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Stem Cell Research & Therapy Nov 2021Biliary atresia (BA) is a severe hepatobiliary disease in infants that ultimately results in hepatic failure; however, its pathological mechanism is poorly elucidated....
BACKGROUND
Biliary atresia (BA) is a severe hepatobiliary disease in infants that ultimately results in hepatic failure; however, its pathological mechanism is poorly elucidated. Current surgical options, including Kasai hepatoportoenterostomy and orthotopic liver organ transplantations, are palliative; thus, innovation in BA therapy is urgent.
METHODS
To examine whether BA-specific post-natal stem cells are feasible for autologous cell source for BA treatment, we isolated from human exfoliated deciduous teeth, namely BA-SHED, using a standard colony-forming unit fibroblast (CFU-F) method and compared characteristics as mesenchymal stem cells (MSCs) to healthy donor-derived control SHED, Cont-SHED. BA-SHED and Cont-SHED were intrasplenically transplanted into chronic carbon tetrachloride (CCl)-induced liver fibrosis model mice, followed by the analysis of bile drainage function and donor integration in vivo. Immunohistochemical assay was examined for the regeneration of intrahepatic bile ducts in the recipient's liver using anti-human specific keratin 19 (KRT19) antibody.
RESULTS
BA-SHED formed CFU-F, expressed MSC surface markers, and exhibited in vitro mesenchymal multipotency similar to Cont-SHED. BA-SHED showed less in vitro hepatogenic potency than Cont-SHED. Cont-SHED represented in vivo bile drainage function and KRT19-positive biliary regeneration in chronic carbon tetrachloride-induced liver fibrosis model mice. BA-SHED failed to show in vivo biliary potency and bile drainage function compared to Cont-SHED.
CONCLUSION
These findings indicate that BA-SHED are not feasible source for BA treatment, because BA-SHED may epigenetically modify the underlying prenatal and perinatal BA environments. In conclusion, these findings suggest that BA-SHED-based studies may provide a platform for understanding the underlying molecular mechanisms of BA development and innovative novel modalities in BA research and treatment.
Topics: Animals; Biliary Atresia; Humans; Infant; Liver Cirrhosis; Liver Transplantation; Mesenchymal Stem Cells; Mice; Stem Cells
PubMed: 34809720
DOI: 10.1186/s13287-021-02652-8 -
Seminars in Pediatric Surgery Aug 2012The cause of biliary atresia is unknown; in the past few decades, the majority of investigations related to its pathogenesis have centered on viral infections and... (Review)
Review
The cause of biliary atresia is unknown; in the past few decades, the majority of investigations related to its pathogenesis have centered on viral infections and immunity. The acquired or perinatal form of biliary atresia entails a progressive inflammatory injury of bile ducts, leading to fibrosis and obliteration of both the extrahepatic and intrahepatic bile ducts. Theories of pathogenesis include viral infection, chronic inflammatory or autoimmune-mediated bile duct injury, and abnormalities in bile duct development. This review will focus solely on human studies pertaining to a potential viral trigger of bile duct injury at diagnosis and provide insight into the interplay of the innate and adaptive immune responses in the pathogenesis of disease.
Topics: Adaptive Immunity; Biliary Atresia; Cytomegalovirus Infections; Humans; Immunity, Cellular; Immunity, Humoral; Immunity, Innate; Reoviridae Infections; Rotavirus Infections
PubMed: 22800972
DOI: 10.1053/j.sempedsurg.2012.05.003 -
Liver Transplantation : Official... Jan 2017Biliary atresia (BA) is a progressive, fibro-obliterative disorder of the intrahepatic and extrahepatic bile ducts in infancy. The majority of affected children will... (Review)
Review
Biliary atresia (BA) is a progressive, fibro-obliterative disorder of the intrahepatic and extrahepatic bile ducts in infancy. The majority of affected children will eventually develop end-stage liver disease and require liver transplantation (LT). Indications for LT in BA include failed Kasai portoenterostomy, significant and recalcitrant malnutrition, recurrent cholangitis, and the progressive manifestations of portal hypertension. Extrahepatic complications of this disease, such as hepatopulmonary syndrome and portopulmonary hypertension, are also indications for LT. Optimal pretransplant management of these potentially life-threatening complications and maximizing nutrition and growth require the expertise of a multidisciplinary team with experience caring for BA. The timing of transplant for BA requires careful consideration of the potential risk of transplant versus the survival benefit at any given stage of disease. Children with BA often experience long wait times for transplant unless exception points are granted to reflect severity of disease. Family preparedness for this arduous process is therefore critical. Liver Transplantation 23:96-109 2017 AASLD.
Topics: Biliary Atresia; Child; Emotional Adjustment; End Stage Liver Disease; Family Relations; Health Policy; Health Services Accessibility; Hepatopulmonary Syndrome; Humans; Hypertension, Portal; Infant; Liver Transplantation; Portoenterostomy, Hepatic; Preoperative Care; Severity of Illness Index; Survival Rate; Time Factors; Waiting Lists
PubMed: 27650268
DOI: 10.1002/lt.24640 -
JAMA Network Open Jan 2024Investigations into the association of antepartum maternal infections with the pathogenesis of biliary atresia (BA) in human offspring are insufficient.
IMPORTANCE
Investigations into the association of antepartum maternal infections with the pathogenesis of biliary atresia (BA) in human offspring are insufficient.
OBJECTIVE
To examine the association between prenatal infections in mothers and the development of BA in their offspring.
DESIGN, SETTING, AND PARTICIPANTS
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.
EXPOSURE
Prenatal maternal infections, including intestinal infection, influenza, upper airway infection, pneumonia, soft-tissue infection, and genitourinary tract infection.
MAIN OUTCOMES AND MEASURES
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.
RESULTS
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.
CONCLUSIONS AND RELEVANCE
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.
Topics: Adult; Female; Humans; Male; Pregnancy; Biliary Atresia; Case-Control Studies; Logistic Models; Pregnancy Trimester, Third; Infant, Newborn
PubMed: 38170523
DOI: 10.1001/jamanetworkopen.2023.50044 -
Einstein (Sao Paulo, Brazil) 2022To relate omphalocele and biliary atresia and investigate possible embryological correlations that justify the simultaneous occurrence. A female preterm newborn...
To relate omphalocele and biliary atresia and investigate possible embryological correlations that justify the simultaneous occurrence. A female preterm newborn diagnosed as omphalocele; cesarean delivery, weight 2,500g, 46 XX karyotype. Initially, the newborn remained fasting and on parenteral nutrition, and enteral diet was introduced later, with good acceptance. On the 12th day of life, the newborn presented direct hyperbilirubinemia, increased levels of liver enzymes and fecal acholia, with a presumptive diagnosis of biliary atresia. However, the ultrasound was inconclusive, due to anatomical changes resulting from omphalocele. A surgical approach was chosen on the 37th day of life aiming to confirm diagnosis of biliary atresia and to repair omphalocele. During the surgical procedure, structural alterations compatible with biliary atresia were observed, later confirmed by pathological examination; a hepatoportoenterostomy was performed and the omphalocele was corrected. She evolved well in the postoperative period, with a decrease in direct bilirubin and liver enzymes, as well as resolution of fecal acholia, and was discharged in good clinical condition. This is a bizarre and extremely rare association, but the prognosis may be good when an early diagnosis is made and surgery performed, besides support and clinical management to prevent complications in the perioperative period. Although the pathogenesis of the diseases has not been fully defined yet, there is, to date, no direct relation between them. The association between omphalocele and biliary atresia is extremely uncommon, with only two published cases.
Topics: Biliary Atresia; Bilirubin; Cholestasis; Female; Hernia, Umbilical; Humans; Infant; Infant, Newborn; Parenteral Nutrition; Pregnancy
PubMed: 36169552
DOI: 10.31744/einstein_journal/2022RC0072 -
Current Gastroenterology Reports Nov 2021Biliary atresia is a serious neonatal liver disease due to obstructed bile ducts that has better outcomes when detected and treated in the first 30-45 days of life.... (Review)
Review
PURPOSE OF REVIEW
Biliary atresia is a serious neonatal liver disease due to obstructed bile ducts that has better outcomes when detected and treated in the first 30-45 days of life. This review examines different methods to screen newborns for biliary atresia as well as discusses observations from ongoing screening programs implemented in parts of the United States.
RECENT FINDINGS
Screening strategies for biliary atresia include detecting persistent jaundice, examining stool color, testing fractionated bilirubin levels, or measuring bile acid levels from dried blood spot cards. The stool color card program is the most widely used screening strategy worldwide. An alternative approach under investigation in the United States measures fractionated bilirubin levels, which are abnormal in newborns with biliary atresia. Fractionated bilirubin screening programs require laboratories to derive reference ranges, nurseries to implement universal testing, and healthcare systems to develop infrastructure that identifies and acts upon abnormal results. Biliary atresia meets the disease-specific criteria for newborn screening. Current studies focus on developing a strategy which also meets all test-specific criteria. Such a strategy, if implemented uniformly, has the potential to accelerate treatment and reduce biliary atresia's large liver transplant burden.
Topics: Bile Acids and Salts; Biliary Atresia; Humans; Infant, Newborn; Liver Transplantation; Neonatal Screening; United States
PubMed: 34817690
DOI: 10.1007/s11894-021-00825-2 -
Zhongguo Dang Dai Er Ke Za Zhi =... Nov 2022The diagnosis of biliary atresia (BA) is mainly based on clinical manifestations, screening, and related biochemistry tests. In recent years, the development of blood... (Review)
Review
The diagnosis of biliary atresia (BA) is mainly based on clinical manifestations, screening, and related biochemistry tests. In recent years, the development of blood biomarkers and the improvement in ultrasound examination have made it possible for BA to be diagnosed at a younger age. In particular, matrix metalloproteinase-7 shows high sensitivity and specificity and has a higher diagnostic efficiency than existing biochemical parameters, thereby holding a promise for clinical application. Sound touch elastography can increase the diagnostic efficiency for BA in terms of diagnosis and prognostic evaluation. Surgery is still the only method for the treatment of BA at present, with the preferred surgical treatment regimen of Kasai portoenterostomy combined with pharmacotherapies for alleviating infection and inflammation, and the patients who fail Kasai portoenterostomy or have liver dysfunction may require liver transplantation to save their lives. Therefore, the current research on BA should focus on the biomarkers for early diagnosis, specifically targeted drugs, and drugs for preventing progressive liver fibrosis. This article reviews the current diagnosis and treatment methods for BA and discusses the potential research directions.
Topics: Humans; Biliary Atresia; Portoenterostomy, Hepatic; Liver Transplantation; Prognosis; Biomarkers
PubMed: 36398555
DOI: 10.7499/j.issn.1008-8830.2205180 -
Archives of Pathology & Laboratory... Jul 2012Biliary atresia is an inflammatory cholangiopathy of infancy that results in progressive fibrosis and obliteration of bile ducts and represents the main indication for... (Review)
Review
CONTEXT
Biliary atresia is an inflammatory cholangiopathy of infancy that results in progressive fibrosis and obliteration of bile ducts and represents the main indication for liver transplant in young children. In spite of extensive investigation, its etiology has remained poorly understood. Timely surgical intervention (Kasai procedure) may result in significant benefit to these patients and represents the final goal of an accurate diagnostic evaluation.
OBJECTIVE
To present an overview of biliary atresia, including clinical and surgical approaches to this disease, with emphasis on the histopathologic evaluation.
DATA SOURCES
Review of relevant literature indexed in PubMed (US National Library of Medicine).
CONCLUSION
A well-coordinated multidisciplinary approach is required in the assessment of suspected cases of biliary atresia. Pathologic examination of biopsy specimens is an integral part of the diagnostic algorithm and, therefore, plays a pivotal role in the diagnostic evaluation of this disease.
Topics: Biliary Atresia; Humans; Liver; Portoenterostomy, Hepatic
PubMed: 22742548
DOI: 10.5858/arpa.2011-0623-RA -
Chang Gung Medical Journal 2006Biliary atresia is a severe progressive cholangiopathy which leads to early liver cirrhosis and is uniformly fatal. Early surgical intervention (the Kasai procedure) is... (Review)
Review
Biliary atresia is a severe progressive cholangiopathy which leads to early liver cirrhosis and is uniformly fatal. Early surgical intervention (the Kasai procedure) is needed for an improved outcome. However, early recognition and diagnosis is not easy during the neonatal period because of the high incidence of neonatal jaundice, ill-informed and less than urgent appraisal of the clinical manifestations among jaundiced neonates. A mass screening program for biliary atresia using a stool color card was conducted in Taiwan from March 2002 (in 49 hospitals and clinics) to December 2003 (in 95 hospitals and clinics). The stool color card for infants has proved to be a sensitive and specific screening method for biliary atresia in infants younger than two months of age.
Topics: Biliary Atresia; Color; Feces; Humans; Incidence; Mass Screening; Taiwan
PubMed: 16924883
DOI: No ID Found -
Hepatology (Baltimore, Md.) Sep 2022The natural history of gastroesophageal variceal hemorrhage (VH) in biliary atresia (BA) is not well characterized. We analyzed risk factors, incidence, and outcomes of...
BACKGROUND AND AIMS
The natural history of gastroesophageal variceal hemorrhage (VH) in biliary atresia (BA) is not well characterized. We analyzed risk factors, incidence, and outcomes of VH in a longitudinal multicenter study.
APPROACH AND RESULTS
Participants enrolled in either an incident (Prospective Database of Infants with Cholestasis [PROBE]) or prevalent (Biliary Atresia Study of Infants and Children [BASIC]) cohort of BA were included. Variceal hemorrhage (VH) was defined based on gastrointestinal bleeding in the presence of varices accompanied by endoscopic or nontransplant surgical intervention. Cumulative incidence of VH and transplant-free survival was compared based on features of portal hypertension (e.g., splenomegaly, thrombocytopenia) and clinical parameters at baseline in each cohort (PROBE: 1.5 to 4.5 months after hepatoportoenterostomy [HPE]; BASIC: at enrollment > 3 years of age). Analyses were conducted on 869 children with BA enrolled between June 2004 and December 2020 (521 in PROBE [262 (51%) with a functioning HPE] and 348 in BASIC). The overall incidence of first observed VH at 5 years was 9.4% (95% CI: 7.0-12.4) in PROBE and 8.0% (5.2-11.5) in BASIC. Features of portal hypertension, platelet count, total bilirubin, aspartate aminotransferase (AST), albumin, and AST-to-platelet ratio index at baseline were associated with an increased risk of subsequent VH in both cohorts. Transplant-free survival at 5 years was 45.1% (40.5-49.6) in PROBE and 79.2% (74.1-83.4) in BASIC. Two (2.5%) of 80 participants who had VH died, whereas 10 (12.5%) underwent transplant within 6 weeks of VH.
CONCLUSIONS
The low risk of VH and associated mortality in children with BA needs to be considered in decisions related to screening for varices and primary prophylaxis of VH.
Topics: Biliary Atresia; Child; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Infant; Varicose Veins
PubMed: 35271743
DOI: 10.1002/hep.32451