Biliary Atresia Group Research Articles

Thresholds for conjugated hyperbilirubinaemia and hepatobiliary scintigraphy in biliary atresia: A 12-year national follow-up.

To investigate liver biochemistry in infants screened for biliary atresia (BA) at the time of hepatobiliary scintigraphy (HS) and to evaluate the effect of change in threshold for HS. Infants born from 2010 to 2021, who underwent HS <6 months postpartum for BA, were included and data sourced from electronic medical records. The change in threshold in 2018 from ≥20 (and/or if conjugated bilirubin exceeds 20% of total bilirubin) to ≥17 μM (regardless of total bilirubin) was evaluated. In the cohort of 635 infants, 48 had BA, 247 had AATD, and the remaining 343 were categorised as 'other'. After the threshold adjustment, HS timing was unaffected (p = 0.27), but the annual HS rate rose from 39 to 87, yet evaluations following the new guideline only accounted for 12%. All liver parameters were elevated in the BA group compared with the additional groups (p < 0.001). Amongst the 104 patients with non-excretory HS, gamma-glutamyl transferase (p < 0.001) and alanine aminotransferase (p = 0.002) remained elevated for BA. The lowest conjugated bilirubin measured in BA children was 36 μM. After threshold change, HS use increased without earlier BA diagnostics, but most were not due to the new guideline. Alanine aminotransferase and gamma-glutamyl transferase should be considered in BA diagnostics.

Shear wave elastography as a diagnostic tool in biliary atresia and liver fibrosis

BackgroundThe study aims to investigate Shear Wave Elastography's accuracy in assessing pediatric cholestasis and differentiating biliary atresia from other causes. The early diagnosis of cholestasis in newborns, when caused by true liver disease and not physiological or transient jaundice is usually eluded. To maximize the diagnostic reliability of ultrasound as an initial imaging modality to diagnose biliary atresia, ultrasound elastography has been introduced as a quantitative non-invasive sonographic technique to measure liver stiffness which is presumed to be different in biliary atresia from other cholestasis as well as follow-up liver stiffness post-Kasai operation.ResultsTen patients (34.48%) were diagnosed with cholestasis with normal/low GGT. Five patients (17.24%) were diagnosed with hepatitis, and 2 patients had syndromes (10.34%). Other causes were found in 11 patients (37.93%). Major bile duct obstruction with fibrosis/cirrhosis was the majority of findings found in biliary atresia patients (100%), most of them with mild fibrosis (40%), followed by moderate (36.67%), then marked fibrosis (13.33%) and secondary cirrhosis (10%). ROC curve analysis shows that the best cut-off value for SWE = 1.97 with a sensitivity of 75.0% and specificity of 83.5%, with positive and negative predictive values were 82.8% and 74.1%, respectively. Mean shear wave elastography was significantly higher among the biliary atresia group (median 2.86) than in non-biliary atresia (median 1.81) and control groups (median 1.64) (P < 0.001) The best cut-off value of shear wear elastography for predicting outcome in pediatric patients post-Kasai procedure was 3.55, with a sensitivity of 66.7%, specificity of 64.7%, positive and negative predictive values were 25% and 91.7% respectively, with accuracy 65%.ConclusionThe results of this study suggest that shear-wave elastography is a useful diagnostic tool for differentiating biliary atresia from other causes of cholestasis in pediatric patients, with a high sensitivity and specificity. Further studies are needed to validate the findings and determine the optimal cut-off value for shear wear elastography in clinical practice.

Assessment of the utility of two-dimensional shear wave elastography and superb microvascular imaging in postoperative patients with biliary atresia.

We aimed to investigate whether prediction of liver fibrosis using two-dimensional shear wave elastography (2D-SWE) and vascular tree grading using superb microvascular imaging (SMI) are useful for postoperative follow-up in patients with biliary atresia (BA). We retrospectively collected data from medical records of 134 patients who underwent ultrasound examination with 2D-SWE or SMI, including 13 postoperative patients with BA and 121 non-BA patients. We investigated the distribution of liver stiffness values with SWE and vascular tree grading with SMI and evaluated correlations between these findings and biochemical indices of liver fibrosis in postoperative BA patients. The SWE values of the BA group were not significantly different from that of any other disease groups in non-BA patients. In postoperative BA patients, SWE values correlated significantly with aspartate aminotransferase to platelet ratio index (Spearman rank correlation coefficient [rs] = 0.6380, p = 0.0256) and with the Fib-4 index (rs = 0.6526, p = 0.0214). SMI vascular tree grading of the BA group was significantly higher than that of the choledochal cyst group (p = 0.0008) and other hepatobiliary disorder group (p = 0.0030). In postoperative BA patients, SMI vascular tree grading was not positively correlated with any biochemical marker of fibrosis. 2D-SWE appears to be useful for follow-up in postoperative BA patients.

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.

The value of serum MMP-7 and SOX9 levels in the diagnosis and prognosis of biliary atresia

IntroductionTo investigate the diagnostic value of serum MMP-7 and SOX9 levels in patients with biliary atresia (BA) and to further analyze their relationship with the liver fibrosis and prognosis. MethodsSixty-eight patients hospitalized for jaundice and underwent surgical treatment from March 2019 to February 2022 were retrospectively analyzed, including 44 patients with BA and 24 patients with other cholestatic liver diseases as disease controls (DC). Serum levels of MMP-7 and SOX9 were detected using enzyme-linked immunosorbent assay (ELISA). The diagnostic value of MMP-7 and SOX9 for BA was evaluated using the receiver operating characteristic (ROC) curve. ResultsSerum levels of MMP-7 and SOX9 were higher in the BA group compared to the DC group (P = 0.0002, P = 0.0006). The AUC for the combined diagnosis of serum MMP-7, SOX9 and GGT was 0.888 (95 % CI:0.788–0.952, P < 0.0001), which was significantly different from the diagnosis of MMP-7 or SOX9 alone (P = 0.034, P = 0.030). Serum levels of MMP-7 and SOX9 were significantly positively correlated with the liver fibrosis score (rs = 0.41, P = 0.006; rs = 0.58, P < 0.0001). BA patients who maintained native liver survival had lower preoperative serum levels of MMP-7 and SOX9 (P = 0.008, P = 0.0008). ConclusionsThe combined diagnosis of BA by MMP-7, SOX9 and GGT has better accuracy than MMP-7 or SOX9 alone. Serum SOX9 levels can assess the severity of BA liver fibrosis and correlate with BA native liver survival, but more sample data are needed to further investigate its predictive value.

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

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. 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. 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. 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.

Factors associated with biliary atresia in children with cholestasis in Surabaya

Introduction. Biliary atresia (BA) represents a progressive and obstructive fibrotic cholangiopathy, serving as a leading cause of liver failure and pediatric liver transplantation worldwide. Identifying risk factors associated with BA incidence is crucial for expediting diagnosis; however, limited research has been conducted in Indonesia. This study aims to investigate the characteristics and analyze the factors associated with the occurrence of BA. Methods. A retrospective observational analysis of medical records encompassing 523 cholestatic patients at the Pediatric Hepatology Outpatient Department and Pediatric Ward of Dr. Soetomo General Academic Hospital, Surabaya, from 2011 to 2022 was conducted. The data was segregated into BA and non-BA groups, and diagnostic chi-square tests were employed to determine interrelationships among variables. Subsequently, logistic regression analysis was performed to identify the most impactful variable. Results. Notably, age at first time visiting specialist (p = 0.003), gestational age (p &lt;0.001), birth weight (p = 0.039), and domicile (p = 0.028) exhibited substantial associations with BA. Moreover, gestational age emerged as the most influential factor (p = 0.004). Infants with normal birth weight (≥2,500 grams) exhibited strongest factor associated factor of BA cholestasis. Conclusion. Initial specialist consultations were predominantly observed within the 0-6 months age range, while term infant and normal birth weight were linked to a higher likelihood of BA cholestasis. Residence in rural areas exhibited a significant correlation with BA incidence.

Diagnostic and prognostic value of the gut microbiota and its metabolite butyrate in children with biliary atresia.

To determine the prevalent microbiological profile of biliary atresia (BA) patients at the time of its occurrence by studying their intestinal flora. A total of 118 gut microbiota samples from three groups of 43 BA patients, 33 disease controls (DC) with other cholestatic diseases and 42 healthy controls (HC), were analyzed by deep mining of public data. Subsequently, a total of 23 fecal samples from three groups of clinically collected patients (11 BA, 6 DC and 6 HC) were sequenced for 16S rRNA gene amplification and analyzed for serum butyrate (BU) level by liquid chromatography. Taxonomic analysis revealed significant differences in the composition of the intestinal microbiota between BA patients and controls, with a reduction in diversity and a higher abundance of Proteobacteria, Streptococcus and Lactobacillus in the BA group. Database and clinical data analyses concluded that Streptococcus/Bacteroides (AUC = 0.9035, 95% CI 0.8347-0.9722, P < 0.0001) or Streptococcus/Eggerthella (AUC = 0.8333, 95% CI 0.6340-1.000, P = 0.027) was the best microbiota to differentiate between BA and DC. Serum butyrate levels were low in the BA and DC groups and differed from the HC group (P = 0.01, P = 0.04). Butyrate levels in BA were negatively correlated with jaundice clearance and cholangitis, but not statistically significant. Our study reveals changes in the composition of the gut microbiota in BA, especially the butyrate-producing microbiota, and suggests the potential for using gut microbiota as a noninvasive diagnostic benefit for BA. Low levels of serum butyrate in BA may indicate a poor prognosis.

Frequency of infiltrating regulatory T-cells in the portal tract of biliary atresia.

Immunological abnormalities have been hypothesized as a pathogenesis of biliary atresia (BA). We previously investigated the frequency and function of circulating regulatory T-cells (Tregs) and reported no differences compared to controls. However, the local Treg profile remains uncertain. We aimed to investigate the frequency of Tregs in BA liver tissues. The number of lymphocytes, CD4+ cells, and CD4+FOXP3+ Tregs infiltrating the portal tract and the percentage of Tregs among CD4+ cells of BA and control patients were visually counted. The correlation between these data and clinical indicators was also examined. The number of lymphocytes, CD4+ cells, and CD4+FOXP3+ Tregs was higher in the BA group. However, the percentage of Tregs among CD4+ cells was similar in both groups. Each parameter was correlated with serum γ-GTP, but there was no clear association with liver fibrosis, jaundice clearance, and native liver survival. The number of Tregs infiltrating the portal tract was higher in BA patients. However, the infiltration of lymphocytes was also generally increased. Tregs appear to be unsuccessful in suppressing progressive inflammation in BA patients, despite recruitment to local sites. Investigation of Treg function in the local environment is warranted.

Rare sequence variants associated with the risk of non-syndromic biliary atresia.

The etiology of non-syndromic biliary atresia (BA) remains largely unknown. In this study, we performed genome-wide screening of genes associated with the risk of non-syndromic BA. We analyzed exome data of 15 Japanese patients with non-syndromic BA and 509 control individuals using an optimal sequence kernel association test (SKAT-O), a gene-based association study optimized for small-number subjects. Moreover, we examined the frequencies of known BA-related single nucleotide polymorphisms (SNPs) in the BA and control groups. SKAT-O showed that rare damaging variants of MFHAS1, a ubiquitously expressed gene encoding a toll-like receptor-associated protein, were more common in the BA group than in the control group (Bonferroni corrected p-value, 0.0097). Specifically, p.Val106Gly and p.Arg556Cys significantly accumulated in the patient group. These variants resided within functionally important domains. SKAT-O excluded the presence of other genes significantly associated with the disease risk. Of 60 known BA-associated SNPs, only eight were identified in the BA group. In particular, p.Ile3421Met of MYO15A and p.Ala421Thr of THOC2 were more common in the BA group than in the control group. However, the significance of these two variants is questionable, because MYO15A has been linked to deafness but not to BA and the p.Ala421Thr of THOC2 represents a relatively common SNP in Asia. The results of this study indicate that rare damaging variants in MFHAS1 may constitute a risk factor for non-syndromic BA, while the contribution of other monogenic variants to the disease predisposition is limited. This article is protected by copyright. All rights reserved.

Intraoperative hepatic subcapsular spider-like telangiectasia sign for the definitive diagnosis of biliary atresia

ObjectiveTo evaluate the accuracy of intraoperative hepatic subcapsular spider-like telangiectasia (HSST) sign for differentiating biliary atresia (BA) from other causes of hepatic cholestasis.MethodsThe data of 69 patients with jaundice treated from January 2019 to December 2021 were retrospectively analyzed. Based on intraoperative cholangiography (IOC), the patients were divided into two groups: the BA group (n = 49) and the non-BA group (n = 20). The biochemistry tests, liver ultrasound, liver stiffness value and HSST sign of the two groups were compared.ResultsThe incidence of abnormal gallbladder, elevated γ-glutamyl transpeptidase (γ-GGT) > 182.0U/L and abnormal liver stiffness (> 6.4 kPa) in BA group were significantly higher than those in non-BA group (P < 0.001). The HSST sign was present in all BA patients and not found in non-BA group. The area under receiver operating curve of direct bilirubin(DBIL), γ-GGT, abnormal gallbladder, liver stiffness value and HSST sign were 0.53, 0.84, 0.78, 0.96, and 1.00, respectively. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value(NPV) of HSST sign in the diagnosis of BA were all 100%.ConclusionPresence of HSST sign on diagnostic laparoscopy is highly suggestive of BA.It can be used in the differential diagnosis of BA and non-BA.Level of evidenceLevel III.

Does amyloid β precursor protein gene expression have a role in diagnosis of biliary atresia?

Biliary atresia (BA) is an important cause of surgical jaundice. Although the precise etiology is unknown, β-amyloid (Aβ) has been observed around the bile ducts in BA livers. It is unclear whether Aβ plays a role in the pathogenesis of this disease. This study aims to assess the amyloid β precursor protein (APP) gene expression in infants with BA in comparison with other causes of neonatal cholestasis. This could help explore the role of Aβ in the pathogenesis and diagnosis of BA. A prospective study was conducted at the outpatient clinic of Paediatric Hepatology, Gastroenterology, and Nutrition Department, National Liver Institute, Menoufia University, Shebin El Kom, Menoufia, Egypt during the period March 2022 to December 2022. Clinical data were gathered and laboratory and radiological investigations were conducted including β precursor protein gene expression measured in liver biopsies of the three groups using quantitative real-time PCR (qPCR). Gene expression of APP was considerably higher in the BA group (p = 0.0001) compared to neonatal cholestasis (NC) patients. Gamma glutamyl transferase (GGT) and APP had a positive correlation (p = 0.001). No significant association was found between APP and fibrosis. APP was noticeably higher in BA than NC other than BA. Also, APP in BA was higher (statistically significant, p = 0.0001) than the control. There was no statistically significant difference among NC, BA, and control groups regarding APP (p = 0.07). Both males and females did not show significant differences as regards APP (p = 0.851). Age did not have a statistically significant correlation with APP (p = 0.532). Also, there were no correlations between APP and alkaline phosphatase (ALP), aspartate transaminase (AST), or total bilirubin (TB) (p > 0.05). We concluded that the development and identification of BA may depend on the liver expression of serum APP. Surgeons may be able to carry out early intraoperative cholangiography for BA confirmation if the combination of APP with GGT and other hepatic function parameters exhibits a high predictive potential as a diagnostic test for BA. To evaluate this hypothesis, more research with sizable sample numbers is necessary.

Questioning Diagnostic Value of Serum Matrix Metalloproteinase 7 for Biliary Atresia

Matrix metalloproteinase 7 (MMP7) has been suggested as a promising biomarker in diagnosing biliary atresia (BA). This study aimed to assess the diagnostic accuracy of serum MMP7 in BA in the Middle Eastern population. In this cross-sectional study, neonates and infants with direct hyperbilirubinemia admitted to Namazi referral hospital, Shiraz, Iran, were studied. Baseline demographic and clinical characteristics and blood samples were obtained on admission. MMP7 serum concentration was measured using an enzyme-linked immunosorbent assay (ZellBio GmbH, Ulm, Germany). 44 infants with a mean age of 65.59 days were studied. Of these patients, 13 cases were diagnosed with BA, and 31 cases' cholestasis related to other etiologies. Serum MMP7 concertation was 2.13ng/mL in the BA group and 1.85ng/mL in the non-BA group. MMP7 was significantly higher in those presented with either dark urine or acholic stool. The predictive performance capability of the MMP7 was not significant in the discrimination of BA from the non-BA group based on receiver operating characteristic curve analysis (area under curve: 0.6, 95% confidence interval: 0.45-0.75). In the optimal cut of point 1.9, the sensitivity and specificity were 84.6% and 45.1%, respectively. Further combination of MMP7 with Gamma-glutamyl transferase (GGT), alkaline phosphatase, direct and total bilirubin, and dark urine or acholic stool was not remarkably boosted the diagnostic accuracy of the test. Interestingly, GGT at a cut-off point of 230 U/L was 84.6% sensitive and 90.3% specific for BA. Our results are not consistent with previous studies on this subject. Considering more conventional and available tests like GGT besides conducting future studies with greater samples and different geographical areas is recommended.

Selective enlargement of left lateral segment liver volume as a potential diagnostic predictor for biliary atresia.

To determine an early diagnostic indicator of biliary atresia (BA), we focused on morphological left-right differences of BA livers. Of 74 infants with suspected BA at our hospital in the last 12years, 25 met the conditions for investigation: 15 infants with BA (BA group) and 10 with other pathologies (non-BA group). CT volumetry of the liver in each patient was performed using a 3D image analysis system. Patient characteristics, blood data, and proportion of the left lateral segment to the total liver volume (LLS ratio) were compared between the two groups. Among the patient characteristics and liver function tests, only γ-glutamyl transpeptidase (GGT) were significantly higher in the BA group (p < 0.001). The LLS ratio was 0.321 (0.227-0.382) in the BA group and 0.243 (0.193-0.289) in the non-BA group (p = 0.01). The summary cut-off, area under the curve, sensitivity, and specificity were 0.322, 0.813, 53.3, and 100% for the LLS ratio and 94.26, 0.95, 86.7, and 100% for the GGT × LLS ratio, respectively. The LLS ratio is highly specific and may be an early diagnostic predictor of BA. Moreover, this segmental LLS enlargement may be associated with the etiology of BA.

Reduced peroxisome proliferator-activated receptor-α and bile acid nuclear receptor NR1H4/FXR may affect the hepatic immune microenvironment of biliary atresia.

BackgroundBiliary atresia (BA) is a childhood liver disease characterized by fibrous obstruction and obstruction of the extrahepatic biliary system and is one of the most common and serious biliary disorders in infants. Significant inflammation and fibrosis of the liver and biliary tract are the most prominent features, regardless of the initial damage to the BA. Abnormalities in innate or adaptive immunity have been found in human patients and mouse models of BA. We previously reported that children with BA had abnormal lipid metabolism, including free serum carnitine.ObjectiveTo study gene and protein expression levels of the hepatic peroxisome proliferator-activated receptor-α (PPARα) signaling pathway and farnesoid X receptor (FXR) in BA and BA fibrosis, and assess their clinical values.MethodsLow expression of PPARα and NR1H4 (FXR) in BA were validated in the Gene Expression Omnibus database. Functional differences were determined by gene set enrichment analysis based on of PPARα and NR1H4 expression. BA patients from GSE46960 were divided into two clusters by using consensus clustering according to PPARα, NR1H4, and SMAD3 expression levels, and immunoinfiltration analysis was performed. Finally, 58 cases treated in our hospital were used for experimental verification. (IHC: 10 Biliary atresia, 10 choledochal cysts; PCR: 10 Biliary atresia, 14 choledochal cysts; WB: 10 Biliary atresia, 4 choledochal cysts).ResultsBioinformatics analysis showed that the expression of PPARα, CYP7A1 and NR1H4 (FXR) in the biliary atresia group was significantly lower than in the control group. More BA-specific pathways, including TGFβ signaling pathway, P53 signaling pathway, PI3K-AKT-mTOR signaling pathway, etc., are enriched in BA patients with low PPARα and NR1H4 expression. In addition, low NR1H4 expression is abundant in inflammatory responses, IL6/STAT3 signaling pathways, early estrogen responses, IL2 STAT5 signaling pathways, and TGFβ signaling pathways. The TGFβ signaling pathway was significant in both groups. According to the expression of PPARα, NR1H4 and SMAD3, a key node in TGFβ pathway, BA patients were divided into two clusters using consensus clustering. In cluster 2, SMAD3 expression was high, and PPARα and NR1H4 expression were low. In contrast to cluster 1, immune cell infiltration was higher in cluster 2, which was confirmed by immunohistochemistry. The mRNA and protein levels of PPARα and NR1H4 in BA patients were lower than in the control group by immunohistochemistry, Western blot analysis and real-time PCR.ConclusionsThe downregulation of PPARα and NR1H4 (FXR) signaling pathway may be closely related to biliary atresia.

Diagnostic value of HA, PC-III, IV-C, and LN in infants with congenital biliary atresia.

Hyaluronic acid (HA), type III procollagen III (PC-III), type IV collagen IV (IV-C), and laminin (LN) have certain diagnostic value for hepatobiliary diseases. No published studies have compared the diagnostic accuracy of these 4 indicators for the diagnosis of congenital biliary atresia (CBA) in infants. This study aimed to investigate the diagnostic value of HA, PC-III, IV-C, and LN in infants with CBA.From January 2017 to December 2020, 185 infants with nonphysiological jaundice in the Second Department of General Surgery at the Children’s Hospital of Hebei were enrolled in this study. Forty-six infants with CBA (CBA group) and 139 infants without CBA (noncongenital biliary atresia group) were diagnosed using ultrasonography, magnetic resonance imaging, intraoperative exploration, and intraoperative cholangiography. The levels of HA, PC-III, IV-C, and LN in the 2 groups were statistically analyzed. The diagnostic accuracy was determined using receiver operating characteristic curves and by calculating the area under the curve. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors.Compared to the noncongenital biliary atresia group, the levels of HA, PC-III, IV-C, and LN were significantly increased in the CBA group (P <.05). The receiver operating characteristic analysis showed the optimal cutoff values for HA, PC-III, IV-C, and LN were 162.7, 42.5, 199.7, and 101.2 ng/mL, and the area under the curves were 0.892, 0.762, 0.804, and 0.768, respectively. The sensitivity values for the diagnosis of CBA were 76.82%, 71.61%, 70.32%, and 72.28%, and the specificity values for the diagnosis of biliary atresia were 70.22%, 70.44%, 66.34%, and 68.71%, respectively. In the multivariate model, HA ≥162.7 ng/mL (odds ratio [OR] = 5.28, 95% confidence interval [CI]: 3.15–8.37), PC-III ≥42.5 ng/mL (OR = 4.61, 95% CI: 2.54–7.16), IV-C ≥199.7 ng/mL (OR = 5.02, 95% CI: 2.98–7.64), and LN ≥101.2 ng/mL (OR = 6.25, 95% CI: 2.41–10.07) remained associated with the occurrence of CBA.HA, PC-III, IV-C, and LN have high accuracy for the diagnosis of CBA in infants, and these factors are potential diagnostic biomarkers for CBA.

Serum TGF-β1 and VEGF Levels Reflect the Liver Hardness and Function in Children with Biliary Atresia.

Objective This study further explored the wind direction correlation analysis between serum levels of TGF-β1 and VEGF and liver function assessment in children with biliary atresia. Methods A total of 62 children with biliary atresia (BA) who received surgical treatment in our hospital from October 2020 to October 2021 were selected as the research objects (BA group), and 50 normal healthy children who received routine physical examination in our hospital during the same period were selected as blank control group. Outcome measures included postoperative total bilirubin levels and conjugality of enrolled patients. Bilirubin level, unbound bilirubin level, serum transforming growth factor-beta-1 (TGF-β1), vascular endothelial growth factor (VEGF), liver function indicators albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and other observation indicators were included. All data in this study were collected and analyzed by SPSS 23.0 software, and t-test was performed. Results The serum levels of TGF-β1, VEGF, ALT, AST, GGT, and liver hardness were significantly higher in children with jaundice than those without jaundice, and the serum ALB level was significantly lower than that in children without jaundice (P < 0.05). The levels of TGF-β1 and VEGF in BA group were positively correlated with the levels of ALT, AST, GGT, and liver hardness (P < 0.05) but negatively correlated with the level of ALB (P < 0.05). Conclusion The levels of serum TGF-β1 and VEGF in children with biliary atresia have a certain risk correlation with liver function damage, which will become a research focus on the mechanism of liver fibrosis in the diagnosis and treatment of biliary atresia in children.

Serum matrix metalloproteinase-7 levels in infants with cholestasis and biliary atresia

BackgroundThe aim of this study was to evaluate the serum level of matrix metalloproteinase 7 (MMP7) in infants with cholestasis and the diagnostic values of this biomarker to differentiate biliary atresia (BA) from other causes of cholestasis.MethodsThis multi-center study is conducted during 2 years in Mofid children’s hospital and Children’s Medical Center, Pediatrics Center of Excellence Tehran, Iran. 54 infants with cholestasis were enrolled in this study with a control group consists of 41 healthy infants with the same age. Serum samples were taken from all these patients to assess serum levels of MMP7, Gamma-glutamyl Transferase (GGT). For each biomarker, we calculated the sensitivity and specificity and other statistical characteristics.ResultsThere were 89 subjects, 22 patients with BA, 32 patients with non-BA cholestasis and 41 subjects as control group. The mean serum MMP7 levels in BA, non-BA cholestasis and control group was 15.91 ng/ml ± 6.64, 4.73 ng/ml ± 2.59 and 0.49 ng/ml ± 0.33, respectively. The best cut-off point is calculated 7.8 ng/ml for MMP7 and 434.5 U/L for GGT. The area under curve (AUC) for these two markers are 0.988 ± 0.008 and 0.854 ± 0.052, respectively. The sensitivity and specificity of MMP7 to differentiate biliary atresia from nonbiliary atresia cholestasis in our study was 95.5% and 94.5%, respectively. The sensitivity and specificity of GGT was 77.3% and 77.8%, respectively. These results show that the MMP7 has more sensitivity and specificity in differentiation.ConclusionMMP7 demonstrated good accuracy to differentiate biliary atresia from other causes of cholestasis.

Identification of Hub Genes and Immune Infiltration in Pediatric Biliary Atresia by Comprehensive Bioinformatics Analysis.

Background: Biliary atresia (BA) is the leading cause of pediatric liver failure and pediatric liver transplantation worldwide. Evidence suggests that the immune system plays a central role in the pathogenesis of BA. Methods: In this work, the novel immune-related genes between BA and normal samples were investigated based on weighted gene co-expression network analysis (WGCNA) and the deconvolution algorithm of CIBERSORT. Results: Specifically, 650 DEGs were identified between the BA and normal groups. The blue module was the most positively correlated with BA containing 3274 genes. Totally, 610 overlapping BA-related genes of DEGs and WGCNA were further used to identify IRGs. Three IRGs including VCAM1, HLA-DRA, and CD74 were finally identified as the candidate biomarkers. Particularly, the CD74 biomarker was discovered for the first as a potential immune biomarker for BA. Conclusions: Possibly, these 3 IRGs might serve as candidate biomarkers and guide the individualized treatment strategies for BA patients. Our results would provide great insights for a deeper understanding of both the occurrence and the treatment of BA.

Neonatal Dubin-Johnson Syndrome and its Differentiation from Biliary Atresia.

The aim was to determine if liver biochemistry indices can be used as biomarkers to help differentiate patients with neonatal Dubin-Johnson syndrome (nDJS) from those with biliary atresia (BA). Patients with genetically-confirmed nDJS or cholangiographically confirmed BA were retrospectively enrolled and randomly assigned to discovery or verification cohorts. Their liver chemistries, measured during the neonatal period, were compared. Predictive values were calculated by receiver operating characteristic curve analysis. A cohort of 53 nDJS patients was recruited, of whom 13 presented with acholic stools, and 14 underwent diagnostic cholangiography or needle liver biopsy to differentiate from BA. Thirty-five patients in the cohort, with complete biochemical information measured during the neonatal period, were compared with 133 infants with cholangiographically confirmed BA. Total and direct bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acids, alkaline phosphatase, and gamma-glutamyl transferase were significantly lower in nDJS than in BA. In the discovery cohort, the areas under the curve for ALT and AST were 0.908 and 0.943, respectively. In the validation cohort, 13/15 patients in the nDJS group were classified as nDJS, and 10/53 in the BA control group were positive (p<0.00001) with an ALT biomarker cutoff value of 75 IU/L. Thirteen of 15 patients were classified as nDJS and none were classified positive in the BA group (13/15 vs. 0/53, p<0.00001) with an AST cutoff of 87 IU/L. Having assembled and investigated the largest cohort of nDJS patients reported to date, we found that nDJS patients could be distinguished from BA patients using the serum AST level as a biomarker. The finding may be clinically useful to spare cholestatic nDJS patients unnecessary invasive procedures.