Use of stool color card as screening tool for biliary atresia in resource-constraint country.

Aim: The study was aimed to find out the efficacy of a stool color card (SCC) in differentiating biliary atresia (BA) from non-BA in resource-limited countries. Background: stool color screening system was introduced in 2004 which lead to marked improvement in sensitivity of detecting BA. Methods: This cross-sectional observational study was conducted from January, 2019 through July, 2022 on purposively sampled infants who developed jaundice before three months of age, had direct bilirubin of > 20 % of total with pale stool and dark urine. Results: 144 cases (male, 96) were included in the study and their mean age at admission was 87.3±37.2 days and mean age at onset of jaundice was 6.1±7.7 days. BA was confirmed in 106 (73.6%) cases and 38 (26.4%) children were in non-BA group. Frequency of persistent pale stool between BA and non- BA were 88 vs 8 (83.0 % Vs 21.0 %) which was highly significant (p=0.000). Mean difference of total and direct serum bilirubin, median alanine transferase and alkaline phosphatase were not statistically significant between two groups. Median of serum gamma glutamyl transpeptidase (GGT) in BA was 570 U/L and in non-BA it was 138.0 U/L which was statistically significant (p=0.000). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SCC were 83%, 78.9%, 91.7%, 62.5% and 81.9% respectively. Conclusion: SCC has good sensitivity to diagnose BA but failed to prove better specificity to rely simply on it. SCC may be used as early screening tool for prompt referral to appropriate medical care centers for final evaluation of BA.

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.

Gut Bifidobacterium longum is associated with better native liver survival in patients with biliary atresia.

Background & Aims: The gut microbiome plays an important role in liver diseases, but its specific impact on biliary atresia (BA) remains to be explored. We aimed to investigate the microbial signature in the early life of patients with BA and to analyze its influence on long-term outcomes. Methods: Fecal samples (n = 42) were collected from infants with BA before and after Kasai portoenterostomy (KPE). The stool microbiota was analyzed using 16S rRNA next-generation sequencing and compared with that of age-matched healthy controls (HCs). Shotgun metagenomic sequencing analysis was employed to confirm the bacterial composition in 10 fecal samples before KPE. The correlation of the microbiome signature with liver function and long-term outcomes was assessed. Results: In the 16S rRNA next-generation sequencing analysis of fecal microbiota, the alpha and beta diversity analyses revealed significant differences between HCs and patients with BA before and after KPE. The difference in microbial composition analyzed by linear discriminant analysis and random forest classification revealed that the abundance of Bifidobacterium longum (B. longum) was significantly lower in patients before and after KPE than in HCs. The abundance of B. longum was negatively correlated with the gamma-glutamyltransferase level after KPE (p <0.05). Patients with early detectable B. longum had significantly lower total and direct bilirubin 3 months after KPE (p <0.005) and had a significantly lower liver transplantation rate (hazard ratio: 0.16, 95% CI 0.03-0.83, p = 0.029). Shotgun metagenomic sequencing also revealed that patients with BA and detectable B. longum had reduced total and direct bilirubin after KPE. Conclusion: The gut microbiome of patients with BA differed from that of HCs, with a notable abundance of B. longum in early infancy correlating with better long-term outcomes. Impact and implications: Bifidobacterium longum (B. longum) is a beneficial bacterium commonly found in the human gut. It has been studied for its potential impacts on various health conditions. In patients with biliary atresia, we found that a greater abundance of B. longum in the fecal microbiome is associated with improved clinical outcomes. This suggests that early colonization and increasing B. longum levels in the gut could be a therapeutic strategy to improve the prognosis of patients with biliary atresia.

Identification of diagnostic biomarkers and potential therapeutic targets for biliary atresia via WGCNA and machine learning methods.

Biliary atresia (BA) is a severe and progressive biliary obstructive disease in infants that requires early diagnosis and new therapeutic targets. This study employed bioinformatics methods to identify diagnostic biomarkers and potential therapeutic targets for BA. Our analysis of mRNA expression from Gene Expression Omnibus datasets revealed 3,273 differentially expressed genes between patients with BA and those without BA (nBA). Weighted gene coexpression network analysis determined that the turquoise gene coexpression module, consisting of 298 genes, is predominantly associated with BA. The machine learning method then filtered out the top 2 important genes, CXCL8 and TMSB10, from the turquoise module. The area under receiver operating characteristic curves for TMSB10 and CXCL8 were 0.961 and 0.927 in the training group and 0.819 and 0.791 in the testing group, which indicated a high diagnostic value. Besides, combining TMSB10 and CXCL8, a nomogram with better diagnostic performance was built for clinical translation. Several studies have highlighted the potential of CXCL8 as a therapeutic target for BA, while TMSB10 has been shown to regulate cell polarity, which was related to BA progression. Our analysis with qRT PCR and immunohistochemistry also confirmed the upregulation of TMSB10 at mRNA and protein levels in BA liver samples. These findings highlight the sensitivity of CXCL8 and TMSB10 as diagnostic biomarkers and their potential as therapeutic targets for BA.

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

BACKGROUND: Prompt 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. METHODS: This 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). RESULTS: The 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. CONCLUSIONS: The 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.

Analysis of gut microecological characteristics and differences between children with biliary atresia and non-biliary atresia in infantile cholestasis.

Introduction: In infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary atresia (BA) and non-BA, prompting a differential analysis of their respective GM profiles. Methods: Using 16S rDNA gene sequencing to analyse the variance in GM composition among three groups: infants with BA (BA group, n=26), non-BA cholestasis (IC group, n=37), and healthy infants (control group, n=50). Additionally, correlation analysis was conducted between GM and liver function-related indicators. Results: Principal component analysis using Bray-Curtis distance measurement revealed a significant distinction between microbial samples in the IC group compared to the two other groups. IC-accumulated co-abundance groups exhibited positive correlations with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, and total bile acid serum levels. These correlations were notably reinforced upon the exclusion of microbial samples from children with BA. Conclusion: The varying "enterohepatic circulation" status of bile acids in children with BA and non-BA cholestasis contributes to distinct GM structures and functions. This divergence underscores the potential for targeted GM interventions tailored to the specific aetiologies of cholestasis.

Amniotic fluid gamma-glutamyl transferase for prediction of biliary atresia in cases of non-visualisation of the fetal gallbladder: a retrospective study using a validated analytical platform and local reference range.

INTRODUCTION: The level of amniotic fluid gamma-glutamyl transferase (AFGGT) may help identify biliary atresia (BA) in cases of non-visualisation of the fetal gallbladder (NVFGB). This study aimed to validate a serum/plasma matrix-based gamma-glutamyl transferase (GGT) assay for amniotic fluid (AF) samples, establish a local gestational age-specific AFGGT reference range, and evaluate the efficacy of AFGGT for predicting fetal BA in pregnancies with NVFGB using the constructed reference range. METHODS: The analytical performance of a serum/plasma matrix-based GGT assay on AF samples was evaluated using a Cobas c502 analyser. Amniotic fluid gamma-glutamyl transferase levels in confirmed euploid singleton pregnancies (16+0 to 22+6 weeks of gestation) were determined using the same analyser to establish a local gestational age-specific reference range (the 2.5th to 97.5th percentiles). This local reference range was used to determine the positive predictive value (PPV) and negative predictive value (NPV) of AFGGT level <2.5th percentile for identifying fetal BA in euploid pregnancies with NVFGB. RESULTS: The serum/plasma matrix-based GGT assay was able to reliably and accurately determine GGT levels in AF samples. Using the constructed local gestational age-specific AFGGT reference range, the NPV and PPV of AFGGT level <2.5th percentile for predicting fetal BA in pregnancies with NVFGB were 100% and 25% (95% confidence interval=0, 53), respectively. CONCLUSION: In pregnancies with NVFGB, AFGGT level ≥2.5th percentile likely excludes fetal BA. Although AFGGT level <2.5th percentile is not diagnostic of fetal BA, fetuses with AFGGT below this level should be referred for early postnatal investigation.

The systemic immune-inflammation index at kasai portoenterostomy: related to clinical outcomes.

BACKGROUND: Systemic Immune-Inflammation Index (SII), known as an easy, economical and useful marker, correlates with the balance of inflammation and immune response. However, the usefulness of SII in biliary atresia (BA) remains unclear. Therefore, we evaluated the relationship of SII level and postoperative clinical outcomes of BA. METHODS: Retrospective review of 168 patients with BA was conducted with assessments of demographic information, histological findings, laboratory parameters, and clinical outcomes. The LASSO logistic regression analysis was established using the "glmnet" software package to explore the influencing factors related to native liver survival time. Numerical variables were dichotomized based on the receiver operating characteristic (ROC) curve and Youden index yielding the best performance of prediction. R software was used for statistical analysis. RESULTS: Overall, the 24 month native liver survival rate was 43.5% (73 cases) after Kasai portoenterostomy. LASSO logistic regression analysis show that preoperative malnutrition (OR = 0.032, 95%CI 0.001-0.424), gamma-glutamyltransferase (GGT, OR = 0.994, 95%CI 0.987-0.998), lymphocyte count (LY, OR = 2.426, 95%CI 1.467-4.604), SII (OR = 0.977, 95%CI 0.960-0.989), and liver fibrosis grading (LFG, reference: Grade 1, Grade 3, OR = 0.076, 95%CI 0.007-0.614) were the independent influencing factors for 24 month native liver survival. ROC curve analysis showed that the area under the curve of SII level (0.919) was larger than that of preoperative malnutrition (0.690), LFG (0.759), GGT (0.747), and Ly (0.773). A SII < 140.09 was found to be a significant marker in the prediction of 24-month native liver survival, with 90.41% sensitivity and 93.68% specificity. Furthermore, the rates of 24-month native liver survival (33.1% vs. 72.7%), jaundice clearance (46.8% vs. 75.0%), and good liver function recovery (46.8% vs. 65.9%) were lower in the SII ≥ 140.09 group than that in the SII < 140.09 group (all P < 0.05), but there was no difference in the occurrence of cholangitis (P > 0.05). CONCLUSION: Preoperative malnutrition, GGT, Ly, SII, and LFG were independent influencing factors for postoperative 24-month native liver survival of BA. The SII level, as a routine haematological marker, has better universality and simplicity and is related to clinical outcomes after Kasai portoenterostomy.

Comparison of Mir122 expression in children with biliary atresia and healthy group.

Biliary atresia (BA) is the primary cause of neonatal jaundice with various pathological mechanisms. Many BA patients may experience progressive liver dysfunction and eventually need a liver transplant. Therefore, identifying potential non-invasive biomarkers for BA is crucial. miR-122, the most abundant microRNA in the liver, plays significant roles in different liver diseases. This study aimed to assess miR-122 levels in BA patients. Eighteen patients with biliary atresia were selected at random from the Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS), along with 18 healthy controls. Blood samples were collected, and biochemical parameters (such as liver function tests) were measured. Quantitative reverse-transcription PCR (RT-PCR) was conducted on serum samples from both the case and control groups to analyze miR-122 levels. The study results indicated that serum miR-122 expression in BA patients was elevated compared to the control group, although it did not reach statistical significance. Additionally, no correlation was found between miR-122 expression and serum levels of liver enzymes or other laboratory findings in BA cases. miR-122 could be a potential target for diagnosing BA; however, further research with a larger population is necessary to determine if miR-122 could serve as a useful biomarker for diagnosing BA.

A Rare Case of Biliary Atresia with Biliary Ascites on a (Hepatobiliary Iminodiacetic Acid) HIDA Scan.

Biliary atresia is one of the most challenging conditions in pediatric surgery even when it is the only finding. Here we present a rare case of biliary atresia complicated with biliary ascites due to ductal perforation identified on a hepatobiliary iminodiacetic acid (HIDA) scan.

Delphi Method Analysis and Consensus of Prevalent Distinctive Practices for Biliary Atresia Management after Kasai Portoenterostomy.

Background: Extrahepatic biliary atresia (BA) is seen in infants, with an incidence of 1 in 15,000 live births. The presentation is progressive jaundice, dark-colored urine, and clay-colored stools. Kasai portoenterostomy (KPE) is the commonly performed surgical procedure in these patients. Postoperatively, phenobarbitone, ursodeoxycholic acid (UDCA), steroids, and other drugs are given to improve bile drainage and prevent inflammation and fibrosis. However, a definitive protocol regarding the need for different drugs, dosage, and duration varies across individual surgeons and centers. No universally accepted protocol exists for postoperative management after KPE. Aim: The aim of this study was to know the prevailing postoperative management of BA by subject experts and use the Delphi process to know if the experts want to change their practice based on the results from the survey. Material and Methods: A questionnaire was made after discussing with two experts in the field of BA. The questionnaire was mailed to 25 subject experts. The first survey data were analyzed and shared with all responders. In the second survey, change in the management based on the results from the first survey was assessed. Results: The Delphi questionnaire was answered by 17 experts. Postoperatively, prophylactic antibiotics are prescribed for 6-12 weeks by around 40% and >12 weeks by 30% of respondents. Phenobarbitone is prescribed for <3 months by nearly 50%. UDCA is prescribed for <3 months, ≤6 months, and 6 months-1 year by 47.1%, 23.5%, and 23.5% responders, respectively. Nearly 50% prescribe steroids (mostly prednisolone), and among them, two-thirds prescribe it for 6-12 weeks. Approximately 60% give antiviral drugs to children who are cytomegalovirus immunoglobulin M positive. In our survey, 50% of experts perform 5-10 KPE per year, and 25% each perform 10-15 and >15 KPE per year. The second survey noted that a significant percentage of responders want to change their practice according to consensus. Conclusion: From our Delphi survey, an overview of the postoperative management of BA could be made. However, multicentric studies are required for uniform protocol on the postoperative management of BA.

Stable two- and three-dimensional cholangiocyte culture systems from extrahepatic bile ducts of biliary atresia patients: use of structural and functional bile duct epithelium models for in vitro analyses.

We herein report two- (2D) and three-dimensional (3D) culture methods of cholangiocytes originating from extrahepatic bile ducts of biliary atresia (BA) patients. Cells were stabilized for in vitro analyses, and 3D culture by two different methods showed the structural and functional features of cholangiocytes in the gel scaffold. First, cells were obtained from gallbladder contents or resected tissues of patients at surgery and then cultured in our original conditioned medium with a cocktail of signaling inhibitors that maintains the immaturity and amplification of cells. Cells were immortalized by inducing SV40T and hTERT genes using lentivirus systems. Immunostaining with CK19 and Sox9 antibodies confirmed the cells as cholangiocytes. 3D organoids were formed in Matrigel in two different ways: by forming spheroids or via vertical growth from 2D cell sheets (2 + 1D culture). Organoids generated with both methods showed the uptake and excretion of rhodamine-123, and duct-like structures were also found. Our culture methods are simpler than previously reported methods and still show the structural and functional characteristics of cholangiocytes. Thus, this system is expected to be useful for the in vitro investigation of cholangiocyte damage or regeneration in BA patients.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Biliary atresia-splenic malformation (BASM) syndrome: A case report.

INTRODUCTION AND IMPORTANCE: Biliary atresia (BA) is characterized by the presence of persistent cholestatic jaundice during the neonatal period. This group of patients is at higher risk for liver disease and/or portal hypertension compared with other chronic liver diseases. CASE PRESENTATION: We present a newborn patient who had biliary stools early postnatally, but her gallbladder was not seen on radiological examination and was referred to our clinic. On examination, polysplenia was seen, and the inferior vena cava was not seen. The patient's stool color changed to a creamy stool without bile three weeks postnatally. The neonate was diagnosed with biliary atresia and splenic malformation (BASM) syndrome. The patient underwent a Kasai portoenterostomy in the 3rd week of age and was preoperatively diagnosed with malrotation and treated with a Ladd procedure at the same time. The patient had a postoperative stool with bile and decreased bilirubinemia with a normal defecation period. CLINICAL DISCUSSION: BASM syndrome, clinically has different causes and a worse prognosis than isolated BA. The syndrome can lead to end-stage cirrhosis and liver failure if left untreated. Although timely Kasai surgery is the standard treatment for BA, the age of the patient at the time of the surgery is different depending on BA groups. CONCLUSION: The most important prognostic factors for BASM syndrome are early diagnosis and treatment. Despite this, the patients need careful follow-up. Postoperative adjuvant steroid therapy may have a good impact on the outcomes.

Effectiveness of Cord blood as a Strategy to rule out Conjugated Hyperbilirubinemia.

Early detection of biliary atresia is crucial for timely intervention and improved outcomes in infants with elevated conjugated bilirubin levels. This study aims to investigate the viability of cord blood gas analysis as a novel method for assessing conjugated bilirubin levels. Infants with high heel stick levels also showed elevated cord blood bilirubin levels, indicating that cord blood testing could replace the need for repeat heel stick tests, especially benefiting low birth weight infants. Ongoing research, including larger cohorts and alternative bilirubin measurement methods, will further validate this innovative screening approach. Infants with biliary atresia have high conjugated bilirubin levels at birth. As a result, infants can be screened with newborn conjugated bilirubin measurements, to allow for early detection, timely treatment, and the best chances of delaying or even avoiding the need for a liver transplant [1]. An important limitation of screening, however, is that infants must undergo a separate blood test. To overcome this limitation, we investigated whether conjugated bilirubin measurements from cord blood could be useful.

A Multicenter Pilot Study of Biliary Atresia Screening Using Digital Stool Color Imaging.

Purpose: The presence of alcoholic stool in biliary atresia (BA) patients is the basis of a stool color card (SCC), a screening tool that has led to more patients receiving Kasai portoenterostomy earlier. This study aimed to evaluate the color image processing of stool images captured using smartphones. We propose that measuring digital color parameters is a more objective method for identifying BA stools and may improve the sensitivity of BA screening. Methods: A prospective study was conducted in five hospitals in Thailand between October 1, 2020, and December 31, 2021. Stools from infants presenting with jaundice, acholic stool, or dark-colored urine were photographed. Digital image color analysis was performed, and software was developed based on the color on the original SCC. Sensitivity and specificity for predicting BA stools were compared between the SCC and the software. Results: Of 33 infants eligible for data collection, 19 were diagnosed with BA. Saturation and blue were two potential digital color parameters used to differentiate BA stools. The receiver operating characteristic curve was used to determine the optimum cutoff point of both values, and when saturation ≤56 or blue ≥61 was set as a threshold for detecting BA stool, high accuracy was achieved at 81.8% and 78.8%, respectively. Conclusion: Digital image processing is a promising technology. With appropriate cutoff values of saturation in hue, saturation, value and blue in red, green, blue color models, BA stools can be identified, and equivocal-colored stools of non-BA patients can be differentiated with acceptable accuracy in infants presenting with jaundice.

Mesocolic hernia, a case series.

INTRODUCTION AND IMPORTANCE: Paraduodenal hernias are difficult to diagnose due to their unusual presentation. Herein, five new cases are added to the literature. CASE PRESENTATION: Four male and one female child complained of paraduodenal hernias, two on the right side and three on the left side. The intestinal part that herniated inside the hernia sac was also malrotated in four patients. One patient had Meckel's diverticulum with a herniated intestine. One infant had extrahepatic biliary disease, a single atrium, polysplenia, intestinal malrotation, and a left paraduodenal hernia. Exploratory labarotomy was done for reduction of the intestine, reorientation, and repair of hernia orifices. CLINICAL DISCUSSION: Paraduodenal hernia is a component of malrotation. Cautious dissection of the hernia orifice is required to keep away from injuries to the inferior mesenteric vein or left colic artery in the course of the restoration of the left paraduodenal hernia. Also, the superior mesenteric vessels may be injured in the course of the restoration of the right paraduodenal hernia. CONCLUSION: There is a correlation between the occurrence of PDH with malrotation. The diagnosis of malrotation can be made with an ultrasound abdomen; however, it is true that ultrasound cannot make a confirmed diagnosis in all patients. Once the diagnosis of a mesocolic hernia has occurred, surgical repair is mandatory by closure of the defect.

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

OBJECTIVE: 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 6 h static imaging review; booster doses are given in cases requiring 24 h delayed scans. This study aimed to evaluate the diagnostic performance of this method. METHODS: 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. RESULTS: 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 6 h 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%). CONCLUSIONS: 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.

Biliary atresia in children (analytical literature review and review of own observation).

OBJECTIVE: Aim: to review information resources and analysis of the own experience on this problem for the provision of modern knowledge in the pathogenesis of the pathology, the latest diagnostic and treatment technologies, with consideration of the need to adhere to a single strategy in the management of patients with BA. PATIENTS AND METHODS: Materials and Methods: The analysis of the data regarding the results of existing studies evaluating the clinical benefit and safety of diagnostic and treatment methods in Biliary atresia. CONCLUSION: Conclusions: BA is the leading cause of neonatal cholestasis development. Early diagnostics of BA, based on the complex evaluation of clinical-laboratory, instrumental and morphological signs of the pathology, has a significant meaning. Surgical correction during the first 2 months of life - the Kasai procedure, as well as dynamic post-surgery follow-up significantly prolong the life of children and allow postponing liver transplantation. The highest patient survival both at the first stage of treatment - conduction of the Kasai procedure and the stage of liver transplantation may be achieved by joined work of surgeons and pediatricians, which allows considering the whole row of possible problems.

Forward genetics combined with unsupervised classifications identified zebrafish mutants affecting biliary system formation.

Impaired formation of the biliary network can lead to congenital cholestatic liver diseases; however, the genes responsible for proper biliary system formation and maintenance have not been fully identified. Combining computational network structure analysis algorithms with a zebrafish forward genetic screen, we identified 24 new zebrafish mutants that display impaired intrahepatic biliary network formation. Complementation tests suggested these 24 mutations affect 24 different genes. We applied unsupervised clustering algorithms to unbiasedly classify the recovered mutants into three classes. Further computational analysis revealed that each of the recovered mutations in these three classes has a unique phenotype on node-subtype composition and distribution within the intrahepatic biliary network. In addition, we found most of the recovered mutations are viable. In those mutant fish, which are already good animal models to study chronic cholestatic liver diseases, the biliary network phenotypes persist into adulthood. Altogether, this study provides unique genetic and computational toolsets that advance our understanding of the molecular pathways leading to biliary system malformation and cholestatic liver diseases.