Kasai Portoenterostomy Research Articles

A Pilot Study for Biliary Atresia Diagnosis: Fluorescent Imaging of Indocyanine Green in Stool

BackgroundBiliary atresia is the most common cause of obstructive jaundice in infants and conventional cholangiography is the current diagnostic gold standard. Fluorescent cholangiography with indocyanine green can enhance biliary tree visualization during surgery because it is exclusively excreted into the bile ducts and eventually into the intestine. Therefore, we hypothesized that indocyanine green presence in stool could confirm bile duct patency in infants. MethodsA prospective single center cohort study was performed on infants (age ≤ 12 months) with and without jaundice after obtaining IRB approval. Indocyanine green was administered intravenously (0.1 mg/kg). Soiled diapers collected post-injection were imaged for fluorescence. ResultsAfter indocyanine green administration, fluorescence was detected in soiled diapers for control patients (n = 4, x = 14 h22 m post-injection) and jaundiced patients without biliary atresia (n = 11, x = 13 h28 m post-injection). For biliary atresia patients (n = 7), post-injection soiled diapers before and after Kasai portoenterostomy were collected. Fluorescence was not detected in stool from 6 of 7 biliary atresia patients. As a test, indocyanine green detection in stool was 97% accurate for assessing biliary patency. ConclusionFluorescent Imaging for Indocyanine Green (FIInd Green) in stool is a fast and accurate approach to assess biliary patency non-invasively in infants. Level of EvidenceLevel III.

Awareness, referral and age at Kasai surgery for biliary atresia in Europe: A survey of the Quality-of-Care Task Force of ESPGHAN.

To identify infants with biliary atresia (BA), European Society of Paediatric Gastroenteroloy and Nutrition (ESPGHAN)/North American Society of Pediatric Gastroenteroloy and Nutrition (NASPGHAN) guidelines recommend measurement of conjugated/direct bilirubin in infants with prolonged jaundice and using a stool colour card (SCC). The 'Quality of Care'Task Force of ESPGHAN performed two surveys to assess current case finding for BA and age at Kasai portoenterostomy (KPE). The first survey approached 26 European hepatology centres to report age at referral and age at KPE of all infants diagnosed with BA from 2015 to 2019. The second survey targeted paediatricians in France to assess awareness and compliance with the recently introduced SCC. Data from 785 patients with BA from 18 centres in 15 countries revealed a mean age at referral to tertiary centre of 55 days (median 53, IQR 48-60) (n = 636). The mean age at KPE was 61 days (median 60; IQR 54-67) (n = 772). For 6% of patients, cirrhosis was too advanced for surgery. Of 392 paediatricians answering the second survey, 53% felt familiar with the target diseases, 80% correctly identified cholestasisand 59% always inquired about the infant's stool colour. If abnormal, 93% would order blood tests and 85% call for advice. The SCC screening was considered helpful for case finding and improving knowledge of cholestatic diseases by 62% and 45% paediatricians, respectively. Referral of infants for KPE remains late, indicating low adherence to search for cholestasis in icteric infants by age 2-3 weeks. Knowledge and structures need improvement to allow earlier guideline conform case finding, diagnosis and therapy.

Primary liver transplantation vs transplant after Kasai portoenterostomy in children with biliary atresia: A retrospective Brazilian single-center cohort.

Biliary atresia (BA) is the most common indication for pediatric liver trans plantation, although portoenterostomy is usually performed first. However, due to the high failure rate of portoenterostomy, liver transplantation has been advocated as the primary procedure for patients with BA. It is still unclear if a previous portoenterostomy has a negative impact on liver transplantation outcomes. To investigate the effect of prior portoenterostomy in infants un dergoing liver transplantation for BA. This was a retrospective cohort study of 42 pediatric patients with BA who underwent primary liver transplantation from 2013 to 2023 at a single tertiary center in Brazil. Patients with BA were divided into two groups: Those under going primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior portoenterostomy. Continuous variables were compared using the Student's t-test or the Kruskal-Wallis test, and categorical variables were compared using the χ2 or Fisher's exact test, as appropriate. Multivariable Cox regression analysis was performed to determine risk factors for portal vein thrombosis. Patient and graft survival analyses were conducted with the Kaplan-Meier product-limit estimator, and patient subgroups were compared using the two-sided log-rank test. Forty-two patients were included in the study (25 [60%] girls), 23 undergoing liver transplantation without prior portoenterostomy, and 19 undergoing liver transplantation with prior portoenterostomy. Patients with prior portoenterostomy were older (12 vs 8 months; P = 0.02) at the time of liver transplantation and had lower Pediatric End-Stage Liver Disease scores (13.2 vs 21.4; P = 0.01). The majority of the patients (35/42, 83%) underwent living-donor liver transplantation. The group of patients without prior portoenterostomy appeared to have a higher incidence of portal vein thrombosis (39 vs 11%), but this result did not reach statistical significance. Prior portoenterostomy was not a protective factor against portal vein thrombosis in the multivariable analysis after adjusting for age at liver transplantation, graft-to-recipient weight ratio, and use of vascular grafts. Finally, the groups did not significantly differ in terms of post-transplant survival. In our study, prior portoenterostomy did not significantly affect the outcomes of liver transplantation.

Bile duct matrix metalloproteinase-7 expression: a new modality for diagnosis of biliary atresia

BackgroundBiliary atresia (BA) is an obliterative cholangiopathy of infancy that results in cholestasis and liver fibrosis. This fibrosis is due to an imbalance in extracellular matrix (ECM) breakdown and deposition. The mechanism by which the progressive injury occurs is not fully elucidated. Matrix metalloproteinases (MMPs) are involved in ECM turnover but also have non-ECM-related functions. Matrix metalloproteinase 7 (MMP7) has been suggested as a promising biomarker in diagnosing BA.ObjectiveThe aim of this study was to assess the hepatic expression of MMP-7 in infants with BA.Patients and methodsThe study was a retrospective-prospective case–control study that included 50 patients who were categorized into two groups, BA group (25 patients) and non-BA cholestatic patients as a control group (25 patients). Liver biochemistry, liver biopsy, histopathology, and immunohistochemical staining for primary antibody MMP-7 were performed for all studied patients.ResultsBile duct MMP7 expression was significantly higher in infants with BA than in non-BA cholestasis (P = 0.003), While the hepatic MMP-7 intensity did not differ significantly between both groups (P > 0.05). Bile duct expression of MMP-7 had a significant positive correlation with the BA Score (P = 0.017), while hepatic MMP-7 intensity had a significant positive correlation with alanine transaminase levels (P = 0.007) and a significant negative correlation with γ glutamyl transferase in the BA group (P = 0. 038). There was no statistically significant difference among different stages of fibrosis as regards the median of the hepatic MMP-7 intensity score and MMP-7 bile duct expression in infants with BA. There was no statistically significant difference between infants with successful and failed Kasai as regard the hepatic MMP-7 intensity and its bile duct expression.ConclusionBile duct expression of MMP-7 measured by immunohistochemistry is useful for the diagnosis of BA, but it is limited in predicting the stage of liver fibrosis and the outcome of Kasai portoenterostomy (KPE).

Biliary atresia in preterm infants: a single center experience and review of literature.

The diagnosis of biliary atresia (BA) remains challenging, and there is still uncertainty regarding the optimal time to perform a Kasai portoenterostomy (KPE). Little is known about the difficulties in the diagnosis and outcomes of BA in preterm infants (PBA). This study, which represents the first Italian report of preterm infants with BA, aims to describe a single-center experience of BA in preterm newborns. We retrospectively reviewed all infants consecutively diagnosed with BA who underwent a Kasai procedure at the Bambino Gesù Children's Hospital between January 1998 and December 2021. Prematurity was defined as a gestational age (GA) of <37 weeks. Demographic, laboratory, and histology data were recorded, and the main outcomes considered were clearance of jaundice (COJ), native liver survival, and mortality. A total of 21 PBA were compared with 117 term BA controls (TBA). The median GA of PBA was 35.1 (32-36.1) weeks, with a mean birth weight of 2,100 (1,897-2,800) g. Age at first presentation was significantly lower in PBA patients: 46 (22-68) vs. 61 (44-72) days; p = 0.02. The median age at KPE was similar between the two groups: 70 days (33 corrected) for PBA vs. 67 in TBA; p = 0.8. At the time of surgery, median serum bilirubin was lower in the PBA group (7.7 vs. 8.6 mg/dl, p = 0.04). Similarly, the median APRi at the time of KPE was lower but not significant in the PBA group: 1.09 vs. 1.16; p = 0.8. No differences were found in terms of COJ between the PBA and TBA groups: n = 9 (43%) vs. 34 (35%); p = 0.2. Overall native liver survival was similar between the two groups: 8.6 (4.8-12.2) for the PBA group vs. 7.6 (5.6-9.5) years for the TBA group with no significant differences; p = 0.45. Post-KPE native liver survival was similar between the two groups: 38% vs. 52% at 5 years for the TBA and PBA groups, respectively; p = 0.54. The PBA and TBA groups appear to have similar outcomes in terms of COJ, overall native liver survival, and 5-year liver survival. Considering the corrected GA, early KPE is related to lower cholestatic damage. Further multicenter studies are required.

Pre-operative Serum Albumin Predicts Native Liver Survival in Biliary Atresia.

To predict native liver survival (NLS) after Kasai portoenterostomy (KP) for biliary atresia (BA) using pre-operative clinical data. Pre-operative data were collected from 29 patients with BA who underwent KP at our department between 1989 and 2017 and were analysed including serum albumin, bilirubin, prothrombin time-international normalised ratio, body height, body weight, age at KP, paediatric end-stage liver disease score calculated using the pre-operative data and the period of NLS. The 10-year NLS rate of all patients was 51%. A multivariate analysis revealed that among all factors, the pre-KP serum albumin level was the only independent predictor of NLS ( P = 0.04, hazard ratio = 0.269, 95% confidence interval = 0.077-0.934). The area under the receiver operating characteristic curve for NLS, determined using pre-KP serum albumin was 0.760 and 3.75 mg/dl was selected as the cut-off value. There was a significant difference in NLS between patients with high (≥3.8 mg/dl) and low (≤3.7 mg/dl) pre-KP serum albumin (90.0% vs. 31.5%, P < 0.01). Decreased pre-KP serum albumin may reflect not only functional impairment of the liver, but also the inflammatory process, which is hypothesized to occur during its advancement. The pre-KP serum albumin level may be a good prognostic factor for NLS in post-KP BA patients.

Long-term outcomes of liver transplantation for biliary atresia and results of policy changes: over 20 years of follow-up experience.

Biliary atresia (BA) patients develop chronic liver disease after the Kasai operation and are eventually indicated for liver transplantation (LT). The purposes of this study were to analyze long-term outcomes after LT and risk factors that affect complications to reduce graft failure. Overall, 145 pediatric patients who underwent LT between June 1996 and June 2020 after a diagnosis of BA were included. We performed a retrospective analysis of medical records and evaluated patient and graft survival, cumulative incidence of complications, risk factors, and the results of policy changes. Patient and graft survival rates in over 20 years were 95.8% and 91.0%, respectively. Post-transplantation lymphoproliferative disease was frequently observed in the early period of immunosuppression within the first 1-2 years after LT. The incidence of cholangitis and rejection steadily increased over time. Weight-to-portal vein size was evaluated as a risk factor for cholangitis and bile duct strictures (OR = 12.82, p = 0.006 and OR = 16.54, p = 0.015, respectively). When evaluated using 2013 as a reference point, the split graft indication was expanded and the group that received LT after 2013 had a significantly lower survival over time compared with that of the group that received LT before 2013 (p = 0.006). This study revealed time differences in prevalence of complications. The evaluation of weight-to-duct or vessel size is a more important factor in considering complications than the graft-to-recipient weight ratio. Survival outcomes may have been altered by a policy change that affects the donor type ratio in transplantation.

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.

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.

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.

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.

Indocyanine green (ICG) fluorescence-enhanced applications in pediatric surgery

The breadth of pediatric surgical practice and variety of anatomic anomalies that characterize surgical disease in children and neonates require a unique level of operative mastery and versatility. Intraoperative navigation of small, complex, and often abnormal anatomy presents a particular challenge for pediatric surgeons. Clinical experience with fluorescent tissue dye, specifically indocyanine green (ICG), is quickly gaining widespread incorporation into adult surgical practice as a safe, non-toxic means of accurately visualizing tissue perfusion, lymphatic flow, and biliary anatomy to enhance operative speed, safety, and patient outcomes. Experience in pediatric surgery, however, remains limited. ICG-fluorescence guided surgery is poised to address the challenges of pediatric and neonatal operations for a growing breadth of surgical pathology. Fluorescent angiography has permitted intraoperative visualization of colorectal flap perfusion for complex pelvic reconstruction and anastomotic perfusion after esophageal atresia repair, while its hepatic absorption and biliary excretion has made it an excellent agent for delineating the dissection plane in the Kasai portoenterostomy and identifying both primary and metastatic hepatoblastoma lesions. Subcutaneous and intra-lymphatic ICG injection can identify iatrogenic chylous leaks and improved yields in sentinel lymph node biopsies. ICG-guided surgery holds promise for more widespread use in pediatric surgical conditions, and continued evaluation of efficacy will be necessary to better inform clinical practice and identify where to focus and develop this technical resource.

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.

Combined Predictors of Long-Term Outcomes of Kasai Surgery in Infants with Biliary Atresia.

Biliary atresia (BA) is the leading cause of neonatal cholestasis (25-45%). The primary treatment is hepatic portoenterostomy (Kasai procedure), but only 20-40% provide long-term benefits. This study aimed to develop a predictive model for surgical efficacy by comparing preoperative and early postoperative indicators in infants with different outcomes. We enrolled 166 infants with BA (93 girls, 73 boys) who underwent the Kasai procedure between September 2002 and December 2021, dividing them into favorable or adverse outcome groups. Over 40 parameters were measured, and the diagnostic significance of the prognostic model was evaluated. Kasai surgery was efficacious in 69 patients (42%) and non-efficacious in 97 (58%). Our model assesses efficacy by day 14 after surgery, improving on the <34 µmol/L direct bilirubin threshold established for 3-6 months after the procedure. Including the Desmet fibrosis score refined the model. Blood cholesterol below 5.41 mmol/L, direct bilirubin below 56.3 µmol/L on postoperative days 14±3, and a low Desmet score indicate a high probability of efficacious Kasai surgery in infants with BA.

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

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. 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. 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.

Relationship between hepatic function recovery and postoperative cholangitis in neonates undergoing hepaticojejunostomy for biliary atresia.

To explore the association between hepatic function recovery and the incidence of postoperative cholangitis in neonates with biliary atresia (BA) who underwent hepaticojejunostomy. We conducted a retrospective analysis of medical records from 173 newborns diagnosed with BA and treated with hepaticojejunostomy (Kasai procedure) between February 2020 and October 2022. Participants were categorized into two cohorts: those who developed cholangitis post-surgery (cholangitis group, n=125) and those who did not (non-cholangitis group, n=48). Liver function indices pre- and post-treatment, the extent of postoperative liver function recovery, and jaundice resolution rates were compared. Risk factors for cholangitis development post-surgery were identified using univariate and multifactorial logistic regression analyses. The cholangitis group exhibited higher surgical weight (P=0.030) and elevated preoperative levels of total bilirubin (TB, P<0.001), direct bilirubin (DB, P<0.001), aspartate aminotransferase (AST, P<0.001), and gamma-glutamyl transferase (GGT, P<0.001). This group also showed better postoperative liver function recovery (P=0.002) and jaundice clearance rates (P=0.003). Logistic regression identified postoperative jaundice clearance (P=0.013), TB (P=0.004), DB (P=0.011), AST (P<0.001), and GGT (P<0.001) as independent risk factors for cholangitis. The nomogram model had a C-index of 0.930 with a goodness-of-fit test p-value of 0.873, and an AUC of 0.930. Postoperative jaundice clearance, TB, DB, AST, and GGT are independent risk factors for cholangitis. The nomogram model offers high predictive accuracy for cholangitis development, aiding early intervention and prognosis improvement in high-risk neonates.

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

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. 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. 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. 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.