Biliary Atresia Research Articles

Alterations of gut microbiota in infants with biliary atresia identified by 16S rRNA-sequencing

BackgroundBiliary atresia (BA) is a severe neonatal disease with progressive intra- and extra-hepatic bile ducts inflammation and hepatic fibrosis. Characterization of gut microbiome profiles in infants with biliary atresia can provide valuable information and potential disease biomarkers. Our study aims to explore the relationship between gut microbiota and biliary atresia.Methods16 S ribosomal RNA (rRNA) gene sequencing was carried out to identify the differences in composition and diversity of gut microbiota between infants with BA and healthy subjects. A total of 31 infants with biliary atresia and 20 healthy subjects were recruited.ResultsThe composition of gut microbiota in BA group was significantly different with the normal control group (P < 0.05) and the abundance ratio of Klebsiella/Bifidobacterium showed great potential for identification of BA (P < 0.01). In addition, the differential bacterial taxa were involved in lipid and vitamins metabolism.ConclusionOur results could provide potential non-invasive biomarker for identification of biliary atresia and contribute to the treatment in terms of ameliorating microbiota dysbiosis.

A305 ANONYMOUS LIVING LIVER DONATION IMPROVES ACCESS FOR MEDICALLY UNDERSERVED CHILDREN IN NEED OF LIVER TRANSPLANTATION

Abstract Background Since our first pediatric anonymous non-directed live donor liver transplant (A-LDLT) performed in April 2005, 62 children have undergone live donor liver transplant (LDLT) with an anonymous non-directed graft. Anon-LDLT organs being allocated as per our deceased donor liver transplant (DDLT) wait list. Aims To evaluate clinical outcomes, recipient characteristics and social determinants of health of pediatric recipients of A-LDLT in comparison to those who received a directed LDLT (Dir-LDLT) and DDLT. Methods Retrospective analysis of all recipients of LDLT performed between January 2005 and March 2023. Demographic and clinical data included age, sex, race, ethnicity, single-parent households, primary diagnosis, recipient blood type, time on waiting list, post-LT intensive care unit (ICU) length of stay (LOS), time to extubation, and post-transplant comorbidities were assessed as covariates. A comparative analysis was conducted between children receiving A-LDLT, Dir-LDLT versus DDLT. Results A total of 422 (50% male, 57% white, 23% Asian, 7% Black, 5% indigenous) childrenunderwent LT during the study period. Biliary atresia (40%) and metabolic diseases (19%) were the commonest primary indications. A-LDLT was done in 62 children (15%) with no directed donor options. Dir-LDLT was in 174 children (41%). Of 186 DDLTs (44%), 25% were split grafts, 26% reduced, and 49% whole liver grafts. In A-LDLT recipients, the primary diseases were more frequently characterized by metabolic disorders (31%), while the incidence of acute liver failure was notably lower (0%). Recipients of Anon-LDLT were more often Indigenous recipients in comparison to Dir-LDLT or DDLT recipients (p=0.044). Anon-LDLT recipients were more frequently living in single parent households (18% vs 3% vs 10%, pampersand:003C0.001) and to require interpreter assistance (11% vs 3% vs 0.5%, pampersand:003C0.001) (Table), compared to children who received Dir-LDLT or DDLT. Median time on the wait list was longer for Anon-LDLT (92 days) compared to Dir-LDLT (62 days) and DDLT (72 days) recipients (p=0.004). Post-LT ICU LOS, time to extubation, other post-LT complications or patient prognosis were better in the A-LDLT and Dir-LDLT recipients than DDLT recipients. Conclusions This retrospective analysis of 422 children undergoing LT at a single institution confirms excellent patient and graft survival for A-LDLT recipients. Patients from Indigenous communities, single parent and households where English is a second language, are more frequently the beneficiaries of Anon-LDLT grafts. Anon-LDLT, as utilized in this single center analysis, benefits medically underserved pediatric patients who otherwise have limited access to the advantages of LT. Funding Agencies None

Successful Steroid Treatment of Extrahepatic Cholestasis: A Case Report

Background: Biliary atresia is the most common cause of cholestasis. However, not all healthcare facilities are capable of performing Kasai surgery and liver transplantation. The involvement of inflammatory processes in the bile ducts triggered by viral infections has been suggested in several theories of pathogenesis. This case report describes the successful steroid treatment of an infant with extrahepatic cholestasis.&#x0D; Case presentation: A girl aged 2 months and 20 days presented with complaints of jaundice since the age of 2 weeks, with no improvement and worsening of the jaundice, with the color of the stools becoming paler than before. The nutritional status is normal. The physical examination revealed icteric sclera, hepatomegaly, and splenomegaly. There was cholestasis (total bilirubin 7.30 mg/dL and direct bilirubin 5.75 mg/dL), as well as elevated levels of AST (249 U/L), ALT (251 U/L), GGT (995.7 U/L) and increased to 1529.6 U/L, CMV reactive IgG 28.9, and Rubella reactive IgG 6.90. A two-phase ultrasound of the abdomen showed a thickening of the gallbladder wall. A liver biopsy showed mild portal fibrosis (F1). Steroids at a dose of 2 mg/kg/day in combination with ursodeoxycholic acid were administered. At follow-up one month later, the jaundice had improved. Stools were yellow-brown, and liver function tests and bilirubin were normal.&#x0D; Conclusion: Adjunctive steroid therapy to suppress the inflammatory process in biliary obstruction may be beneficial in the early phase of the disease, especially in limited surgical and transplant settings.

Bile acid profiles in adult patients with biliary atresia who achieve native liver survival after portoenterostomy

Bile acids have received increasing attention as a marker of the long-term prognosis and a potential therapeutic target in patients with biliary atresia, which is a progressive disease of the hepatobiliary system. A detailed analysis of serum and urinary bile acid compositions was conducted to assess the characteristics of bile acid profiles and the correlation between bile acid profiles and liver fibrosis markers in adult patients with biliary atresia who achieved bilirubin normalization. Serum total bile acids and glucuronide-conjugated (glyco- and tauro-) cholic acids (GCA and TCA) and chenodeoxycholic acids (GCDCA and TCDCA) were significantly higher in patients with biliary atresia than in healthy controls, whereas unconjugated CA and CDCA showed no significant difference. There were no significant differences in CA to CDCA ratios and glycine-to-taurine-conjugated ratios. Urinary glycocholic acid 3-sulfate (GCA-3S) was significantly higher in patients with biliary atresia. Serum GCDCA showed a strong positive correlation with Mac-2 binding protein glycosylation isomer (M2BPGi). These results demonstrate that bile acid congestion persists into adulthood in patients with biliary atresia, even after cholestasis has completely improved after Kasai portoenterostomy. These fundamental data on bile acid profiles also suggest the potential value of investigating bile acid profiles in patients with biliary atresia.

Biliary atresia: the development, pathological features, and classification of the bile duct.

Biliary atresia is an occlusive biliary disease involving intrahepatic and extrahepatic bile ducts. Its etiology and pathogenesis are unclear. There are many manifestations of bile duct involvement in biliary atresia, but little is known about its occurrence and development. In addition, different classification methods have been proposed in different periods of biliary atresia, each with its advantages and disadvantages. The combined application of biliary atresia classification will help to improve the survival rate of patients with native liver. Therefore, this article reviews the development, pathological features, and classification of intrahepatic and extrahepatic bile ducts in biliary atresia, to provide a reference for the study of the pathogenesis and the choice of treatment methods.

Interpretable artificial intelligence-based app assists inexperienced radiologists in diagnosing biliary atresia from sonographic gallbladder images

BackgroundA previously trained deep learning-based smartphone app provides an artificial intelligence solution to help diagnose biliary atresia from sonographic gallbladder images, but it might be impractical to launch it in real clinical settings. This study aimed to redevelop a new model using original sonographic images and their derived smartphone photos and then test the new model’s performance in assisting radiologists with different experiences to detect biliary atresia in real-world mimic settings.MethodsA new model was first trained retrospectively using 3659 original sonographic gallbladder images and their derived 51,226 smartphone photos and tested on 11,410 external validation smartphone photos. Afterward, the new model was tested in 333 prospectively collected sonographic gallbladder videos from 207 infants by 14 inexperienced radiologists (9 juniors and 5 seniors) and 4 experienced pediatric radiologists in real-world mimic settings. Diagnostic performance was expressed as the area under the receiver operating characteristic curve (AUC).ResultsThe new model outperformed the previously published model in diagnosing BA on the external validation set (AUC 0.924 vs 0.908, P = 0.004) with higher consistency (kappa value 0.708 vs 0.609). When tested in real-world mimic settings using 333 sonographic gallbladder videos, the new model performed comparable to experienced pediatric radiologists (average AUC 0.860 vs 0.876) and outperformed junior radiologists (average AUC 0.838 vs 0.773) and senior radiologists (average AUC 0.829 vs 0.749). Furthermore, the new model could aid both junior and senior radiologists to improve their diagnostic performances, with the average AUC increasing from 0.773 to 0.835 for junior radiologists and from 0.749 to 0.805 for senior radiologists.ConclusionsThe interpretable app-based model showed robust and satisfactory performance in diagnosing biliary atresia, and it could aid radiologists with limited experiences to improve their diagnostic performances in real-world mimic settings.

Correlation between Histological Changes of Liver and Early Surgical Outcome of Kasai Portoenterostomy in Biliary Atresia

Background: Biliary atresia (BA) is a progressive fibrosing obstructive cholangiopathy involving both resulting in the intrahepatic and extrahepatic bile ducts. Hepatic portoenterostomy was first described by Kasai and Suzuki in 1959 to re-establish bile flow in biliary atresia patients. Currently, the accepted management of infants with biliary atresia is to re-establish bile flow by Kasai portoenterostomy followed by liver transplantation when indicated. Purpose: The purpose of this study is to correlate the surgical outcome following Kasai portoenterostomy with liver histology at the time of extended Kasai Portoenterostomy for biliary atresia who are operated in this institution. Methods: This prospective study was done in the department of Pediatric Surgery, BSMMU, with study period from October 2017 to march 2020.Wedge biopsies of liver was taken at the time of Extended Kasai portoenterostomy. Liver biopsies were graded as mild (grade-1), moderate (grade-2) and severe (grade-3) degree of fibrosis by single pathologist. Serial measurement of serum bilirubin were made preoperative and postoperatively to assess the degree of bile drainage in relation to degree of liver fibrosis. Results: A total of thirty infants underwent Extended KPE during study period. The mean age at the time of surgery was 89.7 (±23.4SD) days ranging from 57days to 140 days. 16 infants were operated before 90 days and rest 14 were operated beyond 90 days of life. Out of 30 infants, 3 cases were grade -1 fibrosis, 15 cases were grade- 2 and 12 cases were grade-3 fibrosis. 12(40%) infants cleared jaundice at three months after surgery, of which only 2 patients belonged to grade-3 fibrosis. 9(30%) infants were jaundice free at 6 months, among them 8 infants belonged to lower degree of fibrosis (grade-1 and grade-2). Only 1infant belonged to higher degree of fibrosis (grade-3). Conclusion: Currently, the concept for management of infants with biliary atresia considers successful establishment ..

The clinical impact of macrophage polarity after Kasai portoenterostomy in biliary atresia.

Biliary atresia (BA) is a cholestatic hepatopathy caused by fibrosing destruction of intrahepatic and extrahepatic bile ducts, and its etiology has not been clearly revealed. In BA, liver fibrosis progression is often observed even after Kasai portoenterostomy (KPE), and more than half of cases require liver transplantation in their lifetime in Japan. Macrophages play an important role in liver fibrosis progression and are classically divided into proinflammatory (M1) and fibrotic macrophages (M2), whose phenotypic transformation is called "macrophage polarity." The polarity has been reported to reflect the tissue microenvironment. In this study, we examined the relationship between macrophage polarity and the post-KPE clinical course. Thirty BA patients who underwent KPE in our institution from 2000 to 2020 were recruited. Multiple immunostainings for CD68, CD163, CK19, and α-SMA were carried out on liver biopsy specimens obtained at KPE. ROC curves were calculated based on each clinical event, and the correlation with the clinical data was analyzed. The M2 ratio, defined as the proportion of M2 macrophages (CD163-positive cells), was correlated inversely with the occurrence of postoperative cholangitis (AUC: 0.7602). The patients were classified into M2 high (n = 19) and non-high (n = 11) groups based on an M2 ratio value obtained from the Youden index ( = 0.918). As a result, pathological evaluations (Metavir score, αSMA area fraction, and CK19 area fraction) were not significantly different between these groups. In mild liver fibrosis cases (Metavir score = 0-2), the M2 non-high group had a significantly lower native liver survival rate than the high group (p = 0.02). Moreover, 4 out of 8 cases in the M2 non-high group underwent early liver transplantation within 2 years after KPE. Non-M2 macrophages, including M1 macrophages, may be correlated with postoperative cholangitis, and the M2 non-high group in mild liver fibrosis cases had a significantly lower native liver survival rate than the high group, requiring early liver transplantation in this study. Preventing advanced liver fibrosis is a key factor in improving native liver survival for BA patients, and liver macrophages may play important roles in liver homeostasis and the promotion of inflammation and fibrosis.

Challenges faced in establishing a pediatric liver transplant program in a lower-middle-income country with free healthcare service.

Liver transplant is the cure for children with liver failure. Sri Lanka is a lower-middle-income country with a predominant free, state health system. Pediatric liver transplant program in Sri Lanka is still in the budding state where the initial experience of the program is yet to be documented. A retrospective review was performed including the clinical characteristics of all pediatric liver transplant recipients of Colombo North Centre for Liver Diseases since the inception of the program from June 2020 to May 2023. There were 14 PLT performed in 3 years. The median recipient age and weight were 8 years (6 months-15 years) and 23.3 kg (6.4-49.2), respectively. The majority were boys (64%). All were from low-income backgrounds. Indications for LT were acute liver failure (5/14), decompensated chronic liver disease (5/14), and acute on chronic liver failure (4/14). Underlying liver diseases were Wilson disease (6/14), autoimmune liver disease (3/14), biliary atresia (2/14) and progressive familial intrahepatic cholestasis type 3 (1/14), and unknown etiology (2/14). The majority were living donor liver transplants (86%). Of the living donors, 42% (5/12) were Buddhist priests. There were three immediate deaths and two late deaths. The 3-month survival was 78%, and overall survival was 64%. Living donor transplants carried a higher success rate (92%) compared to diseased donor transplants (0%; 2/2). Initial experience of pediatric liver transplant program of Sri Lanka is promising despite being established in a free healthcare system amidst the crisis circumstances.

Temporal Trends of Neonatal Surgical Conditions in Texas and Accessibility to Pediatric Surgical Care

IntroductionTexas consistently accounts for approximately 10% of annual national births, the second highest of all US states. This temporal study aimed to evaluate incidences of neonatal surgical conditions across Texas and to delineate regional pediatric surgeon accessibility. MethodsThe Texas Birth Defects Registry was queried from 1999 to 2018, based on 11 well-established regions. Nine disorders (30,476 patients) were identified as being within the operative scope of pediatric surgeons: biliary atresia (BA), pyloric stenosis (PS), Hirschsprung’s disease, stenosis/atresia of large intestine/rectum/anus, stenosis/atresia of small intestine, tracheoesophageal fistula/esophageal atresia, gastroschisis, omphalocele, and congenital diaphragmatic hernia. Annual and regional incidences were compared (/10,000 births). Statewide pediatric surgeons were identified through the American Pediatric Surgical Association directory. Regional incidences of neonatal disorder per surgeon were evaluated from 2010 to 2018 as a surrogate for provider disparity. ResultsPS demonstrated the highest incidence (14.405/10,000), while BA had the lowest (0.707/10,000). Overall, incidences of PS and BA decreased significantly, while incidences of Hirschsprung’s disease and small intestine increased. Other diagnoses remained stable. Regions 2 (48.24/10,000) and 11 (47.79/10,000) had the highest incidence of neonatal conditions; Region 6 had the lowest (34.68/10,000). Three rural regions (#2, 4, 9) lacked pediatric surgeons from 2010 to 2018. Of regions with at least one surgeon, historically underserved regions (#10, 11) along the Texas–Mexico border consistently had the highest defect per surgeon rates. ConclusionsThere are temporal and regional differences in incidences of neonatal conditions treated by pediatric surgeons across Texas. Improving access to neonatal care is a complex issue that necessitates collaborative efforts between state legislatures, health systems, and providers.

Role of the circular RNA regulatory network in the pathogenesis of biliary atresia.

Circular RNAs (circRNAs) serve an essential role in the occurrence and development of cholangiocarcinoma, but the expression and function of circRNA in biliary atresia (BA) is not clear. In the present study, circRNA expression profiles were investigated in the liver tissues of patients with BA as well as in the choledochal cyst (CC) tissues of control patients using RNA sequencing. A total of 78 differentially expressed circRNAs (DECs) were identified between the BA and CC tissues. The expression levels of eight circRNAs (hsa_circ_0006137, hsa_circ_0079422, hsa_circ_0007375, hsa_circ_0005597, hsa_circ_0006961, hsa_circ_0081171, hsa_circ_0084665 and hsa_circ_0075828) in the liver tissues of the BA group and control group were measured using reverse transcription-quantitative polymerase chain reaction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis demonstrated that the identified DECs are involved in a variety of biological processes, including apoptosis and metabolism. In addition, based on the GO and KEGG pathway enrichment analyses, it was revealed that target genes that can be affected by circRNAs regulatory network were enriched in the TGF-β signaling pathway, EGFR tyrosine kinase inhibitor resistance pathway and transcription factor regulation pathway as well as other pathways that may be associated with the pathogenesis of BA. The present study revealed that circRNAs are potentially implicated in the pathogenesis of BA and could help to find promising targets and biomarkers for BA.

Role of cholinergic innervation in biliary remnants of patients with biliary atresia.

Biliary innervation is considered important in regulating the function of bile ducts, whereas the role of innervation in the hepatobiliary system of patients with biliary atresia (BA) remains unknown. This current study aims to investigate the role of innervation in biliary remnants and analyze the relationship between the innervation and prognosis of BA after surgery. Eighty-seven patients with type III BA who underwent the Kasai procedure were consecutively enrolled from January 2017 to September 2020. Innervation and ductules in remnants were examined by pathologists. Liver function, onset of cholangitis, jaundice clearance, and survival with the native liver were recorded. Patients were followed up for 24 months. The relationship between innervation and prognosis was analyzed. In total, 67 patients had bile drainage postoperatively, and 21 biliary remnants contained neuronal plexuses where there was no neuron but nerve fiber bundles. Acetylcholinesterase staining was positive in all plexuses. In patients with bile drainage, those with plexuses had improved postoperative liver function, significantly better jaundice clearance 3 or 6 months postoperatively (50.0% vs. 19.1%, or 90.0% vs. 63.8%, respectively), fewer episodes of early cholangitis (10.0% vs. 34.0%), and better survival (80.0% vs. 61.7%) compared to those without. In addition, a larger area of plexuses was associated with a larger area of ductules (R2 = 0.786, p = 0.000), less frequent (p = 0.000) and later cholangitis onset (p = 0.012), and better jaundice clearance (p = 0.063). Increased cholinergic innervation in biliary remnants may help reduce the onset of cholangitis and lead to better and earlier jaundice clearance. Thus, it improves the postoperative prognosis of patients with BA.

A convenient nomogram for predicting early death or liver transplantation after the Kasai procedure in patients with biliary atresia.

Many patients with biliary atresia (BA) after the Kasai procedure (KP) progress to death or require liver transplantation to achieve long-term survival; however, most cases of death/liver transplantation (D/LT) occur in the early period after KP (usually within 1year). This study was designed to construct a convenient nomogram for predicting early D/LT in patients with BA after KP. A BA cohort was established in May 2017, and up to May 2023, 112 patients with 1-5years of follow-up were enrolled in the study and randomly (ratio, 3:1) divided into a training cohort for constructing a nomogram (n = 84) and a validation cohort (n = 28) for externally validating the discrimination and calibration. The training cohort was divided into two groups: the early D/LT group (patients who died or had undergone LT within 1year after KP [n = 35]) and the control group (patients who survived through the native liver more than 1year after KP [n = 49]). Multivariate logistic regression and stepwise regression were applied to detect variables with the best predictive ability for the construction of the nomogram. The discrimination and calibration of the nomogram were internally and externally validated. The Kaplan-Meier (K-M) curve showed an actual 1-year native liver transplantation (NLS) rate of 57.1% and an estimated 2-year NLS rate of 55.2%. By multivariate regression and stepwise regression, age at KP, jaundice clearance (JC) speed 1month after KP, early-onset PC (initial time < 36.5days) after KP, sex, aspartate aminotransferase-to-platelet ratio index (APRI), and weight at KP were identified as the independent variables with the best ability to predict early D/LT and were used to construct a nomogram. The developed nomogram based on these independent variables showed relatively good discrimination and calibration according to internal and external validation. Most D/LTs were early D/LTs that occurred within 1year after KP. The established nomogram based on predictors, including sex, weight at the KP, the APRI, age at the KP, JC speed 1month after the KP, and early PC, may be useful for predicting early D/LT and may be helpful for counseling BA patients about patient prognosis after KP. This study was retrospectively registered at ClinicalTrials.gov (NCT05909033) in June 2023.

Is the diagnostic model based on convolutional neural network superior to pediatric radiologists in the ultrasonic diagnosis of biliary atresia?

Many screening and diagnostic methods are currently available for biliary atresia (BA), but the early and accurate diagnosis of BA remains a challenge with existing methods. This study aimed to use deep learning algorithms to intelligently analyze the ultrasound image data, build a BA ultrasound intelligent diagnostic model based on the convolutional neural network, and realize an intelligent diagnosis of BA. A total of 4,887 gallbladder ultrasound images of infants with BA, non-BA hyperbilirubinemia, and healthy infants were collected. Two mask region convolutional neural network (Mask R-CNN) models based on different backbone feature extraction networks were constructed. The diagnostic performance between the two models was compared through good-quality images at the image level and the patient level. The diagnostic performance between the two models was compared through poor-quality images. The diagnostic performance of BA between the model and four pediatric radiologists was compared at the image level and the patient level. The classification performance of BA in model 2 was slightly higher than that in model 1 in the test set, both at the image level and at the patient level, with a significant difference of p = 0.0365 and p = 0.0459, respectively. The classification accuracy of model 2 was slightly higher than that of model 1 in poor-quality images (88.3% vs. 86.4%), and the difference was not statistically significant (p = 0.560). The diagnostic performance of model 2 was similar to that of the two radiology experts at the image level, and the differences were not statistically significant. The diagnostic performance of model 2 in the test set was higher than that of the two radiology experts at the patient level (all p < 0.05). The performance of model 2 based on Mask R-CNN in the diagnosis of BA reached or even exceeded the level of pediatric radiology experts.

Long-term clinical outcomes and health-related quality of life in patients with isolated methylmalonic acidemia after liver transplantation: experience from the largest cohort study in China.

Liver transplantation (LT) has been proposed as a viable treatment option for selected methylmalonic acidemia (MMA) patients. However, there are still controversies regarding the therapeutic value of LT for MMA. The systematic assessment of health-related quality of life (HRQoL)-targeted MMA children before and after LT is also undetermined. This study aimed to comprehensively assess the long-term impact of LT on MMA, including multiorgan sequelae and HRQoL in children and families. We retrospectively evaluated 15 isolated MMA patients undergoing LT at our institution between June 2013 and March 2022. Pre- and post-transplant data were compared, including metabolic profiles, neurologic consequences, growth parameters, and HRQoL. To further assess the characteristics of the HRQoL outcomes in MMA, we compared the results with those of children with biliary atresia (BA). All patients had early onset MMA, and underwent LT at a mean age of 4.3years. During 1.3-8.2years of follow-up, the patient and graft survival rates were 100%. Metabolic stability was achieved in all patients with liberalized dietary protein intake. There was a significant overall improvement in height Z scores (P = 0.0047), and some preexisting neurological complications remained stable or even improved after LT. On the Pediatric Quality of Life Inventory (PedsQL™) generic core scales, the mean total, physical health, and psychosocial health scores improved significantly posttransplant (P < 0.05). In the family impact module, higher mean scores were noted for all subscales post-LT, especially family function and daily activities (P < 0.01). However, the total scores on the generic core scales and transplant module were significantly lower (Cohen's d = 0.57-1.17) when compared with BA recipients. In particular, social and school functioning (Cohen's d = 0.86-1.76), treatment anxiety, and communication (Cohen's d = 0.99-1.81) were far behind, with a large effect size. This large single-center study of the mainland of China showed an overall favorable impact of LT on isolated MMA in terms of long-term survival, metabolic control, and HRQoL in children and families. The potential for persistent neurocognitive impairment and inherent metabolic fragility requires long-term special care. Video Abstract (MP4 153780 KB).

Comparison of Lipid Profiles Between Pediatric Living- and Deceased-Donor Liver Recipients

Background: It has been shown that hyperlipidemia occurs in 71% of patients following liver transplantation. Multiple risk factors, including obesity, diabetes mellitus, and diet, as well as the immunosuppressive medications used, influence the lipid profiles that are seen in these individuals, contributing to the multifactorial etiology of lipid problems. Objectives: The aim of the present study is to compare the lipid profile in liver transplant recipients from living-related (LR) and deceased donors (DDs). Methods: This is a retrospective cross-sectional study performed at Shiraz University of Medical Science between 2005 and 2018. Patients under 18 years old who received liver transplants were included in the study and divided into 2 groups who received from LR and DDs, and lipid profiles were compared between the 2 groups. Results: A total of 397 patients were included in the study; in the first group, 234 received a liver from a DD, and in the second group, 161 from an LR donor. The mean body mass index (BMI) was 17.51 ± 5.49 in the first group and 16.25 ± 3.29 in the second group. The most common underlying diseases were biliary atresia (22%) and autoimmune hepatitis (15%). The mean triglyceride (TG) and high-density lipoprotein (HDL) levels were 133 and 46 mg/dL in the first group and 118 and 54 mg/dL in the second group, while the differences were statistically significant. As age increased, there was a significant difference in the mean values of fasting blood sugar (FBS) and HDL, with FBS increasing and HDL decreasing. There was no significant difference in the use of immunosuppressant drugs between the 2 groups. Conclusions: Patients who received a liver from an LR donor have a significantly lower TG, higher HDL, and a lower cardiovascular risk.

FIB-4 and APRI scores for progressive liver fibrosis diagnosis in children with biliary atresia.

Finding non-invasive methods to predict the degree of liver fibrosis is very important in managing children with biliary atresia. Therefore, we explored the predictive value of APRI, FIB-4, and serological markers for liver fibrosis in children with biliary atresia. This study retrospectively reviewed data from children diagnosed with BA between March and December 2022. Liver tissue pathology specimens were obtained during surgery. The serum markers were measured within 2 days before the Kasai procedure or liver transplantation. The aspartate aminotransferase-to-platelet ratio index (APRI) and the four-factor-based fibrosis index (FIB-4) were calculated. The outcome was the diagnosis of progressive liver fibrosis. This study reviewed the data from 41 children with biliary atresia. APRI had 52% sensitivity and 83% specificity for progressive liver fibrosis, while FIB-4 had 83% sensitivity and 67% specificity. Their areas under the curve were not significantly different from those of conventional markers. Although they were not better than conventional markers, APRI and FIB-4 can be used as follow-up markers for progressive liver fibrosis in patients with biliary atresia, but their predictive value was moderate. Additional studies are necessary to determine whether they could be combined with other markers to improve their predictive value.

Maternal Prenatal Infections and Biliary Atresia in Offspring

Investigations into the association of antepartum maternal infections with the pathogenesis of biliary atresia (BA) in human offspring are insufficient. To examine the association between prenatal infections in mothers and the development of BA in their offspring. This population-based case-control study obtained administrative data from the Taiwan National Health Insurance Research Database with linkage to the Taiwan Maternal and Child Health Database, capturing demographic and medical information on nearly all 23 million of the Taiwan population. The cohort comprised 2 905 978 singleton live births among mother-infant dyads between January 1, 2004, and December 31, 2020, in Taiwan. The case group of infants with BA was identified from use of International Classification of Diseases diagnostic codes for BA and subsequent Kasai procedure or liver transplant. The control group was randomly selected from infants without BA, representing approximately 1 in 1000 study population. Data analyses were performed from May 1 to October 31, 2023. Prenatal maternal infections, including intestinal infection, influenza, upper airway infection, pneumonia, soft-tissue infection, and genitourinary tract infection. The main outcome was exposure to prenatal maternal infections. Inverse probability weighting analysis was performed by building a logistic regression model to estimate the probability of the exposure observed for a particular infant and using the estimated probability as a weight in subsequent analyses. The weighted odds ratio (OR) estimated by logistic regressions was then used to assess the risk of BA in offspring after prenatal maternal infections. Among the mother-infant dyads included, 447 infants with BA were cases (232 females [51.9%]) and 2912 infants without BA were controls (1514 males [52.0%]). The mean (SD) maternal age at childbirth was 30.7 (4.9) years. Offspring exposed to prenatal intestinal infection (weighted OR, 1.46; 95% CI, 1.17-1.82) and genitourinary tract infection (weighted OR, 1.22; 95% CI, 1.05-1.41) in mothers exhibited a significantly higher risk of BA. Furthermore, maternal intestinal infection (weighted OR, 6.05; 95% CI, 3.80-9.63) and genitourinary tract infection (weighted OR, 1.55; 95% CI, 1.13-2.11) that occurred during the third trimester were associated with an increased risk of BA in offspring. Results of this case-control study indicate an association between prenatal intestinal infection and genitourinary tract infection in mothers and BA occurrence in their offspring. Further studies are warranted to explore the underlying mechanisms of this association.

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

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. stool color screening system was introduced in 2004 which lead to marked improvement in sensitivity of detecting BA. 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. 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. 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.

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.