-
Pediatric Surgery International Dec 2017The diagnosis of biliary atresia (BA) remains challenging and delay can lead to significant morbidity with time to surgery a key factor in determining outcome....
AIM OF STUDY
The diagnosis of biliary atresia (BA) remains challenging and delay can lead to significant morbidity with time to surgery a key factor in determining outcome. Prematurity may impact on outcome potentially delaying diagnosis. We sought to assess whether the premature BA infants (PBA) have a delayed time to surgery and as such, worse outcomes?
METHODS
Review of a single-centre prospectively maintained database. Prematurity was defined as delivery < 37/40 gestation. PBA was compared with date-matched term biliary atresia controls on a 2:1 basis. Primary outcomes were clearance of jaundice (< 20 μmol/L) and native liver survival. A retrospective assessment of liver fibrosis was made on biopsies at diagnosis and at Kasai portoenterostomy (KPE) in both premature and term cohorts. Data are quoted as median (range) unless indicated. A P value of ≤ 0.05 was considered statistically significant.
RESULTS
21 (female n = 14, 67%) premature infants with BA were treated in the period Jan. 1988-Dec. 2016 and compared with 41 contemporaneous term BA controls. Median gestation was 33 (29-36) weeks and birth weight 1930 (948-4230)g. Twin pregnancy (n = 10) was the leading cause for prematurity and significantly higher than the controls (48 vs. 0%; P < 0.0001). Maternal co-morbidity was high (n = 10, 48%) including pre-eclampsia (19%) and diabetes (14%). Liver biopsy was performed in 19 (90%) patients (all diagnostic) at a median of 57 (4-266) days. Delayed diagnosis (> 50 days) was seen in n = 13 but not associated with parenteral nutrition use (46 vs. 33%, P = 0.59) or phototherapy (50 vs. 83%, P = 0.19). Both BASM (33 vs. 7.5%; P = 0.01) and duodenal atresia (19 vs. 0%; P = 0.01) were seen more frequently in the PBA cohort. Mean fibrosis scores (Ishak) from diagnostic biopsies were lower in the premature group than the control group (2.71 vs. 3.53, P = 0.043) indicating less fibrosis but this equalized by time of subsequent KPE (P = 0.17). Primary surgery was Kasai portoenterostomy (n = 20) at an older median age than controls (65 vs. 56 days; P = 0.06). Liver transplantation was the primary procedure in one late-presenting child. There was an increased but non-significant clearance of jaundice in the PBA group [n = 12/20 (60%) vs 20/41 (48%); P = 0.23] post-KPE. Native liver survival and true survival were not different (P = 0.58 and 0.23).
CONCLUSIONS
PBA infants have similar outcomes to term infants, despite delayed diagnosis and higher frequency of the syndromic form. The high incidence of discordant twins supports the theory that epigenetic modifications could contribute to the pathogenesis of BA.
LEVEL OF EVIDENCE
IIIc Retrospective Matched Cohort Study.
Topics: Biliary Atresia; Early Diagnosis; Female; Follow-Up Studies; Forecasting; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Liver Transplantation; Male; Portoenterostomy, Hepatic; Retrospective Studies; Survival Rate; Treatment Outcome; United Kingdom
PubMed: 29030699
DOI: 10.1007/s00383-017-4193-1 -
World Journal of Gastroenterology Mar 2024Several diseases originate from bile duct pathology. Despite studies on these diseases, certain etiologies of some of them still cannot be concluded. The most common... (Review)
Review
Several diseases originate from bile duct pathology. Despite studies on these diseases, certain etiologies of some of them still cannot be concluded. The most common disease of the bile duct in newborns is biliary atresia, whose prognosis varies according to the age of surgical correction. Other diseases such as Alagille syndrome, inspissated bile duct syndrome, and choledochal cysts are also time-sensitive because they can cause severe liver damage due to obstruction. The majority of these diseases present with cholestatic jaundice in the newborn or infant period, which is quite difficult to differentiate regarding clinical acumen and initial investigations. Intraoperative cholangiography is potentially necessary to make an accurate diagnosis, and further treatment will be performed synchronously or planned as findings suggest. This article provides a concise review of bile duct diseases, with interesting cases.
Topics: Infant; Child; Infant, Newborn; Humans; Bile Ducts; Biliary Atresia; Choledochal Cyst; Bile Duct Diseases; Cholangiography
PubMed: 38577180
DOI: 10.3748/wjg.v30.i9.1043 -
Tidsskrift For Den Norske Laegeforening... Sep 2020In cases of infants with yellow colouration, both the sclerae and the skin should be examined. The top priority is to rule out conjugated hyperbilirubinaemia, which may...
In cases of infants with yellow colouration, both the sclerae and the skin should be examined. The top priority is to rule out conjugated hyperbilirubinaemia, which may be a symptom of biliary atresia. Children with this condition will first develop yellow sclerae, and will have jaundice that continues beyond the first two weeks of life. Although discoloured stools are a classic sign of biliary atresia, they are not always present. Children over two weeks of age with yellow skin should therefore be assessed immediately, regardless of the colour of the stool.
Topics: Biliary Atresia; Child; Feces; Humans; Infant; Jaundice
PubMed: 32900173
DOI: 10.4045/tidsskr.19.0667 -
Pediatrics and Neonatology Jan 2023
Topics: Infant, Newborn; Humans; Infant; Biliary Atresia; Cholestasis; Diagnosis, Differential
PubMed: 36550017
DOI: 10.1016/j.pedneo.2022.12.002 -
BMC Pediatrics Jun 2022The aim of this study was to evaluate the serum level of matrix metalloproteinase 7 (MMP7) in infants with cholestasis and the diagnostic values of this biomarker to...
BACKGROUND
The aim of this study was to evaluate the serum level of matrix metalloproteinase 7 (MMP7) in infants with cholestasis and the diagnostic values of this biomarker to differentiate biliary atresia (BA) from other causes of cholestasis.
METHODS
This multi-center study is conducted during 2 years in Mofid children's hospital and Children's Medical Center, Pediatrics Center of Excellence Tehran, Iran. 54 infants with cholestasis were enrolled in this study with a control group consists of 41 healthy infants with the same age. Serum samples were taken from all these patients to assess serum levels of MMP7, Gamma-glutamyl Transferase (GGT). For each biomarker, we calculated the sensitivity and specificity and other statistical characteristics.
RESULTS
There were 89 subjects, 22 patients with BA, 32 patients with non-BA cholestasis and 41 subjects as control group. The mean serum MMP7 levels in BA, non-BA cholestasis and control group was 15.91 ng/ml ± 6.64, 4.73 ng/ml ± 2.59 and 0.49 ng/ml ± 0.33, respectively. The best cut-off point is calculated 7.8 ng/ml for MMP7 and 434.5 U/L for GGT. The area under curve (AUC) for these two markers are 0.988 ± 0.008 and 0.854 ± 0.052, respectively. The sensitivity and specificity of MMP7 to differentiate biliary atresia from nonbiliary atresia cholestasis in our study was 95.5% and 94.5%, respectively. The sensitivity and specificity of GGT was 77.3% and 77.8%, respectively. These results show that the MMP7 has more sensitivity and specificity in differentiation.
CONCLUSION
MMP7 demonstrated good accuracy to differentiate biliary atresia from other causes of cholestasis.
Topics: Biliary Atresia; Biomarkers; Child; Cholestasis; Humans; Infant; Iran; Matrix Metalloproteinase 7; gamma-Glutamyltransferase
PubMed: 35717157
DOI: 10.1186/s12887-022-03409-9 -
Indian Pediatrics Oct 2015Biliary atresia is a progressive obstructive cholangiopathy and is fatal if left untreated within 2 years of life. Delay in referral is because of difficulties in... (Review)
Review
NEED AND PURPOSE OF REVIEW
Biliary atresia is a progressive obstructive cholangiopathy and is fatal if left untreated within 2 years of life. Delay in referral is because of difficulties in differentiating it from physiologic jaundice and identifying an abnormal stool color. This paper presents an overview on the diagnosis and discusses the current strategies in the management of this disease in developing countries.
METHODS
Articles were retrieved from the PubMed database using the terms biliary atresia, Kasai portoenterostomy and pediatric liver transplantation. Contents of the article are also based on personal experience of the authors.
CONCLUSION
A national screening program using stool color cards as part of standard care in the neonatal period will greatly improve early detection of biliary atresia. Outcomes will improve if it is diagnosed at the earliest after birth, the child is referred to an experienced pediatric hepatobiliary unit for evaluation, and undergoes an early Kasai procedure. If an early Kasai portoenterostomy is performed, nearly half of all children survive into adolescence, and about one-third are likely to have a long-term, symptom-free life with normal liver biochemistry. Sequential treatment combining Kasai as first line and liver transplantation as second line results in 90% survival for children with biliary atresia.
Topics: Biliary Atresia; Child; Developing Countries; Humans; India; Infant, Newborn; Neonatal Screening
PubMed: 26499012
DOI: 10.1007/s13312-015-0735-6 -
MBio Aug 2020Biliary atresia (BA) is a neonatal liver disease characterized by progressive fibroinflammatory obliteration of both intrahepatic and extrahepatic bile ducts. The...
Biliary atresia (BA) is a neonatal liver disease characterized by progressive fibroinflammatory obliteration of both intrahepatic and extrahepatic bile ducts. The etiologies of BA remain largely unknown, but rotavirus infection has been implicated at least for a subset of patients, and this causal relation has been well demonstrated in mouse models. In this study, we aim to further consolidate this evidence in human biliary organoids. We obtained seven batches of human biliary organoids cultured from fetal liver, adult liver, and bile duct tissues. We found that these organoids are highly susceptible and support the full life cycle of rotavirus infection in three-dimensional culture. The robust infection triggers active virus-host interactions, including interferon-based host defense mechanisms and injury responses. We have observed direct cytopathogenesis in organoids upon rotavirus infection, which may partially recapitulate the development of BA. Importantly, we have demonstrated the efficacy of mycophenolic acid and interferon alpha but not ribavirin in inhibiting rotavirus in biliary organoids. Furthermore, neutralizing antibody targeting rotavirus VP7 protein effectively inhibits infection in organoids. Thus, we have substantiated the causal evidence of rotavirus inducing BA in humans and provided potential strategies to combat the disease. There is substantial evidence indicating the possible involvement of rotavirus in biliary atresia (BA) development, at least in a subset of patients, but concrete proof remains lacking. In a mouse model, it has been well demonstrated that rotavirus can infect the biliary epithelium to cause biliary inflammation and obstruction, representing the pathogenesis of BA in humans. By using recently developed organoids technology, we now have demonstrated that human biliary organoids are susceptible to rotavirus infection, and this provokes active virus-host interactions and causes severe cytopathogenesis. Thus, our model recapitulates some essential aspects of BA development. Furthermore, we have demonstrated that antiviral drugs and neutralizing antibodies are capable of counteracting the infection and BA-like morphological changes, suggesting their potential for mitigating BA in patients.
Topics: Antibodies, Neutralizing; Antigens, Viral; Antiviral Agents; Biliary Atresia; Capsid Proteins; Cytopathogenic Effect, Viral; Host Microbial Interactions; Humans; Interferon-alpha; Mycophenolic Acid; Organoids; Ribavirin; Rotavirus Infections
PubMed: 32843549
DOI: 10.1128/mBio.01968-20 -
Chang Gung Medical Journal 2006Biliary atresia is the most common cause of pathologic jaundice in young infants and results from the obstruction of the extrahepatic bile ducts by an inflammatory and... (Review)
Review
Biliary atresia is the most common cause of pathologic jaundice in young infants and results from the obstruction of the extrahepatic bile ducts by an inflammatory and fibro-obliterative process. Although the pathogenesis of the disease is multifactorial, recent patient- and animal-based studies began deciphering the molecular pathways involved in biliary injury and duct obstruction. Using large-scale genomics and immunostaining of livers from children with biliary atresia, investigators have discovered unique molecular signatures of dominant proinflammatory cytokines at the time of diagnosis. To study hypotheses generated from these patient-based studies, the anatomical and inflammatory profiles of a mouse model of rotavirus-induced biliary atresia were analyzed and found to share striking similarities with the human profiles. Then, using these mice in mechanistic studies, interferon-gamma (IFNgamma) has been shown to regulate the biliary tropism of lymphocytes to the biliary system, and to play a critical role in the inflammatory obstruction of extrahepatic bile ducts. The ability to combine human studies with a laboratory model of neonatal biliary injury and obstruction opens a new era of opportunities to advance the field of biliary atresia, and to develop new therapeutic strategies to improve long-term outcome with the native liver of children with biliary atresia.
Topics: Animals; Biliary Atresia; Cholestasis; Disease Models, Animal; Fetus; Humans; Interferon-gamma; Morphogenesis; Virus Diseases
PubMed: 16924882
DOI: No ID Found -
BMC Pediatrics Oct 2023Early diagnosis of biliary atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis (NC), is challenging. This study aimed to design and... (Observational Study)
Observational Study
BACKGROUND AND AIMS
Early diagnosis of biliary atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis (NC), is challenging. This study aimed to design and validate a predictive model for BA by using the data available at the initial presentation.
METHODS
Infants presenting with NC were retrospectively identified from tertiary referral hospitals and constituted the model design cohort (n = 148); others were enrolled in a prospective observational study and constituted the validation cohort (n = 21). Clinical, laboratory, and abdominal ultrasonographic features associated with BA were assessed. A prediction model was developed using logistic regression and decision tree (DT) analyses.
RESULTS
Three predictors, namely, gamma glutamyl transpeptidase (γGT) level, triangular cord sign (TC sign), and gallbladder abnormalities, were identified as factors for diagnosing BA in multivariate logistic regression, which was used to develop the DT model. The area under the receiver operating characteristic (ROC) curve (AUC) value for the model was 0.905, which was greater than those for γGT level, TC sign, or gallbladder abnormalities alone in the prediction of BA.
CONCLUSION
A simple prediction model combining liver function and abdominal ultrasonography findings can provide a moderate and early estimate of the risk of BA in patients with NC.
Topics: Infant; Infant, Newborn; Humans; Biliary Atresia; Retrospective Studies; Ultrasonography; Cholestasis; Gallbladder Diseases; Early Diagnosis; Diagnosis, Differential
PubMed: 37907911
DOI: 10.1186/s12887-023-04370-x -
BMJ Open Dec 2021Biliary atresia (BA) is regarded as a serious neonatal hepatobiliary disease, and its aetiology and pathogenesis remain unclear. Epidemiological studies are limited,...
OBJECTIVES
Biliary atresia (BA) is regarded as a serious neonatal hepatobiliary disease, and its aetiology and pathogenesis remain unclear. Epidemiological studies are limited, especially for the data from China. This study aims to explore risk factors of BA and provide new evidence to improve understanding of its aetiology.
DESIGN
This is a case-control study from 1 January 2015 to 31 December 2016.
SETTING
Cases were consecutively recruited from an urban tertiary care academic children's hospital in Shanghai, China, while the controls were recruited from a community hospital in Shanghai through a random sampling system.
PARTICIPANTS
721 patients suspected for BA who planned to take the diagnostic surgery were enrolled preoperatively. 613 were diagnosed with BA and recruited into the case group. Meanwhile, 688 infants without any observed major congenital anomalies or jaundice were enrolled. Finally, 594 valid questionnaires from the case group and 681 from the control group were obtained.
PRIMARY AND SECONDARY OUTCOME MEASURES
Standardised questionnaires were used for data collection. Multivariate logistic regression analysis was performed to evaluate associations reported as ORs and precision, by adjusting covariates.
RESULTS
Anxiety or stress during pregnancy was strongly associated with increased risk of BA (OR 8.36 (95% CI: 4.08 to 17.15); p<0.001), respectively. Lower birth weight, fathers from ethnic minorities of China, older age of fathers, lower income of parents, and exposure to infection, diseases and medication during pregnancy all made differences.
CONCLUSIONS
Social factors including the educational and economic background and its related anxiety and stress during pregnancy might be noticed in the occurrence of BA. Maternal infections during pregnancy in the prevalence of BA were demonstrated.
TRIAL REGISTRATION NUMBER
ChiCTR-IPR-15005885.
Topics: Biliary Atresia; Case-Control Studies; Child; China; Female; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Pregnancy; Risk Factors
PubMed: 34903536
DOI: 10.1136/bmjopen-2021-049354