Title :

Liver disease in germline mutations of telomere-related genes: Prevalence, clinical, radiological, pathological features, outcome, and risk factors.

Author(s) :

Sidali, Sabrina [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
CHU Rouen
Borie, Raphaël [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
De Fontbrune, Flore Sicre [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
El Husseini, Kinan [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
CHU Rouen
Rautou, Pierre-Emmanuel [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Lainey, Elodie [Auteur]
Hôpital Robert Debré
Goria, Odile [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
CHU Rouen
Crestani, Bruno [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Cadranel, Jacques [Auteur]
CHU Tenon [AP-HP]
Cottin, Vincent [Auteur]
Hospices Civils de Lyon [HCL]
Bunel, Vincent [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Dumortier, Jerome [Auteur]
Hôpital Edouard Herriot [CHU - HCL]
Jacquemin, Emmanuel [Auteur]
Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
Reboux, Noémi [Auteur]
Hôpital Morvan - CHRU de Brest [CHU - BREST ]
Hirschi, Sandrine [Auteur]
Centre Hospitalier Universitaire [Strasbourg] [CHU Strasbourg]
Bourdin, Arnaud [Auteur]
Centre Hospitalier Régional Universitaire [Montpellier] [CHRU Montpellier]
Meszaros, Magdalena [Auteur]
Centre Hospitalier Régional Universitaire [Montpellier] [CHRU Montpellier]
Dharancy, Sebastien [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Hilaire, Sophie [Auteur]
Hôpital Foch [Suresnes]
Mallet, Vincent [Auteur]
Hôpital Cochin [AP-HP]
Reynaud-Gaubert, Martine [Auteur]
Hôpital Nord [CHU - APHM]
Terriou, Louis [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Gottrand, fréderic [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Abou Chahla, Wadih [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Khan, Jean-Emmanuel [Auteur]
Service de médecine interne [CHU Ambroise Paré]
Carrier, Paul [Auteur]
CHU Limoges
Saliba, Faouzi [Auteur]
Hôpital Paul Brousse
Rubbia-Brandt, Laura [Auteur]
Hôpitaux Universitaires de Genève [HUG]
Aubert, John-David [Auteur]
Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne] [CHUV]
Elkrief, Laure [Auteur]
CHU Trousseau [Tours]
De Lédinghen, Victor [Auteur]
Hôpital Haut-Lévêque [CHU Bordeaux]
Abergel, Armand [Auteur]
CHU Clermont-Ferrand
Tournilhac, Olivier [Auteur]
CHU Clermont-Ferrand
Houssel, Pauline [Auteur]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Jouneau, Stephane [Auteur]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Wemeau, Lidwine [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Bergeron, Anne [Auteur]
Hôpitaux Universitaires de Genève [HUG]
Leblanc, Thierry [Auteur]
Hôpital Robert Debré
Ollivier-Hourmand, Isabelle [Auteur]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Nguyen-Khac, Eric [Auteur]
CHU Amiens-Picardie
Morisse-Pradier, Hélène [Auteur]
CHU Rouen
Ba, Ibrahima [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Boileau, Catherine [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Roudot-Thoraval, Françoise [Auteur]
CHU Henri Mondor [Créteil]
Vilgrain, Vilgrain [Auteur]
Hôpital Beaujon [AP-HP]
Bureau, Christophe [Auteur]
Faculté de Médecine Purpan
Nunes, Hilario [Auteur]
Hôpital Avicenne [AP-HP]
Naccache, Jean-Marc [Auteur]
Centre hospitalier Saint-Joseph [Paris]
Durand, François [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Francoz, Claire [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Roulot, Dominique [Auteur]
Hôpital Avicenne [AP-HP]
Valla, Dominique-Charles [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Paradis, Valérie [Auteur]
Hôpital Beaujon [AP-HP]
Kannengiesser, Caroline [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Plessier, Aurélie [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]

Journal title :

Hepatology

Abbreviated title :

Hepatology

Publication date :

2023-11-07

ISSN :

1527-3350

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Background and Aim: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver ...
Show more >Background and Aim: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases. Approach and Results: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n = 1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological, and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease in 48% and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12–54), ascites, hepato-pulmonary syndrome, variceal bleeding, and HCC occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score ≥ 3·25 and ≥1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group [80/396, (20%)], OR 12.9 (CI 95%: 7.8–21.3, p < 0.001). Conclusions: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild, they may be associated with severe disease. Porto-sinusoidal vascular disease and cirrhosis were the most frequent lesions, suggesting that the mechanism of action is multifactorial.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2024-01-11T22:06:35Z
2024-03-11T10:23:07Z
2024-04-23T11:57:20Z