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Modifier genes in cystic fibrosis-related liver disease

Debray, Dominiquea,b; Corvol, Harrieta,c; Housset, Chantala,d

Current Opinion in Gastroenterology: March 2019 - Volume 35 - Issue 2 - p 88–92
doi: 10.1097/MOG.0000000000000508
BILIARY TRACT: Edited by Chantal Housset

Purpose of review 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.

Recent findings 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.

Summary 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:

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