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Background and aims: Biliary atresia (BA) is a progressive fibro-obliterative cholangiopathy. The histopathological diagnosis is often challenging and an immunohistochemical marker is often sought as an adjunct. We evaluated MMP7 immunohistochemistry in BA and other non-BA pediatric cholestatic liver diseases. Materials and methods: MMP7 immunohistochemistry was applied in 5 age-matched normal control, 23 cases of BA and 43 cases of non-BA pediatric cholestasis including 16 cases of choledochal cyst (CC), and a multiplication score was obtained by multiplying the intensity and percentage positivity in the cholangiocytes. Results: BA showed a high mean MMP7 multiplication score which was significantly different from the normal control and other non-BA pediatric cholestatic diseases including CC (p value < 0.001). The sensitivity, specificity, positive, and negative predictive values of MMP7 immunohistochemistry were 91.3%, 93.02%, 87.5%, and 95.2% respectively. Conclusion: MMP7 immunohistochemistry may be an adjunct to histomorphology in BA. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) in pediatrics has a uniformly poor prognosis. Complete surgical resection or liver transplantation remain the only curative options. In contrast to adult HCC, literature on pediatric HCC is sparse and a majority of the distinct subtypes are undefined with regards to their histology, immunohistochemistry and prognosis. Two infants, one with biliary atresia and another with transaldolase deficiency, underwent living donor liver transplants. Explant-liver histopathology revealed tumor with diffuse neoplastic syncytial giant cell pattern. Immunophenotypic characterization highlighted expression of epithelial cell adhesion molecule, alpha fetoprotein and metallothionein. HCC with syncytial giant cells variant can occur in infants with underlying liver disease, specifically in our experience, with biliary atresia and another with transaldolase deficiency. [ABSTRACT FROM AUTHOR]

Biliary atresia is a potentially fatal condition of the bile ducts – both intra- and extrahepatic, for which we have no cure. Though principally a cholestatic condition, much of its pathology stems from its tendency to aggressively induce liver fibrosis and ultimately cirrhosis, only partially restrained by the portoenterostomy. This review is based on the current literature exploring the heterogeneous nature of biliary atresia. Thus, there are various phenotypes or variants of biliary atresia, each potentially with different etiological backgrounds caused by a number of hypothetical pathological mechanisms thought to be important in the genesis of the condition. Search methodology: the review (Oct. – Nov. 2022) is based on a search of PubMed (NLM) using main keyword 'biliary atresia' with supplementary searches using 'fibrosis'; 'inflammation'; 'BASM'; 'genetics'; 'surgery'; 'experimental'; 'etiology'; 'virology'; 'cases'; and 'syndromes.' Future developments will be made on matching clinical variants with a more distinct pathophysiological discrimination and those pathways linking the initial cholestatic phase of biliary atresia to the early stages of fibrosis. [ABSTRACT FROM AUTHOR]

To analyze the normal development of fetal gallbladder (GB) and evaluate the postnatal outcomes of fetuses with isolated GB anomalies without other structural abnormalities by ultrasound. Methods This was a retrospective study. We collected normal cases during 2016 between 15 and 40 gestational weeks and measured the length and width of GB to establish a normal reference range of GB. Using the 10th and 90th percentiles of the normal reference range, isolated cases of enlarged or small GB without other structural anomalies were selected between January 2017 and December 2019. Simultaneously, cases of echogenic material in the GB were included. Fetuses with non-visualization of the fetal gallbladder (NVFGB) were collected between January 2010 and December 2019. Postnatal outcomes of these cases were followed up and analyzed. Results There were 670 cases in the normal group and a linear correlation was found between the dimensions of GB and the gestational age, including the length (r = 0.69; p < .05; y = 0.97 + 0.70 × gestational age) and width (r = 0.48; p < .05; y = 1.65 + 0.12 × gestational age). Sixty-two cases with isolated GB anomalies were collected, including nine cases of enlarged GB, four cases of small GB, three cases of echogenic material in the GB, and 46 cases of NVFGB. Sixty fetuses (96.8%, 60/62) had good outcomes, except that two neonates (4%, 2/50) in small GB and NVFGB groups were both born with BA. In the NVFGB group, 97.8% (45/46) were with good outcomes, in which gallbladders were finally visualized in 37 (80.4%, 37/46) cases and GB agenesis was postnatally diagnosed in eight (17.4%, 8/46) patients by ultrasound. Conclusion The postnatal outcomes of most fetuses (96.8%) with isolated GB anomalies such as enlarged GB, echogenic material in the GB were favorable. When it comes to cases of small GB or NVFGB in prenatal ultrasound diagnosis, we should alert biliary atresia in prenatal counseling. [ABSTRACT FROM AUTHOR]

Objective: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease related to pregnancy in women. Sortilin-1 is a sorting receptor belonging to the vacuolar protein sorting 10 (Vps10p) domain family, and recent studies have shown that Sortilin-1 has a distinct role in the pathogenesis of biliary fibrosis and cirrhosis. We aimed to evaluate maternal serum Sortilin-1 level as a potential biomarker in pregnant women with intrahepatic cholestasis. Materials and methods: A prospective observational cohort study was conducted. We enrolled 80 pregnant women, 49 with the diagnosis of intrahepatic cholestasis of pregnancy and 31 healthy controls. Then, we measured maternal serum Sortilin-1 levels using an enzyme-linked immunosorbent assay method and compared them between groups. Results: The mean Sortilin-1 level in the ICP group was higher than control group (3.3 ± 1.7 ng/mL vs. 2.0 ± 0.6 ng/mL, respectively, p <.001). The receiver operating characteristic curve (ROC) analysis based on maternal serum Sortilin-1 levels to predict the presence of ICP was 85.3% controls [area under the curve (AUC), 0.853; 95% CI, 0.738–0.938, p <.001]. The optimal cutoff value of Sortilin-1 was 2.24 ng/mL (71.4% sensitivity and 74.2% specificity) to detect intrahepatic cholestasis of pregnancy. Conclusion: Elevated maternal serum Sortilin-1 levels are associated with ICP and can be used as a disease biomarker. Sortilin-1 levels can be combined with total bile acids, transaminases, and blood coagulation profile in the follow-up of ICP. [ABSTRACT FROM AUTHOR]

Introduction: Acinar cystic transformation (ACT) of the pancreas is characterized by multiple cysts lined by dual ductal and acinar-type of epithelium. ACT is typically a disease of adulthood and has not been described in a neonate. Case report: Autopsy of this term 3-day old male demonstrated cystic transformation of the entire pancreas measuring 42 mm in its largest dimension. The main pancreatic duct was patent. The numerous variable-sized cysts were lined by both ductal (CK7-positive) and acinar (trypsin-positive) epithelium. Congenital hemochromatosis of the liver, complete proximal jejunal atresia, gangrene of the post-atretic jejunum, and subglottic stenosis were associated features. Discussion/Conclusion: ACT may occur in the neonate in association with other abnormalities. [ABSTRACT FROM AUTHOR]

CD56 immunostain is used as an adjunct to aid in the preoperative diagnosis of biliary atresia (BA) by liver biopsy. We aimed to study the expression of CD56 in different pediatric cholestatic diseases thereby evaluating its utility in the diagnosis of BA. We performed immunohistochemistry for CD56 on 35 cases of pediatric cholestatic diseases and five age-matched controls. CD56 expression was assessed by a multiplication score (percentage positivity x intensity) in the biliary epithelium. The multiplication score between BA and choledochal cyst was not significantly different. High scores were also encountered in other cholestatic disorders. The score showed a significant negative association with serum albumin and a significant positive correlation with the serum ALT level. Very significant positive correlation between the score and portal fibrosis was obtained. CD56 expression is an infidel marker for the histological diagnosis of BA and rather provides a clue to the disease status in pediatric cholestatic diseases. [ABSTRACT FROM AUTHOR]

Introduction: Bronchial asthma (BA) and obstructive sleep apnea syndrome (OSAS) are common causes of respiratory disturbance. Many cases of patients with both conditions have been reported, and BA and OSAS may exacerbate each other, but information remains sparse. Methods:We retrospectively evaluated 60 patients under treatment for BA in our department between April 2016 and March 2018 who also underwent portable polysomnography (PSG) for suspected OSAS to assess potential association between PSG results and asthma treatment or respiratory function. BA was diagnosed and treated according to the Asthma Prevention and Management Guideline 2015. Results: We found that BA treatment intensity step was significantly higher for patients with BA who had concurrent moderate or severe OSAS (p = 0.0016). However, neither respiratory function, fraction of exhaled nitric oxide (FeNO), nor forced oscillation technique (FOT) differed significantly between patients with and without OSAS, and apnea hypopnea index was not significantly correlated with respiratory function, FeNO or FOT parameters. Conclusion:We conclude that even though BA patients with OSAS had good respiratory function, their BA was more severe than that of patients without OSAS, suggesting that OSAS may exacerbate BA. Background factors and asthma parameters were not predictive of PSG results, and patients with suspected OSAS should be evaluated proactively by using PSG. [ABSTRACT FROM AUTHOR]

Background: Non syndromic paucity of interlobular bile ducts (NS-PILBD) constitutes a miniscule of infantile cholestasis. Method: Clinical details, investigations, surgical findings, management and outcome of cases of NS-PILBD at liver biopsy were analyzed. Specific histopathological features including bile duct to portal tract ratio were studied. Results: Eighteen cases (1993–2013) are detailed. Clinical presentation and investigations were similar to biliary atresia. Hepatic scintigraphy showed no gut excretion in 13/18 and operative cholangiogram was normal in all. Liver biopsy showed a median Scheuer fibrosis stage of 2, the mean bile duct/portal tract ratio was 0.29. The average age at last follow up of twelve cases was 54.9 months. Ten were asymptomatic and anicteric, the liver function tests had normalized over 3–15 months. Conclusion: Histopathology differentiated NS-PILBD from other causes of infantile cholestasis.The idiopathic form generally had a favorable long term outcome with medical management. [ABSTRACT FROM AUTHOR]

Background: The presence of cartilage in extra hepatic biliary tree is an unusual finding. An isolated presence of the cartilage is possibly heterotopic or occurs as a metaplastic response to the inflammatory insult. Material and methods: We had examined the liver biopsy and the resected specimen of a biliary atresia (BA) after Kasai procedure. Results: There was hyaline cartilage around the common hepatic and common bile duct in a 3-months-old male infant with distal obstructive cholangiopathy on liver biopsy and had positive serum IgM for cytomegalovirus (CMV). Similar findings could not be documented in the pericholedochal tissue of any of the 25 other pediatric cases operated for BA or choledochal cyst and three neonatal autopsies performed for liver-related deaths. Conclusion: Peri-bile duct cartilage is a unique finding and could represent an unusual form of heterotopia or connective tissue metaplasia. [ABSTRACT FROM AUTHOR]

Introduction: Both cystic biliary atresia and choledochal cyst present as infantile obstructive cholangiopathy. Methods: We detail an infant with congenital biliary dilatation and obstructive cholangiopathy where clinicoradiological features (antenatally imaged subhepatic cyst, early onset jaundice, intrahepatic dilated biliary radicals) suggested a choledochal cyst but operative findings (lack of a distal communication of cyst with duodenum) and histomorphological features (cicatricial collagen and myofibroblastic hyperplasia in the cyst wall; ductal plate malformation, ductular cholestasis and strong expression of CD56 in the liver) were those associated with biliary atresia. Conclusion: The observations support the contention that BA and CC may be interim entities in a continuum of manifestation of the same pathology. [ABSTRACT FROM AUTHOR]

Background/aims: Variceal bleeding is the main cause of morbidity and mortality in children with portal hypertension and biliary atresia. The aim of this study is to predict high-risk varices by analyzing various clinical factors, thus improve prognosis of patients with biliary atresia. Methods: A total of 157 patients with biliary atresia who underwent Kasai portoentrostomy were enrolled in a single center. Clinical data including laboratory values, endoscopic findings and values of transient elastography (FibroScan®) were analyzed retrospectively. Results: The bleeding group and the non-bleeding group showed statistically significant differences in several variables; The FibroScan® value (HR 1.05, 95% CI (1.03–1.07), p <.01) was higher in the bleeding group. The bleeding group had values of lower albumin after 3 months of operation (HR 0.28, 95% CI (0.11–0.73), p =.01), higher bilirubin after 3 months of operation (total bilirubin: HR 1.18, 95% CI (1.04–1.33), p =.01), (direct bilirubin: HR 1.21, 95% CI (1.05–1.41), p =.01). Gastric varix (HR 4.10, 95% CI (1.62–10.36), p <.01) was more frequent in the bleeding group. And the presence of red sign was also predictive of bleeding. The FibroScan® cut-off value with the predictive power of bleeding was 31.5 kPa (HR 7.7, 95% CI (3.36–17.73), p <.01). Conclusions: Several clinical factors including high value of transient elastography (FibroScan®), gastric varix or red sign of endoscopy, and low albumin or high bilirubin values after 3 months of Kasai operation can be useful in predicting variceal bleeding in patients with biliary atresia. [ABSTRACT FROM AUTHOR]

In living donor liver transplantation (LDLT) patients, the reconstruction of insufficiently long hepatic artery (HA) is difficult. However, no report has described the relationship between the length of HA and its reconstructive procedure. Herein, we aimed to identify the risk factors for the requirement of additional reconstructive procedures of direct anastomosis. Sixty-eight HA reconstructions in LDLT were conducted (37, men; 31, women). The causes of LDLT were hepatitis (n = 36), biliary atresia (n = 13), and primary biliary cirrhosis (n = 12). The graft HA comprised the right HA (n = 37) and left HA (n = 31). The recipient HA comprised the right HA (n = 39), left HA (n = 28), and right gastro-omental artery (n = 1). Two cases had graft HAs measuring 8 mm or more. The gap between the graft and recipient HA was 6 mm or more in nine cases. In 63 cases, direct anastomosis was performed. The extension of graft HA was performed using radial graft (n = 1) and two-step method (n = 1). The extension of recipient HA was performed using arterial graft (n = 2) extraanatomical recipient artery. Less than 8 mm length of graft HA (OR, 84) and 6 mm or greater gap between the recipient and graft HA (OR, 46.0) were identified as the risk factors for the need of additional procedures of direct anastomosis. We must always pay attention to the length of the graft and donor HA. To perform HA reconstruction safely, we should always consider using arterial grafts, extra-anatomical recipient artery, or the two-step method. [ABSTRACT FROM AUTHOR]

Objectives: Pediatric liver disease (PLD) covers a variety of etiologies and severities, from mild temporary illness to diseases with fatal outcomes. There is a demand for minimally invasive and reliable measures for assessment of the severity of PLD. Indocyanine green (ICG) elimination kinetics to estimate hepatic function has been used in adults for decades, however, due to invasiveness, the use in PLD is still limited. The aim of the present study was to evaluate minimally invasive estimation of ICG elimination by pulse spectrophotometry (ICGLi), in comparison with traditional spectrophotometry using serial blood samples (ICGbs). Methods: One hundred children aged 0–18 years were included in the study. ICG elimination kinetics was measured with ICGLi and ICGbs, and results compared by failure rates, mean difference, limits of agreement, Bland Altman plots and linear regression analysis. Plasma disappearance rates (PDRLi and PDRbs) were used for comparison. Results: One hundred and twelve simultaneous measurements in 87 patients were performed successfully. Mean difference for PDR (%/min) was 3.58 (95% CI 2.69; 4.47). Limits of agreement were −5.06; 12.22. A linear correlation between the two methods with a regression coefficient of 0.83 (SE 0.02 95% CI 0.80; 0.87) was found. For conversion we computed the following equation; PDRbs = 0.83 × PDRLi. Conclusions: The present study shows that ICG PDR can be obtained by a minimally invasive method and thus replace measures by serial blood samples in children with liver disease of different etiologies and severities. However, a systematic relative difference between the two methods exists. Our proposed correction factor needs to be validated in larger cohorts. [ABSTRACT FROM AUTHOR]

Biliary atresia (BA) is characterized by progressive destruction of the biliary system leading to liver fibrosis and deterioration of liver function. Serum hepatocyte growth factor (HGF) has been shown to be increased in cirrhotic diseases including BA. The aim of this study was to investigate the prognostic value of HGF levels in sera and liver tissue for the further disease course. A total of 49 serum and liver samples from infants with BA were acquired during Kasai-portoenterostomy (KPE) and analyzed by multiplex immunoassay including HGF, as marker of liver regeneration, and Interleukin 6 (IL-6) as a marker of inflammation. Both mediators showed no correlation with the outcome defined as favorable (survival with native liver (SNL)) or, in contrast, rapid deterioration of liver function requiring transplantation. Our data suggest that the degree of liver regeneration indicated by high levels of HGF within the liver is a dismissible factor in the post-KPE disease course. [ABSTRACT FROM AUTHOR]

Purpose: Hepatobiliary scintigraphy (HBS) is used to aid in the diagnosis of Biliary Atresia in full-term infants with conjugated hyperbilirubinemia. There is little information on the utility of the HBS in premature infants with conjugated hyperbilirubinemia and infants with parenteral nutrition associated cholestasis (PNAC). The purpose of this study is to assess the utility of HBS in differentiating Biliary Atresia and PNAC in premature neonates and full-term infants who received parenteral nutrition (PN). Materials and methods: Retrospective data collection and analysis on infants who developed conjugated hyperbilirubinemia and had HBS performed during their stay at level IV neonatal intensive care unit between 2005 and 2015. Results: A total of 20 patients with exposure to PN had HBS; two patients were confirmed to have Biliary Atresia. There were no statistically significant differences between patients with Biliary Atresia versus PNAC in demographics, days on PN, or gamma glutamyl-transferase levels. Stool color was statistically significantly different between the two groups; patients with Biliary Atresia had acholic stools more consistently than patients without Biliary Atresia. HBS had 100% sensitivity, 17% specificity, positive-predictive value of 12%, and a negative-predictive value (NPV) of 100%. Conclusions: These data indicate that the ability of HBS to aid in diagnosing Biliary Atresia is poor in a population of preterm neonates and full-term infants with PNAC. Although there is 100% sensitivity, the poor specificity (17%) should be acknowledged when utilizing HBS to diagnose Biliary Atresia in this vulnerable patient population. NPV of 100% is helpful in ruling out Biliary Atresia in this population. [ABSTRACT FROM AUTHOR]

Objectives: The importance of case load for treatment of extrahepatic biliary atresia (BA) is debated. The aim of this study was to register results of BA treatment in a small volume centre. Methods: Retrospective chart review study of patients with BA treated from 2000 to 2017. The institutional review board approved the study. Results: Forty-five babies were identified of which 42 (93%) are alive. Forty-one patients had a Kasai portoenterostomy (PE), two had a hepaticojejunostomy and two had a primary liver transplantation. The age at PE/hepaticojejunostomy was median 63 (4-145 days). Seven surgeons performed the operations, and the median duration of the diagnostic work-up was 8 (3-24) days. Clearance of jaundice was achieved in 23/43 (53%) babies, and 3- and 5-year native liver survival was 47% and 40%, respectively. Clearance of jaundice post-PE/hepaticojejunostomy was a strong predictor of native liver survival (adjusted OR: 0.027; 95%; p = .009). Plasma level of conjugated bilirubin at time of referral was also a significant predictor of native liver survival (adjusted OR: 1.053; p = .017). Conclusion: A small volume centre may achieve satisfactory results for BA patients. The study has, however, identified factors that may further improve results; earlier referral, optimizing diagnostic work-up and establishing one dedicated surgical team. [ABSTRACT FROM AUTHOR]

Introduction: Due to a peculiar age-dependent increased susceptibility, neonatal cholestasis affects the liver of approximately 1 in every 2500 term infants. A high index of suspicion is the key to an early diagnosis, and to implement timely, often life-saving treatments. Even when specific treatment is not available or curative, prompt medical management and optimization of nutrition are of paramount importance to survival and avoidance of complications. Areas covered: The present article will prominently focus on a series of newer diagnostic and therapeutic options of cholestasis in neonates and infants blended with consolidated established paradigms. The overview of strategies for the management reported here is based on a systematic literature search published in English using accessible databases (PubMed, MEDLINE) with the keywords biliary atresia, choleretics and neonatal cholestasis. References lists from retrieved articles were also reviewed. Expert commentary: A large number of uncommon and rare hepatobiliary disorders may present with cholestasis during the neonatal and infantile period. Potentially life-saving disease-specific pharmacological and surgical therapeutic approaches are currently available. Advances in hepatobiliary transport mechanisms have started clarifying fundamental aspects of inherited and acquired cholestasis, laying the foundation for the development of possibly more effective specific therapies. [ABSTRACT FROM PUBLISHER]

The article presents a case study of an eight-year-old boy with isolated testicular relapse of stage IV, t(8;14) translocation positive post-transplant lymphoproliferative disease (PTLD), who received immunotherapy with the trifunctional antibody FBTA05, anti-CD3 x anti-CD20 as a single agent consolidation treatment without hematopoietic stem cell transplantation (HSCT). The patient was initially diagnosed with extrahepatic biliary atresia and liver transplantation during his first year.

Objective: Recent studies have identified 10q24-rs17095355 as a susceptibility locus for biliary atresia (BA). To more precisely estimate the association between the rs17095355 polymorphism and BA risk, a meta-analysis was performed.Methods: A comprehensive search was conducted to examine all the eligible studies by electronic databases including Elsevier Science Direct, Pubmed, Google Scholar, China National Knowledge Infrastructure (CNKI) and Chinese Biomedical Literature (CBM) up to December 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the association.Results: A total of 6 comparisons from 5 relevant studies involving 1000 patients and 3257 controls were included to analyze the association between rs17095355 and BA risk. The pooled OR for T allele of rs17095355 was 1.72 (95%CI 1.53-1.92, p < 0.01) in BA. Stratification by ethnicity indicated the degree of risk of rs17095355 with BA susceptibility was similar in populations of Asian origin. The pooled OR was 1.81 (95%CI 1.60-2.06, p < 0.01).Conclusions: This meta-analysis confirms the association of rs17095355 polymorphism and BA development, especially in Asians. More original studies with large sample are needed to replicate this genetic association in different ethnic groups. [ABSTRACT FROM AUTHOR]

The article presents the a case study of a 3-year-old patient who had biliary atresia, which caused irreparable damage and eventually liver failure. Topics discussed the experience and risk towards liver transplantation; mentions the failure of liver transplantation that cause the death of patient; and highlights to improve the process of clinical and moral decision making.

The most common conditions causing cholestatic jaundice in infants are biliary atresia, neonatal hepatitis, and Alagille syndrome. In these disorders, the clinical presentation includes jaundice, pale stools, dark urine and hepatomegaly. Splenomegaly is not an early feature since it is due to portal hypertension, a later event. The finding of cholestatic jaundice and a large spleen usually raises the suspicion of Niemann-Pick type C disease (NP-C), a lysosomal storage disorder. We present and discuss here a case of an infant with liver disease and splenomegaly that were not ascribed to NP-C, but to Gaucher disease type 2. Liver biopsy, enzymatic studies and whole exome sequencing allowed to make the diagnosis. Although rare, Gaucher disease can cause neonatal hepatitis. A prompt recognition is advocated. [ABSTRACT FROM PUBLISHER]

Background/Aims: The basic problem in diagnosis of neonatal cholestasis (NC) is to differentiate biliary atresia (BA) from other non-obstructive disorders. Because if bile flow cannot be provided by surgery, BA leads to cirrhosis and death within the first year of life. The aim of the present study is to determine histopathological features that may help to differentiate BA from neonatal hepatitis (NH). Material and Methods: This retrospective study was carried out on 105 liver biopsy specimens of 74 infants with NC who were diagnosed between 2003 and 2012. Results: The mean age was 76.5 ± 40.64 days. The most valuable biopsy findings for the discrimination between NH and BA, in decreasing order of importance, were ductular proliferation ( p < 0.001), cholestasis in neoductuli ( p < 0.001), fibrosis ( p = 0.002), and extramedullar hematopoiesis ( p = 0.02). While Kasai operations were performed in 19 cases, liver transplantation was performed in 10 cases. Survival rate among the death cases with BA was longer than the survival time of the death cases with NH ( p = 0.023). Currently more children live with a close to normal quality of life with portoenterostomy and/or liver transplantation. On the contrary, NH can be more fatal with associated disorders such as growth retardation, specific infections, respiratory distress, and metabolic or endocrine diseases. [ABSTRACT FROM AUTHOR]

Objective: To analyze serum periostin and liver stiffness in postoperative biliary atresia (BA). Methods: A total of 60 BA patients and 14 controls were enrolled. Serum periostin levels were analyzed by ELISA. Liver stiffness measurement was determined by transient elastography. Results: Biliary atresia patients had significantly higher periostin and liver stiffness values than controls. Serum periostin levels were remarkably increased in BA patients with jaundice compared to those without jaundice. Moreover, serum periostin was correlated with liver stiffness. Conclusions: Serum periostin was associated with liver stiffness in BA. Thus, serum periostin has potential as a parameter reflecting the severity in BA. [ABSTRACT FROM AUTHOR]

Objective: To investigate correlation of serum autotaxin and disease severity in biliary atresia (BA). Methods: Eighty postoperative BA patients and 15 controls were recruited. Serum autotaxin levels were determined by enzyme-linked immunosorbent assay. Results: BA patients had greater serum autotaxin and liver stiffness than controls. Serum autotaxin and liver stiffness were markedly elevated in BA patients with jaundice compared to those without jaundice. Furthermore, serum autotaxin was correlated with liver stiffness and biochemical parameters in BA. Conclusions: Elevated serum autotaxin was correlated with hepatic dysfunction in BA. Accordingly, serum autotaxin is a promising biomarker reflecting the severity in BA. [ABSTRACT FROM AUTHOR]

Purpose: The mechanisms of liver fibrosis in biliary atresia (BA) after a Kasai operation deserve studying to improve the clinical outcomes. This study aimed to create a rat model simulating BA after a Kasai operation. Methods: We inserted a polyethylene tube (PE10) into the common hepatic duct (CHD) and ligated the common bile duct (CBD) in 30 newborn rats and injected 95% ethanol into IHD at postoperative week-one (POW-1). The PE10 was removed at POW-3. The rats were sacrificed at POW-5. The CBD cystojejunostomy was performed on another 10 rats at POW-5. Results: The IHD obliteration and CBD dilatation were noted at POW-3 cholangiography before removal of the PE tube. The gross findings at sacrifice in the rats without cystojejunostomy included biliary fibrosis, CBD cyst, and IHD obliteration. The microscopic findings of the liver were like BA. Seven of the 10 rats with CBD cystojejunostomy were jaundice-free at POW-8. The fibrosis grade at POW-8 of the rats with CBD cystojejunostomy was significantly lower in the jaundice-free rats (Ishak fibrosis score, 3.4 ± 0.9 and 1.5 ± 0.3 in the jaundiced rats and jaundice-free rats, respectively, p < .05). Conclusion: Based on our study, CBD cystojejunostomy five weeks after CBD ligation with ethanol injection into the IHD in newborn rats can provide a model for investigating mechanisms and treatments of liver fibrosis in BA after a Kasai operation. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to develop a model of fibrous cholangitis in the offspring of gravid domestic pigs through the administration of 1,4-phenylene diisothiocyanate (DITC). Material and Methods: Six young domestic pigs and two gravid pigs with their offspring (21 pigs) were used as experimental models and six wild-type animals were used as controls. All pigs were divided into five main groups and five subgroups, according to their developmental stage and time of exposure to DITC. The following histopathological characteristics were quantitatively evaluated on a scale of 0-5: ductal proliferation, periportal fibrosis, inflammatory infiltration, periductal fibrosis and edema, intraluminal fibrosis, duct wall thickening, epithelial apoptosis, and arterial hyperplasia/hypertrophy. Results: Statistically significant differences were observed for most of the histopathological markers between the group of pigs' offspring that received DITC at early gestation and their control group. Moreover, the group of animals that were exposed to the agent at early gestation exhibited significant differences for all histopathological characteristics compared to the animals that were exposed at late gestation. On the other hand, no statistically significant differences were observed between the group of animals that received the agent at late gestation and their healthy controls. Conclusions: Administration of DITC to domestic pigs in early pregnancy may induce histopathological patterns of fibrous cholangitis to their offspring imitating biliary atresia. This model may provide insight to the pathogenesis of the obstructive cholangitis in pigs. [ABSTRACT FROM AUTHOR]

The etiology of biliary atresia (BA) is unknown; however, the liver histology is similar to that observed in immune-mediated hepatic disorders. Liver fibrosis in BA progresses even after bile drainage has been achieved by the Kasai operation. Maternal microchimerism has been purported to play a part in the pathogenesis of BA as well as certain autoimmune diseases. However, the role of maternal cells has not yet been determined in BA. Specifically, it is unknown whether these maternal cells function as maternal effector T lymphocytes, or targets or bystanders. We currently hypothesize that the first hit is due to GvHD interaction by engrafted maternal effector T lymphocytes. Furthermore, we suggest that the secondary effects that are manifested by progressive cirrhosis are caused either by maternal chimeric effector T lymphocytes (e.g., GvHD interaction) or targets (e.g., HvGD interaction). Based on our hypothesis, mixed lymphocyte reactions between patients and their mothers might shed light on the etiopathogenesis and prognostic indicators. [ABSTRACT FROM AUTHOR]

A case of neonatal cholestasis associated with Trisomy 18 (Edward's syndrome) is presented. A 3-day-old boy was referred to our clinic due to respiratory distress, elevated serum direct bilirubin levels, a systolic heart murmur, growth restriction and micrognathia. Liver biopsy and chromosomal analysis revealed paucity of intrahepatic bile ducts and Trisomy 18. Extrahepatic biliary atresia was reported in only a few patients with Trisomy 18. To our knowledge, we described for the first time a patient with Trisomy 18 and neonatal cholestasis associated with paucity of interlobular bile ducts. [ABSTRACT FROM AUTHOR]

This report describes what we believe is the first reported case of clinically significant cholestasis and acute liver injury within three days of meropenem therapy. An 83-year-old Hispanic female was admitted for sepsis of unknown origin and was started on intravenous meropenem. Three days following initiation of the antibiotic, the patient developed mixed hepatocellular and cholestatic liver injury with jaundice and pruritus. Possible causes of cholestasis were excluded after extensive investigations. A drug-induced liver injury was suspected and meropenem was discontinued. Following discontinuation of meropenem, the patient demonstrated symptomatic and laboratory improvements, and her liver enzymes and bilirubin levels were normalized. [ABSTRACT FROM AUTHOR]

Pediatric liver transplantation (LT) is one of the most successful solid organ transplants with long-term survival more than 80%. Many aspects have contributed to improve survival, especially advancements in pre-, peri- and post-transplant management. The development of new surgical techniques, such as split-LT and the introduction of living related LT, has extended LT to small infants. Progress in the last 30 years has also been characterized by the introduction of calcineurin inhibitors. One problem remains the lack of donors. Donation after cardiac death offers a new possibility to increase the pool of potential donors. In children with acute liver failure, increasing interest has centered on the possibility of providing temporary liver support based on extracorporeal devices or hepatocyte transplantation. Similarly, hepatocyte transplantation offers new perspective in children with metabolic failure. As long-term survival increases, attention has now focused on the quality of life achieved by children undergoing LT. [ABSTRACT FROM AUTHOR]

The age threshold at the time of Kasai hepatic portoenterostomy associated with a prognosis of biliary atresia (BA) is becoming clearer as 10-year native liver survival data become more frequent in the recent literature, whereas the age at diagnosis has not dramatically decreased during the last 3 decades. A stool color card screening implemented in 1994 in Japan is now expanding worldwide. However, the contribution of this modality will probably be limited because of the nature of this disease, for example, 'progressive obliterative cholangiopathy'. A cholic stool was actually observed only in 50% before diagnosis according to the Japanese BA Registry data. Thus, color card screening does not appear to be instrumental in detecting patients with BA early enough before 1 month of age. A highly sensitive, adequately specific, noninvasive and quantitative method may be expensive, but the overall cost would be lower than that of liver transplant. [ABSTRACT FROM AUTHOR]

Balloon assisted enteroscopy (BE) expands greatly the therapeutic options in interventional endoscopy; bleeding sites, strictures, polyps, and other small bowel lesions are increasingly been treated by use of BE in the last 10 years. Treatment options for small bowel bleeding include Argon plasma coagulation (APC), injection therapy, and application of TTS metal clips, and thereby bleeding is stopped in most cases. Dilating symptomatic strictures, resecting polyps as seen in Peutz-Jeghers syndrome (PJS), and removing foreign bodies, BE carries most endoscopic treatment techniques to the small bowel. Another new indication field for BE are interventions at the biliary system in patients with surgically modified anatomy such as roux-Y anastomosis. This review offers a full overview on indications of BE and refers to the practical use of the method for all endoscopic interventions. [ABSTRACT FROM AUTHOR]

To explore the possible link between perinatal cytomegalovirus infection and onset of biliary atresia, we build up a perinatal cytomeglovirus induced hepatobiliary system injury model in guinea pigs, verified the biliary tropism of gpCMV and the related inflammatory injury. It suggested host immune status, local response to inflammation, and activation of Th1-cell-mediated antiviral immune responses contributed to newborn geinea pigs' hepatobiliary damage. The model was helpful in study the CMV infection and biliary injury. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of hepatic portocholecystostomy (HPC) and the Kasai procedure for the treatment of biliary atresia with patent distal extrahepatic bile ducts (BA with PDEBD) and to determine the reasons for the differences between the two procedures. Methods: The case files of 29 patients with BA with PDEBD were reviewed retrospectively. Twenty patients were treated with the Kasai procedure, and 9 patients were treated with HPC. We compared the rate of jaundice clearance, the incidence of cholangitis, survival rates of the native liver, and clinical outcomes between the two groups. Healthy gallbladders were collected for comparison with the pathologic specimens. Van-Gieson stains were used to detect the severity of fibrosis, and immunohistochemical methods were used to investigate the expression of CD68. Image analysis technology was used to quantitatively analyze the results. Results: Six months after surgery, the rate of jaundice clearance was 85%% in the Kasai group and 33.3%% in the HPC group ( p == .01). The three-year survival rates of the two groups were 73.68%% and 33.3%%, respectively ( p == .009). According to the criteria that define a cured state, there was an obvious difference between the two groups ( p == .0056). The fibrosis and CD68++ cell infiltration were more severe in the gallbladders of patients with BA than in controls ( p < .05). Conclusion: HPC was inferior to the Kasai procedure in the treatment of BA with PDEBD. This result may be due to the progressive inflammation and fibrosis of the extrahepatic bile duct. [ABSTRACT FROM AUTHOR]

Background: In developed countries, the outlook for patients with biliary atresia has improved remarkably owing to early referral, good diagnostic facilities and the availability of liver transplantation. In Nigeria and most of sub-Saharan Africa, there is little information on the current outlook for these children. Methods: A retrospective review of 14 patients with biliary atresia managed from 1991 to 2004 at Ahmadu Bello University Hospital, Zaria. Results: Six girls and eight boys presented at between 6 and 24 weeks of age (median 16). Seven presented to another hospital with persistent jaundice in the neonatal period. Eleven at presentation already had liver cirrhosis and deranged coagulation and could not have corrective surgery. Three patients aged 8, 10 and 16 weeks had Kasai's porto-enterostomy. Facilities for diagnosis were limited. Ten patients were lost to follow-up and their outcome is unknown. Of the three patients who had porto-enterostomy, one died at 2 years from gastro-enteritis, one from cholangitis after 8 weeks, and one did not recover from anaesthesia. One patient who had a laparotomy and liver biopsy died from peritonitis. Conclusion: Owing to late presentation, delayed referral and difficulties in diagnosis, the outlook for infants with biliary atresia in this environment is poor. A concerted effort to encourage primary practitioners to detect and refer these infants at an earlier age is critical to outcome. [ABSTRACT FROM AUTHOR]

Hypertrophic osteoarthropathy is a syndrome characterized by clubbing of the digits of the hand/foot, periosteal reaction and arthralgia or arthritis which is usually secondary to cyanotic congenital heart disease and chronic pulmonary infections. This syndrome rarely occurs in association with chronic liver disease in childhood. Here, we report on a child with biliary atresia who developed arthralgia and arthritis during follow-up and which was diagnosed as hepatic hypertrophic osteoarthropathy. It is emphasized that hypertrophic osteoarthropathy should be considered in the differential diagnosis of arthralgia and arthritis in children with long-standing chronic liver diseases, especially if finger clubbing is also present. [ABSTRACT FROM AUTHOR]

An experimental model of microsurgical cholestasis is studied as an alternative to the most frequently used surgical techniques, based on the section of the common bile duct. This microsurgical technique consists of the resection of the extrahepatic biliary tract, that is, of the common bile duct in continuity with the bile ducts that drain the four lobes of the rat liver. At 30 days of evolution, rats with microsurgical cholestasis do not develop biliary pseudocysts or intraperitoneal hilar hepatopulmonary abscesses and show an increase ( p < 0.001) in total bilirubin (9.50 ± 1.50 mg/dL vs. 1.60 ± 0.35 mg/dL), bile acids (225 ± 87 μmol/L vs. 12.5 ± 14.50 μmol/L), gamma-glutamyltranspeptidase (375 ± 143 U/L vs. 8 ± 11 U/L), and alkaline phosphatase (73 ± 25 U/L vs. 23 ± 4 U/L) levels. The histological study shows fibrosis with biliary proliferation. The microsurgical cholestasis technique is a valid alternative to other techniques and can be an adequate experimental model for the study of etiopathogenic mechanisms of obstructive jaundice and especially to study extrahepatic biliary atresia. [ABSTRACT FROM AUTHOR]

Bone-conducted auditory brainstem responses (ABRs) elicited by monoaural stimulation are very useful for evaluating hearing in children with congenital atresia of both ears. In a previous study of sound lateralization in children with congenital atresia of both ears, using bilateral bone-conducted stimuli, we found that most of the children could sufficiently retain binaural hearing ability in terms of both intensity and time differences. In this study we attempted to record bilateral bone-conducted ABRs in normal subjects in order to explore binaural interaction objectively. The study revealed that binaural interaction exists in bone-conducted ABRs. This can be taken as neurophysiological evidence that sound lateralization can be detected by children with bilateral microtia and atresia. [ABSTRACT FROM AUTHOR]

Multiple intestinal atresia is a rare disorder with vascular or hereditary etiology. So far, the occurrence of this malformation along with omphalocele has not been reported. We describe a boy born from a nonconsanguineous gypsy couple with intrauterine growth retardation, omphalocele, and multiple intestinal atresia from the pylorus to the rectum. The microscopic examination of the intestine shows multiple small lumina with a sieve-like appearance. This is characteristic of the hereditary atresias and suggests development of a defect in (re)canalization during embryogenesis. The association with omphalocele indicates a common developmental defect may be present. [ABSTRACT FROM AUTHOR]

Bone-conducted sound lateralization tests to determine interaural time difference (ITD) and interaural intensity difference (IID) were conducted by means of a self-recording apparatus in 20 children and a young adult with bilateral microtia and atresia of the ear. This apparatus changes ITD automatically from 0 to 2,000 μs at 50 μs/s and IID from 1 to 40 dB at 1 dB/s. When ITD exceeds approximately 200 μs/s and IID exceeds 5 dB in normal subjects the sounds are recognized separately. The test stimulus was a continuous narrow-band noise at 500 Hz and 30 dB SL applied to the right and left mastoids through bone vibrators. In the patients with bilateral atresia of the ears, ITD results revealed approximately normal thresholds of discrimination in half the patients and IID results revealed threshold elevation in only 10%. It is noted that bone-conducted sound lateralization abilities of ITD or IID are maintained in many of these patients. [ABSTRACT FROM AUTHOR]

Objective: To compare Japanese with Australian/New Zealand (ANZ) children with biliary atresia who were treated by liver transplantation, and evaluate the indications for and timing of transplantation. Design: Retrospective study. Setting: Queensland Liver Transplant Service (QLTS), Australia. Subjects: 43 Japanese and 30 ANZ children with biliary atresia who required transplantation between 1985 and 1992. Interventions: The 43 Japanese children had 52 transplants, and the 30 ANZ children had 33. Main outcome measures: Morbidity, mortality, and long term survival. Results: The Japanese children had significantly lower serum albumin concentrations than the ANZ children preoperatively (mean (SD) 32 (7) g/L compared with 37 (5), p < 0.05). The actuarial survival at 7 years of the ANZ children was significantly higher than that of the Japanese children (79% compared with 49%, p < 0.05). There were 24 deaths (17 Japanese, 40%, and 7 ANZ, 23%); 2 of the ANZ and 7 of the Japanese children died more than a year after transplantation. All 26 children who were well-nourished at the time of transplantation defined as a Z-score (weight or height minus mean weight or height for age, sex, and race, divided by the SD) of -1 or more were alive at 1 month compared with 11 of the 47 poorly-nourished children (Z-score <-1). Survival among the Japanese declined after 1 year, and there was no association with Z-scores. Overall, Z-scores for weight improved significantly after transplantation, whereas those for height improved a little, but not significantly so. Japanese children were significantly shorter than ANZ children, and their Z-scores for height did not improve after transplantation. Conclusion: liver transplantation should be done as soon as possible for children with biliary atresia to maximise survival and growth. [ABSTRACT FROM AUTHOR]

Fourteen infants (under age 3) with biliary atresia were examined prior to transplant surgery to determine if they were at risk for developmental and temperament problems. Results indicate that the infants had significantly lower Mental Developmental Index scores on the Bayley (1969) Scales of Infant Development compared to the standard norms. They also had significantly lower Psychomotor Developmental Index scores. They were rated by their mothers as significantly less responsive on the Infant Characteristics Questionnaire (ICQ; Bares, Bennett-Freeland, & Lounsberry, 1979). There was a significant correlation between galactose elimination rate and the total ICQ score. These results suggest that there may be behavioral indicators of hepatic failure. Furthermore, infants and toddlers with biliary atresia may be at increased risk for developmental delays. Therefore, developmental status should be carefully monitored. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the rates of graft failure and retransplantation in pediatric patients with biliary atresia, a disease with high levels of maternal microchimerism. The study observed lower rates of graft failure and retransplantation in BA recipients of maternal livers compared with BA recipients of paternal livers. The findings also supported the concept that prenatal exposure to non-inherited maternal antigens (NIMA) may have consequences for transplantation.

Describes the new tube model for the diagnosis of cholestasis in infancy. Treatment of biliary atresia; Difficulty of tube placement and decrease radiation exposure; Production of a string test as a diagnostic tool for infants with cholestasis.

Background. Biliary atresia (BA) is characterized by biliary obstruction of unknown origin, occurring in the perinatal period, which leads to cirrhosis and liver failure. It remains the most common indication for pediatric liver transplantation. Several reports show that maternal microchimerism (Mc) is present within livers of patients and suggest that BA could be a graft-vs. host disease (GvHD) triggered by maternal cells. 1 Here we present a case study of a 17 mo old girl with BA who underwent transplantation of a liver from a male donor. Following transplantation, she developed GvHD. The aim of this study is to investigate whether GvHD’s origin is from the donor and to understand whether maternal Mc and/or maternal HLA genotyping could influence the outcome of future liver transplant. Methods. Patient’s typing, performed from whole blood samples was HLA- A*33,*01; HLA-B*15,*14; HLA-DRB1*01,*04 and HLA- DQB1*05,*03. Patient’s mother HLA typing was HLA- A*33,*03; HLA-B*14,*35; HLA-DRB1*01,*01 and HLA-DQB1*05,*05 and donor’s typing was HLA-A*02,*03; HLA-B*44,*07; HLA-DRB1*07,*15; HLA-DQB1*02,*06. Y-chromosome specific Q-PCR was used to identify male donor’s DNA in samples from whole blood, T lymphocytes and B lymphocytes. Q-PCR assays targeting the donor’s HLA alleles were performed as previously described 2 on the same subsets. Results. We found male DNA by Y chromosome QPCR in whole blood samples (0.1%) and in T (0.2%) but not in B lymphocytes. HLA-DQB1*02 specific Q-PCR further confirmed the donor’s origin and its higher presence in T cells (1.7%) rather than B cells (0.03%). This result was further confirmed by HLA-DRB1*15 Q-PCR. Conclusion. GvHD is an extremely rare event after liver transplantation from BA patients. In the current study, we confirmed the origin of donor derived immune cells by Y chromosome and HLA donor specific QPCR. In addition, we showed donor’s chimerism was mostly in the T cell compartment. We will furthermore quantify maternal Mc in blood samples and native liver of the patient. Interestingly, the donor and patient’s mother share a common HLA class I allele. Contrary to what has been previously reported, 3 this raises the question whether transplanting a liver carrying the same HLA than the patient’s non-inherited maternal antigens (NIMA) may be a risk factor for developing GvHD in the context of maternal Mc. [ABSTRACT FROM AUTHOR]