Primary sclerosing cholangitis is associated with abnormalities in CFTR.

Area of Science:

• Hepatology
• Genetics
• Gastroenterology

Background:

• The cause of primary sclerosing cholangitis (PSC) remains unknown.
• PSC shares features with cystic fibrosis (CF)-related liver disease, including inflammation and biliary damage.
• A potential link between PSC and cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is unexplored.

Purpose of the Study:

• To investigate the potential association between PSC and CFTR dysfunction.
• To explore if a subset of PSC patients represents a single-organ manifestation of CF.

Main Methods:

• Patients with PSC underwent nasal potential difference (NPD) measurement.
• Sweat chloride levels were measured in PSC patients.
• Comprehensive CFTR gene sequencing was performed using next-generation sequencing.

Main Results:

• 6 out of 32 PSC patients had CFTR mutations on one allele; 19 had polymorphisms.
• Sweat tests were abnormal in 6 of 23 patients and intermediate in 21.
• Abnormal NPD measurements were observed in 4 out of 32 patients.

Conclusions:

• Approximately 19% of PSC patients showed features indicative of a CFTR-related disorder.
• CFTR mutations were identified in 19% of PSC patients, and 50% had CFTR polymorphisms.
• PSC may represent a single-organ presentation of CF or a CFTR-related condition in some individuals.