端粒相关基因种系突变的肝病：患病率、临床、放射学、病理特征、结果和危险因素。
Liver disease in germline mutations of telomere-related genes: Prevalence, clinical, radiological, pathological features, outcome, and risk factors.
发表日期：2023 Nov 06
作者：
Sabrina Sidali, Raphaël Borie, Flore Sicre de Fontbrune, Kinan El Husseini, Pierre-Emmanuel Rautou, Elodie Lainey, Odile Goria, Bruno Crestani, Jacques Cadrane, Vincent Cottin, Vincent Bune, Jérôme Dumortier, Emmanuel Jacquemin, Noémi Reboux, Sandrine Hirschi, Arnaud Bourdin, Magdalena Meszaros, Sebastien Dharancy, Sophie Hilaire, Vincent Mallet, Martine Reynaud-Gaubert, Louis Terriou, Frédéric Gottrand, Wadih Abou Chahla, Jean-Emmanuel Khan, Paul Carrier, Faouzi Saliba, Laura Rubbia-Brandt, John-David Aubert, Laure Elkrief, Victor de Lédinghen, Armand Abergel, Tournilhac Olivier, Pauline Houssel, Stephane Jouneau, Lidwine Wemeau, Anne Bergeron, Thierry Leblanc, Isabelle Ollivier-Hourmand, Eric Nguyen Khac, Hélène Morisse-Pradier, Ibrahima Ba, Catherine Boileau, Françoise Roudot-Thoraval, Valérie Vilgrain, Christophe Bureau, Hilario Nunes, Jean-Marc Naccache, François Durand, Claire Francoz, Dominique Roulot, Dominique Valla, Valérie Paradis, Caroline Kannengiesser, Aurélie Plessier
来源：
HEPATOLOGY
摘要：
端粒相关基因（TRG）的种系突变可引起多器官功能障碍，而肝脏特异性表现尚未明确概述。我们的目的是描述 TRG 突变相关的肝脏疾病。对 TRG 突变患者的肝脏疾病（转氨酶>30 IU/L 和/或肝脏影像异常）进行回顾性多中心分析。主要测量指标是 TRG 突变队列中肝病的特征、结果和危险因素。将肝病患病率与按年龄分层的社区对照组 (n=1190) 进行比较，并以 1:3 的比例匹配已知的肝病危险因素。在 132 名 TRG 突变患者中，95 名（72%）患有肝脏疾病，相关肺、血液、皮肤、风湿病和眼科 TRG 疾病的病例分别占 82%、77%、55%、39% 和 30%。 52/95 名患者进行了肝活检，48% 的患者患有门窦血管疾病 (PSVD)，15% 的患者患有晚期纤维化/肝硬化。随访21个月（12-54）后，腹水、肝肺综合征、静脉曲张出血和肝细胞癌的发生率分别为14%、13%、13%和2%。五年无肝移植生存率为 69%。 FIB-4评分≥3·25和≥1个肝硬化危险因素与较差的无肝移植生存率相关。 TRG 突变患者发生肝病的频率高于配对对照组 (80/396, (20%))，OR 12.9 (CI95% 7.8-21.3, p<0.001)。TRG 突变显着增加发生肝病的风险疾病。尽管症状可能很轻微，但它们可能与严重疾病有关。 PSVD 和肝硬化是最常见的病变，表明其作用机制是多因素的。版权所有 © 2023 美国肝病研究协会。
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 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).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.Copyright © 2023 American Association for the Study of Liver Diseases.