ABCB4 variant is associated with hepatobiliary MR abnormalities in people with low-phospholipid-associated cholelithiasis syndrome
Moustafa Biyoukar,
Christophe Corpechot,
Sanaâ El Mouhadi,
Edouard Chambenois,
Quentin Vanderbecq,
Véronique Barbu,
Catherine Dong,
Sara Lemoinne,
Mickael Tordjman,
Raphel Jomaah,
Olivier Chazouilleres,
Lionel Arrivé
Affiliations
Moustafa Biyoukar
Department of Radiology, Saint-Antoine Hospital, Assistance Publique – Hôpitaux de Paris (APHP) and Sorbonne University, Paris, France
Christophe Corpechot
Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, ERN Rare-Liver, Department of Hepatology, Saint-Antoine Hospital, Assistance Publique – Hôpitaux de Paris (APHP), and INSERM, UMRS 938 Sorbonne University, Paris, France
Sanaâ El Mouhadi
Department of Radiology, Saint-Antoine Hospital, Assistance Publique – Hôpitaux de Paris (APHP) and Sorbonne University, Paris, France
Edouard Chambenois
Department of Radiology, Saint-Antoine Hospital, Assistance Publique – Hôpitaux de Paris (APHP) and Sorbonne University, Paris, France
Quentin Vanderbecq
Department of Radiology, Saint-Antoine Hospital, Assistance Publique – Hôpitaux de Paris (APHP) and Sorbonne University, Paris, France
Véronique Barbu
Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, ERN Rare-Liver, Department of Hepatology, Saint-Antoine Hospital, Assistance Publique – Hôpitaux de Paris (APHP), and INSERM, UMRS 938 Sorbonne University, Paris, France
Catherine Dong
Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, ERN Rare-Liver, Department of Hepatology, Saint-Antoine Hospital, Assistance Publique – Hôpitaux de Paris (APHP), and INSERM, UMRS 938 Sorbonne University, Paris, France
Sara Lemoinne
Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, ERN Rare-Liver, Department of Hepatology, Saint-Antoine Hospital, Assistance Publique – Hôpitaux de Paris (APHP), and INSERM, UMRS 938 Sorbonne University, Paris, France
Mickael Tordjman
Department of Radiology, Raymond Poincaré Hospital, Assistance Publique – Hôpitaux de Paris (APHP), Garches, France
Raphel Jomaah
Faculty of Arts and Science, University of Toronto, Toronto, ON, Canada
Olivier Chazouilleres
Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, ERN Rare-Liver, Department of Hepatology, Saint-Antoine Hospital, Assistance Publique – Hôpitaux de Paris (APHP), and INSERM, UMRS 938 Sorbonne University, Paris, France
Lionel Arrivé
Department of Radiology, Saint-Antoine Hospital, Assistance Publique – Hôpitaux de Paris (APHP) and Sorbonne University, Paris, France; Corresponding author. Address: Department of Radiology, Saint-Antoine Hospital, 184 rue du Faubourg Saint-Antoine, 75012 Paris, France. Tel.: +33-149282257.
Background & Aims: The low-phospholipid-associated cholelithiasis (LPAC) syndrome is a recently described peculiar form of cholelithiasis associated with the ATP-binding-cassette subfamily B, member 4 (ABCB4) gene deficiency. The purpose of our study was to analyse the relationship between magnetic resonance (MR) features and the genetic status of ABCB4 in people with LPAC syndrome. Methods: A total of 233 individuals with proven LPAC syndrome were enrolled between January 2003 and June 2018 in a retrospective single-centre study. Inclusion criteria included availability of clinical files, MR images, and genetic data. MR images were analysed by consensus among 3 senior radiologists blinded to the status of ABCB4 gene mutation. Results: A total of 125 individuals (mean age at first MR imaging 40.8 years; 66% females; 48% ABCB4 variant) were included. MR abnormalities were found in 61 (49%) of the 125 individuals. Forty (67%) of the 60 individuals with an ABCB4 gene variant had MR abnormalities as compared with 21 (33%) of the 65 individuals without an ABCB4 gene variant (odds ratio [OR] 4.1, 95% CI 1.9–9.5, p = 0.0001). Compared to individuals with no variant, individuals with an ABCB4 variant were more likely to show intrahepatic macrolithiasis (56 vs. 17%; OR 6.3, 95% CI 2.6–16.2, p <0.0001), bile duct dilatation (60 vs. 18%; OR 6.5, 95% CI 2.7–16.3, p <0.0001), and at least 1 MR feature of complication (35 vs. 15%; OR 2.9, 95% CI 1.1–7.8, p <0.05). Conclusions: ABCB4-related LPAC syndrome is associated with more frequent and severe hepatobiliary MR abnormalities. This finding strongly supports the major role of the ABCB4 gene in the pathogenesis of LPAC syndrome and highlights a genotype–phenotype association in this inherited disease with genetic heterogeneity. Lay summary: ABCB4-related LPAC syndrome associated with an ABCB4 gene variant demonstrates more frequent and severe hepatobiliary MR abnormalities. This finding supports the major role of the ABCB4 gene in the pathogenesis of LPAC syndrome.
