Cystic fibrosis (CF; OMIM 219700) is caused by variations in the cystic fibrosis transmembrane conductance regulator gene. CF-related liver disease (CFLD) affects approximately one-third of patients with CF, but the severity of CFLD is highly variable. This review provides the latest knowledge in the pathophysiology and CF genetic modifier research in CFLD.
So far, the only modifier gene validated in CFLD is SERPINA1 (α-1-antitrypsin) Z allele. Recent studies support the view that cholangiopathy arising in CF is the result of an ill-adapted innate immune response to endotoxins coming from the intestine and triggering a pro-inflammatory response.
The pathophysiology of liver disease remains uncertain and so far, no therapy has proven effective to prevent the progression of CFLD. A better understanding of the pathophysiology and the effect of environmental and non-cystic fibrosis transmembrane conductance regulator genetic influences in the context of CFLD development would help improve management and develop new drug therapies.
aINSERM, Centre de Recherche Saint-Antoine (CRSA), Sorbonne Université
bPediatric Hepatology Unit, Reference Centre for Biliary Atresia and Genetic Cholestatic Diseases (CRMR, AVB-CG), Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP) – Université Paris V
cPneumologie Pédiatrique, AP-HP, Hôpital Trousseau
dDepartment of Hepatology, Reference Centre for Inflammatory Biliary Diseases and Autoimmune Hepatitis (CRMR, MIVB-H), AP-HP, Hôpital Saint-Antoine, Paris, France
Correspondence to Dominique Debray, MD, PhD, Pediatric Hepatology Unit, Department of Gastroenterology, Hepatology and Nutrition, Hôpital Necker-Enfants Malades, 149 Rue de Sèvres, 75015 Paris, France. Tel: +33 1 44 49 25 88; e-mail: firstname.lastname@example.org