The Childhood Liver Disease Research Network's prospective characterization of pediatric primary sclerosing cholangitis.

BACKGROUND

Primary sclerosing cholangitis (PSC) is a rare biliary fibrosing disease that leads to significant morbidity and the need for liver transplantation. The Childhood Liver Disease Research Network is conducting a prospective, observational longitudinal study to define the natural history of pediatric PSC. The aim of this report is to characterize the clinical phenotypes of the first 175 children enrolled in the PSC study and to determine correlations of specific phenotypes with clinical and laboratory characteristics.

METHODS

Data collected included a history of inflammatory bowel disease (IBD), autoimmune hepatitis (AIH), laboratories, autoantibodies, liver stiffness measurements (LSM), medications, and IBD activity. Comparison of phenotypes with/without IBD and/or AIH, and small-duct versus large-duct PSC was performed.

RESULTS

The median age at enrollment was 16.1 years, 60% were male, 78% had large-duct PSC, and the median duration of PSC was 2.2 years. The predominant phenotype was PSC/IBD, and 96% had quiescent/mild IBD. The entire cohort had evidence of mild liver disease based on biochemistries and LSMs; <10% had evidence of portal hypertension. Higher LSMs were associated with elevated liver biochemistries. There were no significant characteristics that differentiated the phenotypes; however, there was more frequent autoantibody positivity in PSC/IBD and higher LSMs in PSC/AIH overlap syndrome.

CONCLUSIONS

This prospective cohort of pediatric PSC revealed mild liver disease in the majority. Laboratory biomarkers of liver injury and fibrosis were associated with LSM severity, suggesting LSM as a reliable tool to monitor PSC progression. This dataset encompasses a well-phenotyped cohort of children with PSC that will be followed prospectively for longitudinal assessment of progression of disease, as well as a model for stratification within future treatment trials.