非酒精性脂肪性肝病患者一级亲属发生肝纤维化的风险。
Risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease.
机构信息
Nonalcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
出版信息
J Clin Invest. 2022 Nov 1;132(21):e162513. doi: 10.1172/JCI162513.
BACKGROUNDA pilot, single-center study showed that first-degree relatives of probands with nonalcoholic fatty liver disease (NAFLD) cirrhosis have a high risk of advanced fibrosis. We aimed to validate these findings using 2 independent cohorts from the US and Europe.METHODSThis prospective study included probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD, with at least 1 first-degree relative. A total of 396 first-degree relatives - 220 in a derivation cohort and 176 in a validation cohort - were enrolled in the study, and liver fibrosis was evaluated using magnetic resonance elastography and other noninvasive imaging modalities. The primary outcome was prevalence of advanced fibrosis in first-degree relatives.RESULTSPrevalence of advanced fibrosis in first-degree relatives of probands with NAFLD with advanced fibrosis, NAFLD without advanced fibrosis, and non-NAFLD was 15.6%, 5.9%, and 1.3%, respectively (P = 0.002), in the derivation cohort, and 14.0%, 2.6%, and 1.3%, respectively (P = 0.004), in the validation cohort. In multivariable-adjusted logistic regression models, age of ≥50 years (adjusted OR [aOR]: 2.63, 95% CI 1.0-6.7), male sex (aOR: 3.79, 95% CI 1.6-9.2), diabetes mellitus (aOR: 3.37, 95% CI 1.3-9), and a first-degree relative with NAFLD with advanced fibrosis (aOR: 11.8, 95% CI 2.5-57) were significant predictors of presence of advanced fibrosis (all P < 0.05).CONCLUSIONFirst-degree relatives of probands with NAFLD with advanced fibrosis have significantly increased risk of advanced fibrosis. Routine screening should be done in the first-degree relatives of patients with advanced fibrosis.FUNDINGSupported by NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK106419, R01DK121378, R01DK124318, P30DK120515, K23DK119460), NHLBI (P01HL147835), and NIAAA (U01AA029019); Academy of Finland grant 309263; the Novo Nordisk, EVO, and Sigrid Jusélius Foundations; and the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 777377. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and the EFPIA.
背景
一项初步的、单中心研究表明，非酒精性脂肪性肝病（NAFLD）肝硬化患者的一级亲属有发生晚期纤维化的高风险。我们旨在使用来自美国和欧洲的两个独立队列来验证这些发现。
方法
这项前瞻性研究纳入了具有晚期纤维化、无晚期纤维化的 NAFLD 以及非 NAFLD 的患者及其至少 1 位一级亲属。共有 396 位一级亲属 - 220 位在推导队列中，176 位在验证队列中 - 入组了本研究，并使用磁共振弹性成像和其他非侵入性成像方式评估了肝纤维化。主要结局是一级亲属中晚期纤维化的患病率。
结果
在推导队列中，具有晚期纤维化的 NAFLD 患者、无晚期纤维化的 NAFLD 患者和非 NAFLD 患者的一级亲属中晚期纤维化的患病率分别为 15.6%、5.9%和 1.3%（P=0.002），在验证队列中分别为 14.0%、2.6%和 1.3%（P=0.004）。在多变量调整后的逻辑回归模型中，年龄≥50 岁（调整后的比值比[aOR]：2.63，95%CI 1.0-6.7）、男性（aOR：3.79，95%CI 1.6-9.2）、糖尿病（aOR：3.37，95%CI 1.3-9）以及具有晚期纤维化的 NAFLD 一级亲属（aOR：11.8，95%CI 2.5-57）是存在晚期纤维化的显著预测因子（所有 P＜0.05）。
结论
具有晚期纤维化的 NAFLD 患者的一级亲属有显著增加的晚期纤维化风险。应在患有晚期纤维化的患者的一级亲属中进行常规筛查。
资助
由 NCATS（5UL1TR001442）、NIDDK（U01DK061734、U01DK130190、R01DK106419、R01DK121378、R01DK124318、P30DK120515、K23DK119460）、NHLBI（P01HL147835）和 NIAAA（U01AA029019）提供支持；由芬兰科学院拨款 309263；诺和诺德、EVO 和 Sigrid Jusélius 基金会；以及创新药物倡议 2 联合企业，根据协议 777377 提供资助。该联合企业得到了欧盟地平线 2020 研究和创新计划以及 EFPIA 的支持。
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