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Toxins Mar 2024Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. Biliatresone, a plant toxin, causes BA-like syndrome in some...
Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. Biliatresone, a plant toxin, causes BA-like syndrome in some animals, but its relevance in humans is unknown. To validate the hypothesis that biliatresone exposure is a plausible BA disease mechanism in humans, we treated normal human liver organoids with biliatresone and addressed its adverse effects on organoid development, functions and cellular organization. The control organoids (without biliatresone) were well expanded and much bigger than biliatresone-treated organoids. Expression of the cholangiocyte marker CK19 was reduced, while the hepatocyte marker HFN4A was significantly elevated in biliatresone-treated organoids. ZO-1 (a tight junction marker) immunoreactivity was localized at the apical intercellular junctions in control organoids, while it was markedly reduced in biliatresone-treated organoids. Cytoskeleton F-actin was localized at the apical surface of the control organoids, but it was ectopically expressed at the apical and basal sides in biliatresone-treated organoids. Cholangiocytes of control organoids possess primary cilia and elicit cilia mechanosensory function. The number of ciliated cholangiocytes was reduced, and cilia mechanosensory function was hampered in biliatresone-treated organoids. In conclusion, biliatresone induces morphological and developmental changes in human liver organoids resembling those of our previously reported BA organoids, suggesting that environmental toxins could contribute to BA pathogenesis.
Topics: Humans; Infant, Newborn; Animals; Biliary Atresia; Cilia; Liver; Bile Ducts; Benzodioxoles
PubMed: 38535810
DOI: 10.3390/toxins16030144 -
The American Journal of Case Reports Mar 2024BACKGROUND The VACTEREL association is an acronym that includes vertebral malformations (V), anal atresia (A), cardiac defects (C), tracheoesophageal fistula (TE), renal...
BACKGROUND The VACTEREL association is an acronym that includes vertebral malformations (V), anal atresia (A), cardiac defects (C), tracheoesophageal fistula (TE), renal defects (R), and limb malformations (L). The aortic arch is the section between the ascending aorta and the descending aorta, where some variants have been described, such as the right aortic arch and bovine aortic arch, among others. A rare presentation in the Natsis classification is the "type X" where a bovine aortic arch and anomalous origin of the left vertebral artery are present. Several structural cardiac malformations have been described in the VACTEREL association. Still, there is no bovine arch or an anomalous left vertebral artery. CASE REPORT Our patient was a 3-year-old boy with a diagnosis of VACTEREL association (type III esophageal atresia, congenital hip dislocation, scoliosis, bilateral clubfoot, and grade IV biliary ureteral reflux). Echocardiographic findings showed changes in the aortic arch, and angiotomography and magnetic resonance angiography showed a bovine aortic arch and an anomalous left vertebral artery. At the time of diagnosis, there were no clinical manifestations or complications due to the anomalous origin of the left vertebral artery. CONCLUSIONS This is the first description of a bovine type X arch according to the Natsis classification in a VACTEREL association. In general, knowledge of the anatomical variants of the aortic arch and the origin and course of the vertebral arteries is of great clinical and interventional importance, mainly because of the risk of cerebral ischemia.
Topics: Male; Humans; Child, Preschool; Aorta, Thoracic; Vertebral Artery; Aorta; Limb Deformities, Congenital; Spine; Esophagus; Kidney; Heart Defects, Congenital; Trachea; Anal Canal
PubMed: 38526305
DOI: 10.12659/AJCR.942974 -
South African Medical Journal =... Nov 2023Biliary atresia (BA) is an obstructive inflammatory disease of the bile ducts. Without intervention, the disease rapidly progresses to liver cirrhosis and fibrosis, with...
BACKGROUND
Biliary atresia (BA) is an obstructive inflammatory disease of the bile ducts. Without intervention, the disease rapidly progresses to liver cirrhosis and fibrosis, with end-stage liver failure and death occurring within the first 3 years of life. It is the most common indication for liver transplantation (LT) in the paediatric population. The management of BA in South Africa (SA) faces multiple challenges, such as late referrals and socioeconomic burdens, with suboptimal outcomes.
OBJECTIVES
To determine risk factors and shortcomings that are detrimental to the outcome of the paediatric patient population by reviewing the profile, management and outcome of patients with BA treated at Universitas Academic Hospital Complex (UAHC), Bloemfontein, SA.
METHODS
This was a retrospective analytical record review of all patients diagnosed with BA and treated at UAHC from 1 January 2009 to 31 December 2019.
RESULTS
In total, 67 patients were included; 74.6% were female, and 86.6% were black Africans. Most (62.7%) had isolated BA. A Kasai portoenterostomy (KPE) was performed in 32 patients (47.8%). Of 5 patients referred for LT evaluation, 2 received a transplant. Of 55 patients with known outcomes, 5.5% (n=3) survived and 94.5% (n=52) died after receiving a KPE or palliative treatment. Of the 3 patients who were alive at the end of the study period, 1 had a KPE and 2 had LTs.
CONCLUSION
Late presentation, cholangitis and cessation of bile flow after an initial successful KPE, and socioeconomic challenges are issues of concern and had a detrimental influence on the outcome of BA in our study population. Implementing screening measures and education programmes at the primary healthcare level is essential to diagnose and refer BA patients timeously. Establishing support systems to assist socioeconomically disadvantaged patients will enable them to qualify for LT.
Topics: Child; Humans; Female; Infant; Male; Biliary Atresia; Portoenterostomy, Hepatic; Tertiary Care Centers; Retrospective Studies; South Africa; Treatment Outcome; End Stage Liver Disease
PubMed: 38525639
DOI: 10.7196/SAMJ.2023.v113i11.845 -
Frontiers in Surgery 2024The diagnosis of biliary atresia (BA) remains challenging, and there is still uncertainty regarding the optimal time to perform a Kasai portoenterostomy (KPE). Little is...
INTRODUCTION
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.
METHODS
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.
RESULTS
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; = 0.02. The median age at KPE was similar between the two groups: 70 days (33 corrected) for PBA vs. 67 in TBA; = 0.8. At the time of surgery, median serum bilirubin was lower in the PBA group (7.7 vs. 8.6 mg/dl, = 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; = 0.8. No differences were found in terms of COJ between the PBA and TBA groups: = 9 (43%) vs. 34 (35%); = 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; = 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; = 0.54.
CONCLUSION
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.
PubMed: 38496210
DOI: 10.3389/fsurg.2024.1353424 -
Frontiers in Pediatrics 2023Biliary atresia (BA) patients develop chronic liver disease after the Kasai operation and are eventually indicated for liver transplantation (LT). The purposes of this...
OBJECTIVE
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.
STUDY DESIGN
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.
RESULTS
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, = 0.006 and OR = 16.54, = 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 ( = 0.006).
CONCLUSION
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.
PubMed: 38495838
DOI: 10.3389/fped.2023.1242009 -
Endoscopy Dec 2024
Transpapillary biliary drainage using a forward-viewing endoscope for distal malignant biliary obstruction after placement of a duodenal stent for type I duodenal stenosis.
Topics: Humans; Duodenal Obstruction; Stents; Endoscopes; Drainage; Cholestasis; Intestinal Atresia
PubMed: 38485156
DOI: 10.1055/a-2271-6994 -
African Journal of Paediatric Surgery :... Mar 2024To predict native liver survival (NLS) after Kasai portoenterostomy (KP) for biliary atresia (BA) using pre-operative clinical data.
BACKGROUND
To predict native liver survival (NLS) after Kasai portoenterostomy (KP) for biliary atresia (BA) using pre-operative clinical data.
METHODS
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.
RESULTS
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).
CONCLUSIONS
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.
PubMed: 38426534
DOI: 10.4103/ajps.ajps_158_22 -
Journal of Clinical and Translational... Mar 2024Biliary atresia (BA) is a congenital cholestatic disease that can seriously damage children's liver function. It is one of the main reasons for liver transplantation in... (Review)
Review
Biliary atresia (BA) is a congenital cholestatic disease that can seriously damage children's liver function. It is one of the main reasons for liver transplantation in children. Early diagnosis of BA is crucial to the prognosis of patients, but there is still a lack of reliable non-invasive diagnostic methods. Additionally, as some children are in urgent need of liver transplantation, evaluating the stage of liver fibrosis and postoperative native liver survival in children with BA using a straightforward, efficient, and less traumatic method is a major focus of doctors. In recent years, an increasing number of BA-related biomarkers have been identified and have shown great potential in the following three aspects of clinical practice: diagnosis, evaluation of the stage of liver fibrosis, and prediction of native liver survival. This review focuses on the pathophysiological function and clinical application of three novel BA-related biomarkers, namely MMP-7, FGF-19, and M2BPGi. Furthermore, progress in well-known biomarkers of BA such as gamma-glutamyltransferase, circulating cytokines, and other potential biomarkers is discussed, aiming to provide a reference for clinical practice.
PubMed: 38426193
DOI: 10.14218/JCTH.2023.00260 -
Journal of Indian Association of... 2024The aim is to study intrahepatic biliary architecture in patients following Kasai's portoenterostomy for extrahepatic biliary atresia using magnetic resonance...
AIM
The aim is to study intrahepatic biliary architecture in patients following Kasai's portoenterostomy for extrahepatic biliary atresia using magnetic resonance cholangiopancreatography (MRCP).
MATERIALS AND METHODS
It is a prospective observational study in a cohort of patients who have survived with a complete jaundice-free period for at least 1 year. MRCP was done to look for various intrahepatic architectural changes during their last visit. Findings were correlated with liver functions and growth and development.
RESULTS
Twenty-one patients were included in the study. The male-to-female sex ratio was 1.6:1, the median age at surgery was 75 days (18-140 days), and the median age at magnetic resonance imaging (MRI) was 4 years (18 months-18 years). More than 2 years of follow-up was in seven patients. Left lobe hypertrophy was observed in six patients, right lobe hypertrophy was in three patients, intrahepatic biliary tract dilatation was in five patients, and altered signal intensity between intrahepatic ducts was seen in five patients. In addition, hypointense foci in the spleen were seen in one patient. Twelve children had normal weight for their age, ten children had the normal height for their age, and gamma-glutamyl transferase was elevated in all children. Only four children had a history of fever and jaundice.
CONCLUSIONS
The patients who survive after successful surgical intervention have near-normal liver gross architecture as on MRI/MRCP. Occasional findings of dilatation and lobar atrophy/hypertrophy are possible, especially in those with a history of cholangitis. The survivors also have acceptable growth parameters and normal liver functions.
PubMed: 38405247
DOI: 10.4103/jiaps.jiaps_24_23 -
Indian Journal of Pathology &... Nov 2023Biliary atresia (BA) is the most common cause of the obstructive type of neonatal cholestasis that requires prompt surgical intervention. About 10% of neonates with BA...
Biliary atresia (BA) is the most common cause of the obstructive type of neonatal cholestasis that requires prompt surgical intervention. About 10% of neonates with BA have other congenital anomalies, of which splenic malformation (BASM) is a well-known distinct sub-group. There is sparse literature on the association of duodenal atresia and ductal plate malformation (DPM) in patients of BASM. We describe a BASM associated with DPM and duodenal atresia in a 35-day-old infant, who succumbed at 40 days, before portoenterostomy could be performed. Duodenal atresia can be one of the associated malformations associated with BASM and ductal plate abnormalities. In our case, the child did not survive.
PubMed: 38394407
DOI: 10.4103/ijpm.ijpm_182_23