Cystic fibrosis-related liver disease: Clinical presentations, diagnostic and monitoring approaches in the era of CFTR modulator therapies

Cystic fibrosis (CF) is the most common autosomal recessive disease in the Caucasian population. Cystic fibrosis-related liver disease (CFLD) is defined as the pathogenesis related to the underlying CFTR defect in biliary epithelial cells. CFLD needs to be distinguished from other liver manifestations that may not have any pathological significance. The clinical/histological presentation and severity of CFLD vary. The main histological presentation of CFLD is focal biliary fibrosis, which is usually asymptomatic. Portal hypertension develops in a minority of cases (about 10%) and may require specific management including liver transplantation for end-stage liver disease. Portal hypertension is usually the result of the progression of focal biliary fibrosis to multilobular cirrhosis during childhood. Nevertheless, noncirrhotic portal hypertension as a result of porto-sinusoidal vascular disease is now identified increasingly more frequently, mainly in young adults. To evaluate the effect of new CFTR modulator therapies on the liver, the spectrum of hepatobiliary involvement must first be precisely classified. This paper discusses the phenotypic features of CFLD, its underlying physiopathology and relevant diagnostic and follow-up approaches, with a special focus on imaging. (c) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Automated summary

Cystic fibrosis-related liver disease (CFLD) is a pathological mechanism caused by the defect in biliary epithelial cells in cystic fibrosis patients. CFLD presents with varying clinical/histological manifestations and severity, with focal biliary fibrosis being the main histological presentation. A minority of cases develop portal hypertension, requiring specific management including liver transplantation. Noncirrhotic portal hypertension, in addition to cirrhotic portal hypertension, is also increasingly prevalent. Accurate classification of CFLD is necessary for evaluating the effect of new therapies on the liver.