Early Diagnosis Of Biliary Atresia Research Articles

Comparison for the diagnostic performance of early diagnostic methods for biliary atresia: a systematic review and network meta-analysis.

Biliary atresia (BA), a progressive condition affecting canalicular-bile duct function/anatomy, requires prompt surgical intervention for favorable outcomes. Therefore, we conducted a network meta-analysis of common diagnostic methods to assess their performance and provide evidence-based support for clinical decision-making. We reviewed literature in PubMed, EMBASE, and Cochrane for BA diagnostics. The search included gamma-glutamyl transferase (GGT), direct/combined bilirubin, matrix metalloproteinase 7 (MMP-7), ultrasonic triangular cord sign (TCS), hepatic scintigraphy (HS), and percutaneous cholangiocholangiography/percutaneous transhepatic cholecysto-cholangiography (PCC/PTCC). QUADAS-2 assessed study quality. Heterogeneity and threshold effect were evaluated using I2 and Spearman's correlation. We combined effect estimates, constructed SROC models, and conducted a network meta-analysis based on the ANOVA model, along with meta-regression and subgroup analysis, to obtain precise diagnostic performance assessments for BA. A total of 40 studies were included in our analysis. GGT demonstrated high diagnostic accuracy for BA with a sensitivity of 81.5% (95% CI 0.792-0.836) and specificity of 72.1% (95% CI 0.693-0.748). Direct bilirubin/conjugated bilirubin showed a sensitivity of 87.6% (95% CI 0.833-0.911) but lower specificity of 59.4% (95% CI 0.549-0.638). MMP-7 exhibited a total sensitivity of 91.5% (95% CI 0.893-0.934) and a specificity of 84.3% (95% CI 0.820-0.863). TCS exhibited a sensitivity of 58.1% (95% CI 0.549-0.613) and high specificity of 92.9% (95% CI 0.911-0.944). HS had a high sensitivity of 98.4% (95% CI 0.968-0.994) and moderate specificity of 79.0% (95% CI 0.762-0.816). PCC/PTCC exhibited excellent diagnostic performance with a sensitivity of 100% (95% CI 0.900-1.000) and specificity of 87.0% (95% CI 0.767-0.939). Based on the ANOVA model, the network meta-analysis revealed that MMP-7 ranked second overall, with PCC/PTCC ranking first, both exhibiting superior diagnostic accuracy compared to other techniques. Our analysis showed no significant bias in most methodologies, but MMP-7 and hepatobiliary scintigraphy exhibited biases, with p values of 0.023 and 0.002, respectively. MMP-7 and ultrasound-guided PCC/PTCC show diagnostic potential in the early diagnosis of BA, but their clinical application is restricted due to practical limitations. Currently, the cutoff value of MMP-7 is unclear, and further evidence-based medical research is needed to firmly establish its diagnostic value. Until more evidence is available, MMP-7 is not suitable for widespread diagnostic use. Therefore, considering cost and operational simplicity, liver function tests combined with ultrasound remain the most clinically valuable non-invasive diagnostic methods for BA.

Proteomics Defines Plasma Biomarkers for the Early Diagnosis of Biliary Atresia.

Early diagnosis of biliary atresia (BA) is crucial for improving the chances of survival and preserving the liver function of pediatric patients with BA. Herein, we performed proteomics analysis using data-independent acquisition (DIA) and parallel reaction monitoring (PRM) to explore potential biomarkers for the early diagnosis of BA compared to other non-BA jaundice cases. Consequently, we detected and validated differential protein expression in the plasma of patients with BA compared to the plasma of patients with intrahepatic cholestasis. Bioinformatics analysis revealed the enriched biological processes characteristic of BA by identifying the differential expression of specific proteins. Signaling pathway analysis revealed changes in the expression levels of proteins associated with an alteration in immunoglobulin levels, which is indicative of immune dysfunction in BA. The combination of polymeric immunoglobulin receptor expression and immunoglobulin lambda variable chain (IGL c2225_light_IGLV1-47_IGLJ2), as revealed via machine learning, provided a useful early diagnostic model for BA, with a sensitivity of 0.8, specificity of 1, accuracy of 0.89, and area under the curve value of 0.944. Thus, our study identified a possible effective plasma biomarker for the early diagnosis of BA and could help elucidate the underlying mechanisms of BA.

Progress in Biomarkers Related to Biliary Atresia.

Biliary atresia (BA) is a congenital cholestatic disease that can seriously damage children's liver function. It is one of the main reasons for liver transplantation in children. Early diagnosis of BA is crucial to the prognosis of patients, but there is still a lack of reliable non-invasive diagnostic methods. Additionally, as some children are in urgent need of liver transplantation, evaluating the stage of liver fibrosis and postoperative native liver survival in children with BA using a straightforward, efficient, and less traumatic method is a major focus of doctors. In recent years, an increasing number of BA-related biomarkers have been identified and have shown great potential in the following three aspects of clinical practice: diagnosis, evaluation of the stage of liver fibrosis, and prediction of native liver survival. This review focuses on the pathophysiological function and clinical application of three novel BA-related biomarkers, namely MMP-7, FGF-19, and M2BPGi. Furthermore, progress in well-known biomarkers of BA such as gamma-glutamyltransferase, circulating cytokines, and other potential biomarkers is discussed, aiming to provide a reference for clinical practice.

Development and validation of a model for early diagnosis of biliary atresia

Background and aimsEarly diagnosis of biliary atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis (NC), is challenging. This study aimed to design and validate a predictive model for BA by using the data available at the initial presentation.MethodsInfants presenting with NC were retrospectively identified from tertiary referral hospitals and constituted the model design cohort (n = 148); others were enrolled in a prospective observational study and constituted the validation cohort (n = 21). Clinical, laboratory, and abdominal ultrasonographic features associated with BA were assessed. A prediction model was developed using logistic regression and decision tree (DT) analyses.ResultsThree predictors, namely, gamma glutamyl transpeptidase (γGT) level, triangular cord sign (TC sign), and gallbladder abnormalities, were identified as factors for diagnosing BA in multivariate logistic regression, which was used to develop the DT model. The area under the receiver operating characteristic (ROC) curve (AUC) value for the model was 0.905, which was greater than those for γGT level, TC sign, or gallbladder abnormalities alone in the prediction of BA.ConclusionA simple prediction model combining liver function and abdominal ultrasonography findings can provide a moderate and early estimate of the risk of BA in patients with NC.

A novel prediction tool based on shear wave elastography, gallbladder ultrasound, and serum biomarkers for the early diagnosis of biliary atresia in infants younger than 60 days old

Early Kasai surgery before 60 days of life results in better clinical outcomes in patients with biliary atresia (BA). We aimed to develop and validate a prediction tool for the early diagnosis of BA in infants younger than 60 days old. This prospective study recruited consecutive infants younger than 60 days old with conjugated hyperbilirubinemia who were evaluated with an ultrasound (US) scan, including B-mode US with color Doppler flow imaging (CDFI) features and liver two-dimensional shear wave elastography (2D SWE), from March 2017 to July 2021. The reference standard for diagnosis was intraoperative cholangiography, liver biopsy, or the resolution of jaundice. Area under the receiver operating characteristic curve (AUC) analysis, logistic regression analysis, and establishment of a nomogram were performed. A total of 174 patients (mean age, 46 days), including 87 infants with BA and 87 non-BA cholestatic infants, were included in the study. The established nomogram based on gallbladder (GB) abnormality, liver 2D SWE, and serum γ-glutamyl transferase (GGT) and alanine aminotransferase (ALT) had an AUC of 0.99 [95% confidence interval (CI): 0.94-1.00], a sensitivity of 92%, and a specificity of 100%. The nomogram in the validation cohort also had good diagnostic performance in the diagnosis of BA, with an AUC of 0.98 (95% CI: 0.95-1.00). The new prediction tool had a good diagnostic performance in the early prediction of BA in infants younger than 60 days old and will facilitate timely Kasai surgery.

Management of children with operable biliary atresia, single center experience

Biliary Atresia (BA) is a devastating pediatric cholangiopathy affecting the bile ducts of the liver. Early diagnosis of BA is important, as the negative impact of late surgery is worse coming. Aim: We aimed to highlight the characteristics, management strategies and outcome of BA patients managed in our center.

Diagnostic Efficacy of Advanced Ultrasonography Imaging Techniques in Infants with Biliary Atresia (BA): A Systematic Review and Meta-Analysis.

The early diagnosis of biliary atresia (BA) in cholestatic infants is critical to the success of the treatment. Intraoperative cholangiography (IOC), an invasive imaging technique, is the current strategy for the diagnosis of BA. Ultrasonography has advanced over recent years and emerging techniques such as shear wave elastography (SWE) have the potential to improve BA diagnosis. This review sought to evaluate the diagnostic efficacy of advanced ultrasonography techniques in the diagnosis of BA. Six databases (CINAHL, Medline, PubMed, Google Scholar, Web of Science (core collection), and Embase) were searched for studies assessing the diagnostic performance of advanced ultrasonography techniques in differentiating BA from non-BA causes of infantile cholestasis. The meta-analysis was performed using Meta-DiSc 1.4 and Comprehensive Meta-analysis v3 software. Quality Assessment of Diagnostic Accuracy Studies tool version 2 (QUADAS-2) assessed the risk of bias. Fifteen studies consisting of 2185 patients (BA = 1105; non-BA = 1080) met the inclusion criteria. SWE was the only advanced ultrasonography technique reported and had a good pooled diagnostic performance (sensitivity = 83%; specificity = 77%; AUC = 0.896). Liver stiffness indicators were significantly higher in BA compared to non-BA patients (p < 0.000). SWE could be a useful tool in differentiating BA from non-BA causes of infantile cholestasis. Future studies to assess the utility of other advanced ultrasonography techniques are recommended.

Diagnostic values of plasma matrix metalloproteinase-7, interleukin-8, and gamma-glutamyl transferase in biliary atresia.

Biliary atresia (BA) is a severe cholestatic liver disease in children featuring cholestasis and liver fibrosis. The early diagnosis of BA is still challenging. This study aimed to evaluate the diagnostic values of matrix metalloprotease-7 (MMP-7), interleukin-8 (IL-8), and gamma-glutamyl transferase (GGT) in BA. Infants diagnosed with BA and non-BA between 2013 and 2018 were retrospectively analyzed. Plasma levels of MMP-7, IL-8, and GGT were measured in these infants. The receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were used to assess the diagnostic values of MMP-7, IL-8, and GGT. The expression of MMP-7 and IL-8 in the livers was detected by immunofluorescence staining. A total of 229 infants were enrolled in this study: 156 BA infants and 73 non-BA infants including 16 ones with infantile hepatitis syndrome. The plasma levels of MMP-7, IL-8, and GGT in BA infants had a median of 11.8ng/mL (interquartile range, IQR: 5.3-57.5), 1.5ng/mL (IQR: 1.0-2.8), and 381.0 U/L (IQR: 197.0-749.0), respectively, which were higher than non-BA subjects [MMP-7, 4.4ng/mL (IQR: 3.3-6.1); IL-8, 0.7ng/mL (IQR: 0.5-1.0); GGT, 59.0 U/L (IQR: 26.0-124.0)]. The AUC values of MMP-7, IL-8, and GGT for the diagnosis of BA were 0.8035, 0.8083, and 0.9126, respectively. The AUC values of MMP-7 + IL-8, MMP-7 + GGT, IL-8 + GGT, and MMP-7 + IL-8 + GGT for the diagnosis of BA were 0.8248, 0.9382, 0.9168, and 0.9392, respectively. The AUC values of MMP-7, IL-8, and GGT for differentiating BA infants with cholic stool from non-BA infants with cholic stool were 0.8006, 0.8258, and 0.9141, respectively. The expression of MMP-7 and IL-8 was increased in the cholangiocytes in BA livers. Conclusion: Plasma MMP-7, IL-8, and GGT alone or a combination of them has good accuracy to differentiate BA from non-BA and may be reliable biomarkers for BA. What is Known: • Biliary atresia (BA) is a severe cholestatic liver disease in children featuring cholestasis and progressive liver fibrosis. • Although early diagnosis of BA is crucial for good outcomes, it remains a clinical challenge. What is New: • Plasma MMP-7, IL-8, and GGT alone or a combination of them has good accuracy to differentiate BA from non-BA. • Plasma MMP-7, IL-8, and GGT have good accuracy for differentiating BA infants with cholic stool from non-BA infants with cholic stool.

Demographic Characteristics of Children with Biliary Atresia in dr. Kariadi General Hospital, Semarang

Background: Biliary atresia (BA) is a progressive fibrosing obstructive cholangiopathy involving both the intrahepatic and extrahepatic biliary system; resulting in obstruction of bile flow and neonatal jaundice. Early diagnosis of biliary atresia and Kasai procedure improves patients outcome. Data form several studies revealed that BA is the most common cause of neonatal cholestasis (25%) and the leading cause of end-stage liver disease in pediatric population. The aim of this study is to determine the outcome and characteristics of children with biliary atresia in dr. Kariadi General Hospital, Semarang.
 Methods: In this study, a retrospective database analysis of 80 infants diagnosed with biliary atresia was conducted. Patient’s demographic data including age, sex, age at disease onset, were collected from year 2018 to 2022; including all comorbidities and complications. Data regarding procedure performed for each patient and their outcome were included in this study. 
 Results: Eighty children were included in this study. The mean age of children referred with biliary atresia was 1.89 month, while the mean age at diagnosis was 2.5 month. Most of the patients were girls. The incidence of cytomegalovirus infection comorbidity in patients with biliary atresia is quite high, which were reported at 82%. Children diagnosed with biliary atresia and cytomegalovirus infection resulted in worse prognosis than those without.
 Conclusion: Our study support the theories that biliary atresia may be caused by the exposure of external environment during perinatal period such as viral infection. The prognosis of patients with cytomegalovirus comorbidity is worse than that without.

Gamma-glutamyl transpeptidase has different efficacy on biliary atresia diagnosis in different hospital patient groups: an application of machine learning approach.

Gamma-glutamyl transpeptidase (GGT) is the most widely used biomarker in the early diagnosis of biliary atresia (BA), but its diagnostic efficacy is questionable in different sub-populations. We aim to identify subgroups that are defined by specific variables with cut-offs and can significantly affect the diagnostic efficacy of GGT for detecting BA. Clinical data from 1273 infants with neonatal obstructive jaundice (NOJ) diagnosed between January 2012 and December 2017 at the Children's Hospital of Fudan University were enrolled, reviewed, and analyzed. Random forest-based Virtual Twins method was used to identify potential subgroups. Hemoglobin (HGB) and fasting gallbladder filling were selected as defining variables. The diagnostic efficacy of GGT was significantly better (AUC = 0.855) for patients with hemoglobin (HGB) ≤ 105g/L and a gallbladder that was not or poorly filled. Diagnostic efficacy was worst in the subgroup defined by HGB > 105g/L (AUC = 0.722). The inclusion of interaction terms between GGT and the subgroups in a logistic regression model significantly improved (p = 0.002) prediction performance. This study provides evidence that the diagnostic efficacy of GGT can differ significantly across different subgroups. Therefore, a GGT diagnostic result should be interpreted cautiously when patients belong to subgroups with low diagnostic efficacy. The development of a prediction model and/or clinical diagnostic pathway for early detection of BA should also account for the heterogeneous diagnostic efficacy of GGT.

Ultrasound for the Diagnosis of Biliary Atresia: From Conventional Ultrasound to Artificial Intelligence.

Biliary atresia is an aggressive liver disease of infancy and can cause death without timely surgical intervention. Early diagnosis of biliary atresia is critical to the recovery of bile drainage and long-term transplant-free survival. Ultrasound is recommended as the initial imaging strategy for the diagnosis of biliary atresia. Numerous ultrasound features have been proved helpful for the diagnosis of biliary atresia. In recent years, with the help of new technologies such as elastography ultrasound, contrast-enhanced ultrasound and artificial intelligence, the diagnostic performance of ultrasound has been significantly improved. In this review, various ultrasound features in the diagnosis of biliary atresia are summarized. A diagnostic decision flow chart for biliary atresia is proposed on the basis of the hybrid technologies, combining conventional ultrasound, elastography and contrast-enhanced ultrasound. In addition, the application of artificial intelligence in the diagnosis of biliary atresia with ultrasound images is also introduced.

Latest diagnostic performance of different ultrasonic features for biliary atresia.

Early diagnosis of biliary atresia (BA) is an important clinical challenge. To summarize the latest diagnostic performance of different ultrasonic (US) features for BA. MeSH terms "biliary atresia" and "ultrasonography" and related hyponyms were used to search PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Eligible articles were included and data were retrieved. The methodologic quality was assessed by version 2 of the Quality Assessment of Diagnostic Accuracy Studies tool. Estimated sensitivity and specificity of each US feature were calculated by Stata 14.0. Fifty eligible studies on 5622 patients were included. Respective summary sensitivity and specificity were 77% (95% CI=69-84) and 98% (95% CI=96-99) for triangular cord sign (TCS) in 32 studies, 86% (95% CI=78-92) and 86% (95% CI=72-94) for shear wave elastography (SWE) in seven studies, 75% (95% CI=65-83) and 92% (95% CI=86-95) for gallbladder and biliary system abnormality (GBA) in 25 studies, and 81% (95% CI=69-90) and 79% (95% CI=67-87) for hepatic artery (HA) enlargement in seven studies. The overall US features from 11 studies yielded a summary sensitivity of 84% (95% CI=72-92) and specificity of 86% (95% CI=77-92). TCS and GBA were the two most widely accepted US features currently used for differential diagnosis of BA. The newly developed SWE was an objective and convenient method with good diagnostic performance. HA enlargement can be used as an auxiliary sign.

The triangular cord ratio and the presence of a cystic lesion in the triangular cord. Suggested new ultrasound findings in the early diagnosis of Biliary Atresia.

In biliary atresia (BA), the ultrasonic triangular cord (TC) sign is positive at ≥ 3mm, but sometimes there is BA even if it is ≤ 3mm. For improving the ultrasonographic diagnosis, we have established a new evaluation, adding the ratio of the anterior/posterior thickness (TC ratio) in the hyperechoic area and the presence of a cystic lesion in the triangular cord (TCC). We examined 24 cases of suspected BA who demonstrated acholic stools from 2006 to 2020. We retrospectively reviewed the timing of ultrasonographic diagnosis, the gallbladder diameter, gallbladder mucosal irregularity, the TC sign, TCC, and the TC ratio. In the BA group (n = 10) vs the Non-BA group (n = 14), the age at ultrasonography was 75 ± 41.7 vs. 81 ± 39.1days (p = 0.72), the gallbladder diameter was 12.1 ± 9.7 vs. 24.2 ± 6.96mm (p = 0.02), irregularity of gallbladder mucosa was 7 cases vs. 1 case (p < 0.01), and TC sign was 3.9 ± 1.3 vs. 2.0 ± 0.49mm (p = 0.01), respectively. TCC was observed in 8/10 cases in the BA group and none in the Non-BA group (p < 0.01). TC ratio was 3.40 ± 0.68 (BA group) and 1.59 ± 0.41 (Non-BA group) (p < 0.01). The ultrasonic TC ratio improves the diagnostic accuracy of BA. TCC is a specific finding in the BA group.

Biomarkers for the diagnosis and post-Kasai portoenterostomy prognosis of biliary atresia: a systematic review and meta-analysis

To evaluate the accuracy of biomarkers for the early diagnosis of biliary atresia (BA) and prognostic stratification after Kasai portoenterostomy (KPE). We conducted a systematic review of PubMed, Web of Science, Embase, Scopus and OVID for English literature reporting BA biomarkers published before August 2020. Screening, data extraction, and quality assessment were performed in duplicate. A total of 51 eligible studies were included in the systematic review, and data from 12 (4182 subjects) were extracted for meta-analysis regarding the following 2 domains: (1) serum matrix metallopeptidase-7 (MMP-7), interleukin33 (IL-33) and γ-glutamyl transferase (GGT) to differentiate BA from non-BA; (2) the aspartate aminotransferase to platelet ratio index (APRi) to predict post-KPE liver fibrosis/cirrhosis. The summary sensitivity, specificity and area under the curve (AUC) of MMP-7 for diagnosing BA were 96%, 91% and 0.9847, respectively, and those of GGT were 80%, 79% and 0.9645, respectively. The summary sensitivity and specificity of IL-33 for diagnosing BA were 77% and 85%, respectively. The summary sensitivity and specificity of APRi for predicting post-KPE liver fibrosis were 61% and 80%, respectively, and the summary sensitivity, specificity and AUC of APRi for predicting post-KPE cirrhosis were 78%, 83% and 0.8729, respectively. Moreover, good evidence was shown in investigations of serum IL-18 and IL-33 in distinguishing BA from healthy controls, serum IL-18 for prognosis of post-KPE persistent jaundice, and serum hyaluronic acid and MMP-7 for prognosis of post-KPE significant liver fibrosis. MMP-7, IL-33 and GGT are useful biomarkers to assist in the diagnosis of BA. APRi might be used to predict post-KPE significant liver fibrosis and cirrhosis. These noninvasive biomarkers can be integrated into the management protocol of BA.

Diagnostic Performance of Transient Elastography in Biliary Atresia Among Infants With Cholestasis.

Biliary atresia (BA) is a challenging liver disease in infancy. Early diagnosis of BA is important for timely hepatoportoenterostomy. We evaluated the age‐specific diagnostic performance of transient elastography (TE) with a liver stiffness measurement (LSM) greater than 7.7 kPa in BA among infants with cholestasis. A total of 61 infants with cholestasis (5‐121 days of age) were enrolled in this prospective follow‐up study; 15 infants were BA. Four age groups were defined (≤30, 31‐60, 61‐90, and 91‐180 days). Picrosirius red staining was performed to quantify the percentage of collagen fibers in liver specimens. The utility of an LSM greater than 7.7 kPa for diagnosis of BA among infants with cholestasis was compared among age groups. In all four groups, TE showed high diagnostic power for BA using the criterion of an LSM greater than 7.7 kPa. Positive predictive values were 100%, 100%, and 100% in the groups aged 30 days or younger, 31 to 60 days, and 61 to 90 days, respectively. Respective negative predictive values were 90.9%, 94.7%, and 100%, and respective diagnostic accuracies were 92.9%, 95.2%, and 100%. The positive predictive value, negative predictive value, and diagnostic accuracy were 100%, 100%, and 100%, respectively, for LSM greater than 8.8 kPa in the group aged 91 to 180 days. The LSM was positively correlated with the percentage of collagen fibers stained by picrosirius red (P = 0.03). Conclusion: In this prospective follow‐up study, TE had good diagnostic accuracy for differentiation of BA from non‐BA cholestasis in infants with cholestasis who were 90 days of age or younger. The LSM was significantly positive correlated with the liver fibrosis status stained by picrosirius red in infants with cholestasis.

Efficacy of Shear Wave Elastography for the Early Diagnosis of Biliary Atresia

Efficacy of Shear Wave Elastography for the Early Diagnosis of Biliary Atresia

A novel mobile phone application for infant stool color recognition: An easy and effective tool to identify acholic stools in newborns.

Early diagnosis of biliary atresia is essential to improve long-term outcomes. Newborn screening with an infant stool color card allows early recognition of biliary atresia patients. Our aim was to develop and validate a mobile phone application (PopòApp) able to identify acholic stools. An intuitive app was developed for iOS and Android smartphones. A learning machine process was used to generate an algorithm for stools color recognition based on the seven colors of the infant stool color card, which were considered as the gold standard. Consecutive images of stools were taken by the PopòApp, directly into the diapers of children aged ≤6 months. The PopòApp classified the photographs as "normal", "acholic" or "uncertain". To validate the PopòApp, four doctors independently classified all images, and only those for which all doctors agreed were included. The sensitivity, specificity, positive/negative predictive values, and accuracy of the PopòApp were evaluated. Of 165 images collected, 160 were included in the study. All acholic stools were recognized by the PopòApp. The PopòApp sensitivity was 100% (95% CI:93.9%-100%) with no false negatives, regardless of the brand of phone. The specificity was 99.0% (95% CI:94.6%-99.9%). The accurancy of the PopòApp was 99.4% (95% CI:96.6%-99.9%), with a positive predictive value of 98.4% (95% CI:89.8%-99.8%). The current study proved, in a large cohort, that the PopòApp is an accurate and easy tool for recognition of acholic stools. The mobile App may represent an effective strategy for the early referral of children with acholic stools, and potentially could improve the outcomes of biliary atresia.

Gamma-Glutamyl Transpeptidase Has Different Efficacy on Biliary Atresia Diagnosis in Different Hospital Patient Groups - An Application of Machine Learning Approach

Background: Gamma-glutamyl transpeptidase (GGT) is the most widely used biomarker in the early diagnosis of biliary atresia (BA), but its diagnostic efficacy is questionable in different sub-populations. We aim to identify subgroups that are defined by specific variables with cut-offs and can significantly affect the diagnostic efficacy of GGT for detecting BA. Methods: Clinical data from 1273 infants with neonatal obstructive jaundice (NOJ) diagnosed between January 2012 and December 2017 at the Children’s Hospital of Fudan University were collected, reviewed, and analyzed. Random forest-based Virtual Twins method was used to identify potential subgroups . Findings: Hemoglobin (HGB) and fasting gallbladder filling were selected as defining variables. The diagnostic efficacy of GGT was significantly better (AUC=0.855) for patients with hemoglobin (HGB)≤105 g/L and a gallbladder that was not or poorly filled. Diagnostic efficacy was worst in the subgroup defined by HGB>105 g/L (AUC=0.722). The inclusion of interaction terms between GGT and the subgroups in a logistic regression model significantly improved (p=0.002) prediction performance. Interpretation: This study provides evidence that the diagnostic efficacy of GGT can differ significantly across different subgroups. Therefore, a GGT diagnostic result should be interpreted cautiously when patients belong to subgroups with low diagnostic efficacy. The development of a prediction model and/or clinical diagnostic pathway for early detection of BA should also account for the heterogeneous diagnostic efficacy of GGT. Funding Statement: This study received financial support from Shanghai Key Disciplines (no.2017ZZ02022), National Natural Science Foundation of China (no. 81770519, no. 81771633, no. 81873545 and no. 81974059), The Science Foundation of Shanghai (no. 14411969800, no. 16411952200, no. 18411969100 and 19ZR1406600), and Children's National Medical Center (no. EK1125180104, no. EKYY20180204, EK112520180211 and no. EK112520180310). Declaration of Interests: The authors have no conflict of interest to disclose. Ethics Approval Statement: The study was approved by the Ethics Committee of the Children’s Hospital of Fudan University. Written informed consent was obtained from the legal guardians of all patients before the enrollment of the study.

The evolution of early liver biopsy findings in babies with jaundice may delay the diagnosis and treatment of biliary atresia

BackgroundThe early diagnosis of biliary atresia (BA) is associated with a better outcome after portoenterostomy. However, very early liver biopsy findings may appear atypical for BA and delay diagnosis. Repeat biopsy histology may change rapidly to show more typical features. MethodsBetween 1997 and 2018, 6 babies with jaundice had more than one biopsy to establish diagnosis. Clinical and histologic data were collected. chi-Square was used for analysis (p < 0.05 significant). ResultsFive patients had two biopsies, and one had three. Median age at first, second, and third biopsy was 40 (13–57), 68.5 (35–78), and 133 days, respectively. Biopsy readings showed no portal edema initially (0/6), but in all 6 on repeat biopsy (p = 0.001). Bile duct proliferation was seen in 6/6 final biopsies, but in only 1/6 initially (p = 0.003). All patients underwent a portoenterostomy (median age 75 days (43–113)). Median delay between initial biopsy and Kasai was 29 days (14–67). Transplant free survival (n = 5 patients) ranged from 184 to 716 days (median 309 days). One patient died before being transplanted. ConclusionEarly biopsies may not display characteristic findings of BA, but these can appear quickly on subsequent evaluation. The interval needed to repeat a biopsy may have an adverse effect on bile drainage. Level of EvidenceIV

Hepatic Subcapsular Flow as a Significant Diagnostic Marker for Biliary Atresia: A Meta-Analysis.

Aim Increasing evidence indicates that hepatic subcapsular flow (HSF) can serve as a noninvasive ultrasonographic marker for the early diagnosis of biliary atresia (BA). However, results regarding its diagnostic accuracy are inconsistent and inconclusive. We conducted this meta-analysis with an aim to systematically evaluate the diagnostic value of HSF in predicting BA. Methods A comprehensive literature search of four databases was conducted to identify the eligible studies. All analyses were performed using STATA 12.0. Results Nine studies from eight articles containing 368 patients and 469 controls were included in our meta-analysis. Briefly, the values for pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.95 (95% CI 0.88-0.98), 0.92 (95% CI 0.85-0.96), 11.6 (95% CI 6.3-21.5), 0.06 (95% CI 0.02-0.14), 201 (95% CI 59-689), and 0.98 (95% CI 0.96-0.99), respectively. Additionally, metaregression along with subgroup analysis based on various covariates revealed the potential sources of heterogeneity and the detailed diagnostic value in each subgroup. Conclusion Our meta-analysis showed that HSF assay could provide high accuracy in predicting BA patients and non-BA individuals. However, further studies with better design and larger sample size are required to support the results of the present study.