WS16.6 Is primary sclerosing cholangitis (PSC) a cystic fibrosis-related disorder? Electrophysiological testing and full sequencing of the CFTR gene

Abstract

Objectives PSC and Cystic Fibrosis related liver disease (CFLD) have features in common: chronic inflammation and bile duct damage with similar cholangiographic findings. There is controversy if PSC is related to CFTR dysfunction. The aim of this study is to determine whether PSC is associated with mutations in the cftr gene and abnormalities in CFTR function assays. Methods Patients with PSC were referred for Nasal Potential Difference (NPD) measurement, sweat chloride concentration and complete cftr sequencing of the full coding sequence by NGS (new generation sequencing-PGM life technology). Results 32 patients aged 46±13 yrs (IBD in 17) were examined. Cftr sequencing showed 6 patients with cftr mutations on one allele and 19 with polymorphisms in the cftr gene. 28 patients had normal NPD results (Basal NPD −14.6±4.9, response to amiloride 9.2±4.7, response to Cl − free + isoproterenol −11.1±5.7 mV), sweat chloride 43±19 mmol/L and 4 patients had abnormal NPD results (Basal NPD −21.1±8.6, response to amiloride 15.7±7.4, response to Cl − free + isoproterenol −1.1±4.4 mV); sweat chloride was 69, 54, 65 and 44 mmol/L. Of note, one of these patients is infertile; one patient has chronic pancreatitis. Two patients with abnormal NPD carried W1282X/5T mutation and the 2620–26A Conclusion 4 patients out of 32 (12.5%) with PSC have been found to have some features of CFTR related disorder and 18.75% carry cftr mutations and 50% have polymorphisms of the cftr gene. This study will improve our understanding of the etiology of PSC and its relationship to cftr dysfunction.