Elevated trimethylamine-N-oxide (TMAO) is associated with poor prognosis in primary sclerosing cholangitis patients with normal liver function
Elevated trimethylamine-N-oxide (TMAO) is associated with poor prognosis in primary sclerosing cholangitis patients with normal liver function
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DOI：
10.1177/2050640616663453
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发表时间：
2017-06-01
影响因子：
6
通讯作者：
Hov, Johannes Roksund
中科院分区：
文献类型：
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作者：
Kummen, Martin;Vesterhus, Mette;Hov, Johannes Roksund
背景资料：目的：探讨原发性硬化性胆管炎（PSC）患者血清中氧化三甲胺（TMAO）的含量与PSC的关系及其临床特点。方法：对305例PSC患者、90例溃疡性结肠炎患者及99例健康对照者进行血清TMAO检测。结果：PSC患者血清中TMAO含量明显高于正常对照组（P < 0.01）。在肝功能正常的PSC患者（n = 197）中，在随访期间达到肝移植或死亡的患者的TMAO高于未达到肝移植或死亡的患者，最佳TMAO截止值为4.1 μ M（AUC = 0.64，p< 0.001）。具有高TMAO（>4.1 μ M，n = 77）的PSC患者比具有低TMAO的患者表现出更短的无移植存活（n = 120，对数秩检验：p< 0.0001）。高TMAO（> 4.1 μ M）与无移植存活率降低（HR 1.87，p = 0.011）相关，与马约风险评分无关（HR 1.74，p< 0.001）。总体而言，与溃疡性结肠炎和健康对照相比，PSC患者表现出TMAO值降低，主要由肝功能降低（INR> 1.2）的PSC患者引起，表明三甲胺氧化为TMAO受损。患有和不患有炎症性肠道疾病的PSC患者的TMAO水平相似。结论：在肝功能正常的PSC患者中，TMAO升高与较短的无移植生存期相关，可能反映了饮食与肠道微生物群相互作用引起的临床相关代谢变化。
Background: Trimethylamine-N-oxide (TMAO) is produced in the liver from trimethylamine, which is exclusively generated by gut bacteria.Objective: The objective of this article is to investigate the relationship between TMAO and primary sclerosing cholangitis (PSC) and its clinical characteristics.Methods: Serum TMAO was measured in 305 PSC patients, 90 ulcerative colitis patients and 99 healthy controls.Results: In PSC patients with normal liver function (n = 197), TMAO was higher in patients reaching liver transplantation or death during follow-up than those who did not, with an optimal TMAO cut-off of 4.1 mu M (AUC = 0.64, p< 0.001). PSC patients with high TMAO (>4.1 mu M, n = 77) exhibited shorter transplantation-free survival than patients with low TMAO (n = 120, log-rank test: p< 0.0001). High TMAO (> 4.1 mu M) was associated with reduced transplantation-free survival (HR 1.87, p = 0.011), independently of the Mayo risk score (HR 1.74, p< 0.001). Overall, PSC patients demonstrated reduced TMAO values compared with ulcerative colitis and healthy controls, mainly caused by PSC patients with reduced liver function (INR> 1.2), suggesting impaired oxidation of trimethylamine to TMAO. PSC patients with and without inflammatory bowel disease had similar TMAO levels.Conclusion: In PSC patients with normal liver function, elevated TMAO was associated with shorter transplantation-free survival, potentially reflecting clinically relevant metabolic changes resulting from dietary interactions with the gut microbiota.