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Background: Biliary atresia (BA) is associated with extrahepatic congenital malformations in a minority of affected infants. The term commonly applied to this subgroup is 'BASM' for biliary atresia splenic malformation syndrome, as spleen abnormalities are prominent. Aims and methods: To examine clinical outcome in Canadian BA patients with extrahepatic congenital malformations in the Canada-wide BA database of patients born between 1985 and 2002, and additionally, to recharacterized the syndrome. Patients had ≥1 of the following: a/polysplenia, abnormal abdominal situs, intestinal malrotation, abdominal vascular anomaly or congenital heart disease. Results: Among 328 BA patients, 44 (13%) had associated congenital abnormalities. Intra-abdominal anomalies included polysplenia ( n=25), abnormal abdominal situs ( n=9), intestinal malrotation ( n=19), portal vein anomaly ( n=12), hepatic artery anomaly ( n=3) and inferior vena cava interruption ( n=20). Twenty-six patients had cardiac malformations including pulmonary stenosis ( n=11), ventricular septal defect ( n=10), atrial septal defect ( n=7), total anomalous pulmonary venous return ( n=3), double outlet right ventricle ( n=3), tetralogy of Fallot ( n=2), atrioventricular canal ( n=2), dextrocardia ( n=2), bicuspid aortic valve ( n=2), hypoplastic left heart ( n=1) and partial anomalous pulmonary venous return ( n=1). Age at Kasai operation, performance of liver transplant, overall survival, post-Kasai native liver survival and transplant survival were comparable to isolated BA. Presence of polysplenia or complex cardiac disease did not reduce post-Kasai native liver survival. Three patients had ≥2 typical abnormalities without polysplenia: thus, splenic malformations are not essential to this BA subgroup. Hierarchical cluster analysis demonstrated characteristic abnormalities grouped in a multiplicity of combinations, consistent with a spectrum of defective lateralization. Conclusion: We suggest that the acronym 'BASM' be redefined as 'biliary atresia structural malformation'. [ABSTRACT FROM AUTHOR]

Background: We evaluated the proportion, clinical features, and outcomes of previously healthy children presenting to a large Canadian quaternary pediatric center with severe acute hepatitis of unknown etiology., Methods: All patients with serum alanine aminotransferase (ALT) > 500 U/L or aspartate aminotransferase (AST) > 500 U/L between June 1, 2018, and May 31, 2022, at The Hospital for Sick Children, were identified. Subjects with only AST > 500 U/L were excluded. Clinical characteristics, investigations, and outcomes for patients without clear etiology for ALT > 500 U/L (severe acute hepatitis of unknown etiology) for our study period and from October 1 to May 31 of each year 2018-2021 were reviewed., Results: Of 977 patients with ALT/AST> 500 U/L, 720 had only ALT > 500 U/L. We excluded age below 6 months (n = 99) or above 16 years (n = 66), known pre-existing liver conditions (n = 66), and ALT > 500 U/L in already admitted patients (n = 151). Among the remaining 338 children with ALT > 500 U/L at presentation, an etiology was identified in 303 subjects. 33 (9.8%) children [median age 6.1 y (range 0.5-15.5); 61% male] were confirmed as severe acute hepatitis of unknown etiology. Twenty patients (60.6%) were tested for blood adenovirus by PCR, and 1 (5%) was positive (serotype B7). Liver tissue specimens from 18 patients revealed no evidence of viral inclusions or adenovirus. Twelve (36.3%) presented with pediatric acute liver failure, with 8 (24.2%) requiring liver transplantation. There were no deaths. Hepatitis-associated aplastic anemia occurred in 5 (15%) patients., Conclusions: Of children presenting with severe acute hepatitis to a quaternary children's hospital over a 48-month period, 9.8% had unknown etiology with no change over time. Liver transplantation remains an important treatment strategy for those presenting with pediatric acute liver failure phenotype. The frequency of cases associated with human adenovirus infection was noncontributory., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Introduction: As a step toward evaluating the association between Epstein-Barr virus genetic diversity and post-transplant lymphoproliferative disorder (PTLD), we conducted a preliminary study to compare the genetic diversity of the EBNA-1 gene among transplant patients and patients with infectious mononucleosis (IM)., Methods: We sequenced the EBNA-1 gene in blood samples from study subjects using Sanger methodology. The sequences were aligned with a reference strain and compared with publicly available sequences., Results: We analyzed 33 study samples and 25 publicly available sequences along with the reference strain B95-8. The evaluable samples were from sixteen patients with IM (median age 14.0 years, range 2-24) and 17 transplant patients. There were six children without PTLD (median age 1.93 years, range 0.79-7.46) and 11 who developed PTLD (median age 5.67 years, range 0.96-17.45). A predominant EBNA-1 variant (P-thr) was identified across the study groups. Differences were observed between the samples from the IM patients compared with the transplant samples., Conclusion: The predominant EBNA-1 strain is in contrast to reports of the predominant strain in North America. The results suggest differences between the EBNA-1 strains among the study groups. Further studies will examine the relationship between EBNA-1 strains and PTLD occurrence and outcomes., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Many pediatric patients with acute liver failure (PALF) do not receive a specific diagnosis (such as herpes simplex virus or Wilson disease or fatty acid oxidation defects)-they are left with an indeterminate diagnosis and are more likely to undergo liver transplantation, which is contraindicated for some disorders. Strategies to facilitate complete diagnostic testing should increase identification of specific liver diseases and might reduce liver transplantation. We investigated whether performing recommended age-specific diagnostic tests (AS-DTs) at the time of hospital admission reduces the percentage PALFs with an indeterminate diagnosis., Methods: We performed a multinational observational cohort study of 658 PALF participants in the United States and Canada, enrolled at 10 medical centers, during 3 study phases from December 1999 through December 2014. A learning collaborative approach was used to implement AS-DT using an electronic medical record admission order set at hospital admission in phase 3 of the study. Data from 10 study sites participating in all 3 phases were compared before (phases 1 and 2) and after (phase 3) diagnostic test recommendations were inserted into electronic medical record order sets., Results: The percentage of subjects with an indeterminate diagnosis decreased significantly between phases 1-2 (48.0%) and phase 3 (to 30.8%) (P = .0003). The 21-day cumulative incidence rates for liver transplantation were significantly different among phase 1 (34.6%), phase 2 (31.9%), and phase 3 (20.2%) (P = .030). The 21-day cumulative incidence rates for death did not differ significantly among phase 1 (17.9%), phase 2 (11.9%), and phase 3 (11.3%) (P = .20)., Conclusions: In a multinational study of children with acute liver failure, we found that incorporating diagnostic test recommendations into electronic medical record order sets accessed at time of admission reduced the percentage with an indeterminate diagnosis that may have reduced liver transplants without increasing mortality. Widespread use of this approach could significantly enhance care of acute liver failure in children., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life., Study Design: Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB <2.0, all others TB ≥ 2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression., Results: Fifty percent (68/137) of infants had TB < 2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB < 2.0 group vs TB ≥ 2 (86% vs 20%, P < .0001). Infants with TB ≥ 2 had diminished weight gain (P < .0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P < .0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P < .0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P < .0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001)., Conclusions: Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB <2.0 mg/dL within 3 months of HPE may enhance early outcomes., Trial Registration: ClinicalTrials.gov: NCT00061828 and NCT00294684., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Objectives: Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease of unknown etiology, with limited population-based estimates of pediatric incidence. We reported the incidence of pediatric AIH in Canada and described its clinical characteristics., Methods: We conducted a retrospective cohort study of patients aged <18 years diagnosed with AIH between 2000-2009 at all pediatric centers in Canada., Results: A total of 159 children with AIH (60.3% female, 13.2% type 2 AIH) were identified. Annual incidence was 0.23 per 100000 children. Median age at presentation for type 1 was 12 years (interquartile range: 11-14) versus 10 years for type 2 (interquartile range: 4.5-13) (P = .03). Fatigue (58%), jaundice (54%), and abdominal pain (49%) were the most common presenting symptoms. Serum albumin (33 vs 38 g/L; P = .03) and platelet count (187 000 vs 249 000; P <.001) were significantly lower and the international normalized ratio (1.4 vs 1.2; P <.001) was higher in cirrhotic versus noncirrhotic patients. Initial treatment included corticosteroids (80%), azathioprine (32%), and/or cyclosporine (13%). Response to treatment at 1 year was complete in 90%, and partial in 3%. 3% of patients had no response, and 3% responded and later relapsed. Nine patients underwent liver transplantation, and 4 patients died at a mean follow-up of 4 years., Conclusions: AIH is uncommon in children and adolescents in Canada. Type 1 AIH was diagnosed 5.5 times more frequently than type 2 AIH. Most patients respond well to conventional therapy, diminishing the need for liver transplantation., (Copyright © 2015 by the American Academy of Pediatrics.)

Objectives: Pediatric acute liver failure (PALF) is a rare but serious event, with poorly understood functional outcomes. The goal was to determine the prevalence of reduced neuropsychological functioning and health-related quality of life (HRQOL) following PALF., Methods: This multicenter study examined neuropsychological functioning and HRQOL 1 to 6 (median 3.8) years after PALF. Participants ages 6 to 16 (median 9.9) years were recruited from the PALF registry and administered measures of intelligence, visual spatial/visual motor coordination, attention, executive function, depression, and adaptive skills. HRQOL and fatigue were assessed using the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL 4.0) and PedsQL Multidimensional Fatigue Scale., Results: A total of 36 patients participated; 50% were boys and 67% were white. Median age at PALF was 5.6 years. A history of grade 3 or 4 hepatic encephalopathy was reported in 5/36 (14%) participants and 23/36 (64%) received a liver transplant. Visual spatial ability was significantly better than norms (P = 0.009), but motor coordination was worse (P = 0.04). Teachers (P = 0.04 to P < 0.0001) and parents (P = 0.005) reported more executive deficits versus norms, and participants had worse attention (P = 0.02). Participants did not differ significantly from norms on IQ, depression, or adaptive functioning. All of the child self-report PedsQL Generic Core and fatigue scales were significantly lower than a matched healthy sample (P = 0.001 to P < 0.0001) and parent proxy report was lower on the fatigue scales (P = 0.001 to P < 0.0001)., Conclusions: Long-term PALF survivors demonstrate average IQ and visual spatial ability, but greater than expected impairments in motor skills, attention, executive function, HRQOL, and fatigue.