Liver disease in cystic fibrosis

Cystic fibrosis (CF) is a multiorgan disorder, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in abnormal regulation of salt and water movement across membranes. In the liver this leads to hyperviscous bile accumulating in the biliary tree, causing cholangiocyte and hepatocyte injury and inflammation, stimulating focal fibrosis. With increased life expectancy CF related liver disease (CFLD) has become a leading cause of morbidity and mortality in patients with CF. Most patients with CFLD remain asymptomatic even though approximately 5-10% develop multilobular cirrhosis during the first decade of life. Most will develop signs of portal hypertension. Active screening for CFLD and introduction of non-invasive imaging techniques and novel biomarkers would identify individuals at risk for cirrhosis prior to its development in order to institute therapy to prevent or reduce disease progression, and can detect patients who have developed clinically silent cirrhosis to allow monitoring and interventions to reduce or mitigate complications. Liver transplant should be considered for those who develop hepatic dysfunction or advanced portal hypertension, although deteriorating pulmonary function and quality of life should also be taken into account. Current research in CFLD focuses on repairing the basic defect and reducing inflammation thus aiming to find treatment modalities that prevent development and/or progression of CLFD.