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

Details

Serval ID
serval:BIB_387484FF240F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Liver disease in germline mutations of telomere-related genes: Prevalence, clinical, radiological, pathological features, outcome, and risk factors.
Journal
Hepatology
Author(s)
Sidali S., Borie R., Sicre de Fontbrune F., El Husseini K., Rautou P.E., Lainey E., Goria O., Crestani B., Cadranel J., Cottin V., Bunel V., Dumortier J., Jacquemin E., Reboux N., Hirschi S., Bourdin A., Meszaros M., Dharancy S., Hilaire S., Mallet V., Reynaud-Gaubert M., Terriou L., Gottrand F., Abou Chahla W., Khan J.E., Carrier P., Saliba F., Rubbia-Brandt L., Aubert J.D., Elkrief L., de Lédinghen V., Abergel A., Olivier T., Houssel P., Jouneau S., Wemeau L., Bergeron A., Leblanc T., Ollivier-Hourmand I., Nguyen Khac E., Morisse-Pradier H., Ba I., Boileau C., Roudot-Thoraval F., Vilgrain V., Bureau C., Nunes H., Naccache J.M., Durand F., Francoz C., Roulot D., Valla D., Paradis V., Kannengiesser C., Plessier A.
ISSN
1527-3350 (Electronic)
ISSN-L
0270-9139
Publication state
Published
Issued date
01/06/2024
Peer-reviewed
Oui
Volume
79
Number
6
Pages
1365-1380
Language
english
Notes
Publication types: Journal Article ; Multicenter Study
Publication Status: ppublish
Abstract
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.
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).
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.
Keywords
Humans, Male, Female, Retrospective Studies, Middle Aged, Adult, Risk Factors, Liver Diseases/genetics, Liver Diseases/epidemiology, Liver Diseases/pathology, Germ-Line Mutation, Prevalence, Telomerase/genetics, Aged, Young Adult, Telomere/genetics, Adolescent, DNA Helicases
Pubmed
Web of science
Create date
10/11/2023 12:20
Last modification date
22/05/2024 6:59
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