular echoes; HSF = hepatic subcapsular flow; GB = gallbladder; NVGB = non-visualization of GB; MMP-7 = matrix metallopeptidase-7; BA = biliary atresia.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2864824/v1/5172b9c207490d59f7c54b46.jpg"},{"id":38359914,"identity":"1a5188af-e24d-43c6-803e-92848a78dd72","added_by":"auto","created_at":"2023-06-11 19:14:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2155116,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2864824/v1/8063c25f-09ab-464b-8e33-d82e8572c7be.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Study on Etiological Shunting of Neonatal Cholestasis by High-Frequency Ultrasound Combined with Clinical Indicators","fulltext":[{"header":"What is Known","content":"\u003cp\u003eEarly etiological screening of NC is a task, and as the most common and severe cause of it, a timely exclusion of BA is the main concern. However, existing diagnostic indicators are numerous, and their performances are controversial. Especailly, the US method is complicated and non-standardized.\u003c/em\u003e \u003c/p\u003e"},{"header":"What is New","content":"\u003cp\u003e We evaluated the clinical and US indicators in a large sample study and the most effective indicators were selected out. The scanning of significant US features was optimized. We conclude that the summarized two-step strategy is effective and practical in ruling out BA accurately.\u003c/em\u003e \u003c/p\u003e "},{"header":"Introduction","content":"\u003cp\u003eNeonatal cholestasis (NC), characterized by conjugated hyperbilirubinemia in newborn and young infants, is a common sign of over 100 hepatobiliary and/or metabolic disorders, affecting approximately 1 in every 2,500 live births [1]. The guideline for the evaluation of\u0026nbsp;cholestatic jaundice in infants made by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition in 2004 (abbr. the 2004 Guideline) [2] was widely used in clinical practice. Its details were the serum direct bilirubin (DBIL) \u0026gt; 1 mg/dL (17.1 \u0026mu;mol/L) when the total bilirubin (TBIL) \u0026lt; 5 mg/dL (85.5 \u0026mu;mol/L), or DBIL/TBIL (D/T) \u0026gt; 20% while the TBIL \u0026gt; 5 mg/dL. Further, the new guideline made by the NASPGHAN and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition in 2017 (abbr. the 2017 Guideline) [3] emphasized that it could be judged abnormal when the TBIL was elevated (regardless of the degree) and the DBIL \u0026gt; 1 mg/dL.\u003c/p\u003e\n\u003cp\u003eAmong its surgical etiologies, biliary atresia (BA) is the most common one. Early etiological screening of NC children is difficult, and a timely, accurate medical and surgical shunting is the main concern in clinics. Meanwhile, reducing unnecessary and invasive examinations is also an unavoidable problem.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study retrospectively analyzed the physical, laboratory, and ultrasound (US) indicators of NC children with difficulties in etiological shunting in our hospital over the past 7 years, aiming to recommend those most effective indicators and simplified schemes by using the most basic and non-invasive methods.\u0026nbsp;\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eⅠ\u003c/strong\u003e\u003cstrong\u003e. Patients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the\u0026nbsp;Ethics Committee of Scientific Research of\u0026nbsp;Shandong University Qilu Hospital. Due to its retrospective design, written informed parental consent was exempted.\u003c/p\u003e\n\u003cp\u003eThe NC children younger than 90 days from January 2016 to December 2022 in the Department of Ultrasound, Qilu Hospital of Shandong University were retrospectively analyzed. The clinical diagnostic criteria of NC referred to the 2004 Guideline. The inclusion criteria were undergoing at least once US scan in the Department of Ultrasound within 90 days of age, prolonged jaundice (longer than 2 weeks), the final diagnosis was clear, and the clinical data were complete. The exclusion criteria were very low birth weight or premature infants with total parenteral nutrition, genetic metabolic disorders, severe bacterial infection, or complex congenital anomalies such as polysplenic syndrome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eⅡ\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;US scan methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter fasting for 4-6 hours, the liver, gallbladder fossa, portal area, and spleen were systematically scanned by color Doppler US instrument (Philips iU22 with probe L12-5, Philips EPIC 7 with probe e18-4, or Mindray Resona 7S with probe L14-5. We had made a uniform and standard scan strategy for the US signs required to be analyzed, as showed in Table. 1 and Figs. 1-3.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eⅢ\u003c/strong\u003e\u003cstrong\u003e. Clinical characteristics and groupings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe collected the basic clinical information - age, gender, mode of delivery, feeding pattern, stool color and physical examination results. Meanwhile the results of their first biochemical tests were documented, including serum TBIL, DBIL, D/T (DBIL/TBIL), \u0026gamma;-glutamyl transferase (GGT), and alkaline phosphatase alkaline (AKP),\u0026nbsp;as they were the most widely used indicators in clinics. TORCH screening, quantitative analysis of cytomegalovirus (CMV) copy number test, and matrix metallopeptidase-7 (MMP-7) levels were also be collected if they had performed. Moreover, intraoperative cholangiography (IOC), liver biopsy, and genetic diagnosis were also be collected to gain the final diagnoses. The clinical outcomes of the children were followed up for 6 months to 7 years.\u0026nbsp;According to their final diagnoses, they were divided into the BA group and the non-BA group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eⅣ\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eStatistical analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Kolmogorov - Smirnov tests were performed to test whether quantitative variables were normally distributed. Quantitative variables were expressed as the mean \u0026plusmn; standard deviation if they followed the normal distribution, and the unpaired t test was used for comparisons between groups. Otherwise, they were expressed as median and quartiles (quartile 1 [Q1], quartile 3 [Q3]) and the Mann - Whitney U test was used for comparisons. Chi-Square and Fisher\u0026apos;s exact tests were used for qualitative data. We developed receiver operating characteristic (ROC) curves to calculate the cut-off values and area under curves (AUCs) to estimate the probability of predicting BA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to show the diagnostic performances of single or combined parameters. SPSS software (version 26.0, IBM Corp, New York, USA) and MedCalc software (version 19.0.4, MedCalc Software, Ostend, Belgium) were used for data analysis. The differences were considered statistically significant with \u003cem\u003ep\u003c/em\u003e value \u0026lt; 0.01.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eⅠ. Clinical and laboratory indicators\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.Basic demographic information and physical characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 152 children were enrolled at last. The BA group contained 80 cases, which were confirmed by IOC in 66 cases, by liver biopsy in 1 case, and by clinical follow-up in 13 cases (12 cases died at 5-12 months of age, and 1 case had survived to 11 months old with cirrhosis and ascites at the last follow-up visit). Among the 72 cases of the non-BA group, 5 cases showed a patent biliary tree and 7 cases were diagnosed with inspissated bile syndrome by IOC. There were 1 case of Alagille syndrome, 1 case of gallbladder hypoplasia and 2 cases of biliary stones, while the other 28 cases underwent medical treatments and their jaundice completely resolved after medical therapy within 14-day to 5-month follow-up, leading to the final diagnosis of idiopathic neonatal hepatitis.\u003c/p\u003e\n\u003cp\u003eAs summarized in Table. 2, the median age at first US scan in our department of the two groups was comparable [49 (39, 70) vs. 55.5 (40, 68.25) days, \u003cem\u003ep\u003c/em\u003e = 0.444]. There were 39 male infants (48.8%) in the BA group and 48 male infants (66.7%) in the non-BA group (\u003cem\u003ep\u003c/em\u003e =\u0026nbsp;0.026). Pale stool (progressive or transient) was more common in BA group than in non-BA group (51.3% vs.\u0026nbsp;12.5%, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), as well as hepatomegaly (32.5% vs. 13.9%, \u003cem\u003ep\u003c/em\u003e = 0.007).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.Routine laboratory indicators\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGGT, TBIL, DBIL, and CMV infection rate had statistically significant differences between groups (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) (Table. 2). Among them, GGT showed the highest diagnostic efficacy for differential diagnosis of BA (AUC 0.825) with a cut-off value of \u0026gt; 117 U/L, then followed DBIL (AUC 0.699, cut-off value \u0026gt; 87.7\u0026mu;mol/L) and TBIL (AUC 0.668, cut-off value \u0026gt; 131.9 \u0026mu;mol/L) (Table. 3). Concomitant CMV infection showed a higher incidence in non-BA group (BA 11.3% vs. non-BA 29.2%, \u003cem\u003ep\u003c/em\u003e = 0.006, Table. 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.MMP-7\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 27 cases of NC children in our hospital were tested for serum MMP-7 since 2021. Among them, 15 cases in BA group had a median level of 43.2 (20.51, 59.64) ng/ml, while 12 cases in non-BA group had a median level of 10.99 (9.95, 13.38) ng/ml (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001). The cut-off value was \u0026gt; 14.04 ng/ml, showing an excellent diagnostic value (AUC 0.989, sensitivity 100%, specificity 91.67%, PPV 93.7% and NPV 100%) and being much better than all the other laboratory indicators.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eⅡ. US signs in NC etiological shunting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1. US signs with statistical significances\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong all these single US signs, the following nine were statistically significant between groups (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001): hepatomegaly,\u0026nbsp;hepatic subcapsular flow (HSF), portal vein (PV) diameter, triangular cord (TC) sign, thickened anterior wall of the right portal vein, reduced length of the gallbladder, non-visualization of gallbladder (NVGB), irregular gallbladder wall, and portal cystic or tubular echoes (PCTE) (Table. 4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2. Performance assessment of the US signs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs listed in Table. 5, the top five signs with the better diagnostic efficiencies (ranked by AUC, high to low) were ATRPV \u0026gt; 1.6 mm, the PV diameter \u0026gt; 5.1 mm, irregular gallbladder wall, TC sign and gallbladder length \u0026le; 1.8cm. The PPVs of these following signs exceeded 90%: PCTE, TC sign, HSF, and thickened ATRPV.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong all the sign-combinations, the best diagnostic efficiency came from the combinations - \u0026ldquo;ATRPV \u0026gt; 1.6 mm\u0026nbsp;or TC sign\u0026rdquo;\u0026nbsp;(AUC 0.919) and \u0026ldquo;ATRPV \u0026gt; 1.6 mm or PV diameter\u0026nbsp;\u0026gt;\u0026nbsp;5.1 mm or TC sign or HSF or PCTE\u0026rdquo; (AUC 0.891), and the latter had better sensitivity (94.4% vs. 100%) and NPV (92.6% vs. 100%) (Table. 5).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAbnormal echoes in the portal area included the TC sign in the porta hepatis (the confluence site of left and right portal branches), thickened ATRPV, PCTE and the dilated PV diameter. All of them had great diagnostic performances, the PPV of first three exceeding 90% (Table. 5). In this study, 20 cases (25%, 20/80) of BA children showed PCTE in the portal area, with high specificity and PPV (both 100%), but the diagnostic performance was limited (AUC 0.625) due to its lower sensitivity (25.0%). Multiple cysts were commoner (70%, 14/20), with the mean diameter ranging 0.15-0.8 cm (Fig. 3a). Among the 6 cases with solitary cyst, 3 were in the gallbladder fossae, with the mean diameter ranging 0.5-0.85 cm, and dysplastic gallbladders were proved by laparoscopy later. And the other 3 cases were cystic BA with the diameter ranging 1.1-2.0 cm. Their preoperative USs showed that the cyst was connected with the gallbladder or common bile duct with a suspicious diagnosis of bile duct dilatation, but type I BA was finally confirmed by IOC. The diameters of the tubular echoes (different form the normal bile ducts) ranged 0.1-0.6 cm. In addition, children with TC sign, or ATRPV \u0026gt; 1.6 mm accounted for 80% (16/20) of them. Hilar cysts, combined with multiple irregular tubular-like echoes accounted for 50% (10/20) of them, and combined with a dysplastic or non-visualized gallbladder in 25% (5/20) of cases.\u003c/p\u003e\n\u003cp\u003eAmong all the morphological signs of the abnormal gallbladder, the diagnostic accuracy of irregular gallbladder wall was the highest (AUC 0.733). The following two were gallbladder length \u0026le; 1.8 cm (AUC 0.682) and NVGB (AUC 0.590). Obviously, their diagnostic efficacies as independent indicators were all limited and so did as they combined with other signs (not list).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cstrong\u003eⅠ\u003c/strong\u003e\u003cstrong\u003e. Clinical and laboratory indicators in NC etiological shunting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.Physical characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsistent with previous literatures and guidelines [1,3], our study showed that pathological jaundice with progressive or transient pale stool and hepatomegaly were the most important clinical features related to BA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.Routine laboratory indicators\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs showed in Table. 3, GGT had the relatively better efficacy in the differential diagnosis of BA, and the cut-off value was \u0026gt; 117 U/L, which was lower than previous literatures [4,5]. And our results suggested that NC neonates with whose DBIL exceeding 87.7 \u0026mu;mol/L and TBIL exceeding 131.9 \u0026mu;mol/L should be alert to the possibility of BA. Accordingly, biochemical examinations might be helpful, but it was insufficient to rely on them alone for NC etiological shunting due to the considerable overlap between the BA and non-BA causes.\u003c/p\u003e\n\u003cp\u003eAt present, there is insufficient clinical evidence for perinatal CMV infection as a cause or trigger of BA [6,7]. Previous studies had shown that non-white BA children had a higher rate of co-infection with CMV [6]. The jaundice clearance rate after Kasai operation and autologous liver survival rate decreased, and postoperative mortality increased in CMV (+) BA children [8,9]. However, the rate of CMV infection in the BA group was lower than the non-BA group in this study cohort. Therefore, the relationship between CMV infection and NC (especially BA) needs further research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.MMP-7\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMMP-7 is a protease responsible for tissue remodeling. It was found to be significantly associated with liver fibrosis [10,11]. Its diagnostic application in BA children was described firstly by Bezerra et al. in 2002 [12]. In 2021, a large sample cohort study based on Chinese people by Chen Yaxing et al. had found that the cut-off value of MMP-7 for the diagnosis of BA was 12.8 ng/ml (AUC 0.98, sensitivity 99%, specificity 93.0% and PPV 94.44%) [11]. In this study, the optimal cut-off value for MMP‐7 was 14.04 ng/ml, with the sensitivity, specificity, PPV and NPV of 100%, 91.67%, 93.7% and 100%, demonstrating an excellent predictive accuracy. Therefore, MMP-7 is a quite valuable biomarker for BA diagnosis, which is superior to GGT and other routine laboratory indicators.\u003c/p\u003e\n\u003cp\u003eIn consequence, when NC children have any of the following clinical characteristics: pale stool, hepatomegaly, GGT \u0026gt; 117U/L, DBIL \u0026gt; 87.7 \u0026mu;mol/L, TBIL \u0026gt;131.9 \u0026mu;mol/L, they should be alert to the possibility of BA. They may act as the early warning indicators for detailed US scans. The widespread application of MMP-7 in clinics is worth popularizing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eⅡ.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eUS signs in NC etiological shunting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1. Observation of abnormal echoes in the portal area\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe typical histopathological features of BA include edema in the portal area, bile duct proliferation, bile plugs, portal or perilobular fibrosis, and inflammatory cell infiltrating around bile ducts [13]. That is the pathological basis for the TC sign, thickened ATRPV and PCTE formation. And another new significant US sign was found in this study \u0026ndash; \u0026ldquo;PV Diameter \u0026gt; 5.1mm\u0026rdquo;.\u003c/p\u003e\n\u003cp\u003eThe TC sign was first discovered by Choi SO et al. in 1996 [14]. Series literatures had showed its high value for the diagnosis of BA [7,15,16]. But there was\u0026nbsp;no clear consensus on where and how to measure\u0026nbsp;the TC, as well as the cut-off value [17,18]. There were two common sites for TC measurement: the maximum anteroposterior diameter of the proliferative fibrous cord in the porta hepatis at a cut-off of \u0026gt; 3-4 mm [14,19], or ATRPV\u0026nbsp;excluding the right HA\u0026nbsp;with a cut-off value as low as 2 mm [5,17,20,21]. In fact, these two parameters all represented the fibrous proliferation in portal area and their measuring sites were very close. In this study, we had lowered the cut-off value of ATRPV down to 1.6 mm by using high-frequency probe and standardizing scan, and it had higher sensitivity than TC sign (90.9% vs. 43.8%) (Table. 5). Combination of them could elevate the sensitivity to 94.4%.\u003c/p\u003e\n\u003cp\u003eThe occurrence of PCTE in BA is related to biliary hyperplasia, bile aggregation, or biliary cystic dilation above obstruction.\u0026nbsp;It can be manifested as solitary or multiple cysts or clustered, irregular tubulars (different from normal hepatic bile ducts) within or adjacent to the proliferative fibrous tissue in the porta hepatis (Fig. 3). If the cyst is large and connected with the gallbladder and extrahepatic biliary tract, it can be detected prenatally and misdiagnosed as biliary dilatation, also known as\u0026nbsp;cystic BA. In previous large sample studies,\u0026nbsp;cystic BA\u0026nbsp;could be found in 5-10% of BA children [6,22]. Overall, PCTE had extremely high specificity and PPV (both 100%) for the discrimination of BA. Once appears, it\u0026nbsp;must evoke the strong suspicion of\u0026nbsp;BA.\u003c/p\u003e\n\u003cp\u003eAlthough not been reported previously, this study found that\u0026nbsp;in NC children younger than 90 days, there was a significant difference in the PV diameter between the two groups - 5.30 (4.40, 5.70) mm in the BA group and 4.30 (3.80, 4.98) mm in the non-BA group, \u003cem\u003ep\u003c/em\u003e = 0.007). When the PV diameter \u0026gt; 5.1 mm, the sensitivity for diagnosing BA was 53.3%, the specificity 91.7% and the PPV 80%. The dilated PV in BA children might be related to liver fibrosis and portal hypertension.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2. Abnormal gallbladder morphological signs\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBefore the use of the TC sign and ATRPV, gallbladder abnormalities were the\u0026nbsp;most\u0026nbsp;widely\u0026nbsp;used\u0026nbsp;US signs for BA. However, the diversities and similarities in shape and size of the gallbladder still made it confusing to discriminate BA from NC children according to the existing classification [17,19,20,23].\u0026nbsp;This study showed that among all the gallbladder morphological signs,\u0026nbsp;the \u0026ldquo;irregularity\u0026rdquo; of the gallbladder wall might be relatively better,\u0026nbsp;which referred to\u0026nbsp;the tortuous, uneven, or irregularly thickened wall (Fig. 2).\u0026nbsp;In the analysis process, the use of double contour lines profilometry in controversial cases could help in the judgment of this sign (Fig. 2).\u0026nbsp;The next two were fasting gallbladder length \u0026le; 1.8 cm and NVGB. But as showed above, the differential performances of all the gallbladder-related signs were not so satisfactory, and they couldn\u0026rsquo;t improve the diagnostic accuracy for BA when\u0026nbsp;combined\u0026nbsp;with other signs.\u0026nbsp;A normal gallbladder couldn\u0026rsquo;t rule out BA. Even so, gallbladder morphological signs still seemed easier to be\u0026nbsp;identified and mastered by the beginners, and an abnormal morphology of gallbladder could help\u0026nbsp;raising our vigilance for further inspection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.HSF and HA diameter\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe presence of the HSF had been considered useful in identifying BA, which was associated with subcapsular telangiectatic vessels. We observed a high specificity of it (96.4%), but a lower positive rate (38.9%) than previous literatures. The differences between literatures might be related to the US probe\u0026rsquo;s sensibility to distinguish slender blood flows with a lower velocity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurthermore, different from previous literatures [4,24,25], there was no significant difference in the HA diameter between the two groups without definite reasons.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.Suggestion for US shunting signs and strategies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSo, based on the above research, any one of the following five US signs: ATRPV \u0026gt; 1.6 mm, PV diameter \u0026gt; 5.1 mm, TC sign, HSF, PCTE could be used as indicators for surgical shunting. Morphological signs of abnormal gallbladder had limited diagnostic efficacy, and they were best to be used combined with the above signs.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThorough clinical indicators and intensive US scan may provide an effective etiological shunting scheme for NC children. We have recommended an optimized diagnosis process as shown in Fig. 4. When the clinical early warning indicators appears, the NC children need detailed US scan, especially the US shunting signs. The abnormal gallbladder morphological signs can be used as useful supplements for clinical judgment. Widely use of MMP-7 in NC shunt is promising.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNC Neonatal cholestasis\u003c/p\u003e\n\u003cp\u003eDBIL Direct bilirubin\u003c/p\u003e\n\u003cp\u003eTBIL Total bilirubin\u003c/p\u003e\n\u003cp\u003eBA Biliary atresia\u003c/p\u003e\n\u003cp\u003eUS Ultrasound\u003c/p\u003e\n\u003cp\u003eGGT \u0026gamma;-glutamyl transferase\u003c/p\u003e\n\u003cp\u003eAKP Alkaline phosphatase alkaline\u003c/p\u003e\n\u003cp\u003eCMV Cytomegalovirus\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMMP-7 Matrix metallopeptidase-7\u003c/p\u003e\n\u003cp\u003eIOC Intraoperative cholangiography\u003c/p\u003e\n\u003cp\u003eROC Operating characteristic\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAUC Area under curve\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePPV Positive predictive value\u003c/p\u003e\n\u003cp\u003eNPV Negative predictive value\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHSF Hepatic subcapsular flow\u003c/p\u003e\n\u003cp\u003ePV Portal vein\u003c/p\u003e\n\u003cp\u003eTC Triangular cord sign\u003c/p\u003e\n\u003cp\u003eNVGB Non-visualization of gallbladder\u003c/p\u003e\n\u003cp\u003ePCTE Portal cystic or tubular echoes\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e Thanks to Dr. Edward C. Mignot, Shandong University, for linguistic advice.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e Data that support the findings of this study are available and can be provided by the corresponding author, based upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e The study protocol was approved by the Ethics Committee of Scientific Research of Shandong University Qilu Hospital. Due to the retrospective design of this study, written informed parental consent was exempted. This study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eNo funding.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRanucci G, Della Corte C, Alberti D, Bondioni MP, Boroni G, Calvo PL, Cananzi M, Candusso M, Clemente MG, D'Antiga L, et al (2022) Diagnostic approach to neonatal and infantile cholestasis: a position paper by the SIGENP liver disease working group. 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Radiology 245 (2): 549\u0026ndash;555. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1148/radiol.2452061093\u003c/span\u003e\u003cspan address=\"10.1148/radiol.2452061093\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e US signs and scan methods of hepatobiliary system and spleen\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"left\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"34%\" colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eUS signs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"66%\"\u003e\n \u003cp\u003e\u003cstrong\u003eScan methods\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.11111111111111%\" rowspan=\"7\"\u003e\n \u003cp\u003eLiver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" colspan=\"2\"\u003e\n \u003cp\u003esize (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"66.66666666666667%\"\u003e\n \u003cp\u003emeasure the maximum subcostal diameter of the right lobe, \u0026gt; 2 cm was hepatomegaly\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\"\u003e\n \u003cp\u003eHA diameter (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"75%\"\u003e\n \u003cp\u003emeasure along the direction of the main PV\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\"\u003e\n \u003cp\u003ePV diameter (mm)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"75%\"\u003e\n \u003cp\u003emeasure within 1.5 cm from the bifurcation of the main PV (Fig 1a)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\"\u003e\n \u003cp\u003eHSF\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"75%\"\u003e\n \u003cp\u003eunder CDFI mode, the velocity scale was \u0026plusmn; 3-5 cm/s, the color box was placed within 3 cm deep from the hepatic capsule, and the HA flow extended to the liver surface without grossly visible artifacts (Fig 1b)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\"\u003e\n \u003cp\u003eTC sign\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"75%\"\u003e\n \u003cp\u003ea hyperechoic cord in the porta hepatis and its size (long, transverse, and anteroposterior diameters) was measured, those with anteroposterior diameters \u0026ge; 3 mm were positive (Fig 1c)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\"\u003e\n \u003cp\u003eATRPV (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"75%\"\u003e\n \u003cp\u003ethe maximum thickness of the anterior wall of the right PV was measured vertically (Fig 1d)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\"\u003e\n \u003cp\u003ePCTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"75%\"\u003e\n \u003cp\u003eit could be cystic or tubular echoes, distributing around the porta hepatis or along the PV (Fig 3); measure the size (length*width) of the cystic echo (cm) or the width of the tubular echo (cm); the vascular structures were excluded by CDFI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.11111111111111%\" rowspan=\"3\"\u003e\n \u003cp\u003eGallbladder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\" colspan=\"2\"\u003e\n \u003cp\u003esize (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"66.66666666666667%\"\u003e\n \u003cp\u003emeasure the length and the width after 4-6 hours fasting and 40-60 minutes later after breastfeeding\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\"\u003e\n \u003cp\u003ewall echo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"75%\"\u003e\n \u003cp\u003ewith or without \u0026ldquo;bilateral sign\u0026rdquo; and \u0026ldquo;irregularity\u0026rdquo; (tortuous, uneven wall or irregular thickening) (Fig 2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25%\" colspan=\"2\"\u003e\n \u003cp\u003econtraction rate (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"75%\"\u003e\n \u003cp\u003e[1- (length*width)\u0026nbsp;after breastfeeding / (length*width) during fasting] *100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.11111111111111%\" colspan=\"2\"\u003e\n \u003cp\u003eSpleen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.22222222222222%\"\u003e\n \u003cp\u003elength (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"66.66666666666667%\"\u003e\n \u003cp\u003emeasure the maximum length of the spleen, \u0026gt; 7 cm was splenomegaly\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eUS\u003c/em\u003e ultrasound, \u003cem\u003eHA\u003c/em\u003e hepatic artery, \u003cem\u003ePV\u003c/em\u003e portal vein, \u003cem\u003eHSF\u003c/em\u003e hepatic subcapsular flow, \u003cem\u003eTC\u003c/em\u003e sign triangular cord sign, \u003cem\u003eATRPV\u003c/em\u003e anterior wall of the right portal vein, \u003cem\u003ePCTE\u003c/em\u003e portal cystic or tubular echoes\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u0026nbsp;\u003c/strong\u003eComparison of clinical and routine laboratory indicators between the BA and non-BA groups\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"83%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBA group (n = 80)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003enon-BA group (n = 72)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003eAge(d)\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e49.0 (39.0, 70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e55.5 (40.0, 68.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e0.444\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; male\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e39 (48.8%)\u003c/p\u003e\n \u003cp\u003e41 (51.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e48 (66.7%)\u003c/p\u003e\n \u003cp\u003e24 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.026\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003eMode of delivery\u003c/p\u003e\n \u003cp\u003ecesarean\u003c/p\u003e\n \u003cp\u003evaginal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e51 (63.8%)\u003c/p\u003e\n \u003cp\u003e29 (36.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38 (52.8%)\u003c/p\u003e\n \u003cp\u003e34 (47.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.170\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003eFeeding pattern\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;exclusive breast\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; formula or mixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e43 (53.8%)\u003c/p\u003e\n \u003cp\u003e37 (46.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e33 (45.8%)\u003c/p\u003e\n \u003cp\u003e39 (54.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.330\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003ePale stool\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e41 (51.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e9 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003eHepatomegaly\u003csup\u003e\u0026dagger;\u003c/sup\u003e \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e26 (32.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e10 (13.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e0.007\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003eSplenomegaly\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e10 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e3 (4.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e0.123\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003eTBIL (\u0026mu;mol/L)\u003csup\u003e\u0026nbsp;#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e158.4 (136.7, 188.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e131.9 (104.6, 166.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003eDBIL (\u0026mu;mol/L)\u003csup\u003e\u0026nbsp;#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e109.7 (93.6, 128.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e85.4 (66.2, 113.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003eD/T (%)\u003csup\u003e\u0026nbsp;#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e71.2 (65.7, 73.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e71.2 (62.4, 73.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e0.518\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003eGGT (U/L)\u003csup\u003e\u0026nbsp;#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e372 (176.0, 669.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e96 (62.0, 182.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003eAKP (U/L)\u003csup\u003e\u0026nbsp;#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e508.5 (424.8, 696.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e625.5 (478.5, 875.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e0.023\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003eCytomegalovirus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.489795918367346%\" valign=\"top\"\u003e\n \u003cp\u003e9 (11.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" valign=\"top\"\u003e\n \u003cp\u003e21 (29.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\" valign=\"top\"\u003e\n \u003cp\u003e0.006\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eBA\u003c/em\u003e biliary atresia, \u003cem\u003eTBIL\u003c/em\u003e total bilirubin, \u003cem\u003eDBIL\u003c/em\u003e direct bilirubin, \u003cem\u003eD/T\u003c/em\u003e DBIL/TBIL, \u003cem\u003eGGT\u003c/em\u003e \u0026gamma;-glutamyl transferase, \u003cem\u003eAKP\u003c/em\u003e alkaline phosphatase alkaline\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e#\u0026nbsp;\u003c/sup\u003eAbnormal distribution, data were medians with the interquartiles (quartile 1 [Q1], quartile 3 [Q3]).\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003eMann-Whitney \u003cem\u003eU\u003c/em\u003e test, \u003csup\u003eb\u0026nbsp;\u003c/sup\u003eChi-Square test, \u003csup\u003e\u0026dagger;\u0026nbsp;\u003c/sup\u003eBy physical examination\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e Diagnostic performances of routine laboratory indicators for the diagnosis of biliary atresia\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"98%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCut-off\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.24742268041237%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAUC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSensitivity (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpecificity (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.309278350515465%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePPV (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNPV (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eGGT (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;117.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e0.825\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"top\"\u003e\n \u003cp\u003e94.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"top\"\u003e\n \u003cp\u003e60.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e78.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e88.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eDBIL (\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;87.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e0.699\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"top\"\u003e\n \u003cp\u003e85.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"top\"\u003e\n \u003cp\u003e58.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e75.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e73.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.916666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eTBIL (\u0026mu;mol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;131.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.333333333333334%\" valign=\"top\"\u003e\n \u003cp\u003e0.668\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"top\"\u003e\n \u003cp\u003e82.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"top\"\u003e\n \u003cp\u003e50.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e71.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"top\"\u003e\n \u003cp\u003e65.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eGGT\u003c/em\u003e \u0026gamma;-glutamyl transferase,\u003cem\u003e\u0026nbsp;DBIL\u003c/em\u003e direct bilirubin, \u003cem\u003eTBIL\u003c/em\u003e total bilirubin, \u003cem\u003eAUC\u003c/em\u003e area under curve, \u003cem\u003ePPV\u003c/em\u003e positive predictive value, \u003cem\u003eNPV\u003c/em\u003e negative predictive value\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u0026nbsp;\u003c/strong\u003eComparison of US signs between the BA and non-BA groups\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"92%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003e\u003cstrong\u003eUS signs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBA group (n=80)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-BA group (n=72)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCut-off\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiver\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eHepatomegaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e46 (57.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e17 (23.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eHSF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e14 (17.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e1 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e0.003\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eHA diameter (mm)\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e1.73 \u0026plusmn; 0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e1.63 \u0026plusmn; 0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e0.236\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003e\u0026gt;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003ePV diameter (mm)\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e5.3 (4.40-5.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e4.3 (3.80-4.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e0.007\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003e\u0026le;5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eTC sign\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e35 (43.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e1 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eATRPV (mm)\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e2.8 (2.15-4.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e1.0(0.80-1.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003e\u0026gt;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003ePCTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e20 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003eGB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eLength (cm)\u003csup\u003e\u0026nbsp;*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e1.86 \u0026plusmn; 0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e2.36 \u0026plusmn; 0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e0.002\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003e\u0026le;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eWidth (cm)\u003csup\u003e\u0026nbsp;#\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e0.4 (0.3-0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e0.5 (0.4-0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e0.014\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003e\u0026le;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eLength-to-width ratio\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e4.17 (3-5.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e4.15 (3.07-6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e0.945\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eNVGB\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e21 (26.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e6 (8.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e0.004\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eUnfilled GB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e5 (6.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e4 (5.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e1.000\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eBilateral sign\u0026nbsp;of GB wall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e42 (52.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e39 (54.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e0.837\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eIrregular GB wall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e54 (67.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e15 (20.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eGB contraction rate (%)\u003csup\u003e\u0026nbsp;#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e3.57 (0-45.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e61.63 (2.42-79.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e0.028\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003e\u0026le;50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpleen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.673469387755105%\"\u003e\n \u003cp\u003eSplenomegaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e10 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.448979591836736%\"\u003e\n \u003cp\u003e6 (8.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e0.261\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eUS\u003c/em\u003e ultrasound, \u003cem\u003eBA\u003c/em\u003e biliary atresia, \u003cem\u003eHSF\u003c/em\u003e hepatic subcapsular flow, \u003cem\u003eHA\u003c/em\u003e hepatic artery, \u003cem\u003ePV\u003c/em\u003e portal vein, \u003cem\u003eTC\u003c/em\u003e sign triangular cord sign, \u003cem\u003eATRPV\u003c/em\u003e anterior wall of the right portal vein, \u003cem\u003ePCTE\u003c/em\u003e portal cystic or tubular echoes, \u003cem\u003eGB\u003c/em\u003e gallbladder, \u003cem\u003eNVGB\u003c/em\u003e Non-visualization of GB, \u003cem\u003eNA\u003c/em\u003e not available\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e*\u0026nbsp;\u003c/sup\u003eNormal distribution, data were means \u0026plusmn; standards deviation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e#\u0026nbsp;\u003c/sup\u003eAbnormal distribution, data were medians with the interquartiles (quartile 1 [Q1], quartile 3 [Q3]).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003eChi-Square test, \u003csup\u003eb\u0026nbsp;\u003c/sup\u003eT test, \u003csup\u003ec\u0026nbsp;\u003c/sup\u003eMann-Whitney \u003cem\u003eU\u003c/em\u003e test, \u003csup\u003ed\u0026nbsp;\u003c/sup\u003eFisher\u0026apos;s exact test\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5\u003c/strong\u003e Diagnostic performances of single or combined US signs for the diagnosis of biliary atresia\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"34.69387755102041%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUS signs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.16326530612245%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAUC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.346938775510203%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Sensitivity (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpecificity (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePPV (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNPV (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cstrong\u003eSingle signs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.05154639175258%\"\u003e\n \u003cp\u003eATRPV\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u0026gt; 1.6 mm \u003cstrong\u003eA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" colspan=\"2\"\u003e\n \u003cp\u003e0.933\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\"\u003e\n \u003cp\u003e90.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e88.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e90.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e88.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.05154639175258%\"\u003e\n \u003cp\u003ePV diameter \u0026gt; 5.1 mm \u003cstrong\u003eB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" colspan=\"2\"\u003e\n \u003cp\u003e0.760\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\"\u003e\n \u003cp\u003e53.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e91.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e80.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e75.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.05154639175258%\"\u003e\n \u003cp\u003eirregular GB wall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" colspan=\"2\"\u003e\n \u003cp\u003e0.733\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\"\u003e\n \u003cp\u003e67.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e79.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e78.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e68.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.05154639175258%\"\u003e\n \u003cp\u003eTC sign \u003cstrong\u003eC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" colspan=\"2\"\u003e\n \u003cp\u003e0.712\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\"\u003e\n \u003cp\u003e43.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e98.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e97.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e61.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.05154639175258%\"\u003e\n \u003cp\u003eGB length \u0026le; 1.8 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" colspan=\"2\"\u003e\n \u003cp\u003e0.682\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\"\u003e\n \u003cp\u003e56.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e74.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e65.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e65.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.05154639175258%\"\u003e\n \u003cp\u003eHSF \u003cstrong\u003eD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" colspan=\"2\"\u003e\n \u003cp\u003e0.677\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\"\u003e\n \u003cp\u003e38.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e96.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e93.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e55.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.05154639175258%\"\u003e\n \u003cp\u003ehepatomegaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" colspan=\"2\"\u003e\n \u003cp\u003e0.669\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\"\u003e\n \u003cp\u003e57.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e76.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e73.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e61.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.05154639175258%\"\u003e\n \u003cp\u003ePCTE\u003cstrong\u003e\u0026nbsp;E\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" colspan=\"2\"\u003e\n \u003cp\u003e0.625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\"\u003e\n \u003cp\u003e25.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e100.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e100.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e54.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.05154639175258%\"\u003e\n \u003cp\u003eNVGB\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" colspan=\"2\"\u003e\n \u003cp\u003e0.590\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\"\u003e\n \u003cp\u003e26.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e91.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e77.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e52.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cstrong\u003eBest sign-combinations (AUC\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u0026ge;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e0.891)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.05154639175258%\"\u003e\n \u003cp\u003eA or C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" colspan=\"2\"\u003e\n \u003cp\u003e0.919\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\"\u003e\n \u003cp\u003e94.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e89.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e91.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e92.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.05154639175258%\"\u003e\n \u003cp\u003eA or B or C or D or E\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.34020618556701%\" colspan=\"2\"\u003e\n \u003cp\u003e0.891\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\"\u003e\n \u003cp\u003e100.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.463917525773196%\"\u003e\n \u003cp\u003e78.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e88.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.371134020618557%\"\u003e\n \u003cp\u003e100.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eUS\u003c/em\u003e ultrasound, \u003cem\u003eATRPV\u003c/em\u003e anterior wall of the right portal vein, \u003cem\u003ePV\u003c/em\u003e portal vein, \u003cem\u003eGB\u0026nbsp;\u003c/em\u003egallbladder, \u003cem\u003eTC\u003c/em\u003e sign triangular cord sign, \u003cem\u003eHSF\u0026nbsp;\u003c/em\u003ehepatic subcapsular flow, \u003cem\u003ePCTE\u003c/em\u003e portal cystic or tubular echoes, \u003cem\u003eNVGB\u003c/em\u003e Non-visualization of GB, \u003cem\u003eAUC\u003c/em\u003e area under curve, \u003cem\u003ePPV\u003c/em\u003e positive predictive value, \u003cem\u003eNPV\u003c/em\u003e negative predictive value\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Neonatal cholestasis, Biliary atresia, Ultrasound, γ-glutamyl transferase, Matrix metallopeptidase-7","lastPublishedDoi":"10.21203/rs.3.rs-2864824/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2864824/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose \u003c/strong\u003eRetrospectively evaluating the biliary atresia (BA) - related ultrasound (US) and clinical indictors and exploring the feasibility of surgical shunting for neonatal cholestasis (NC) with a simplified two-step strategy: clinical indicators and US evaluation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eA total of 152 infants were enrolled and divided into BA group (80 cases) and non-BA group (72 cases). Their detailed US signs, clinical features and laboratory tests were collected, and their diagnostic performances were compared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003eAmong physical and routine laboratory indicators: pale stool, hepatomegaly, γ-glutamyl transferase \u0026gt; 117 U/L, direct bilirubin \u0026gt; 87.7 μmol/L, total bilirubin \u0026gt; 131.9 μmol/L appeared significantly different between the two groups. They could act as the early warning indicators\u003cstrong\u003e \u003c/strong\u003efor detailed US evaluation. The combination of the following five US signs had better diagnostic efficiency with highest sensitivity (100%): “anterior-wall thickness of the right portal vein \u0026gt;1.6 mm”, “triangular cord sign”, “portal vein diameter \u0026gt; 5.1 mm”, “hepatic subcapsular flow” or “porta hepatic cystic or tubular echoes”. They might act as US shunting signs\u003cstrong\u003e \u003c/strong\u003efor surgical exploration. Among the signs of abnormal gallbladder, “irregular gallbladder wall” showed higher efficiency (AUC 0.733), which followed by fasting gallbladder length ≤ 1.8 cm and non-visualization of gallbladder. Moreover, a new laboratory indicator - the matrix metallopeptidase-7 (MMP-7)had an excellent diagnostic value (AUC 0.989) with a cut-off value of 14.04 ng/ml.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions \u003c/strong\u003eWhen the early clinical\u003cstrong\u003e \u003c/strong\u003ewarning indicators appears in NC children, the intensive US evaluation may be helpful in the etiology shunting. And widely use of MMP-7 is promising.\u003c/p\u003e","manuscriptTitle":"Study on Etiological Shunting of Neonatal Cholestasis by High-Frequency Ultrasound Combined with Clinical Indicators","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-05-09 13:50:57","doi":"10.21203/rs.3.rs-2864824/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"08952ea3-2643-4183-ba2b-0276b99dc474","owner":[],"postedDate":"May 9th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-06-11T19:14:19+00:00","versionOfRecord":[],"versionCreatedAt":"2023-05-09 13:50:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2864824","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2864824","identity":"rs-2864824","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}