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[83][84] In sum, support for BA as a cholangiociliopathy comes from evidence of reduced ciliated cholangiocytes in BA and in cholangiocyte-organoids derived from BA patients, [12][64][65] ciliary alterations being known effectors in developmental cholangiopathies, [14][59][85] and in multiple ciliary-related gene variants identified through GWAS and exome analyses (Table 2). Keywords: epigenetics; cilia; cholangiocyte; mutation; cholestasis EN epigenetics cilia cholangiocyte mutation cholestasis 323 335 13 11/03/23 20230801 NES 230801 Biliary atresia (BA) is the principal serious liver disease of infancy worldwide and is the main indication to transplant any solid organ in infants less than 1 year of age. This study additionally identified another BA patient with compound heterozygous I PKHD1 i mutations, adding to an isolated finding of I PKHD1 i mutations in a BA patient with renal cysts. [67] In 89 BA patients, focusing upon ciliary genes and using downstream gene set burden analysis, 31.5% of the patients had de novo or biallelic variants in liver-expressed ciliary genes (OR = 2.6). [Extracted from the article]

Objective  Congenital anomalies are important causes of morbidity and mortality in children. Oxidative stress (OS) is involved in the physiopathology of pregnancy-related congenital malformations. This review summarizes the role of OS in the pathogenesis of congenital malformations; in particular, its purpose is to describe how OS influences the development of heart congenital malformations, oesophageal atresia, biliary atresia, diaphragmatic hernia, and autosomal dominant polycystic kidney disease. Study Design  Systematic review of previous studies about the role of OS in pregnancy and its possible effects in developing of congenital malformations. One electronic database (PubMed) was searched and reference lists were checked. Results  An imbalance between the production of reactive oxygen species (ROS) and antioxidant defense can occur early in pregnancy and continue in the postnatal life, producing OS. It may destroy the signaling pathways needed for a correct embryogenesis leading to birth defects. In fact, cell functions, especially during embryogenesis, needs specific signaling pathways to regulate the development. These pathways are sensitive to both endogenous and exogenous factors; therefore, they can produce structural alterations of the developing fetus. Conclusion  Because OS plays a significant role in pathogenesis of congenital malformations, studies should be developed in order to better define their OS mechanisms and the beneficial effects of supplemental therapeutic strategies. Key Points Oxidative stress is involved in the pathogenesis of congenital malformations. Heart malformations, oesophageal atresia, biliary atresia, diaphragmatic hernia, and autosomal dominant polycystic kidney are analyzed. A knowledge of pathomechanism of OS-related congenital malformations could be useful to prevent them. [ABSTRACT FROM AUTHOR]

Introduction:  The majority of pediatric surgeons and hepatologists recommend the centralization of biliary atresia (BA) treatment within experienced liver units. We aimed to investigate whether voluntary self-restriction and acceptance of the need for this change in practice changed the BA referral policy in Germany during the last decade.Materials and Methods:  In cooperation with pediatric surgeons, gastroenterologists or hepatologists, and pediatric liver transplant units, the 2-year follow-up data of infants with BA born in Germany between 2010 and 2014 were collected using www.bard-online.com or pseudonymized data transfer. Results were compared with our previous analysis of the outcome data of infants with BA born between 2001 and 2005 in Germany.Result:  Overall, 173 infants with BA were identified, of whom 160 underwent Kasai portoenterostomy (KPE; 92.5%) and 13 (7.5%) underwent primary liver transplantation at 21 German centers. At 2-year follow-up, overall survival was 87.7% (vs. 81.9% in 2001-2005 [p = 0.19]), survival with native liver post-KPE was 29.2% (vs. 22.8% in 2001-2005 [p = 0.24]), and jaundice-free survival with native liver post-KPE was 24.0% (vs. 20.1% in 2001-2005 [p = 0.5]). Compared with the 2001-2005 analysis, all criteria showed improvement but the differences are statistically not significant.Conclusion:  Our observation shows that KPE management requires improvement in Germany. Centralization of BA patients to German reference liver units is not yet mandatory. However, European and national efforts with regard to the centralization of rare diseases support our common endeavor in this direction. [ABSTRACT FROM AUTHOR]

Introduction:  Age at Kasai portoenterostomy (KPE) has been identified as a predictive factor for native-liver survival in patients with biliary atresia (BA). Outcomes of pediatric liver transplantation (LT) have improved over recent years. It has been proposed to consider primary LT as a treatment option for late-presenting BA infants instead of attempting KPE. We present our experience with patients older than 90 days undergoing KPE.Materials and Methods:  A retrospective chart review of patients with BA undergoing KPE at our institution between January 2010 and December 2020 was performed. Patients 90 days and older at the time of surgery were included. Patients' characteristics, perioperative data, and follow-up results were collected. Eleven patients matched the inclusion criteria. Mean age at KPE was 108 days (range: 90-133 days).Results:  Postoperative jaundice clearance (bilirubin < 2 mg/dL) at 2-year follow-up was achieved in three patients (27%). Eight patients (73%) received a liver transplant at a mean of 626 days (range: 57-2,109 days) after KPE. Four patients (36%) were transplanted within 12 months post-KPE. Two patients died 237 and 139 days after KPE due to disease-related complications. One patient is still alive with his native liver, currently 10 years old.Conclusion:  Even when performed at an advanced age, KPE can help prolong native-liver survival in BA patients and offers an important bridge to transplant. In our opinion, it continues to represent a viable primary treatment option for late-presenting infants with BA. [ABSTRACT FROM AUTHOR]

Introduction:  Age of patient and experience of biliary atresia (BA) center are well-known factors associated with early jaundice clearance (EJC) after Kasai portoenterostomy (KPE) in infants with BA. This study focused on the impact of age and surgeon factor on the short-term outcome after KPE within a single center.Materials and Methods:  Fifty-four consecutive infants (18 boys and 36 girls) who underwent KPE from January 2010 to January 2020 were reviewed. KPE was performed in the earliest available operative session once the initial work-up was completed. In group A (n = 41), KPE was performed by surgeon A. In group B (n = 13), KPE was performed by specialists under the supervision of surgeon B (who is the mentor of surgeon A) when surgeon A was not available for operation. The demographics of patients, the EJC (total bilirubin <20 μmol/L within 6 months of KPE), and 2-year native liver survival (NLS) between the two groups were studied.Results:  The median age at operation was 52 days (range 26-135 days). The overall EJC rate and 2-year NLS were 85.2 and 89.4%, respectively. Group A (p = 0.015) and male gender (p = 0.029) were statistically associated with EJC but not the age at operation (p = 0.101). Group A was also statistically associated with superior 2-year NLS (p = 0.047).Conclusion:  Balancing between the impact of age at operation and the experience of surgeon on the outcome after KPE, our result suggested that KPE may be deferred until a more experienced surgeon to operate. [ABSTRACT FROM AUTHOR]

Introduction:  Evidence supports long-term oral antibiotic prophylaxis to prevent cholangitis after Kasai procedure. Data regarding perioperative intravenous prophylaxis are lacking. Ascending pathogens from the intestine are made responsible for recurrent cholangitis. Therefore, we analyzed the flora in the upper jejunum during the Kasai procedure and their potential impact on postoperative cholangitis.Materials and Methods:  In 26 patients, swabs were taken at the bowel prepared for the Roux-en-Y-loop. Our postoperative protocol includes intravenous third-generation cephalosporins for 2 weeks and rectal steroids starting at day 4. Cholangitis was defined as the postoperative reappearance of acholic stools or increase of serum bilirubin in combination with fevers or increase of inflammatory parameters. In this scenario, Tazocin was administered for another 2 weeks.Results:  Swabs remained sterile in nine patients (34.6%). In 17 patients (65.4%), gram-positive and gram-negative pathogens were identified; all belonging to physiological intestinal flora. A total of 96.2% pathogens were covered by the antibiotic prophylaxis. The cholangitis incidence was 55.6% in the sterile cohort, and 23.5% in the gram-positive and gram-negative cohort (p = 0.06). In the cholangitis cohort, no significant differences were detected for the age at Kasai and the pre- and postoperative total bilirubin.Conclusion:  We found that our antibiotic regiment covered bacteria in the upper gastrointestinal (GI) tract in the majority of our patients at the time of Kasai. Nonetheless, a significant proportion of patients developed signs of cholangitis. There was no higher rate of cholangitis in patients with resistant bacteria. Thus, our data do not support the hypothesis of extended postoperative intravenous antibiotics to prevent ascending cholangitis. [ABSTRACT FROM AUTHOR]

Intrahepatic cholestasis of pregnancy (ICP) is a common disorder in the second half of pregnancy characterized by pruritus and elevated serum bile acids (BAs) with spontaneous resolution after delivery. ICP carries a risk of adverse effects on the fetus which correlates with the degree of BA elevation. ICP occurs in genetically susceptible women as the reproductive hormones increase during pregnancy. Ursodeoxycholic acid is still considered the first-line treatment for ICP though it is of unproven benefit in preventing adverse effects on the fetus. Fetal complications, such as stillbirth, increase with gestational age, so preterm delivery is generally performed in cases of severe ICP, defined as BA levels above 40 μmol/L. ICP may recur in future pregnancies and is associated with an increased risk for future hepatobiliary, immune mediated, and cardiovascular diseases. Children born of mothers with ICP have normal development but may have a risk for subsequent metabolic disease. [ABSTRACT FROM AUTHOR]

Objective:  To investigate the efficiency of free carnitine, unconjugated bilirubin (UBIL), bilirubin monoglucuronide (BMG), and bilirubin diglucuronide (BDG) in dry blood spots (DBSs) measured using tandem mass spectrometry (MS/MS) for screening biliary atresia (BA).Materials and Methods:  All the patients with BA, residing in Shanghai, were collected from four different children's hospitals in Shanghai from January 1, 2015, to June 30, 2017. UBILMS, BMG, BDG, and free carnitine were measured in the DBS samples of 48 patients with BA, 10,008 pediatric patients, and 52,862 newborns using MS/MS. Conjugated bilirubin was measured by MS/MS (CBMS) = BMG + BDG, and total bilirubin was measured by MS/MS (TBMS) = UBILMS + CBMS. Four hundred pediatric patients' direct bilirubin (DB) and total bilirubin (TB), measured by the clinical laboratory and MS/MS, were used as a control.Results:  The total number of births at the registered permanent residences in Shanghai was 233,000; among them, the occurrence of BA was in 33 patients in 2 years. Therefore, the incidence of BA in Shanghai was 1:7,060. The ratio of DB/TB and CBMS/TBMS of most patients with BA was elevated gradually in the neonatal period and higher than the normal range after 1 month after birth. The area under the receiver operating characteristic curve of DB, DB/TB, CBMS/TBMS, CBMS, and free carnitine for predicting BA was 0.98, 0.95, 0.73, 0.57, and 0.92, respectively. Using the 95% percentile as a cutoff, the sensitivity of DB and free carnitine to predict BA was 100 and 85%, respectively, and the specificity was 52 and 85%, respectively.Conclusion:  In free carnitine, DB, and CBMS/TBMS tests, blood concentrations are elevated in all infants with BA. However, they may not be elevated while they are newborns. These tests will result in high false negatives or positives. Thus, they should not be used as newborn screening tests for BA due to their lower sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Introduction:  Hepatoportoenterostomy (HPE) is the first-line treatment for biliary atresia (BA) patients. This study aims to describe perioperative complications after HPE and to analyze their impact on outcome.Materials and Methods:  Patients with HPE (Swiss National Biliary Atresia Registry, 1994-2017) were retrospectively analyzed. Perioperative complications were defined as complications occurring up to 30 days after surgery. Surgical complications were defined as directly related to the surgical act; medical complications were defined as any other deviation from the uneventful postoperative course.Results:  Sixty-two patients were included. Median age at HPE was 63 days (18-126). Twenty six patients out of 62 (42%) had ≥ 1 complications: 6/62 (10%) surgical, 24/62 (39%) medical, that is, we observed 7 surgical and 28 medical complications. As for medical complications, cholangitis was the most frequent: 19/28 (68%). Lower gestational age at birth correlated with more overall complications (p = 0.02). Age, weight at HPE, syndromic BA, and postoperative steroid administration were not significantly correlated. There were no perioperative deaths. Perioperative complications did not correlate with overall survival (p = 0.14) and survival with native liver (p = 0.55).Conclusion:  HPE is often associated with perioperative medical complications. Lower gestational age at birth was significantly associated with more complications. Perioperative complications had no impact on overall outcome. [ABSTRACT FROM AUTHOR]

Introduction:  We aimed to assess health-related quality of life (HrQoL) in biliary atresia (BA) patients, based on original data and a literature review, and to determine factors associated with their HrQoL.Materials and Methods:  We reviewed available studies describing HrQoL in BA patients. We assessed HrQoL in Dutch BA patients (6-16 years) using the validated Child Health Questionnaire. We compared HrQoL scores in BA patients with healthy peers and with children who had undergone major surgery in infancy or children with chronic conditions. We determined the relationship between specific patient-related factors and HrQoL.Results:  Literature data indicated that HrQoL in children with BA is lower than in healthy peers. In Dutch BA patients (n = 38; age 10 ± 3 years), parent-proxy physical HrQoL (48 ± 11) was significantly lower compared with two reference groups of healthy peers (59 ± 4 and 56 ± 6, respectively, each p < 0.001), and lower than in children with attention deficit hyperactivity disorder (60 ± 5), asthma (54 ± 6), attending a cardiology clinic (52 ± n/r), congenital diaphragmatic hernia (53 ± 7) or D-transposition of the great arteries (54 ± 6; all p < 0.05). Psychosocial HrQoL (50 ± 9) was lower than in healthy peers (54 ± 6, p = 0.02, and 53 ± 6, p = 0.07) and children with asthma (54 ± 6, p = 0.02), and largely comparable to children with other chronic conditions. Parent-proxy physical HrQoL was adversely related to adverse medical event in the past year, special education, and motor impairments; psychosocial HrQoL was adversely related to behavioral problems.Conclusion:  Children with BA are at risk of impaired HrQoL. Special attention is warranted for children with adverse medical events and special education. [ABSTRACT FROM AUTHOR]

Autoreactive B cells can promote autoimmunity through antigen presentation to autoreactive T cells, production of autoantibodies, generation of cytokines promoting T cell activation and differentiation, and inhibition of regulatory T cells and B cells. Here, the authors highlight studies pertaining to B cell mechanisms associated with disease pathogenesis and outcomes in autoimmune hepatitis and the immune-mediated cholangiopathies (primary biliary cholangitis, primary sclerosing cholangitis, and biliary atresia). The vast majority of investigations focus on autoantibodies and future research endeavors should include deciphering the role of the B cell in T cell activation (through antigen presentation, cytokine/chemokine production, and inhibition of regulation). Targeting B cell mechanisms in the treatment of autoimmune liver diseases is also highlighted. [ABSTRACT FROM AUTHOR]

Biliary atresia (BA) is a fibro-obliterative cholangiopathy of unknown etiology. While Kasai portoenterostomy achieves temporary biliary drainage in some cases, BA remains the most common indication for liver transplantation during childhood. During the last few decades, observations on BA, like cholestatic diseases in animals and the introduction of different animal models for BA, have not achieved the anticipated results, and we are still not able to translate the basic research to the patient's bedside. This article presents a review of the literature on available BA animal models and gives a glimpse of future developments. [ABSTRACT FROM AUTHOR]

Introduction:  Biliary atresia (BA) is a progressive inflammatory obstructive cholangiopathy in infants. High mobility group box 1 (HMGB1) is known to play an important role as a late mediator of inflammation. However, it is not clear whether HMGB1 levels are of clinical significance in patients with BA. The aim of this study was to determine correlations between serum HMGB1 levels and the clinicopathologic features of BA.Materials and Methods:  Serum samples were collected from 19 infants with BA, 7 infants with anicteric choledochal cysts (CC) and normal liver function, and 8 healthy controls. Serum HMGB1 levels were measured with an enzyme-linked immunosorbent assay. Routine liver function tests were performed on serum samples. Quantitative real-time polymerase chain reaction and western blot analyses were used to detect HMGB1 expression in BA liver biopsy tissues. Localization of HMGB1 expression in the hepatic lobule was determined by immunohistochemical analysis.Results:  HMGB1 levels in serum collected from BA infants were significantly elevated compared with CC and healthy control patients. Furthermore, elevated serum levels of HMGB1 in BA infants positively correlated with gamma-glutamyl transferase levels. HMGB1 messenger ribonucleic acid and protein expression levels were upregulated in BA liver biopsy tissues compared with CC patients. Immunohistochemical analysis also revealed increased positive immunostaining for HMGB1 in BA liver tissues as compared with CC tissues.Conclusion:  HMGB1 may play a crucial role in the pathogenesis of BA. Additionally, the correlation of serum HMGB1 levels with gamma-glutamyl transferase levels may provide a novel marker for the diagnosis of BA. [ABSTRACT FROM AUTHOR]

Aim:  Biliary atresia (BA) remains a rare disease in Europe with an estimated incidence of 1 in 15-20,000 livebirths. While the Kasai portoenterostomy (KPE) is regarded as the standard operation for BA, there is no consensus on optimum adjuvant therapy. We sought to determine the variation in therapy and opinion in centers known to have an interest in pediatric hepatobiliary surgery across Europe.Methods:  A survey of current pre- and postoperative practice was circulated to surgeons and centers known to have an interest in BA. Data are quoted as median (range).Results:  There were 19 completed center forms from 12 different countries. Annual (new) caseload varied with 10 centers reported seeing ≤5 patients/year and 4 centers >15 patients/year. The distribution of BA variants was isolated BA (80 [60-100]%), syndromic BA (10 [3-35]%), cystic BA (5 [1-15]%), and cytomegalovirus (CMV) immunoglobulin M (IgM)-positive BA (5 [0-15]% (CMV serology only formally tested in 16 centers). The commonest age group at KPE was 51 to 60 days (n = 8). All centers performed an exclusively open KPE, although one used laparoscopy for diagnosis. A steroid-based postoperative regimen was used in 11/19 (58%) centers, but with marked variation in dose and duration. Commonest perioperative antibiotics were a combination of piperacillin-tazocin (n = 7) and gentamicin (n = 8). Oral prophylactic antibiotics, with varying duration (4-52 weeks) were used in 13/19 (68%) centers. If CMV serology was positive, seven centers would treat with specific antiviral therapy. Other postoperative medication included ursodeoxycholic acid (UDCA) (n = 19), phenobarbitone (n = 4), and cholestyramine (n = 2). Self-declared clearance of jaundice in centers varied from 30 to 40% (n = 3) to > 60% (n = 5).Conclusion:  All surveyed European centers continue to perform an exclusively open KPE, but there is no consensus on a standard adjuvant drug regimen. Self-declared outcome post-KPE also appears to be variable though the reasons are obscure. [ABSTRACT FROM AUTHOR]

Introduction:  Portal hypertension often occurs in biliary atresia (BA). The subsequent development of esophageal varices and bleeding from these varices are a well-known complication. We aim to describe the incidence and severity of variceal bleeding in patients with BA. In addition, we describe the characteristics of patients who experienced variceal bleeds.Materials and Methods:  We included all infants treated for BA at our center between March 1987 and August 2015. Variceal bleeding was defined as hematemesis and/or melena with presence of varices at endoscopy. Findings at endoscopy and ultrasound, laboratory tests, clearance of jaundice, fibrosis-grade at Kasai portoenterostomy, and several varices prediction scores were documented. Routine endoscopies were not performed.Results:  In this study, 74 patients were included. During follow-up, 18 out of 74 patients (24%) developed variceal bleeding at an age of 9 months (range, 4-111). Twelve patients were listed for liver transplantation at the time of bleeding. Patients who did not clear their jaundice developed variceal bleeds more often and earlier in life. Bleeds were treated with sclerotherapy, banding, or octreotide. Four patients did not receive treatment. No bleeding-related mortality occurred.Conclusion:  One-fourth of the children diagnosed with BA experience variceal bleeds during follow-up. Most of these children are younger than 1 year and often already listed for transplantation. Major complications did not occur after variceal bleeding. [ABSTRACT FROM AUTHOR]

Introduction:  Biliary atresia (BA) is a rare destructive inflammatory obliterative cholangiopathy of neonates. Early diagnosis is important in disease management. The aim was to evaluate the role of endoscopic retrograde cholangiopancreatography (ERCP) in diagnosing BA in a large cohort. In addition, we evaluated whether parameters such as bile trace, GGT, bilirubin, and laboratory values in combination can be used to develop a risk score that could indicate the referral to specialized centers.Materials and Methods:  All infants with neonatal cholestasis (2000-2014) who presented to our endoscopy unit for suspected BA were included. Demographics, laboratory parameters, ultrasound findings, liver biopsy results, ERCP diagnosis, and surgical outcome were collected. Value and safety of ERCP and risk factors for BA were retrospectively analyzed.Results:  We included 251 infants in our cohort (55% males, median age: 53 days). BA was intraoperatively diagnosed in 155 (83.4%) patients and was excluded in 30 (16.2%). Fifty-six cases were not operated due to the ERCP findings. ERCP was successful in 224/251 patients (89.2%) with no procedure-related complications. The operative and endoscopic diagnosis matched in 96.6% of the patients (positive predictive value: 92.2%, negative predictive value: 97.1%). In comparison to cases with excluded BA, the ones with this disease were significantly associated with absence of duodenal bile traces (98.4 vs. 1.6%, p < 0.001), higher bilirubin (p < 0.001, cutoff 7.3 mg/dL), and higher GGT (p < 0.001, cutoff 250 U/L).Conclusion:  ERCP is safe and accurate in the hands of experts in diagnosing BA if the cause of cholestasis is unclear. While evaluating the role of ERCP for diagnosing this disease, we found that the secondary parameters GGT > 250 U/L, bilirubin > 7.3 mg/dL (125 μmol/L), and the absence of bile traces are risk factors. [ABSTRACT FROM AUTHOR]

Biliary atresia (BA) and congenital choledochal malformations (CCM) are rare. Both pathologies must (BA) or may (CCM) be operated during the neonatal period or early infancy. We briefly describe the classical operative techniques for both pathologies, followed by the most common and severe perioperative complications encountered during and up to 30 days after surgery in children operated for BA and CCM early in life. For patients with BA, intestinal complications represent the most common and hazardous perioperative surgical complications. Cholangitis is the most frequently encountered medical complication post hepato-porto-enterostomy. For CCM, it seems that neonates encounter little perioperative complications; however, reports are scarce; bile leak and/or cholangitis are the most reported. Overall, for patients with CCM, the literature is ambivalent whether more perioperative complications occur in the younger or in the older patient, and whether these occur more frequently in those symptomatic or asymptomatic at operation. It is difficult to give clear advice for when children with asymptomatic CCM should be operated, and benefits and risks must be carefully counterbalanced. Perioperative mortality for both BA and CCM is low and is reported to be around 1 to 2%. [ABSTRACT FROM AUTHOR]

The NHS provides more than 98% of all surgical procedures in infants and children in the United Kingdom through a comprehensive network of secondary (typically for the general surgery of childhood) and tertiary (specialist neonatal and specialist pediatric surgery) centers [n = 22]), typically located within large conurbations. It was originally envisaged that these specialized centers would be able to provide the full range of surgical interventions (aside from organ transplantation). However, there has been a trend toward centralization of some key procedures, previously thought to be within general neonatal surgery. The architype for centralization is the management of biliary atresia (BA). Since 1999, within England and Wales, this has been exclusively managed in three centers (King's College Hospital, London; Birmingham Children's Hospital and Leeds General Infirmary). All of these provide facilities for the diagnosis of BA, primary surgical management (Kasai portoenterostomy), and liver transplantation if required. The case for centralization was made by rigorous national outcome analysis during the 1990s showing marked disparity based on case volume and driven by parents' organizations and national media. Following centralization, national outcome data showed improvement and provided a benchmark for others to follow. The management of bladder exstrophy was later centralized in England and Wales, albeit not based on strict outcome data, to two centers (Great Ormond Street, London and Royal Manchester Children's Hospital). [ABSTRACT FROM AUTHOR]

Purpose Systemic and local immune environments in human biliary atresia (BA) were analyzed. Methods Plasma concentrations of 19 inflammatory components in 16 preoperative BA patients (median age, 51 days), 13 normal controls (NCs) (44 days), and 15 cholestatic controls (CC) (23 days) were measured using flow cytometry, and compared according to post-Kasai outcomes in BA patients. Hepatic mRNA levels of representative helper T (Th) cell cytokines and forkhead box protein 3 (FoxP3) quantified by real-time reverse transcription polymerase chain reaction were compared between BA and non-BA. Results No significant differences were observed between BA and control in serum Th1, Th2, or macrophage markers, while soluble cellular adhesion molecule (CAM) levels were significantly higher in BA (p < 0.0001 for NC; p = 0.0003 for CC). No statistically significant difference was discovered between BA with favorable and unfavorable prognosis. Hepatic mRNA levels of interferon-gamma or interleukin-4 showed no significant differences between BA and non-BA, while FoxP3 was significantly higher in BA (p = 0.01). Conclusions A skewed bias toward specific Th-oriented immunity was not demonstrated in either the systemic or local environment in the early stage of human BA, with patient prognoses not necessarily revealed by preoperative plasma inflammatory component levels. CAM and regulatory T cell roles and functions warrant further investigation. [ABSTRACT FROM AUTHOR]

Background Biliary atresia (BA) is a rare cholestatic disease of infancy. Kasai portoenterostomy and liver transplantation (LT) are the two sequential treatment options. An increasing number of patients survive into adulthood. Little is known about their health-related quality of life (HRQOL). This study aims to compare HRQOL of transplanted and nontransplanted patients in a cohort of young adult BA survivors. Patients and Methods RAND-36 and Liver Disease Index Score (LDSI) questionnaires were sent to eligible adult patients with BA. Clinical characteristics were obtained from the NeSBAR (Netherlands Study group on Biliary Atresia Registry) and the national pediatric LT database. RAND-36 domain and summary scores were compared with those of an age-matched Dutch reference group. The correlations between several clinical variables and HRQOL were analyzed. Results Mean RAND-36 domain and summary scores of transplanted (n = 15) and nontransplanted (n = 25) patients with BA (response 74%) were similar to the reference scores, with the exception of a decreased general health perception in nontransplanted patients (63 ± 21 vs. 75 ± 17; [p < 0.001], particularly in females. RAND-36 domain and summary scores were not significantly correlated to age at LT, time since LT, serum bilirubin, aspartate amino transferase or albumin levels, but were moderately to strongly correlated to LDSI total scores (r values 0.35-0.77). Conclusions Overall, young adult patients with BA have a HRQOL similar to an age-matched reference group. However, general health perception of nontransplanted patients, particularly of females, was decreased. HRQOL is correlated to liver disease symptoms but not to liver biochemistry parameters. Nontransplanted females and patients suffering from liver disease-associated symptoms may be a target for tailored supportive interventions. [ABSTRACT FROM AUTHOR]

Purpose The aim of this article is to differentiate neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) from biliary atresia (BA) by total hexose. Methods A total of 11 patients with NICCD, 29 patients with BA, and 4,898 children as controls were involved in this study. The blood concentration of amino acids, carnitine, acylcarnitines, and total hexose were measured in dry blood spots (DBS) using tandem mass spectrometry (MS/MS). Results In the patients with NICCD, the blood concentration of the total hexose (15.3 ± 9.0 mmol/L vs. 7.3 ± 2.7 mmol/L; p < 0.001), citrulline (Cit) (197.9 ± 93.7 µmol/L vs. 17.5 ± 7.4 µmol/L; p < 0.001) were higher than those of patients with BA. Using total hexose (> 10 mmol/L), Cit (> 55 µmol/L) to diagnose NICCD, the sensitivity and specificity were 66.7 and 97.8% and 90.0 and 99.1%, respectively, and all of the areas under the receiver-operating characteristic curves were greater than 0.85. Conclusion Elevated total hexose in DBS measured by MS/MS associated with elevated amino acids, especially Cit can be used to diagnose NICCD and differentiate it from BA. [ABSTRACT FROM AUTHOR]

Introduction: Early diagnosis and surgery (< 60 days of age) improve outcomes in children with biliary atresia. Only 56% of patients undergo timely surgery in the Netherlands. Lack of acquaintance with symptoms such as discolored stools might underlie this delay. We analyzed whether Dutch parents, youth healthcare doctors, or general practitioners recognized discolored stools and evaluated the effect of the Infant Stool Color Card (ISCC) on recognizing discolored stools.Material and Methods: We asked 100 parents, 33 youth healthcare doctors, and 50 general practitioners to classify photographs of stools as "normal" or "abnormal." Subsequently, we asked whether parents would seek medical help and doctors would refer the patient for medical investigation. Finally, parents scored stools using the ISCC.Results: Two-third of both parents and youth healthcare doctors recognized all discolored stools. Only half of them would seek medical help for all discolored stools resp. refer patient for medical investigation. Only one-third of the general practitioners recognized all discolored stools and would refer for medical investigation for all discolored stools. Using the ISCC, the percentage of parents recognizing all discolored stool increased from 66 to 87% (p < 0.01).Conclusion: Neither parents nor youth healthcare doctors nor general practitioners reliably recognize discolored stool. The ISCC is an effective screening method for discolored stool. Our data indicate that the ISCC should be accompanied by unequivocal advices regarding referral for medical investigation upon detection of discolored stools. [ABSTRACT FROM AUTHOR]

Most neonatal cholestatic disorders are rare diseases (RD), but they represent the leading indication for pediatric liver transplantation. From the pediatric surgical point of view, biliary atresia (BA) and choledochal cyst are from particular interest because diagnostic pathways and therapeutic algorithms are diverging as well as outcome parameters of follow-up studies. In addition, screening programs for BA are still at an early stage while transition of those patients with and without liver transplantation is not established yet. The newly created Web site www.bard-online.com focuses on BA and related diseases and includes decentralized online registries, information for patients and health workers, as well as a platform for interdisciplinary communication and service offerings. This initiative was started to compensate for disadvantages for patients with RD and to help unifying the community of clinicians and researchers in this field. [ABSTRACT FROM AUTHOR]

Cholangiocytes, the epithelial cells lining the biliary tree, represent only a small portion of the total liver cell population (3-5%), but they are responsible for the secretion of up to 40% of total daily bile volume. In addition, cholangiocytes are the target of a diverse group of liver diseases affecting the biliary tract, the cholangiopathies; for most of these conditions, the pathological mechanisms are unclear. MicroRNAs (miRNAs) are small, noncoding RNAs that posttranscriptionally regulate gene expression. Thus, it is not surprising that altered miRNA profiles underlie the dysregulation of several proteins involved in the pathobiology of the cholangiopathies, as well as showing promise as diagnostic and prognostic tools. Here the authors review recent work relevant to the role of miRNAs in the etiopathogenesis of several of the cholangiopathies (i.e., fibroinflammatory cholangiopathies and polycystic liver diseases), discuss their value as prognostic and diagnostic tools, and provide suggestions for further research. [ABSTRACT FROM AUTHOR]

Introduction Gaining an insight into the quality of life (QOL) in long-term biliary atresia (BA) survivors is becoming more important. Identifying patients with limitations might make tailor made interventions possible. This is the first study investigating the health status (HS) and QOL in adults surviving BA with their native livers, and comparing them with healthy peers. Methods BA patients surviving with their native liver were identified in the Netherlands Study Group on Biliary Atresia Registry database. The RAND-36 and the World Health Organization Quality of Life assessment instrument-100 (WHOQOL-100) were used to measure HS and QOL, respectively. Correlation between the RAND-36 and WHOQOL-100 was also assessed. Hospital Anxiety and Depression Scale (HADS) and the Impact Event Scale (IES) were also completed. Results In total, 25 (83%) of the 30 eligible patients after Kasai portoenterostomy completed the questionnaires (median age 23.2 years). A lower perceived level of general health in HS was found as compared with the reference group and a higher score on the social domain was reported in QOL. Correlations between HS and QOL questionnaires were moderate to good. For the group, overall HADS and IES scores were good, though individual patients did score above the cutoff of both the questionnaires. Conclusion Adult BA patients surviving with their native liver have similar HS and QOL as compared with their healthy peers. RAND-36 and WHOQOL-100 questionnaires are not interchangeable, but complementary to assess the patients' outcomes. The overall scores did not point to increased levels of anxiety and depression. However, on an individual level, three and six patients had a score above the cutoff of the HADS subscales demonstrating clinically relevant levels of anxiety and depression, respectively. [ABSTRACT FROM AUTHOR]

We tried to insert internal-external drainage tubes as percutaneous transhepatic biliary drainage tubes; however, the guidewire could not be inserted through the bile duct owing to complete atresia of the anastomosis site (Fig. We punctured the bile duct at the anastomosis site with a puncture needle and placed the guidewire into the bile duct. [Extracted from the article]

Biliary atresia (BA) is an infantile obstructive cholangiopathy of unknown etiology with suboptimal therapy, which is responsible for 40 to 50% of all pediatric liver transplants. Although the etiology of bile duct injury in BA in unknown, it is postulated that a pre- or perinatal viral infection initiates cholangiocyte apoptosis and release of antigens that trigger a Th1 immune response that leads to further bile duct injury, inflammation, and obstructive fibrosis. Humoral immunity and activation of the innate immune system may also play key roles in this process. Moreover, recent investigations from the murine BA model and human data suggest that regulatory T cells and genetic susceptibility factors may orchestrate autoimmune mechanisms. What controls the coordination of these events, why the disease only occurs in the first few months of life, and why a minority of infants with perinatal viral infections develop BA are remaining questions to be answered. [ABSTRACT FROM AUTHOR]

Introduction Infants with biliary atresia (BA) develop a degree of hepatic fibrosis as a consequence of their cholangiopathy. Some of them present clinically evident ascites thatmight predispose to inguinal hernias.We aimed to investigate whether infants with BA have a higher incidence of inguinal hernias. Methods Single-center retrospective review of all BA infants diagnosed between January 2006 and December 2010. Infants with a clinical diagnosis of inguinal hernia were identified and compared with those without. Data were expressed as median (range) and compared with nonparametric statistical tests. p _ 0.05 was regarded as significant. Results A total of 123 infants underwent Kasai portoenterostomy (KP) during the period. Of these, 10 (8.1%) infants (7 boys) developed inguinal hernias (bilateral n = 4, right n = 5, left n = 1); 9 were repaired (at KP [n = 3] and post-KP [n = 6] at 15 [7 to 30] days) using nonabsorbable sutures, and 1 died before repair. There was no difference in median age at KP (66 vs. 58 days, p = 0.31); cytomegalovirus (IgM positive) status (p = 1.0); use of postoperative corticosteroids (p = 0.49); or ultimate need for liver transplant (p = 1.0). However, aspartate aminotransferase-to-platelet ratio (surrogate marker of liver fibrosis) was higher in hernia infants (2.0 vs. 1.0; p = 0.02). Recurrence has not been identified at a follow-up of 27 months (4 to 55). Conclusions This is the first report to suggest that BA infants have a high incidence of inguinal hernias, which seems related to degree of liver fibrosis at presentation and presumably degree of ascites and increased intra-abdominal pressure. [ABSTRACT FROM AUTHOR]

Introduction Biliary atresia (BA) is a fatal disease in children. Its main pathological feature is progressive immune-mediated cholangiopathy. Interleukin (IL)-12, IL-18, and interferon-gamma (IFN-gamma) play important roles in various immunological diseases. The objective was to investigate whether these serum markers were associated with clinical outcome in BA.Methods Serum levels of IL-12, IL-18, and IFN-gamma were determined using enzyme-linked immunosorbent assay from 46 BA patients (median age of 9 years) and 19 normal controls. The BA patients were then categorized into three groups according to their outcome: jaundice-free (29 cases), mild to moderate jaundice (10 cases), and marked jaundice (7 cases). The comparisons of serum IL-12, IL-18, and IFN-gamma levels among groups of the patients were performed using one-way analysis of variance with post-hoc tests. Data are expressed as mean + standard deviation.Results Serum IL-18 and IFN-gamma in BA patients were higher than the normal controls (IL-18: 113.3 + 82.6 vs. 80.5 + 9.9 pg/mL, p = 0.011 and IFN-gamma: 41.7 + 5.1 vs. 38.0 + 1.9 pg/mL, p < 0.001). There was no difference in serum IL-12 between BA and controls. Further analysis demonstrated that, in BA patients, only serum IL-18 levels significantly increased with the degree of jaundice (test for trend, p = 0.004).Conclusions Serum IL-18 and IFN-gamma levels were increased in medium-term survivors of BA. The elevated serum IL-18 in BA patients was associated with worse clinical outcome. These results suggest that IL-18 and IFN-gamma play roles in the pathophysiology of BA. Additionally, IL-18 is likely to be involved in the disease progression. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIM: Biliary atresia (BA) is an intractable neonatal liver disease characterized by progressive fibrosclerotic obliteration of the extrahepatic biliary tree. The aim of this study was to evaluate serum galectin-3 in postoperative BA patients and the association between galectin-3, clinical outcome and liver stiffness score. METHODS: 58 BA patients post Kasai operation and 20 controls were enrolled. None of the patients had undergone liver transplantation. BA patients were classified into 2 groups according to their serum total bilirubin (TB) levels (TB<2?mg/dL, no jaundice vs. TB?2?mg/dL, persistent jaundice) and alanine aminotransferase (ALT) levels (ALT<45?IU/L, normal ALT vs. ALT?45?IU/L, elevated ALT). Serum galectin-3 levels were determined by enzyme-linked immunosorbent assay. Liver stiffness scores were measured by transient elastography (FibroScan). RESULTS: BA patients had higher serum galectin-3 levels (5.1?0.3 vs. 3.8?0.4?ng/mL, p=0.01) and greater liver stiffness values than healthy controls (29.7?3.0 vs. 5.1?0.5?kPa, p<0.001). Serum galectin-3 levels were markedly elevated in BA patients with jaundice compared to those without jaundice (6.4?0.5 vs. 4.4?0.3?ng/mL, p=0.001). Furthermore, BA patients with elevated ALT displayed significantly higher levels of serum galectin-3 than those with normal ALT (5.9?0.4 vs. 3.8?0.3?ng/mL, p=0.001). Additionally, BA patients with portal hypertension had considerably higher serum galectin-3 levels than those without portal hypertension (6.1?0.4 vs. 3.7?0.3?ng/mL, p<0.001). CONCLUSIONS: Increased serum galectin-3 is associated with a poor outcome in postoperative BA patients. Serum galectin-3 could be used as a biochemical parameter reflecting the deterioration of liver function and the severity of liver fibrosis in postoperative BA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Biliary atresia (BA) is a rare disease in Denmark (population ??5.5 million) and there has been some controversy on how smaller countries should manage such conditions to obtain the best possible outcomes. The aim of this study was to evaluate the efficacy of primary surgery (i.?e., Kasai portoenterostomy [KP]) over a prolonged period of time, during which one center has become the primary referral unit for the entire country. METHODS: A retrospective cohort study was carried out. RESULTS: During the period 1976-2010, 89 infants were referred to Rigshospitalet, Copenhagen. The median age at KP was 59 days, with 11 (12%) older than 100 days. Overall, 47 (53%) resolved their jaundice and achieved normal bilirubin levels within 6 months of KP. There was a significant increase in resolution of jaundice over time (X2=8.8; p=0.03) with a rate of 79% in the latest period. Overall, 52 are still alive (58%); 37 (39%) with their native liver at a median age of 6.8 years (2 months - 34 years), and 15 (18%) are alive following LT with a median age of 12 years (33 months - 23 years). The 5- and 10-year native liver survival rates are 44 and 37%, respectively. CONCLUSION: The overall results of this series reinforce our impression that even (or perhaps especially) in a small country, the same principles of concentrating patients and expertise will lead to better results. [ABSTRACT FROM AUTHOR]

Introduction: Aim of the study was to carry out a 5-year survey of German patients with biliary atresia (BA) and to launch a discussion regarding the feasibility of voluntary registries in unregulated healthcare systems. Methods: A retrospective analysis of German BA patients born between 2001 and 2005, based on data collected from the voluntary European Biliary Atresia Registry (EBAR), was carried out and supplemented by data from all BA patients who underwent liver transplantation at the only 4 pediatric transplantation centers (pLTx) in Germany which are so far not registered at EBAR. Survival rates were calculated using Kaplan- Meier analysis and compared by Cox regression to determine the predictive value of age at surgery and the influence of the center size (fewer or more than 5 patients / study period) on overall survival and survival with native liver. Results: A critical review of the 148 German EBAR charts revealed that 11 patients (7.4 % ) had no biliary atresia. The remaining 137 patients from EBAR together with 46 BA patients who underwent LTx without prior registration at EBAR were evaluated with a median follow-up of 39 months (range: 25 - 85 months). 29 hospitals performed a total of 159 Kasai procedures, but only 7 centers treated 5 or more patients (116 patients, range: 5 - 68), and 22 hospitals performed less than 5 KP (43 patients, range: 1 - 4). Primary LTx was performed in 21 patients (11.5 % ) and 3 patients died without surgical intervention. 16 patients were lost to follow-up (8.7 % ). Overall survival after 2 years was 83.3 % (139 patients), including 105 patients (63 % ) who had undergone LTx and 34 patients (20.3 % ) with native liver. 28 patients died (16.7 % ), 8 after LTx (5.8 % ). The experience of the center was the only factor with a significant predictive value for jaundice- free survival with native liver (p = 0.001). Conclusion: 25 % of all German BA patients were not registered at EBAR, and 29 clinics were involved in the surgical management of BA patients. Therefore a new approach consisting of an internet-based decentralized registry for rare neonatal liver diseases is outlined which could improve the future management of patients with BA. The centralization of such patients at experienced centers with higher caseloads is necessary in Germany and would improve the outcome of patients with biliary atresia. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIM: Biliary atresia (BA) is a chronic progressive inflammatory disorder of the extrahepatic and intrahepatic biliary system in children. The aim of the present study was to investigate circulating endoglin levels in BA patients compared with healthy controls and to determine the relationship between plasma endoglin levels and outcome parameters of BA patients after Kasai operation. METHODS: Fifty-five postoperative BA patients and 14 healthy controls were recruited. The patients were divided into two groups based on their serum total bilirubin levels (TB<34.2, no jaundice vs. TB?34.2??mol/L, persistent jaundice) and serum alanine aminotransferase (ALT<45, normal ALT vs. ALT?45?IU/L, high ALT). Circulating endoglin levels were analyzed by enzyme-linked immunosorbent assay. RESULTS: Average levels of plasma endoglin were significantly higher in BA patients compared to healthy controls (7.8?0.4 vs. 6.5?0.4?ng/mL; P=0.02). BA patients with persistent jaundice had higher plasma endoglin levels than those without jaundice (9.2?0.8 vs. 6.9?0.3?ng/mL; P=0.006). Furthermore, the concentrations of plasma endoglin in BA patients with high ALT were significantly higher compared to those with normal ALT (8.5?0.5 vs. 6.3?0.5?ng/mL, P=0.003). In addition, BA patients with portal hypertension had more elevated plasma endoglin levels than those without portal hypertension (8.8?0.6 vs. 6.1?0.3?ng/mL, P=0.001). Plasma endoglin was positively correlated with serum ALT (r=0.36, P=0.007) and serum GGT (r=0.44, P=0.001). CONCLUSION: High circulating endoglin correlated with a poor outcome for BA. Plasma endoglin can be utilized as a potential biomarker reflecting the severity of ongoing liver injury and biliary obstruction in BA patients after Kasai procedure. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to investigate the association between cyclooxygenase-2 (COX-2) expression and clinical outcome in biliary atresia (BA) patients. METHODS: Six months after surgery, twenty-eight BA patients were divided into three groups according to their liver function tests: group A with satisfactory liver function (n=11), group B with moderate liver dysfunction (n=8), and group C with severe liver dysfunction (n=9). COX-2 expression was determined by immunohistochemistry. Choledochal cysts (n=5) and normal liver samples (n=4) served as controls. RESULTS: Our data have shown that the intrahepatic biliary epithelium in BA specimens expressed COX-2. The mean immunoreactive score of COX-2 in BA patients was significantly higher than that in choledochal cyst and normal liver (4.0?0.6, 0.9?0.3, and 0.7?0.3, respectively, p<0.002). Strong expression of COX-2 was observed in BA patients with severe liver dysfunction. Subgroup analysis showed that the mean COX-2 immunoreactive scores of patients in group A, B, and C were 2.1?0.6, 3.6?1.1, and 5.9?0.9, respectively. The COX-2 immunoreactive score in BA patients with severe liver dysfunction was higher than in patients with satisfactory liver function (p<0.005). CONCLUSION: Increased COX-2 expression of biliary epithelial cells at the time of Kasai operation was associated with an adverse therapeutic outcome in BA, suggesting that COX-2 could play a plausible role in the liver pathology of BA. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Biliary atresia (BA) in humans resembles BA induced in Balb/c-mice by Rhesus Rotavirus (RRV). In mice, susceptibility to BA is ascribed to the lack of maternally derived immune protection. This study investigated whether vaccination of dams against RRV protected their offspring from developing BA. MATERIALS AND METHODS: Before mating, female mice were vaccinated orally with RotaTeq ?or Rotarix ?. Pups (n=243) from both test groups and a control group were intraperitoneally infected with RRV. Sacrifice of the animals was scheduled for days 7, 14 and 21 after infection. Then, gross and mircoscopia findings of the liver and the hepatoduodenal ligament gave evidence of BA, and hepatic viral load was tested by virus-specific real-time PCR, as well as plaque forming units. RESULTS: Two weeks after infection, the incidence of cholestasis was 100% in controls, 77% in pups of RotaTeq ?-vaccinated dams, and 56% in pups of Rotarix ?-vaccinated dams. However, in contrast to controls (incidence of BA: 82%) most pups in the test groups recovered (incidence of BA in pups of RotaTeq ?-vaccinated dams 11%; incidence of BA in pups of Rotarix ?-vaccinated dams 3%). Hepatic viral load was identical at various time-points in all pups, suggesting that differences in RRV clearance did not underlie this effect. CONCLUSION: In this mouse model, oral vaccination with RotaTeq ?and Rotarix ?prevented most RRV-induced BA. This provides a new approach to a better understanding of both the pathomechanism of BA development and the capabilities of the innate immune system. It also suggests a first approach for prophylaxis against BA. [ABSTRACT FROM AUTHOR]

Endoscopic retrograde cholangiopancreatography (ERCP) with placement of self-expandable metal stents (SEMS) for palliation of malignant obstruction may not be possible in patients with an inaccessible biliary orifice. Endoscopic ultrasound (EUS)-guided drainage methods may be useful in this setting. This study aimed to determine the outcomes of EUS-guided anterograde SEMS placement across malignant strictures in patients with an inaccessible biliary orifice. Over a 2-year period, procedural and outcomes data on all patients undergoing EUS-guided anterograde SEMS drainage after failed ERCP were prospectively entered into a database and reviewed. Five patients underwent EUS-guided anterograde SEMS. Indications included: advanced pancreatic cancer (n = 3), metastatic cancer (n = 1), and anastomotic stricture (n = 1). The biliary orifice could not be reached endoscopically due to duodenal stricture (n = 4) or inaccessible hepaticojejunostomy (n = 1). EUS-guided punctures were performed transgastrically into left intrahepatic ducts (n = 4) or transbulbar into the common bile duct (n = 1). Guide wires were passed and SEMS were successfully deployed across strictures in an anterograde fashion in all patients. Jaundice resolved and serum bilirubin levels decreased in all cases. No procedure-related complications were noted during a mean follow-up of 9.2 months. EUS-guided anterograde SEMS placement appears to be a safe and efficient technique for palliation of biliary obstruction in patients with an endoscopically inaccessible biliary orifice. The procedure can be performed at the time of failed standard ERCP, and provides an alternative drainage option to percutaneous or surgical decompression and to EUS-guided creation of bilioenteric fistulae. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIM: Biliary atresia (BA) is one of the most serious liver disorders in children. The purposes of the present study were to investigate serum levels of bone morphogenetic protein 7 (BMP7) in BA children compared with healthy controls and to evaluate the association between serum BMP7 and the clinical outcome of BA patients post Kasai operation. METHODS: Sixty-two BA patients post Kasai operation and 14 healthy controls were enrolled. The patients were divided into two groups according to their serum total bilirubin levels (TB<2, no jaundice vs. TB?2?mg/dL, persistent jaundice) and alanine aminotransferase levels (ALT<45, normal ALT vs. ALT?45?IU/L, elevated ALT). Serum BMP7 levels were determined by commercial enzyme-linked immunoabsorbent assay. RESULTS: The mean serum BMP7 was higher in BA patients compared with that of healthy controls (35.4?3.6 vs. 20.6?2.7?pg/mL, p=0.002). The BA patients with persistent jaundice had more elevated serum BMP7 levels than those without jaundice (59.5?6.5 vs. 20.3?1.6?pg/mL, p=0.001). There was also a correlation between serum total bilirubin and serum BMP7 levels (r=0.57, p<0.001). Moreover, the levels of serum BMP7 in BA patients with elevated ALT were significantly higher than those with normal ALT (41.6?4.7 vs. 22.4?4.2?pg/mL, p=0.003). Additionally, BA patients with portal hypertension had higher increased serum BMP7 levels compared to those without portal hypertension (45.3?4.9 vs. 18.7?2.8?pg/mL, p<0.001). CONCLUSION: The significant increment of serum BMP7 was associated with a deterioration of hepatic function and the progression of liver fibrosis. Serum BMP7 could be used as a prognostic marker to reflect disease severity and monitor disease progression in BA patients post Kasai operation. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIM: Biliary atresia (BA) is a serious liver disease in children. Since transforming growth factor-?1 (TGF-?1) and epidermal growth factor (EGF) are involved in the hepatic reparative process, our objective was to investigate whether serum TGF-?1 and serum EGF levels were associated with therapeutic outcomes in BA. METHODS: Serum levels of TGF-?1 and EGF were determined with the ELISA method in 67 postoperative BA patients with a median age of 7 years and in 10 age-comparable healthy children. The BA patients were then divided into two groups depending on their therapeutic outcome: good outcome (jaundice-free) and poor outcome (persistent jaundice). Clinical data, serum TGF-?1 and serum EGF levels were compared between the two groups of BA patients. Correlation analysis of serum TGF-?1 with serum EGF was carried out. Data are expressed as mean???SD. RESULTS: Serum TGF-?1 levels of BA patients were higher than those of controls (86.6???15.7 vs. 75.7???8.8?ng/ml, p?=?0.0362). However, there was no difference in serum EGF between BA patients and controls (133.1???66.6 vs. 125.4???88.9?pg/ml, p?=?0.744). Further subgroup analysis showed that patients with good outcomes (n?=?40) had higher serum TGF-?1 and serum EGF levels than patients with poor outcomes (TGF-?1: 91.2???16.5 vs. 79.6???11.7?ng/ml, p?=?0.002; EGF: 148.5???65.0 vs. 110.3???63.4?pg/ml, p?=?0.02). In addition, serum TGF-?1 was positively correlated with serum EGF (Pearson's r?=?0.3418, p?=?0.0046). CONCLUSION: Elevated serum TGF-?1 and serum EGF levels were associated with a good outcome in BA patients. There was a positive correlation between serum TGF-?1 and serum EGF. This suggests that the resultant TGF-?1 and EGF pathways may be involved in the pathophysiological process in postoperative BA. [ABSTRACT FROM AUTHOR]

BACKGROUND/PURPOSE: Indications for a laparoscopic approach for the management of biliary atresia in children are not clearly defined. We have recently shown that persistent intra-abdominal pressure (IAP) significantly decreased portal vein (PV) flow. Ventilation with a high concentration of oxygen after abdomen deflation raises concerns of increased oxidative stress but has also been shown to exert beneficial effects on splanchnic ischemia/reperfusion. The purpose of the present study was to evaluate the effects of IAP and hyperoxia on liver histology, hepatocyte proliferation and apoptosis in a rat model of abdominal compartment syndrome (ACS). METHODS: Male Sprague-Dawley rats were anesthetized with intraperitoneal ketamine and xylasine. After a midline laparotomy, the PV was isolated. Ultrasonic blood flow probes were placed on the vessel for continuous measurement of regional blood flow. Mean arterial blood pressure (MABP) was continuously measured. Two large-caliber percutaneous peripheral intravenous catheters were introduced into the peritoneal cavity for inflation of air and measurement of IAP. Rats were divided into three experimental groups: 1) Sham rats were subjected to IAP of 0?mmHg; 2) ACS rats were subjected to IAP of 6?mmHg for 2 hours and were ventilated with air; and 3) ACS-O 2rats were subjected to IAP of 6?mmHg for 2 hours and were ventilated with 100?% O 2during the operation and ventilation was continued for 6 hours after operation. Liver structural changes, hepatocyte proliferation (using BrdU assay) and apoptosis (using Tunel assay) were determined 24 hours following operation. RESULTS: IAP at 6?mmHg caused a twofold decrease in PV flow compared to sham animals. Hyperoxia resulted in a less significant decrease in PV flow compared to air-ventilated animals. Despite a significant decrease in PV blood flow, 24 hours after abdominal deflation only a few animals demonstrated histological signs of liver damage. The small histological changes were accompanied by increased hepatocyte apoptosis and enhanced hepatocyte proliferation in 25?% of animals, suggesting a liver repair response. CONCLUSIONS: Despite a significant decrease in PV blood flow, persistent IAP for 2 hours results in few changes in liver histology, and stimulates hepatocyte proliferation and apoptosis in only a few animals, supporting the presence of a recovering mechanism. Treatment with hyperoxia did not significantly change hepatocyte proliferation and apoptosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Aim of the study was to investigate the pathomorphological changes in the liver and triangular cord of the porta hepatis in biliary atresia and assess the relationship between the degree of differentiation of fibroblasts in the triangular cord of the porta hepatis and the liver fibrosis scores. METHODS: From September 2005 to May 2006, 21 patients with biliary atresia (66 ? 20 days old) underwent a Kasai procedure. The liver biopsy and the remnant of the porta hepatis were conserved. Five cases with cholestasis syndrome and 10 cases with choledochal cyst were used as a control group. Liver biopsies were performed in the control group. The micro- and ultrastructure of the liver and the remnant of the porta hepatis were assessed in the biliary atresia and the control group. Ultrastructural features were examined by transmission electron microscopy. The semiquantitative differences in liver fibrosis grading between the biliary atresia and the control group was evaluated with a 3-grade staging system. The degree of differentiation of fibroblasts (FB) in the triangular cord of the porta hepatis was assessed as follows: 1) juvenile type: above 50 % FBs were juvenile, 2) senior type: above 50 % FBs were senior, 3) median type: between the former 2 types. The differentiation scores of FB in the porta hepatis were assessed in relation to the liver fibrosis score. RESULTS: 1) The pathological changes with BA are characterized by inflammation and fibrosis in the hepatic portal area. The fibrosis scores in the biliary atresia group (I: 2 cases, II: 12 cases, III: 7 cases) were significantly higher than in the control group (I: 8 cases, II: 5 cases, III: 2 cases; p = 0.01. 2) In the biliary atresia group, the extrahepatic biliary system of all cases showed a triangular cord in the porta hepatis. The triangular cord of porta hepatis was characterized by hyperplasia of canaliculi, atresia or stenosis of the bile ducts, inflammation infiltration, cholestasis, and interstitial fibrosis. 3) The ultrastructural features of BA showed active fibroblasts, a loss of microvilli, dense deposits in the hepatocytes and liver sinusoid, and dilatation of canaliculi. 4) The differentiation scores of FB in the porta hepatis were positively related to the liver fibrosis score (p = 0.04). CONCLUSION: The main pathological changes of biliary atresia are inflammation and fibrosis in the hepatic portal area. The ultrastructural features of biliary atresia suggested that the differentiation scores of FB in the triangular cord of the porta hepatis were positively related to the liver fibrosis score. [ABSTRACT FROM AUTHOR]

Biliary atresia (BA) is a rare but potentially devastating disease. The European Biliary Atresia Registry (EBAR) was set up to improve data collection and to develop a pan-national and interdisciplinary strategy to improve clinical outcomes. From 2001 to 2005, 100 centers from 22 countries registered with EBAR via its website (www.biliary-atresia.com). In June 2006, the first meeting was held to evaluate results and launch further initiatives. During a 5-year period, 60 centers from 19 European countries and Israel sent completed registration forms for a total of 514 BA patients. Assuming the estimated incidence of BA in Europe is 1 : 18 000 live births, 35 % of the expected 1488 patients from all EBAR participating countries were captured, suggesting that reporting arrangements need improvement. At the meeting, the cumulative evaluation of 928 BA patients including patients from other registries with variable follow-up revealed an overall survival of 78 % (range from 41 % to 92 %), of whom 342 patients (37 %) have had liver transplants. Survival with native liver ranged from 14 % to 75 %. There was a marked variance in reported management and outcome by country (e.g., referral patterns, timing of surgery, centralization of surgery). In conclusion, EBAR represents the first attempt at an overall evaluation of the outcome of BA from a pan-European perspective. The natural history and outcome of biliary atresia is of considerable relevance to a European population. It is essential that there is further support for a pan-European registry with coordination of clinical standards, further participation of parent support groups, and implementation of online data entry and multidisciplinary clinical and basic research projects. [ABSTRACT FROM AUTHOR]

PURPOSE/BACKGROUND: The aim of this study was to investigate latent manganese toxicity in patients with biliary atresia and to use this tool to predict the prognosis of biliary atresia patients after Kasai''s portoenterostomy. METHODS: 14 patients who underwent Kasai''s portoenterostomy between 1993 and 2005 were included in the study. Whole blood manganese assays were performed using atomic adsorption spectroscopy (Philips PU 9200, Cambridge, UK) and verified by repeat analysis; these were done at the time of surgery and 6 months later. All blood samples were collected in an identical manner, blinded and then assayed by technicians. Whole blood manganese levels were correlated with the development of manganese deposits in the globus pallidus on T1-weighted images on magnetic resonance imaging (MRI) of the brain. Serum bilirubin of all 14 patients were noted both at the time of surgery and 6 months later. A hepatobiliary (HIDA) scan was done in all patients 6 months after Kasai''s portoenterostomy. RESULTS: The bilirubin declined in all except 2 patients after surgery. Both these patients developed ascites and severe jaundice and 1 expired one year after surgery. HIDA scan was excretory in all 14 patients. Whole blood manganese ranged from 1.26 - 27.58 ?g/dl (mean 4.63 ? 7.00) at the time of surgery; the levels were normal in 11 patients and elevated in 3. The postoperative assay at 6 months after surgery demonstrated values from 1.08 - 74.46 ?g/dl (mean 13.55 ? 24.17); 4 patients showed an increase from the previous value. Globus pallidus hyperintensity on T1-weighted images was noted in 1 patient on MRI; this patient had a sharp rise in the postoperative manganese level. All other MRI examinations were normal. All 14 patients were neurologically intact. CONCLUSIONS: Although the study size is small, it shows that there is a risk of latent manganese toxicity in patients with biliary atresia who have undergone Kasai''s portoenterostomy. Whole blood manganese assay in conjunction with brain MRI can be used to serially monitor these patients for early detection of these complications. This tool can be used for prognosis after Kasai''s portoenterostomy and can also be extremely useful in selecting patients who will need a liver transplant on a priority basis. [ABSTRACT FROM AUTHOR]

Biliary atresia is a mystifying cause of neonatal cholestasis, manifested by progressive inflammation and fibrosis of both the extrahepatic and intrahepatic bile ducts. It is a devastating disease that leads to cirrhosis and the need for liver transplantation in the majority of children. The etiology is unknown, and one theory is that it may involve a primary perinatal hepatobiliary viral infection and a secondary generation of an autoimmune-mediated bile duct injury. This review will outline the evidence from both human and murine studies supporting a potential cholangiotropic viral infection as the initiator of bile duct injury in biliary atresia and the role of the adaptive immune response and autoimmunity in progression of disease. Delineating the pathways of immune and autoimmune-mediated bile duct injury within biliary atresia could stimulate development of new medical interventions aimed at suppressing the specific immune response, decreasing the inflammatory damage to bile ducts, and delaying or negating the need for liver transplantation. [ABSTRACT FROM AUTHOR]

Initial surgical therapy of biliary atresia (BA) consists of the radical excision of extrahepatic remnants and portoenterostomy. However, despite this procedure, which was introduced by Kasai, BA remains the commonest indication for paediatric liver transplantation. The goal of the work group on the technical aspects of Kasai portoenterostomy procedures during the European Biliary Atresia Registry Conference 2007 was to achieve consensus on various operative and perioperative aspects relevant for paediatric surgeons. Although there is still disagreement regarding some of the technical details of the Kasai operation, a remarkable consensus has emerged in most areas of the actual surgery. No consensus was achieved on the role of postoperative drainage, the routine application of steroids, the use of oral prophylactic antibiotics, and the treatment of postoperative cholangitis. Nevertheless, the wide variation in reported results, which was a feature of this conference, suggests that there are still areas where improvement in outcomes can be anticipated by changes in technique or practice. [ABSTRACT FROM AUTHOR]

BACKGROUND: The necessity of carrying out pre- or intra-operative imaging of the biliary tree to rule out a possible anatomical abnormality or the presence of common bile duct (CBD) stones in patients undergoing laparoscopic cholecystectomy (LC) is debated. We prospectively assessed the risk of developing symptoms related to bile duct injury or CBD stones after LC in children not receiving peri-operative cholangiography. MATERIALS AND METHODS: All patients ? 14 years undergoing elective LC at our institution from January 2003 to June 2005 were included in this study. Peri-operative cholangiography of the CBD was not performed unless there was a suspicion of CBD stones based on clinical examination, liver biochemistry, serum amylase levels or liver ultrasound scan. Patients were prospectively followed up, looking for possible symptoms or clinical, biochemical and radiological signs related to bile duct injury or CBD stones. RESULTS: Twenty-six patients fulfilled the inclusion criteria. The median age at elective LC was 9.8 (4.1 - 14.3) years. Surgery was uneventful in all patients. All patients were discharged on postoperative day 1. None developed early symptoms of stone migration. USS performed 1 month after surgery did not show dilatation of the biliary system or stones in the CBD in any patient and no patient developed symptoms related to CBD stones after a median postoperative follow-up of 25 (6 - 37) months. CONCLUSIONS: Patients scheduled for elective LC presenting with unremarkable clinical examination, normal liver biochemistry and serum amylase levels, and without dilatation of the biliary tree on ultrasound scan do not need pre- or intra-operative cholangiography. [ABSTRACT FROM AUTHOR]

Biliary obstruction at the hepatic hilus is most often due to malignancy. Clinically, it can be very difficult to differentiate malignant from benign obstruction when a mass lesion is not evident on cross-sectional imaging. In this article, we describe three cases of benign biliary obstruction due to so-called malignant masquerades to familiarize the reader with the clinical, radiographic, and pathological features of these uncommon but important entities. [ABSTRACT FROM AUTHOR]

Because it is difficult to distinguish preoperatively between a prenatally diagnosed choledochal cyst (CC) and type-1 cystic biliary atresia (BA) by ultrasound scanning or magnetic resonance imaging, some mode of discriminating between the 2 entities is required. The aim of this study was to investigate the immunohistological differences between prenatally diagnosed CC and type-1 cystic BA, using liver biopsy specimens immunostained for CD56. Five children with prenatally diagnosed CC and two children with prenatally diagnosed type-1 cystic BA were identified by fetal ultrasonography between 1985 and 2004. The control group included two children who were operated on at an earlier period due to postnatally diagnosed BA. Liver wedge biopsy in the right lobe was performed at the time of the radical operation. Histological findings of the CD56-stained liver biopsy specimens were classified into 4 categories each, with particular focus on staining distribution and intensity. The staining distribution was classified according to the scale 0 = no staining; 1 = some staining of bile ducts/ductules but staining in less than one-third of portal tracts; 2 = staining in one-third to less than two-thirds of portal tracts; and 3 = staining in more than two-thirds of portal tracts. Staining intensity was scored as follows: 0 = no staining, 1 = weak staining, 2 = moderate staining, and 3 = strong staining. The staining intensity and distribution in the CC group was zero in all 5 cases. The type-1 cystic BA group consisted of patients with scale 1 or 3 staining distribution and score 1 or 2 staining intensity. In the control group, staining distribution was 1 or 3, and staining intensity was 1 or 3. These results indicate that CD56-positive biliary duct cells are present in prenatally diagnosed type-1 cystic BA. The authors suggest that exploratory laparotomy might be avoided and, instead, immunohistological examination using liver biopsy specimens may be a reliable test for the differential diagnosis of CC and type-1 cystic BA in prenatally diagnosed neonates. [ABSTRACT FROM AUTHOR]

Biliary atresia constitutes a serious problem in early infancy, due to the concomitant cholestasis. The conventional classification falls into 3 main types: type I, atresia of the common bile duct; type II, atresia of the hepatic duct; and type III, atresia of the porta hepatis. We report 2 unusual cases of biliary atresia type III with a cystic structure that could be mistaken for correctable biliary atresia or choledochal cyst. [ABSTRACT FROM AUTHOR]