Cystic fibrosis

Cystic fibrosis is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR is expressed in the apical surface of cholangiocytes.42

CFTR gene mutations result in excessive viscous bile secretion secondary to deficient surface fluid and bicarbonate efflux. The viscous bile causes obstructions in the ducts, resulting in hepatotoxicity, which leads to fibrosis and ultimately cirrhosis.42 Cirrhosis occur in 5 to 25% of children and the risk increases with age.4
Cystic fibrosis is the most common genetic disorder among Caucasian children, with estimated incidence ranging from between 1 in 8,000 to 1 in 10,000 individuals.3 Cystic fibrosis is the main cause of pancreatic exocrine insufficiency in children and can be either isolated or coexist with a more general disease, for example Shwachman syndrome.4 Liver complications in these patients are also common with 25-60% of patients presenting with hepatic steatosis, 15% with cholelithiasis and cholecystitis, and under 10% with neonatal cholestasis.42
Diagnosis
  • Since the advent of routine newborn screening for cystic fibrosis, neonatal screening is by far the most widespread diagnostic tool43
If the disease cannot be identified by neonatal screening of immunoreactive trypsin levels, a quick diagnosis can be made by performing a sweat test (chloride concentration above 60 mmol/L), a faecal elastase test and by CFTR gene sequencing4,44
Back to diagnostic algorithm

3. INSERM. Orphanet. European Union: The portal for rare diseases and orphan drugs. 2021 (accessed 09/2021 at https://www.orpha.net/consor/cgi-bin/Disease.php?lng=EN.)

4. Protocole national de diagnostic et de soins : Déficits de synthèse des acides biliaires primaires. Centre de Référence Coordonnateur de l’Atrésie des Voies Biliaires et des Cholestases Génétiques; 2019.

42. Al Sinani S, Al-Mulaabed S, Al Naamani K, Sultan R. Cystic fibrosis liver disease: know more. Oman Med J 2019;34:482-9.

43. Ross LF. Newborn screening for cystic fibrosis: a lesson in public health disparities. J Pediatr 2008;153:308-13.

44. Farrell PM, Rosenstein BJ, White TB, et al. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report. J Pediatr 2008;153:S4-s14.