A0551 - Cystic Fibrosis-Associated Liver Disease: A Rare Etiology of Cirrhosis

Introduction: Cystic fibrosis (CF) is a rare etiology of cirrhosis. Alteration in bile hydration and alkalinity cause bile duct injury and CF-associated liver disease (CFLD). Factors associated with rapid progression of CFLD include class I-III mutations in CF transmembrane conductance regulator (CFTR), male sex, history of pancreatic insufficiency and meconium ileus. Approach to prevention and management of CFLD is unclear in current guidelines. We present a patient with CF who progressed to cirrhosis.

Case Description/Methods: A 24-year-old man with history of CF complicated by Staphylococcal and Pseudomonal lung colonization, pancreatic exocrine insufficiency was evaluated for chronic liver disease. He was diagnosed with CF at age of 14 years with c.489+1G >T/c.579+1G >T mutations on genetic testing. Two years later, he developed cholestatic pattern of elevated liver enzymes that progressively worsened. At time of evaluation, the patient was asymptomatic with unremarkable examination. Laboratory work showed total bilirubin 1.62 mg/dL, alkaline phosphatase 259 U/L, AST 88 U/L. ALT 246 U/L and thrombocytopenia (126 x109/L). Abdominal ultrasound showed coarse hepatic echotexture and splenomegaly. MRCP revealed markedly nodular hepatic contour, splenomegaly to 17 cm, caudate lobe hypertrophy, diffuse hepatic steatosis with morphological changes of cirrhosis and fatty replacement of pancreas. Workup for other causes of liver diseases was unremarkable. Liver biopsy demonstrated regenerative nodules, prominent ductular reaction and thick biliary secretions in the lumen consistent with cirrhosis due to CFLD. He was started on ursodeoxycholic acid (UDCA) with recommendation to continue multivitamin, pancreatic enzyme supplements, dornase alfa and follow up in 6 months for hepatocellular cancer screening.

Discussion: A high index of clinical suspicion is required for early identification of CFLD in patients with cholestatic pattern of elevated liver enzymes, male sex, class I-III mutation of CFTR, and history of pancreatic insufficiency. There is no effective treatment of CFLD. Efficacy of UDCA is controversial as it improves biochemical parameters but its effects on outcomes of CFLD remain unknown. Further, while steatosis has been described in patients with CFLD, its impact on CFLD outcomes need to be addressed in large cohorts. Primary goals in managing CFLD is close monitoring of liver function, early identification of cirrhosis, its complications and liver transplant in progressively liver failure.