Diagnosis Of Biliary Atresia Research Articles

Utility of Serum Matrix Metalloproteinase-7 as a Biomarker in Cholestatic Infants with Congenital Heart Disease.

Background: Matrix metalloproteinase 7 (MMP-7) is a novel biomarker for diagnosis of biliary atresia (BA), the most common cholestatic liver disease in infancy. There is a pressing need to determine the utility of MMP-7 levels in infants with congenital heart disease (CHD) to avoid unnecessary invasive diagnostic procedures in this high-risk population. We investigated the utility of MMP-7 in discriminating BA from non-BA cholestasis in infants with CHD and whether MMP-7 elevation was present in infants requiring treatment for clinically significant PH. Methods: This is a single center cross sectional study including infants <180 days of age with cholestasis and serum MMP-7 levels collected from 2019-2023. Demographic data and descriptive statistics were summarized with medians with interquartile ranges and frequencies with percentages. Median MMP-7 levels were assessed via Wilcoxon rank-sum test. Results: A total of 149 patients were included. Patients with CHD had significantly elevated MMP-7 levels relative to the non-CHD cohort (50 vs. 34 ng/mL, p=0.009). Sub-analysis comparing infants with and without PH revealed significantly elevated median MMP-7 levels in those with clinically significant PH (125 vs. 39 ng/mL, p=0.010). CHD patients with PH had greater median MMP-7 compared to CHD patients without PH (154 vs 43 ng/mL, p=0.028). Conclusions: Serum MMP-7 levels in infants with CHD-C were significantly elevated compared to those with cholestasis alone. MMP-7 may help identify non-BA cholestatic infants who have concurrent clinically significant pulmonary hypertension. Larger, prospective studies are needed to validate this finding and establish CHD-specific MMP-7 cutoffs.

Deep learning-driven ultrasound-assisted diagnosis: optimizing GallScopeNet for precise identification of biliary atresia.

Biliary atresia (BA) is a severe congenital biliary developmental abnormality threatening neonatal health. Traditional diagnostic methods rely heavily on experienced radiologists, making the process time-consuming and prone to variability. The application of deep learning for the automated diagnosis of BA remains underexplored. This study introduces GallScopeNet, a deep learning model designed to improve diagnostic efficiency and accuracy through innovative architecture and advanced feature extraction techniques. The model utilizes data from a carefully constructed dataset of gallbladder ultrasound images. A dataset comprising thousands of ultrasound images was employed, with the majority used for training and validation and a subset reserved for external testing. The model's performance was evaluated using five-fold cross-validation and external assessment, employing metrics such as accuracy and the area under the receiver operating characteristic curve (AUC), compared against clinical diagnostic standards. GallScopeNet demonstrated exceptional performance in distinguishing BA from non-BA cases. In the external test dataset, GallScopeNet achieved an accuracy of 81.21% and an AUC of 0.85, indicating strong diagnostic capabilities. The results highlighted the model's ability to maintain high classification performance, reducing misdiagnosis and missed diagnosis. GallScopeNet effectively differentiates between BA and non-BA images, demonstrating significant potential and reliability for early diagnosis. The system's high efficiency and accuracy suggest it could serve as a valuable diagnostic tool in clinical settings, providing substantial technical support for improving diagnostic workflows.

Independent Risk Factors and Economic Burden Associated With Delayed Extubation Following Pediatric Liver Transplantation.

Successful early extubation (EE) after liver transplant (LT) has been shown to reduce intensive care unit (ICU) and hospital length of stay and infectious, vascular, and sedation-related complications in adults. EE may not always be feasible in children, and many may require prolonged mechanical ventilation. Limited data exists regarding the candidacy of EE, risk factors, consequences, and hospital costs of delayed extubation (DE) in pediatric LT. We conducted a retrospective review to investigate predictive factors and associated costs of EE and DE in infants and children after orthotopic LT at our institution between 2011 and 2021. Of 338 LT (median age 39 months, 54% females), 246 (73%) had EE (within 24 h of LT), while 27% had DE. Age < 1 year (p = 0.0019), diagnosis of biliary atresia (0.02), abnormal pre-LT echocardiogram (0.02), and patients with ongoing hospital admission before LT (0.0001) were independently associated with DE. Hospital costs were significantly (∼3-fold) higher (p < 0.0001) in the DE group. In addition, factors associated with increased total hospital costs were age < 1 year and hospitalization before LT. EE post-LT is feasible and merits a trial. The prevalence of DE though modest is associated with increased resource utilization and hospital costs. Children who can be extubated early and those at risk for DE can be identified pre-operatively for optimal planning and allocation of resources.

The Assessment and Management of Biliary Atresia in Hawai'i, 2009-2023.

Although biliary atresia (BA) is a rare neonatal disorder, it remains the leading cause of pediatric end-stage liver disease. Early diagnosis of BA and treatment with the Kasai procedure can significantly reduce the need for pediatric liver transplant. Current data suggests that performing the Kasai procedure at 30-45 days of life is associated with longer native liver survival rates and reduction of the need for liver transplant. The incidence rate of BA in the state of Hawai'i is nearly double the incidence rate in the continental US. International studies have demonstrated that screening programs for BA reduce the age at diagnosis and treatment. However, there has been no statewide analysis on the ages at diagnosis or at Kasai, nor does a statewide screening program for BA exist. The purpose of this study is to review the age of diagnosis and treatment of BA to determine if the current practice in Hawai'i is in line with the published data. A retrospective chart review of all patients diagnosed with BA at the state's primary children's hospital was performed (2009-2023) and 19 patients who underwent the Kasai procedure were identified. The mean age at diagnosis is 71.4 days (n=19) and the mean age at Kasai procedure is 72.0 days (n=19). Both the average age at diagnosis and treatment for BA in Hawai'i is significantly higher than published data suggesting best outcomes at 30-45 days of life. This review suggests that the implementation of a statewide screening program for BA in Hawai'i is warranted.

Identification of Novel Biomarkers for Post-Kasai Portoenterostomy in Biliary Atresia through Shotgun Proteomics Analysis

Introduction: Biliary Atresia (BA) causes neonatal cholestasis jaundice. The primary therapeutic treatment for BA is the Kasai portoenterostomy. Current diagnostic approaches for BA are imprecise and time-consuming, making early diagnosis crucial for successful treatment outcomes. Objective: This study aims to analyze proteins from Peripheral Blood Mononuclear Cells (PBMCs) obtained from children with BA compared with healthy children Methods and Study Design: We employed a large-scale, total shotgun quantitative serum proteomics approach to analyze the protein from PBMC samples from a discovery cohort. This approach allowed for the simultaneous identification and quantification of multiple proteins, enabling the detection of disease-specific protein expression patterns. The study is proteomic-based study. Results: We identified 24 proteins, by Liquid Chromatography-Mass Spectrometry (LC-MS) analysis that exhibited high discriminatory power for five subjects with BA post-Kasai operation compared to ten healthy controls. ATP2A3, LIN28B, SLC25A3, ITGB3, COX5A, and HLA-B identified proteins of upregulation were predicted to associate with BA post-Kasai operation. Discussion: Our findings highlight the utility of proteomic techniques in BA research. The identified proteomic markers offer promise for improving BA diagnostic accuracy and timeliness, leading to enhanced treatment outcomes for affected children. Conclusion: Proteomic analysis revealed a set of potential biomarkers for early and accurate diagnosis of biliary atresia. These biomarkers hold significant clinical value and have the potential to transform the management of biliary atresia by facilitating timely intervention and improving patient outcomes.

Polymeric immunoglobulin receptor promotes Th2 immune response in the liver by increasing cholangiocytes derived IL-33: a diagnostic and therapeutic biomarker of biliary atresia

Biliary atresia (BA) is a devastating neonatal cholangiopathy with an unclear pathogenesis, and prompt diagnosis of BA is currently challenging. Proteomic and immunoassay analyses were performed with serum samples from 250 patients to find potential BA biomarkers. The expression features of polymeric immunoglobulin receptor (PIGR) were investigated using human biopsy samples, three different experimental mouse models, and cultured human biliary epithelial cells (BECs). Chemically modified small interfering RNA and adenovirus expression vector were applied for invivo silencing and overexpressing PIGR in a rotavirus-induced BA mouse model. Luminex-based multiplex cytokine assays and RNA sequencing were used to explore the molecular mechanism of PIGR involvement in the BA pathogenesis. Serum levels of PIGR, poliovirus receptor (PVR), and aldolase B (ALDOB) were increased in BA patients and accurately distinguished BA from infantile hepatitis syndrome (IHS). Combined PIGR and PVR analysis distinguished BA from IHS with an area under the receiver operating characteristic curve of 0.968 and an accuracy of 0.935. PIGR expression was upregulated in the biliary epithelium of BA patients; Th1 cytokines TNF-α and IFN-γ induced PIGR expression in BECs via activating NF-κB pathway. Silencing PIGR alleviated symptoms, reduced IL-33 expression, and restrained hepatic Th2 inflammation in BA mouse model; while overexpressing PIGR increased liver fibrosis and IL-33 expression, and boosted hepatic Th2 inflammation in BA mouse model. PIGR expression promotes the proliferation and epithelial-mesenchymal transition, and reduced the apoptosis of BECs. PIGR participated in BA pathogenesis by promoting hepatic Th2 inflammation via increasing cholangiocytes derived IL-33; PIGR has the value as a diagnostic and therapeutic biomarker of BA. This study was financially supported by the National Natural Science Foundation of China (82170529), the National Key R&D Program (2021YFC2701003), and the National Natural Science Foundation of China (82272022).

A case series of prenatal hepatic hilar cyst in the presence of a gallbladder - navigating the dilemma between biliary atresia and choledochal cyst

BackgroundPrenatally diagnosed hepatic hilar cysts are a challenging finding for the clinician. They can either be a sign of cystic biliary atresia (BA) or a choledochal cyst (CC), two diagnoses with different postnatal management and prognosis. Based on a case report of four patients, we aim to propose a management algorithm for prenatally diagnosed “hepatic hilar cysts”.Case presentationA hepatic hilar cyst, ranging from 5 to 25 mm, was detected prenatally in all four girls confirmed postnatally along with the presence of a gallbladder. Stool color was normal until two weeks of life at which time the stool color became lighter, and the patients developed cholestasis. All were operated before seven weeks of life: Case 1 had a CC with patent but irregular intrahepatic bile ducts at intraoperative cholangiogram, and no communication with the duodenum. A Roux-en-Y bilioenteric anastomosis was performed. The cyst showed complete epithelial lining loss, and liver pathology showed BA features. Case 2 had the final diagnosis of cystic BA with patent but abnormal intrahepatic bile ducts. She underwent two operations: the first operation at four weeks as described for case 1, since intraoperative findings were similar, as was histology. As cholestasis increased postoperatively, she underwent a Kasai hepato-porto-enterostomy six weeks later, where distinct BA findings were found with complete scarring of the hilar plate. Case 3 had a cystic BA with the cyst located within the common bile duct and atretic bile ducts proximal to the porta hepatis. It exhibited no communication with the liver or duodenum. A Kasai operation was performed, with histology showing complete epithelial loss within the cyst wall and scarring of the hilar plate. Case 4 had a cystic BA presenting a completely obliterated hepatic duct with the cyst lying within the common bile duct. A Kasai procedure was performed. Histology showed a common bile duct with a residual lumen of 0.1 mm.ConclusionsThe spectrum of disease from CC to BA in the setting of a prenatally discovered hepatic hilar cyst is emphasized. Even if cholangiogram differentiates most patients with BA from those with CC, caution is advised for transitional types.

Are Medical Students and Primary Health-care Professionals Aware of Neonatal Cholestasis and Acholic Stool.

Early diagnosis of biliary atresia (BA) and the timing of Kasai hepatic portoenterostomy are associated with improved survival rates of the native liver. Acholic stool is a major and earliest sign of BA. We evaluated the awareness and recognition of medical students and primary health care professionals (PHCPs) about neonatal cholestasis and acholic stool as a marker of BA. The knowledge of students and PHCP about prolonged jaundice and acholic stool was evaluated through a questionnaire. In the first step, 5 questions evaluating the knowledge of prolonged jaundice were asked. The sixth question was "Have you ever seen acholic stool before?" Following this question, stool color cards with 9 colors were shown, and participants were asked "Which of the following stool pictures would you define as acholic?" A total 724 students and 88 PHCPs were included in the study. In both groups, about half of the participants could not answer the first 4questions related to prolonged jaundice and cholestasis correctly. Twenty-four percent of the students and 11.4% of PHCP answered correctly to all of the stool colors. The rate of correct answers to acholic stool colors were approximately 43.9%-87.6% and 23.9%-86.4% for students and PHCP, respectively. Whitish acholic stool colors were better known than mild yellowish pale stool colors. The percentages of recognition were less than about 50% for these stool colors. This study showed that recognition and awareness of prolonged jaundice are low, and acholic stool is not well known. This may lead to delay in diagnosis. Considering the international success of stool color cards, using stool color cards will improve the outcomes of biliary atresia in our country as well.

A prospective multicentre study evaluating the performance of the modified simple biliary atresia scoring system in predicting biliary atresia.

Early diagnosis of biliary atresia (BA) is critical for best outcomes, but is challenged by overlapping clinical manifestations with other causes of obstructive jaundice in neonates. We evaluate the performance of the modified Simple BA Scoring System (SBASS) in diagnosing BA. We performed a prospective, cross-sectional study on infants with cholestatic jaundice (June 2021-December 2022). Modified SBASS scoring was applied and compared to the eventual diagnosis (as per intraoperative cholangiogram (IOC) and liver histopathology). The score (0-6), consists of gall bladder length < 1.6cm (+ 1), presence of triangular cord sign (+ 1), conjugated bilirubin:total bilirubin ratio > 0.7(+ 2), gamma-glutamyl transferase (GGT) ≥ 200 U/L (+ 2). 73 were included: Fifty-two (71%) had BA. In the non-BA group, 6 (28%) had percutaneous cholangiography (PTC) while 15 (72%) had intraoperative cholangiogram (IOC). At a cut-off of 3, the modified SBASS showed sensitivity of 96.2%, specificity of 61.9% and overall accuracy of 86.3% in diagnosing BA. Area under receiver operating characteristic curve was 0.901. GGT had the highest sensitivity (94.2%), while triangular cord sign showed the highest specificity at 95.2%. The SBASS provides a bedside, non-invasive scoring system for exclusion of BA in infantile cholestatic jaundice and reduces the likelihood of negative surgical explorations.

Biliary atresia with rare associations: a case report and literature review

Introduction and Importance: Biliary atresia is a rare, progressive cholangiopathy that affects newborns, causing jaundice and other manifestations of hyperbilirubinemia. The incidence is higher in Asia than in Europe. The only available treatment is a surgical operation called Kasai portoenterostomy. In our case, we highlighted rare congenital anomalies that came with biliary atresia. Case Presentation: A 10-day-old male infant was admitted to the hospital due to recurrent vomiting, yellowish skin, and scleral icterus. Laboratory investigations revealed elevated total serum and direct bilirubin levels. An atrophic gallbladder was observed on ultrasound. Intrahepatic cholangiography confirmed the diagnosis of biliary atresia, leading to the performance of a Kasai procedure. Additionally, the patient had intestinal malrotation and volvulus, which were managed with a Ladd’s procedure. Following surgery, there was notable improvement in liver enzymes and bilirubin levels, and the patient was discharged after 7 days. The infant has been initiated on oral vitamins, ursodeoxycholic acid, and antibiotics. Clinical Discussion: Biliary atresia is a challenging condition characterized by progressive narrowing and fibrosis of the biliary tree. It is rarely associated with rare congenital anomalies like situs inversus totalis, intestinal malrotation, and volvulus. Diagnosis involves abdominal ultrasound and MRCG. The biliary atresia was managed by the kasai procedure and the intestinal malrotation, and volvulus were managed by Ladd’s procedure. Conclusion: This case report highlights the importance of considering rare associations such as situs inversus, intestinal malrotation and volvulus in the diagnosis of biliary atresia in newborn. Early diagnosis and prompt intervention are crucial for optimal outcomes.

Development of a diagnostic model for biliary atresia based on MMP7 and serological tests using machine learning.

To develop a machine learning diagnostic model based on MMP7 and other serological testing indicators for early and efficient diagnosis of biliary atresia (BA). A retrospective analysis was conducted on patient information from those hospitalized for pathological jaundice at Beijing Children's Hospital between January 1, 2019, and December 31, 2023. Patients with serum MMP7, liver stiffness measurements, and other routine serological tests were included in the study. Six machine learning models were constructed, including logistic regression (LR), random forest (RF), decision tree (DET), support vector machine classifier (SVC), neural network (MLP), and extreme gradient boosting (XGBoost), to diagnose BA. The area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the various models. A total of 98 patients were included in the study, comprising 64 BA patients and 34 patients with other cholestatic liver diseases. Among the six machine learning models, the XGBoost algorithm model and RF algorithm model achieved the best predictive performance, with an AUROC of nearly 100% in both the training and validation sets. In the training set, these two algorithm models achieved an accuracy, precision, recall, F1 score, and AUROC of 1. Through model interpretation analysis, serum MMP7 levels, serum GGT levels, and acholic stools were identified as the most important indicators for diagnosing BA. The nomogram constructed based on the XGBoost algorithm model also demonstrated convenient and efficient diagnostic efficacy. Machine learning models, especially the XGBoost algorithm and RF algorithm models, constructed based on preoperative serum MMP7 and serological tests can diagnose BA more efficiently and accurately. The most important influencing factors for diagnosis are serum MMP7, serum GGT, and acholic stools.

Biliary atresia and cholestasis plasma non-targeted metabolomics unravels perturbed metabolic pathways and unveils a diagnostic model for biliary atresia

The clinical diagnosis of biliary atresia (BA) poses challenges, particularly in distinguishing it from cholestasis (CS). Moreover, the prognosis for BA is unfavorable and there is a dearth of effective non-invasive diagnostic models for detection. Therefore, the aim of this study is to elucidate the metabolic disparities among children with BA, CS, and normal controls (NC) without any hepatic abnormalities through comprehensive metabolomics analysis. Additionally, our objective is to develop an advanced diagnostic model that enables identification of BA. The plasma samples from 90 children with BA, 48 children with CS, and 47 NC without any liver abnormalities children were subjected to metabolomics analysis, revealing significant differences in metabolite profiles among the 3 groups, particularly between BA and CS. A total of 238 differential metabolites were identified in the positive mode, while 89 differential metabolites were detected in the negative mode. Enrichment analysis revealed 10 distinct metabolic pathways that differed, such as lysine degradation, bile acid biosynthesis. A total of 18 biomarkers were identified through biomarker analysis, and in combination with the exploration of 3 additional biomarkers (LysoPC(18:2(9Z,12Z)), PC (22:5(7Z,10Z,13Z,16Z,19Z)/14:0), and Biliverdin-IX-α), a diagnostic model for BA was constructed using logistic regression analysis. The resulting ROC area under the curve was determined to be 0.968. This study presents an innovative and pioneering approach that utilizes metabolomics analysis to develop a diagnostic model for BA, thereby reducing the need for unnecessary invasive examinations and contributing to advancements in diagnosis and prognosis for patients with BA.

Serum matrix metalloproteinase-7 for discriminating biliary atresia: a diagnostic accuracy and validation study

BackgroundPrompt and precise differential diagnosis of biliary atresia (BA) among cholestatic patients is of great importance. Matrix metalloproteinase-7 (MMP-7) holds great promise as a diagnostic marker for BA. This study aimed to investigate the accuracy of age-specific serum MMP-7 for discriminating BA from other cholestatic pediatric patients.MethodsThis was a single center diagnostic accuracy and validation study including both retrospective and prospective cohorts. Serum MMP-7 concentrations were measured using an ELISA kit, the trajectory of which with age was investigated in a healthy infants cohort aged 0 to 365 days without hepatobiliary diseases (n = 284). Clinical BA diagnosis was based on intraoperative cholangiography and subsequent histological examinations. The diagnostic accuracy of age-specific cutoffs of serum MMP-7 were assessed in a retrospective cohort of cholestatic patients (n = 318, with 172 BA) and validated in a prospective cohort (n = 687, including 395 BA).ResultsThe MMP-7 concentration declines non-linearly with age, showing higher levels in healthy neonates as well as higher cutoff value in neonatal cholestasis. The area under the ROC curve (AUROC) was 0.967 (95% confidence interval [CI]: 0.946–0.988) for the retrospective cohort, and the cutoff of 18 ng/mL yielded 93.0% (95%CI: 88.1-96.3%), 93.8% (95%CI: 88.6-97.1%), 94.7% (95%CI: 90.1-97.5%), and 91.9% (95%CI: 86.4-95.8%) for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), respectively. The performance of MMP-7 was successfully validated in the larger prospective cohort, resulting in a diagnostic sensitivity of 95.9% (379/395; 95% CI: 93.5–97.7%), a specificity of 87.3% (255/292; 95% CI: 83.0–90.9%), a PPV of 91.1% (379/416; 95% CI: 87.9–93.7%), and a NPV of 94.1% (255/271; 95% CI: 90.6–96.6%), respectively. Besides, higher cutoff value of 28.1 ng/mL achieved the best sensitivity, specificity, PPV, and NPV for infants aged 0–30 days, which was 86.4% (95% CI: 75.0–94.0%), 95.5% (95% CI: 77.2–99.9%), 98.1% (95% CI: 89.7–100%), and 72.4% (95% CI: 52.8–87.3%), respectively.ConclusionsThe serum MMP-7 is accurate and reliable in differentiating BA from non-BA cholestasis, showing its potential application in the diagnostic algorithm for BA and significant role in the future research regarding pathogenesis of BA.

Role of Ultrasound and Color Doppler in Diagnosis of Biliary Atresia

Role of Ultrasound and Color Doppler in Diagnosis of Biliary Atresia

A Case Report Of An Isolated Dextrogastria Diagnosed In First Trimester Ultrasound Screening

Isolated dextrogastria is an uncommon congenital abnormality defined by rightward stomach rotation. Although it was usually thought to be a harmless discovery with no long-term implications, potential connections with other congenital malformations have been documented. In our case, a 30-year-old primigravida’s fetus with isolated dextrogastria and an abdominal cyst gave birth at 38 weeks of pregnancy and later received a biliary atresia diagnosis. This case report contributes to the expanding collection of literature on solitary dextrogastria and highlights the importance of ongoing monitoring for any related anomalies and long-term repercussions.

Porta hepatis lymph nodes on US: not only identify biliary atresia but also predict outcomes after Kasai portoenterostomy surgery

ObjectivesTo evaluate the usefulness of porta hepatis lymph nodes (PHLNs) on ultrasonography (US) scans in diagnosing biliary atresia (BA) and predicting the outcomes after Kasai portoenterostomy (KPE) surgery.MethodsA total of 668 patients from one hospital were enrolled in the study (542 non-BA and 126 BA). The independent and combined diagnostic efficacy of PHLNs, triangular cord (TC) thickness, and gallbladder morphology were assessed by drawing the receiver operating characteristic (ROC) curves and counting the area under the ROC curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The US features, histopathological findings of PHLNs, and serum total bilirubin (TBIL) levels 3 months post-KPE were correlated.ResultsThe AUC, sensitivity, specificity, PPV, and NPV of PHLNs with hyperechogenicity and a maximum length larger than 8.4 mm were 0.898, 81.8%, 97.8%, 89.6%, and 95.8%, respectively. The combination of PHLNs, TC thickness, and gallbladder morphology achieved the best overall diagnostic efficacy among all indicators with an AUC of 0.927 and a sensitivity of 99.2%. The germinal center number and bile particle number of PHLNs were positively correlated with pathological size and US echogenicity intensity of PHLNs, respectively (r = 0.591, 0.377, p = 0.001, 0.004). The pathological size of PHLNs in BA patients was negatively correlated with jaundice clearance status 3 months after KPE surgery (r = −0.385, p = 0.047).ConclusionPHLNs with hyperechogenicity and a maximum length > 8.4 mm are useful US indicators for BA diagnosis. Additionally, the enlargement of PHLNs might play a role in predicting outcomes of KPE surgery.Critical relevance statementThe article proposed for the first time that PHLNs with hyperechogenicity and a maximum length > 8.4 mm are a useful US indicator for diagnosing BA.Key PointsPHLNs may be helpful in diagnosing BA and predicting outcomes after surgery.Enlarged hyperechoic PHLNs are a useful diagnostic indicator for BA, and play a role in predicting surgical outcomes.These findings can assist clinicians in more accurately diagnosing BA, enabling more timely treatments.Graphical

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.

Booster administration of Tc-99m PMT for delayed static imaging in patients with biliary atresia.

Tc-99m N-pyridoxyl-5-methyl-tryptophan (PMT) hepatobiliary scintigraphy has high diagnostic performance for biliary atresia. Our hospital implements standard Tc-99m PMT administration followed by a 6h static imaging review; booster doses are given in cases requiring 24h delayed scans. This study aimed to evaluate the diagnostic performance of this method. A total of 37 pediatric patients who underwent Tc-99m PMT biliary scintigraphy were classified into the surgically-diagnosed biliary atresia or non-biliary atresia groups. The absence of tracer accumulation in the small bowel was considered a hepatobiliary scintigraphic diagnosis of biliary atresia. The Clopper-Pearson method was used to calculate the 95% confidence intervals (CIs) for determining the diagnostic accuracy, negative predictive value, positive predictive value, sensitivity, and specificity of Tc-99m PMT biliary scintigraphy. Among the 37 patients, 12 were classified into the diagnosis of biliary atresia group. Regarding biliary scintigraphy findings, 16 of 37 patients demonstrated tracer accumulation in the small bowel within 6h of testing. These cases were diagnosed as non-biliary atresia, requiring no further testing or booster administration. In contrast, 21 patients underwent delayed testing requiring booster administration, which revealed 13 without tracer excretion and 11 who were diagnosed with biliary atresia. Among the eight patients with tracer accumulation, only one was diagnosed with biliary atresia. Furthermore, two cases without tracer excretion and seven cases with tracer excretion were clinically diagnosed as non-biliary atresia. The diagnostic performance of our examination was as follows: a diagnostic accuracy of 91.9% (34/37; 95% CIs 78.0-98.3%), sensitivity of 91.6% (11/12; 95% CIs 61.5-99.8%), specificity of 92.0% (23/25; 95% CIs 74.0-99.0%), a positive predictive value of 84.6% (11/13; 95% CIs 54.6-98.0%), and a negative predictive value of 95.8% (23/24; 95% CIs 78.9-99.9%). Our protocol for Tc-99m PMT biliary scintigraphy using tracer booster administration demonstrated reliable diagnostic performance for biliary atresia. Notably, 43% of cases did not require booster administration, indicating that lesser radiation exposure may still yield comparable diagnostic accuracy.

L'ittero di un lattante

The diagnosis of biliary atresia was ultimately made in an infant who still presented with jaundice after his first month of life and had previously been misdiagnosed with breast milk jaundice.The authors underline that biliary atresia should always be suspected in an infant with persistent jaundice after the third week of life.

Exploring causality with biliary atresia at different levels: two-sample Mendelian randomization study

BackgroundIn recent years, Mendelian randomization (MR) has been widely used to infer causality of related disease risk exposures. However, this strategy has not been applied to biliary atresia (BA).MethodsGenome-wide association...