The natural history of primary sclerosing cholangitis in 781 children. A multicenter, international collaboration

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes

Fulminant hepatic failure in a neonate with systemic echovirus infection

We report the fatal case of neonatal fulminant hepatic failure due to Echovirus infection mimicking an acute metabolic decompensation. After exclusion of several metabolic disorders, the diagnosis of the infectious etiology was confirmed by Polymerase Chain Reaction of Echovirus in liver and spleen tissue. Establishment of etiological diagnosis and exclusion of inherited metabolic disease helped the family counseling regarding risk for future pregnancies. Fulminant hepatic failure in the neonate is a diagnostic and therapeutic challenge that requires a multidisciplinary management. Our case illustrates the broad differential diagnosis, the common final pathway leading to severe liver injury, and the multidisciplinary approach to diagnosis and treatment

Functional dyspepsia, upper gastrointestinal symptoms, and transit in children

To assess the prevalence of abnormal gastric emptying and small bowel transit in children with functional dyspepsia at a tertiary care center, and the relationship between abnormal gastric and small bowel transit and symptoms in pediatric patients with functional gastrointestinal disorders. Patients were selected by a cross-sectional chart review based on the following inclusion criteria: (1) completion of scintigraphic study of the gastric emptying of solids at 2 hours (GE2), 4 hours (GE4), and small bowel transit at 6 hours (SBT) using a standardized egg meal labeled with 99mTechnetium sulfur colloid, and (2) gastrointestinal (GI) complaints without mucosal or organic disease. Logistic regression analysis was used to assess the association between the presence of upper GI symptoms, and each parameter of gastric and small bowel transit. Children with upper GI symptoms (n=96) were identified. Among 57 children with functional dyspepsia, 40% had slow SBT. Fast GE at 4 hours, and slow SBT were independently associated with bloating. Children with fast SBT were less likely to report abdominal pain. Incorporating assessments of gastric and small bowel transit may be useful in the evaluation of pediatric patients with upper GI symptoms and functional dyspepsi

The role of pelvic floor dysfunction and slow colonic transit in adolescents with refractory constipation

Although pelvic floor dysfunction (PFD) is recognized as a cause of refractory constipation in adults, this diagnosis is not frequently considered in children and adolescents with refractory constipation. The purpose of this study was to examine the symptoms and colonic transit in adolescents with constipation evaluated for a disorder in pelvic floor function. Adolescents with refractory constipation who had undergone anorectal manometry (ARM) and balloon expulsion test (BET) were identified by retrospective review of records. Initial symptoms and the clinician's assessment were used to categorize patients by pediatric Rome II criteria, that is, functional constipation (FC), constipation-predominant irritable bowel syndrome (C-IBS) or functional fecal retention (FFR). Results of scintigraphic colonic transit studies were evaluated. A chi2 test was used to assess the association between individual clinical symptoms and Rome II criteria. Sixty-seven adolescents underwent evaluation of pelvic floor function by tests for PFD: BET was abnormal in 42%. There was no underlying disease or alternative diagnosis to account for the constipation in these patients. Among the 41 patients who also underwent scintigraphic colonic transit, 30% had slow transit constipation and 12% had both slow colonic transit and abnormal BET. Patients classified as C-IBS were more likely to report weight loss (p = 0.03), bloating (p = 0.04), and incomplete rectal evacuation (p = 0.03). Abnormal pelvic floor function and delayed colonic transit are demonstrable as single or combined problems in adolescents with refractory constipatio

Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis

Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long-term outcomes in pediatric PSC patients. We evaluated GGT normalization (75% versus 75% by 1 year after PSC diagnosis predicts favorable 5-year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.Peer reviewe