Hepatic Manifestations of Cystic Fibrosis

Abstract

Cystic fibrosis liver disease (CFLD) remains the third leading cause of death in patients with cystic fibrosis. Although most patients with CFLD present in childhood, recent studies suggest a second wave of liver disease in adulthood. There are no clear guidelines for diagnosing CFLD. Treatment options for CFLD remain limited, and while UDCA is widely used, its long-term benefit is unclear. Those who develop hepatic decompensation or uncontrolled variceal bleeding may benefit from liver transplant, either alone, or in combination with lung transplant.

Keywords: CFLD; Cystic fibrosis liver disease; Focal biliary cirrhosis; Liver disease in cystic fibrosis; Non-cirrhotic portal hypertension.

Figure 1:

Schematic demonstrating the proposed pathogenesis of liver disease related to cystic fibrosis. Defective functioning of cystic fibrosis transmembrane conductance regulators (CFTR) expressed in the intra- and extra-hepatic cholangiocytes results in impaired Cl⁻ secretion across the apical membrane, leading to decreased bile flow and increased bile precipitation. This results in ductular obstruction with subsequent periportal inflammation and fibrosis and focal biliary cirrhosis. Progressive disease may manifest as multifocal biliary cirrhosis and portal hypertension.

Figure 2:

Liver histology demonstrating: a) ductular reaction with bile stasis, neutrophilic infiltration, and granular debris (arrows). b) focal cirrhosis changes. c) marked, pan-acinar steatosis. d) nodular regenerative hyperplasia

Figure 3:

Algorithmic evaluation for cystic fibrosis liver disease in patients with cystic fibrosis and abnormal liver tests.