Decoding hepatorenal tyrosinemia type 1: Unraveling the impact of early detection, NTBC, and the role of liver transplantation.

Hepatorenal tyrosinemia type 1 (HT-1) is a rare autosomal recessive disease that results from a deficiency of fumaryl acetoacetate hydrolase (FAH), a critical enzyme in the catabolic pathway for tyrosine. This leads to the accumulation of toxic metabolites such as fumaryl and maleylacetoacetate, which can damage the liver, kidneys, and nervous system. The discovery of 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione (NTBC or nitisinone) has significantly improved the management of HT-1, particularly when initiated before the onset of symptoms. Therefore, newborn screening for HT-1 is essential for timely diagnosis and prompt treatment. The analysis of succinyl acetone (SA) in dried blood spots of newborns followed by quantification of SA in blood or urine for high-risk neonates has excellent sensitivity and specificity for the diagnosis of HT-1. NTBC combined with dietary therapy, if initiated early, can provide liver transplant (LT) free survival and reduce the risk of hepatocellular carcinoma (HCC). Patients failing medical treatment (eg, due to non-adherence), and who develop acute liver failure (ALF), have HCC or evidence of histologically proven dysplastic liver nodule(s), or experience poor quality of life secondary to severe dietary restrictions are currently indicated for LT. Children with HT-1 require frequent monitoring of liver and renal function to assess disease progression and treatment compliance. They are also at risk of long-term neurocognitive impairment, which highlights the need for neurocognitive assessment and therapy.

Liver Biopsy Handling of Metabolic-Associated Fatty Liver Disease (MAFLD): the Children's Hospital of Eastern Ontario grossing protocol.

Metabolic-(non-alcoholic) associated fatty liver disease (MAFLD/NAFLD) has increasingly become a worldwide epidemic. It has been suggested that renaming NAFLD to MAFLD is critical in identifying patients with advanced fibrosis and poor cardiovascular outcomes. There are concerns that the progression to non-alcoholic steatohepatitis (NASH) may become a constant drive in the future healthcare of children and adolescents. There is a necessity to tackle the emerging risk factors for NASH-associated hepatocellular carcinoma (HCC). In this narrative review, we present the current protocol of liver biopsy separated between pre-analytical, analytical, and post-analytical handling. Genetic association investigations have identified single nucleotide polymorphisms implicated in the progression of MAFLD-HCC, many of which seem to belong to the lipid metabolism pathways. PNPLA3 rs738409 variant, TM6SF2 rs58542926 variant, MBOAT7 rs641738 variant, and GCKR variants seem to be significantly associated with NAFLD disease susceptibility. In disclosing the current comprehensive protocol performed at the Children's Hospital of Eastern Ontario, Ottawa, ON, Canada, we support the most recent Kulkarni-Sarin's pledge to rename NAFLD to MAFLD. Grossing of the liver biopsy is key to identifying histologic, immunophenotypical, and ultrastructure data and properly preserving tissue for molecular genomics data.

Handling a biopsy with fatty liver disease Fatty liver disease is increasing worldwide. There is a necessity to tackle the emerging risk factors for the development of liver cancer following years of fatty liver disease. In this paper, we show our protocol at the Children's Hospital of Eastern Ontario, University of Ottawa, Ontario, Canada.

The Benefit of Early and Frequent Antitumor Necrosis Factor-Alpha Trough Level Determination in Very Early-Onset Inflammatory Bowel Disease.

A patient with infantile-onset Crohn's disease had a partial response to corticosteroid therapy that worsened on its tapering, leading to treatment with antitumor necrosis factor-alpha monoclonal antibody therapy. Infliximab rapidly cleared before administration of the third accelerated induction dose with the development of antibodies. Adalimumab was initiated with a good clinical effect but also rapidly cleared, requiring dose intensification to improve drug levels and to maintain a good clinical response. The amount of medication could eventually be decreased. Accelerated induction and maintenance drug monitoring can prevent secondary loss of response in very young children with inflammatory bowel disease.

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency.

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (p <0.001). Without siEHC, NLS in the BSEP1/3 group was similar to that in BSEP3/3, but considerably lower than in BSEP1/1 (at age 10 years: 38%, 30%, and 71%, respectively; p = 0.003). After siEHC, BSEP1/3 and BSEP3/3 were associated with similarly low NLS, while NLS was much higher in BSEP1/1 (10 years after siEHC, 27%, 14%, and 92%, respectively; p <0.001). Conclusions: Individuals with BSEP deficiency with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as those with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment. Impact and implications: This manuscript defines the clinical features and prognosis of individuals with BSEP deficiency involving the combination of one relatively mild and one very severe BSEP deficiency mutation. Until now, it had always been assumed that the mild mutation would be enough to ensure a relatively good prognosis. However, our manuscript shows that the prognosis of these patients is just as poor as that of patients with two severe mutations. They do not respond to biliary diversion surgery and will likely not respond to the new IBAT (ileal bile acid transporter) inhibitors, which have recently been approved for use in BSEP deficiency.

Incidence of chronic immune-mediated inflammatory diseases after diagnosis with Kawasaki disease: a population-based cohort study.

OBJECTIVES: Kawasaki disease (KD) is an immune-mediated vasculitis of childhood with multi-organ inflammation. We determined the risk of subsequent immune-mediated inflammatory disease (IMID), including arthritis, type 1 diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis and multiple sclerosis. METHODS: We conducted a matched population-based cohort study using health administrative data from Ontario, Canada. Children aged <18 years born between 1991 and 2016 diagnosed with KD (n = 3753) were matched to 5 non-KD controls from the general population (n = 18 749). We determined the incidence of IMIDs after resolution of KD. Three- and 12-month washout periods were used to exclude KD-related symptoms. RESULTS: There was an elevated risk of arthritis in KD patients compared with non-KD controls, starting 3 months after index date [103.0 vs 12.7 per 100 000 person-years (PYs); incidence rate ratio 8.07 (95% CI 4.95, 13.2); hazard ratio 8.08 (95% CI 4.95, 13.2), resulting in the overall incidence of IMIDs being elevated in KD patients (175.1 vs 68.0 per 100 000 PYs; incidence rate ratio 2.58 (95% CI 1.93, 3.43); hazard ratio 2.58, 95% CI 1.94, 3.43]. However, there was no increased risk for diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis or multiple sclerosis in KD patients. Similar results were observed using a 12-month washout period. CONCLUSION: Children diagnosed with KD were at increased risk of arthritis following the acute KD event, but not other IMIDs. Health-care providers should monitor for arthritis in children following a diagnosis of KD.

Care Pattern for Fontan-Associated Liver Disease by Academic Pediatric Hepatologists in Canada.

Fontan-Associated Liver Disease (FALD) is a common extracardiac complication seen in patients following the Fontan procedure. There are no consensus guidelines on screening and management of children with FALD. Objective: The current study aims to determine academic pediatric hepatologists' practices and identify variability in management provided to children with FALD in Canada. Methods: Using the infrastructure of the Canadian Pediatric Hepatology Research Group, a nationwide survey was distributed electronically to all pediatric hepatologists practicing in university-affiliated hospitals. Results: Twelve pediatric hepatologists from 12 of 13 academic centers (92%) responded to the survey. The institutions of only 2 (17%) physicians offer post-Fontan care with a multidisciplinary team, both from different provinces. The screening for other comorbidities, use of noninvasive modality, and timing of liver biopsy for estimation of liver fibrosis and screening for esophageal varices differ from program to program. The frequency of outpatient clinic follow-up varies significantly. Education and counseling concerning liver health are generally used as treatment; only 58% of academic centers have a formal adult care transition plan. Conclusions: Significant discrepancies exist in the care provided to children with FALD by hepatologists practicing in academic centers across Canada. Future study is needed to develop a standardized protocol for managing and following children and youth with FALD.

Incidence and short-term outcomes of Kawasaki disease.

OBJECTIVE: Kawasaki disease (KD) is a childhood vasculitis with conflicting reported North American trends in incidence and patient characteristics. OBJECTIVES: (1) determine KD incidence between 1995 and 2017; (2) compare patient characteristics by era and age group; (3) determine complication and cardiovascular follow-up rates. METHODS: We used population-based health administrative data to identify children (0-18 yr) hospitalized with KD in Ontario, Canada between 1995 and 2017. We excluded children with prior KD diagnosis or incomplete records. We determined the annualized incidence and follow-up trends. RESULTS: KD was diagnosed in 4,346 children between 1995 and 2017. Annual KD incidence was 22.0 (<5 yr), 6.1 (5-9 yr), and 0.6 (10-18 yr) per 100,000 children. KD incidence increased significantly for all age groups, including from 18.4 to 25.0 cases per 100,000 children <5 yr. Ninety-day mortality occurred in ≤5 children (≤0.1%). Coronary artery aneurysm (CAA) occurred in 106 children (2.4%, 95% confidence interval 2.0-2.9) during admission and 151 (3.5%, 95% confidence interval 3.0-4.1) during 11-year median follow-up. Children 10-18 yr had longer hospitalizations (4.3 vs. 3.5 days, p = 0.003) and more CAA (7.4% vs. 3.4%, p = 0.007). By 1-year post-diagnosis, 3970 (91.3%) and 2576 (59.3%) children had echocardiography and cardiology follow-up, respectively. CONCLUSIONS: KD incidence is increasing in Ontario, with greater healthcare utilization from hospitalizations and subsequent follow-up. IMPACT: 4346 children were hospitalized for Kawasaki disease over 22 years in Ontario, and Kawasaki disease incidence increased significantly for all age groups, males and females. Older children (10-18 years) had longer hospital length of stay, more PICU admissions and more frequent coronary artery aneurysms. Nearly all children with Kawasaki disease had follow-up echocardiography within 1 year.

Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.

BACKGROUND AND AIMS: Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide insights by using the largest genetically defined cohort of patients with FIC1 deficiency to date. APPROACH AND RESULTS: This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication), FIC1-A (n = 67; no PPTMs), FIC1-B (n = 29; one PPTM), or FIC1-C (n = 34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18 years. NLS was comparable among FIC1-A, FIC1-B, and FIC1-C (% NLS at age 10 years: 67%, 41%, and 59%, respectively; P = 0.12), despite FIC1-C undergoing SBD less often (% SBD at age 10 years: 65%, 57%, and 45%, respectively; P = 0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10 years, sBAs < 194 µmol/L: 49% vs. sBAs ≥ 194 µmol/L: 15%; P = 0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] µmol/L; P = 0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P = 0.06) and post-SBD sBA concentrations < 65 µmol/L (P = 0.05) tended to be associated with improved NLS. CONCLUSIONS: Less than half of patients with FIC1 deficiency reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS.

Conversion from tacrolimus to sirolimus as a treatment modality in de novo allergies and immune-mediated disorders in pediatric liver transplant recipients.

De novo PTAID may develop in pediatric solid organ transplant recipients, have a diverse spectrum, and are occasionally treatment resistant. Previous reports showed resolution of immune cytopenias in solid organ transplant recipients following replacement of the calcineurin inhibitor tacrolimus with the mTOR inhibitor sirolimus. Herein we describe a retrospective review (2000-2017) of subjects who developed PTAID in whom immunosuppression was changed to sirolimus. Eight recipients (6 males) of either liver (n = 7) or multivisceral transplant (n = 1) suffered from severe, treatment-resistant PTAID and were switched from tacrolimus to sirolimus. The median age at transplant was 1 year (range 0.5-2.4 years). Six (75%) recipients developed de novo allergy and 2 immune-mediated diseases. The median age at presentation of PTAID was 2.7 (1.4-9) years at a median of 1.3 (0.25-8) years after transplantation. The median time from PTAID presentation to conversion to sirolimus was 1.8 (0.45-10) years. Complete resolution of symptoms was seen in 4 (50%) patients after a median of 12 (range 4-24) months including 2 patients with immune-mediated disease, 1 eczema, and 1 with eosinophilic colitis. One patient with multiple food allergies had a partial response and 3 (38%) had no response. None of the 8 recipients developed sirolimus-attributed adverse events or acute rejection during a median follow-up of 5 (0.6-8) years after the conversion. Immunosuppression conversion from tacrolimus to sirolimus can be an effective therapy in patients suffering severe or treatment-resistant PTAID, suggesting a potential role for tacrolimus in the pathogenesis of PTAID.

Direct Health Care Costs, Health Services Utilization, and Outcomes of Biliary Atresia: A Population-based Cohort Study.

OBJECTIVES: Biliary atresia (BA) is the most common reason for liver transplant in childhood, and outcomes worsen with older age at hepatoportoenterostomy (HPE). We determined direct health care costs in children with BA, compared to controls in a population-based cohort of children in Ontario, Canada. METHODS: We used health administrative data to identify all children diagnosed with BA between 2002 and 2016 (n = 121) and matched controls (n = 602). We determined annual direct healthcare costs, and rates of health services utilization, liver transplantation, death, portal hypertension, cirrhosis, esophageal varices, and major upper gastrointestinal bleeding requiring hospitalization. Multivariable regression models determined the association between age at HPE, risk of liver transplant, and direct costs. RESULTS: Incidence of BA was 6.07 (4.99-7.15) per 100,000 live births. The annual median (interquartile range) direct health care costs were higher in BA cases ($4210; interquartile range $1091-$16,765) compared to controls ($283; $112-$634). Compared to age at HPE <45 days, there was no significant association between direct costs and HPE ≥90 days (rate ratio 1.24, 95% confidence interval [CI] 0.78-1.97) or 45 to 90 days (rate ratio 1.05, 95% CI 0.73-1.50). Age at HPE ≥90 days was significantly associated with risk of undergoing liver transplant compared to age <45 days (hazard ratio 5.27, 95% CI 2.45-11.34). Direct costs were higher in patients with BA who underwent liver transplantation compared to those who did not ($39,476±$84,367 vs $22,579 ±â€Š$67,913). CONCLUSIONS: Direct ealth care costs were high in patients with BA, especially in those who underwent liver transplantation. Age at HPE was associated with risk of liver transplantation, but not direct health care costs, utilization, or other risk outcomes.

Prevalence and risk factors for non-alcoholic fatty liver in children and youth with obesity.

BACKGROUND: Non- Alcoholic Fatty Liver (NAFL) is a spectrum of liver diseases (LD) that ranges from benign fatty infiltration of the liver to cirrhosis and hepatic failure. Hepatic ultrasound (US) and serum alanine aminotransferase (ALT) are often used as markers of NAFL. Our aim is to describe prevalence of NAFL and associated findings on ultrasound (US) and biochemical parameters in a population of children and adolescents with obesity at the Children's Hospital of Eastern Ontario. METHODS: Children with Obesity (BMI >95th percentile) ages 8-17 years presenting to the Endocrinology and Gastroenterology clinics, without underlying LD were prospectively recruited from 2009 to 2012. Fasting lipid profile, HOMA IR) and serum adiponectin levels were measured. NAFL was defined as ALT > 25 and >22 IU/mL (males and females respectively) and/or evidence of fatty infiltration by US. Logistic regression was performed to assess associations. RESULTS: 97 children with obesity included in the study (Male 43%). Mean age was 12.9 ± 3.2 years (84% were older than 10 y). Mean BMI-Z score was 3.8 ± 1.4. NAFL was identified in 85%(82/97) of participants. ALT was elevated in 61% of patients. Median triglyceride (TG) level was higher in children with NAFL(1.5 ± 0.9 vs. 1.1 ± 0.5 mmol/L, p = 0.01). Total cholesterol, HDL, LDL and Non HDL cholesterol were similar in both groups(p = 0.63, p = 0.98, p = 0.72 and p = 0.37 respectively). HOMA IR was ≥3.16 in 53% of children(55% in those with NAFL and 40% in those without NAFL). Median serum adiponectin was 11.2 µg/ml(IQR 7.3-18.3) in children with NAFL vs. 16.1 µg/ml(IQR 9.0-21.9) in those without NAFL(p = 0.23). Liver US was reported as normal in 30%, mild fatty infiltration in 38%, moderate in 20% and severe in 12%. TG were significantly higher(1.5 mmol/L vs. 1.0 mmol/L, p < 0.01) and HDL-C was lower(1.0 mmol/L vs. 1.1 mmol/L, p = 0.05) in children with moderate and severe NAFL by US. BMI-Z score, HOMA IR, serum adiponectin and HDL levels were not associated with NAFL, however TG were significantly associated(OR = 3.22 (95% CI: 1.01-10.25, p = 0.04)). CONCLUSION: NAFL is highly prevalent in obese children and youth. Elevated TG levels are associated with NAFL; these findings may serve as a noninvasive screening tool to help clinicians identify children with obesity needing liver biopsy and/or more aggressive therapeutic interventions.

A national retrospective study of paediatric end-stage liver disease as a predictor of change to second-line therapy in children with autoimmune hepatitis.

BACKGROUND & AIMS: Adult studies of autoimmune hepatitis (AIH) have shown that the model of end-stage liver disease is associated with resistance to first-line treatment. Using a multicentre retrospective database, we sought to determine if the paediatric end-stage liver disease (PELD) score would similarly predict treatment resistance in paediatric AIH. METHODS: One hundred and seventy-one children from 13 Canadian centres who fulfilled the International Autoimmune Hepatitis Group (IAIHG) criteria were included and assessed for change to second-line therapy within 24 months of primary treatment onset. Those with PSC overlap at presentation, or missing data on the PELD variables were excluded. PELD was calculated for all remaining patients. Univariate analysis and receiver-operator characteristic (ROC) curves were performed to determine the predictive ability of the PELD score to change to second-line therapy. RESULTS: A total of 103 children were included with median age of 11 years (range 2-17). Mean PELD was -2.51±8.58. Second-line therapy was used within 24 months of diagnosis in 13 patients. Univariate analysis revealed that change to second-line therapy was associated with higher PELD (P=.028) and internal normalized ratio (INR) (P=.011). ROC curves for PELD and its individual components were performed. The strength of association was strongest with INR (AUC 0.72; CI: 0.58-0.86) although the composite PELD score also showed some predictive ability (AUC 0.67; CI: 0.52-0.81). CONCLUSION: In this paediatric AIH cohort, higher PELD at presentation predicted change to second-line therapy within the first 2 years of follow-up. INR appeared to be the main contributor to that association.

Variability of diagnostic approach, surgical technique, and medical management for children with biliary atresia in Canada - Is it time for standardization?

BACKGROUND: The Canadian 4-year native liver survival rate for biliary atresia (BA) after Kasai Portoenterostomy (KP) is 39%. The Canadian Biliary Atresia Registry (CBAR) was used to examine variability of surgical and medical management of BA. METHODS: Gastroenterologists and surgeons in all 14 Canadian pediatric tertiary centers were invited to complete an online survey of their BA management practices. RESULTS: Of gastroenterologists, diagnostic procedures included liver biopsy (92%), HIDA scan (58%), and percutaneous cholangiogram (46%). Surgeons reported Roux-en-Y lengths of 20-50cm with 78% avoiding diathermy at the portal plate; 16% performed laparoscopic exploration, but none laparoscopic KP. Postoperative corticosteroids and antibiotics were used by 24% and 85% of gastroenterologists, respectively, with similar rates for surgeons. At discharge, gastroenterologists prescribed oral antibiotics (80%), and ursodeoxycholic acid (95%), while surgeons reported lower rates (62% and 55%). Considerable variation existed in follow-up monitoring. No center had a standard protocol for evaluating suspected cholangitis. There was a lack of consensus for defining failed KP and referral criteria for transplant evaluation. CONCLUSION: In Canada, treatment of BA is not centralized, and there is variability in diagnostic approaches and management. Collaboration through CBAR will allow for implementation and evaluation of standardized surgical and medical management with a goal to improve outcomes. LEVEL OF EVIDENCE: Survey study. Level IV evidence.

Outcomes in infants listed for liver transplantation: A retrospective cohort study using the United Network for Organ Sharing database.

LT in neonates and young infants can be challenging due to a variety of factors. To describe the waitlist mortality rates and outcomes of patients listed and transplanted as infants identified from the UNOS database. Infants listed for LT between January 1985 and September 2010 were identified from the UNOS database. Mortality on the waitlist as well as outcomes post-LT was compared between infants aged ≤60 days (Group 1), 61-179 days (Group 2), and 180-364 days (Group 3). Of 6763 infants listed for LT (Group 1 n = 496, Group 2 n = 2404, Group 3 n = 3863), mean age at listing was 196 ± 87 days (Group 1, 29 ± 16 days; Group 2, 132 ± 32 days; Group 3, 257 ± 52 days). Waitlist mortality was highest in Group 1 (Group 1 vs. 3 HR 3.01, 95% CI 2.19-4.15, Group 2 vs. Group 3 HR 0.82, 95% CI 0.66-1.03). One- and five-yr graft survival was 59.6% and 42% (Group 1), 66% and 45% (Group 2), and 66.8% and 41% (Group 3) (one-yr survival p = 0.20; five-yr survival p = 0.19). Infants listed for LT at age ≤60 days had greater waitlist mortality risk than older infants. Infants undergoing LT at age ≤60 days had similar rates of patient and graft survival to older infants.

Incidence and Characteristics of Autoimmune Hepatitis.

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.

Parenteral nutrition-induced cholestasis in neonates: where does the problem lie?

Background. Parenteral nutrition (PN) is an effective method of nourishing the neonate who is unable to receive full enteral feeds. Cholestasis can be a complication of PN and can lead to severe liver damage. Aim. We describe our patient population and determine risk factors for developing PN cholestasis. Methods. Retrospective chart review of newborns admitted from January 2006 to May 2011 to the Neonatal Intensive Care Unit at our institution and received PN >14 days. Cholestasis was defined as serum conjugated bilirubin >50 µ mol/L. Results. Eighty-seven newborns were included; 18 (20.7%) developed PN cholestasis. The most frequent surgical condition for both groups was gastroschisis (8/87; 9.2%). No significant differences were found between the cholestasis and control groups for the following parameters: birth weight, gestational age, intrauterine growth restriction, Apgar scores, and day of life at initiation of enteral feeds. Duration of PN in days and dosage of carbohydrates in g/kg/day were significantly higher in the cholestasis group than the control group. Conclusion. PN-related cholestasis presented in one-fifth of neonates receiving PN for more than two weeks. Longer duration of PN and higher dosage of carbohydrates were independent risk factors for the development of PN cholestasis in this population.

International incidence and outcomes of biliary atresia.

OBJECTIVES: International trends in incidence and outcomes of biliary atresia (BA) are controversial and a wide range of estimates have been reported worldwide. We reviewed the population-based literature to assess international variation of BA incidence and outcomes, and to assess the evidence for seasonal variation in incidence, centralization of Kasai hepatoportoenterostomy, and newborn screening. METHODS: We conducted a systematic review (registration number CRD42011001441) of observational or interventional research within MEDLINE, EMBASE, and the Cochrane Database, which reported incidence, prevalence, or outcomes of infants with BA. Population-based studies, defined by inclusion of an entire population or representative sample, were included. Outcomes included overall survival, native liver survival (NLS), and time to Kasai hepatoportoenterostomy. Single- or multicenter studies were excluded unless those centers captured all potential patients within a jurisdiction. Two independent data extractors reviewed the abstracts and articles. RESULTS: A total of 40 studies were included following review of 3128 references. A wide range of incidence was reported internationally. Ten-year overall survival ranged from 66.7% to 89%. NLS ranged from 20.3% to 75.8% at 1 to 3 years and 24% to 52.8% at 10 years. Earlier age at Kasai was a predictor of improved NLS. Seasonality was reported in 11 studies, and 3 reported an increased incidence during the months of August to March. The evidence for centralization of Kasai to high-volume centers is promising but does not account for all case-mix, provider, or health system factors involved in volume-outcome relations. Stool color card screening resulted in earlier Kasai and improved NLS in Taiwan. CONCLUSIONS: Large, international studies could help fill the gaps in knowledge identified by this review.

Viral hepatitis: retrospective review in a canadian pediatric hospital.

Introduction. Clinical presentation of viral hepatitis ranges from mild symptoms to fulminant hepatitis. Our aim is to describe clinical presentation and outcomes of children with viral hepatitis from the Eastern Ontario/Western Quebec regions of Canada. Methods. Retrospective chart review of children diagnosed with viral hepatitis at our institution from January 1, 1998, to December 31, 2007. Results. There were 261 charts reviewed, only 64 had a confirmed viral etiology: 34 (53%) hepatitis B (HBV), 16 (25%) hepatitis C (HCV), 4 (6.3%) hepatitis A (HAV), 7 (11%) cytomegalovirus (CMV), and 3 (4.7%) Epstein-Barr virus (EBV). Children with HBV presented at a mean age of 6.4 ± 4.6 years. Spontaneous seroconversion (appearance of HBVeAb and loss of HBVeAg) occurred in 21/34 (61.7%). Children with acute hepatitis (HAV, CMV, and EBV) presented with mild abdominal pain, jaundice, and fevers. Overall outcome was excellent. Conclusion. Acute and chronic hepatitis in children has a benign course; moreover, HBV spontaneous seroconversion is common in pediatric patients.