Primary Sclerosing Cholangitis in Childhood is Associated with Abnormalities in Cystic Fibrosis–Mediated Chloride Channel Function

ObjectiveTo determine whether primary sclerosing cholangitis (PSC) in childhood is associated with abnormalities in cystic fibrosis transmembrane conductance regulator (CFTR).Study designSubjects with PSC diagnosed in childhood (n = 20) were recruited from Children’s Hospital. Subjects had testing with sweat chloride concentration, nasal transmembrane potential difference, and extensive genetic analysis of the CFTR gene. Disease control subjects consisted of 14 patients with inflammatory bowel disease alone and no liver disease. t Tests were performed to determine statistical significance.ResultsIn the PSC group, CFTR chloride channel function (ΔChloride free + isoproterenol) was markedly diminished at −8.6 ± 8.2 mV (reference range: −24.6 ± 10.4 mV). In contrast, disease control subjects had normal function, at −17.8 ± 9.7 mV (P = .008). Sweat chloride concentration in subjects with PSC was greater than in disease control subjects (20.8 ± 3.4 mmol/L vs 12.0 ± 1.6 mmol/L, P = .045). Comprehensive CFTR genotyping revealed that 5 of 19 (26.3%) subjects with PSC had a CFTR mutation or variant, compared with 6 of 14 (42.9%) disease control subjects.ConclusionsThere is a high prevalence of CFTR-mediated ion transport dysfunction in subjects with childhood PSC.