Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
Labcorp, 100 Perimeter Park, Morrisville, NC 27560, USA.
Int J Mol Sci. 2024 May 30;25(11):6031. doi: 10.3390/ijms25116031.
Liver transplant recipients (LTRs) have lower long-term survival rates compared with the general population. This underscores the necessity for developing biomarkers to assess post-transplantation mortality. Here we compared plasma trimethylamine-N-oxide (TMAO) levels with those in the general population, investigated its determinants, and interrogated its association with all-cause mortality in stable LTRs. Plasma TMAO was measured in 367 stable LTRs from the TransplantLines cohort (NCT03272841) and in 4837 participants from the population-based PREVEND cohort. TMAO levels were 35% higher in LTRs compared with PREVEND participants (4.3 vs. 3.2 µmol/L, < 0.001). Specifically, TMAO was elevated in LTRs with metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and polycystic liver disease as underlying etiology ( < 0.001 for each). Among LTRs, TMAO levels were independently associated with eGFR (std. β = -0.43, < 0.001) and iron supplementation (std. β = 0.13, = 0.008), and were associated with mortality (29 deaths during 8.6 years follow-up; log-rank test = 0.017; hazard ratio of highest vs. lowest tertile 4.14, = 0.007). In conclusion, plasma TMAO is likely elevated in stable LTRs, with impaired eGFR and iron supplementation as potential contributory factors. Our preliminary findings raise the possibility that plasma TMAO could contribute to increased mortality risk in such patients, but this need to be validated through a series of rigorous and methodical studies.
肝移植受者（LTR）的长期生存率低于普通人群。这突显了开发生物标志物来评估移植后死亡率的必要性。在这里，我们比较了稳定的 LTR 患者和普通人群的血浆三甲胺 N-氧化物（TMAO）水平，研究了其决定因素，并探讨了其与稳定的 LTR 患者全因死亡率的关系。在 TransplantLines 队列（NCT03272841）的 367 名稳定的 LTR 患者和基于人群的 PREVEND 队列的 4837 名参与者中测量了血浆 TMAO。与 PREVEND 参与者相比，LTR 患者的 TMAO 水平高 35%（4.3 对 3.2 µmol/L，<0.001）。具体而言，代谢功能障碍相关脂肪性肝病、酒精相关性肝病和多囊肝病作为潜在病因的 LTR 患者 TMAO 水平升高（每种疾病均<0.001）。在 LTR 中，TMAO 水平与 eGFR（标准β=-0.43，<0.001）和铁补充剂（标准β=0.13，=0.008）独立相关，并且与死亡率相关（8.6 年随访期间有 29 例死亡；对数秩检验=0.017；最高与最低三分位比的危险比为 4.14，=0.007）。总之，稳定的 LTR 患者的血浆 TMAO 水平可能升高，eGFR 受损和铁补充可能是潜在的促成因素。我们的初步发现提出了这样一种可能性，即血浆 TMAO 可能导致此类患者的死亡率风险增加，但这需要通过一系列严格和系统的研究来验证。
