Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Internal Medicine, Division of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Liver Int. 2021 Oct;41(10):2371-2382. doi: 10.1111/liv.14963. Epub 2021 Jun 8.
Trimethylamine-N-oxide (TMAO), a gut microbiota-liver metabolite, has been associated with cardiometabolic disease. However, whether TMAO is associated with nonalcoholic fatty liver disease (NAFLD) and NAFLD-related health outcomes remains unclear. We aimed to investigate the association of TMAO with NAFLD and to assess the extent to which the association of TMAO with all-cause mortality is dependent on the presence of NAFLD in the general population.
We included 5292 participants enrolled in the Prevention of Renal and Vascular End-stage Disease (PREVEND) cohort study. Cox proportional-hazards regression analyses were performed to study the association of TMAO with all-cause mortality in subjects with and without a fatty liver index (FLI) ≥60, which was used as a proxy of NAFLD.
During a median follow-up of 8.2 years, 307 subjects died, of whom 133 were classified with NAFLD. TMAO was positively and independently associated with baseline FLI (Std β 0.08, 95% CI 0.05, 0.11, P < .001). Higher TMAO was associated with increased risk of all-cause mortality in subjects with NAFLD, in crude analysis (hazard ratio [HR] per 1 SD, 2.55, 95% CI 1.60, 4.05, P < .001) and after full adjustment ( HR 1.90, 95% CI 1.18, 3.04, P = .008). Such an association was not present in subjects without NAFLD (crude HR 1.14, 95% CI 0.81, 1.71, P = .39; HR 0.95, 95% CI 0.65, 1.39, P = .78).
This prospective study revealed that plasma concentrations of TMAO were associated with all-cause mortality in subjects with NAFLD, independently of traditional risk factors.
三甲胺 N-氧化物（TMAO）是一种肠道微生物群-肝脏代谢物，与心血管代谢疾病有关。然而，TMAO 是否与非酒精性脂肪性肝病（NAFLD）以及与 NAFLD 相关的健康结局有关尚不清楚。我们旨在研究 TMAO 与 NAFLD 的相关性，并评估 TMAO 与全因死亡率的相关性在普通人群中是否依赖于 NAFLD 的存在。
我们纳入了 5292 名参加预防肾脏和血管终末期疾病（PREVEND）队列研究的参与者。采用 Cox 比例风险回归分析研究 TMAO 与无脂肪性肝病指数（FLI）≥60 的受试者全因死亡率之间的相关性，该指数用作 NAFLD 的替代标志物。
在中位 8.2 年的随访期间，307 名受试者死亡，其中 133 名被诊断为 NAFLD。TMAO 与基线 FLI 呈正相关且独立相关（标准β 0.08，95%CI 0.05，0.11，P<0.001）。在有 NAFLD 的受试者中，TMAO 水平较高与全因死亡率增加相关，在粗分析中（每 1SD 的危险比[HR]，2.55，95%CI 1.60，4.05，P<0.001）和充分调整后（HR 1.90，95%CI 1.18，3.04，P=0.008）。在没有 NAFLD 的受试者中，这种相关性并不存在（粗 HR 1.14，95%CI 0.81，1.71，P=0.39；HR 0.95，95%CI 0.65，1.39，P=0.78）。
这项前瞻性研究表明，TMAO 的血浆浓度与有 NAFLD 的受试者的全因死亡率相关，独立于传统的危险因素。
