Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis
Nonalcoholic fatty liver disease with cirrhosis increases familial risk for advanced fibrosis
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DOI：
10.1172/jci93465
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发表时间：
2017-06-30
影响因子：
15.9
通讯作者：
Loomba, Rohit
中科院分区：
文献类型：
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作者：
Caussy, Cyrielle;Soni, Meera;Loomba, Rohit
背景。非酒精性脂肪性肝病合并肝硬化（nafld -肝硬化）患者的一级亲属发生晚期纤维化的风险尚不清楚，需要系统量化。本研究旨在前瞻性评估nafld肝硬化先证一级亲属发生晚期纤维化的风险。这是一项对26名nafld -肝硬化先证患者和39名一级亲属的前瞻性队列横断面分析。对照人群包括69对社区居住的双胞胎、兄弟姐妹或父母-后代对（n = 138），包括69名随机确定无NAFLD证据的个体和69名他们的一级亲属。主要终点是是否存在晚期纤维化（3期或4期纤维化）。通过MRI质子密度脂肪分数（MRI- pdff）对NAFLD进行临床评估和量化。磁共振弹性成像（MRE）检查肝脏硬度大于3.63 kPa时诊断为晚期纤维化。先证nafld -肝硬化一级亲属的晚期纤维化患病率显著高于对照组（17.9% vs. 1.4%, P = 0.0032）。与对照组相比，先证nafld -肝硬化的一级亲属发生晚期纤维化的几率为14.9 （95% CI, 1.8-126.0, P = 0.0133）。即使在年龄、性别、西班牙裔种族、BMI和糖尿病状况等多变量调整后，晚期纤维化的风险在统计学和临床上仍具有显著性（多变量调整优势比12.5;95% CI, 1.1-146.1, P = 0.0438）。通过一个表型良好的家族队列研究，我们证明了患有nafld -肝硬化的先证的一级亲属发生晚期纤维化的风险高出12倍。nafld -肝硬化患者的一级亲属可考虑进行晚期纤维化筛查。
BACKGROUND. The risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease and cirrhosis (NAFLD-cirrhosis) is unknown and needs to be systematically quantified. We aimed to prospectively assess the risk of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis.METHODS. This is a cross-sectional analysis of a prospective cohort of 26 probands with NAFLD-cirrhosis and 39 first-degree relatives. The control population included 69 community-dwelling twin, sib-sib, or parent-offspring pairs (n = 138), comprising 69 individuals randomly ascertained to be without evidence of NAFLD and 69 of their first-degree relatives. The primary outcome was presence of advanced fibrosis (stage 3 or 4 fibrosis). NAFLD was assessed clinically and quantified by MRI proton density fat fraction (MRI-PDFF). Advanced fibrosis was diagnosed by liver stiffness greater than 3.63 kPa using magnetic resonance elastography (MRE).RESULTS. The prevalence of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis was significantly higher than that in the control population (17.9% vs. 1.4%, P = 0.0032). Compared with controls, the odds of advanced fibrosis among the first-degree relatives of probands with NAFLD-cirrhosis were odds ratio 14.9 (95% CI, 1.8-126.0, P = 0.0133). Even after multivariable adjustment by age, sex, Hispanic ethnicity, BMI, and diabetes status, the risk of advanced fibrosis remained both statistically and clinically significant (multivariable-adjusted odds ratio 12.5; 95% CI, 1.1-146.1, P = 0.0438).CONCLUSION. Using a well-phenotyped familial cohort, we demonstrated that first-degree relatives of probands with NAFLD-cirrhosis have a 12 times higher risk of advanced fibrosis. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients.