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代谢组学生物标志物与原发性胆汁性胆管炎或原发性硬化性胆管炎所致肝硬化患者的死亡率相关。

Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis.

作者信息

Mindikoglu Ayse L, Coarfa Cristian, Opekun Antone R, Shah Vijay H, Arab Juan P, Lazaridis Konstantinos N, Putluri Nagireddy, Ambati Chandrashekar R, Robertson Matthew J, Devaraj Sridevi, Jalal Prasun K, Rana Abbas, Goss John A, Dowling Thomas C, Weir Matthew R, Seliger Stephen L, Raufman Jean-Pierre, Bernard David W, Vierling John M

机构信息

Margaret M & Albert B Alkek Department of Medicine, Section of Gastroenterology & Hepatology, Baylor College of Medicine, Houston, TX, USA.

Michael E DeBakey Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA.

出版信息

Future Sci OA. 2019 Dec 17;6(2):FSO441. doi: 10.2144/fsoa-2019-0124.

Abstract

AIM

To assess the ability of signature metabolites alone, or in combination with the model for end-stage liver disease-Na (MELD-Na) score to predict mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis.

MATERIALS & METHODS: Plasma metabolites were detected using ultrahigh-performance liquid chromatography/tandem mass spectrometry in 39 patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis. Mortality was predicted using Cox proportional hazards regression and time-dependent receiver operating characteristic curve analyses.

RESULTS

The top five metabolites with significantly greater accuracy than the MELD-Na score (area under the receiver operating characteristic curve [AUROC] = 0.7591) to predict 1-year mortality were myo-inositol (AUROC = 0.9537), N-acetylputrescine (AUROC = 0.9018), trans-aconitate (AUROC = 0.8880), erythronate (AUROC = 0.8345) and N6-carbamoylthreonyladenosine (AUROC = 0.8055). Several combined MELD-Na-metabolite models increased the accuracy of predicted 1-year mortality substantially (AUROC increased from 0.7591 up to 0.9392).

CONCLUSION

Plasma metabolites have the potential to enhance the accuracy of mortality predictions, minimize underestimates of mortality in patients with cirrhosis and low MELD-Na scores, and promote equitable allocation of donor livers.

摘要

目的

评估单独使用特征性代谢物或联合终末期肝病钠模型(MELD-Na)评分预测原发性胆汁性胆管炎或原发性硬化性胆管炎所致肝硬化患者死亡率的能力。

材料与方法

采用超高效液相色谱/串联质谱法检测39例原发性胆汁性胆管炎或原发性硬化性胆管炎所致肝硬化患者的血浆代谢物。使用Cox比例风险回归和时间依赖性受试者工作特征曲线分析预测死亡率。

结果

预测1年死亡率时,准确性显著高于MELD-Na评分(受试者工作特征曲线下面积[AUROC]=0.7591)的前五种代谢物为肌醇(AUROC=0.9537)、N-乙酰腐胺(AUROC=0.9018)、反乌头酸(AUROC=0.8880)、赤藓糖酸(AUROC=0.8345)和N6-氨甲酰苏氨酰腺苷(AUROC=0.8055)。几种MELD-Na-代谢物联合模型显著提高了预测1年死亡率的准确性(AUROC从0.7591提高到0.9392)。

结论

血浆代谢物有可能提高死亡率预测的准确性,最大限度地减少对肝硬化且MELD-Na评分低的患者死亡率的低估,并促进供体肝脏的公平分配。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db6a/6997913/9e7cef40400d/fsoa-06-441-g1.jpg

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