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Background: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. Methods: We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic. Results: Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. Conclusions: All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.

Children with chronic liver disease are at risk for vitamin K deficiency because of fat malabsorption and inadequate dietary intake. The objective of this study was to determine the prevalence of vitamin K deficiency in children with mild to moderate chronic cholestatic and noncholestatic liver disease.Vitamin K status was examined in 43 children (0.25-15.9 years) with mild to moderate chronic cholestatic liver disease, 29 children (0.9-16.9 years) with chronic mild to moderate noncholestatic liver disease, and in 44 healthy children (1-18 years). Vitamin K status was assessed by the plasma PIVKA-II (protein induced in vitamin K absence) assay (enzyme-linked immunosorbent assay). Plasma PIVKA-II values greater than 3 ng/mL are indicative of vitamin K deficiency.The mean plasma PIVKA-II (+/-SD) in cholestatic, noncholestatic, and healthy children was 61.9 +/-144, 1.2 +/- 3, and 2.1 +/- ng/mL, respectively (P0.002). Fifty-four percent of the children supplemented with vitamin K had plasma PIVKA-II greater than 3 ng/mL. Plasma conjugated bilirubin, total bile acids, and severity of liver disease were positively correlated with plasma PIVKA-II levels (P0.05).Vitamin K deficiency is prevalent in children with mild to moderate chronic cholestatic liver disease, even with vitamin K supplementation. Elevated PIVKA-II levels occurred in children with a normal prothrombin, indicating that more sensitive markers of vitamin K status should be used in children with chronic liver disease. Vitamin K deficiency was related to degree of cholestasis and severity of liver disease in children. Children without cholestasis did not exhibit vitamin K deficiency.

A male infant presenting with neonatal hepatitis syndrome, characterized by conjugated hyperbilirubinemia and very mild liver function test abnormalities, at 2 weeks of age was found to have no excretion of radioisotope into the intestinal tract on hepatobiliary scan. Liver biopsy revealed severe interlobular bile duct paucity. Other features of Alagille's syndrome were not present; other conditions frequently associated with interlobular bile duct paucity were also excluded. Subsequently, the infant was found to have cystic fibrosis. Cystic fibrosis is thus another disease that may be associated with paucity of interlobular bile ducts presenting as neonatal hepatitis syndrome, and this represents a different pathogenesis of cholestatic jaundice in neonates with cystic fibrosis besides those previously recognized.

Fulminant hepatic failure (FHF) is associated with high mortality; few patients survive without liver transplantation. It is important to have a sensitive, specific early predictor of outcome to distinguish potential survivors (S) from nonsurvivors (NS).Because we had previously shown that glycine conjugation of para-aminobenzoic acid (PABA) quantitatively reflects liver function in children with chronic liver disease, in this pilot study we wanted to determine whether the measurement of the glycine conjugates of PABA could distinguish S from NS in FHF in comparison with standard prognostic indices.Twenty-four patients were studied: acute severe hepatitis (n = 7), subfulminant hepatic failure (n = 7), and FHF (n = 10). Assessment of King's College criteria, measurement of factor V and VII levels, PABA testing, and transjugular liver biopsies were performed in almost all patients within 48 hours of admission. Serum PABA and its glycine conjugates (para-aminohippurate (PAHA) and para-acetamidohippurate (PAAHA)) were measured thirty minutes after oral administration by high-pressure liquid chromatography. Poor prognostic categories as previously established in the literature were defined as factor V0.20U/ml, factor VII0.08 U/ml, % necrosis70%, hippurate ratio = 0%, and PAHA = 0M.The measurement of PAHA was the best predictor of a poor outcome in patients with acute liver failure with a sensitivity of 92%, and negative predictive value (NPV) of 92% compared with a sensitivity of 54% and a NPV of 63% with King's College criteria.Measurement of serum PAHA is the best early prognostic marker of death in children who suffer from FHF.