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

J Hepatol. 2022 Feb;76(2):420-434. doi: 10.1016/j.jhep.2021.09.042. Epub 2021 Oct 20.

Abstract

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, non-cirrhotic 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.

Keywords: Cystic Fibrosis Liver Disease; Focal Biliary Fibrosis; Non-invasive Diagnostic; Porto-sinusoidal Vascular Disease; Radio-pathologic correlations.

Publication types

  • Review

MeSH terms

  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / physiopathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors
  • Cystic Fibrosis Transmembrane Conductance Regulator / drug effects*
  • Cystic Fibrosis Transmembrane Conductance Regulator / therapeutic use
  • Elasticity Imaging Techniques / methods
  • Elasticity Imaging Techniques / statistics & numerical data
  • Humans
  • Hypertension, Portal / diagnostic imaging
  • Hypertension, Portal / physiopathology
  • Liver / pathology
  • Liver Diseases / diagnostic imaging
  • Liver Diseases / etiology*
  • Liver Diseases / physiopathology
  • Severity of Illness Index
  • Ultrasonography / methods
  • Ultrasonography / statistics & numerical data

Substances

  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator