Cystic Fibrosis and Liver Disease

Excerpt

Cystic fibrosis (CF) is an autosomal recessive disorder that commonly affects the White population, with an annual incidence of approximately 1 in 3,500 live births. This multisystem disorder is characterized by genetic mutations in the CF transmembrane conductance regulator (CFTR) gene on chromosome 7, which encrypts a protein essential for regulating transmembrane chloride reabsorption. CFTR, a chloride channel, is expressed in secretory epithelial cells lining the airways, digestive system, reproductive system, and skin. Homozygous mutations in the CFTR gene impair the transport of chloride ions and the movement of water into and out of cells, resulting in the inspissation of secretions and leading to organ dysfunction. Although CF commonly affects the airways, approximately 10% to 15% of patients with CF demonstrate cystic fibrosis-associated liver disease (CFLD). The improvement in the diagnostic modalities and management of CF has positively impacted the life expectancy of patients with CF. Consequently, there has been a significant emergence of liver dysfunction in CF, complicating the clinical course of the disease. CFTR dysfunction has a significant effect on cholangiocyte function causing an alteration in the final bile composition that causes chronic damage to the biliary epithelium, resulting in the development of a broad spectrum of hepatobiliary complications ranging from cholestasis, progressive periportal fibrosis, biliary obstruction causing focal biliary cirrhosis which may progress to multinodular cirrhosis, portal hypertension, and hepatic decompensation.