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Article Dans Une Revue Hepatology Année : 2024

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

1 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
2 Service d'Hépato-Gastroentérologie [CHU Rouen]
3 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
4 AP-HP - Hopital Saint-Louis [AP-HP]
5 Service de pneumologie, oncologie thoracique et soins intensifs respiratoires [Rouen]
6 Service d'Hématologie Biologique [Hôpital Robert Debré, Paris]
7 Service de pneumologie [AP-HP CHU Tenon]
8 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
9 CRMR des maladies pulmonaires rares de l’adulte - Centre de référence maladies rares des maladies pulmonaires rares de l’adulte (CHU Dijon)
10 Hôpital Edouard Herriot [CHU - HCL]
11 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
12 CHU - BREST - Hôpital Morvan - CHRU de Brest
13 HUS - Les Hôpitaux Universitaires de Strasbourg
14 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
15 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
16 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
17 Hôpital Foch [Suresnes]
18 Département d'hépatologie [CHU Cochin]
19 Service de Pneumologie et Allergie - Hôpital Nord [Marseille]
20 Hôpital Claude Huriez [Lille]
21 INFINITE - Institute for Translational Research in Inflammation - U 1286
22 Hôpital Jeanne de Flandre [Lille]
23 Service de médecine interne [CHU Ambroise Paré]
24 Service d'Hépato-gastro-entérologie et Nutrition [CHU Dupuytren 1, Limoges]
25 CHB - Centre hépato-biliaire
26 Service de Pathologie clinique [Hôpitaux universitaires de Genève]
27 Service de Pneumologie [lausanne]
28 Département d'Hépato-Gastroentérologie [Hôpital Trousseau, Tours]
29 CHU Bordeaux
30 Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand]
31 CHU Estaing [Clermont-Ferrand]
32 Service des maladies du foie [CHU Rennes]
33 Service de pneumologie [Rennes] = Pneumology [Rennes]
34 Clinique de pneumologie [CHRU Lille]
35 Service de pneumologie [Hôpitaux Universitaires Genève]
36 Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen]
37 Service d'Hépato Gastroenterologie [CHU Amiens-Picardie]
38 GRAP - Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 UPJV
39 Laboratoire de Génétique Moléculaire [Hôpital Bichat]
40 Hôpital Henri Mondor
41 Hôpital Beaujon [AP-HP]
42 Service Hépatologie [CHU Toulouse]
43 Service de pneumologie [Avicenne]
44 Service de Pneumologie-Allergologie-Oncologie thoracique [Hôpital Paris Saint-Joseph]
45 Hôpital Avicenne [AP-HP]
46 Service d'Anatomo-Pathologie
Vincent Cottin
Jérôme Dumortier

Résumé

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 multicentre 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 (PSVD) in 48%, and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12-54), ascites, hepato-pulmonary syndrome, variceal bleeding, and hepatocellular carcinoma 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 (CI95% 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. PSVD and cirrhosis were the most frequent lesions suggesting that the mechanism of action is multifactorial.
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Dates et versions

hal-04281096 , version 1 (12-11-2023)

Identifiants

Citer

Sabrina Sidali, Raphaël Borie, Flore Sicre de Fontbrune, Kinan El Husseini, Pierre-Emmanuel Rautou, et al.. Liver disease in germline mutations of telomere-related genes: Prevalence, clinical, radiological, pathological features, outcome, and risk factors. Hepatology, 2024, 79 (6), pp.1365-1380. ⟨10.1097/HEP.0000000000000667⟩. ⟨hal-04281096⟩
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