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代谢组学对酒精性肝病有何作用?

What's in Metabolomics for Alcoholic Liver Disease?

作者信息

Suciu Alina M, Crisan Dana A, Procopet Bogdan D, Radu Corina I, Socaciu Carmen, Tantau Marcel V, Stefanescu Horia O, Grigorescu Mircea

机构信息

3rd Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy;Hepatology Unit, Regional Institute of Gastroenterology and Hepatology Cluj, Cluj-Napoca, Romania.

5th Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

出版信息

J Gastrointestin Liver Dis. 2018 Mar;27(1):51-58. doi: 10.15403/jgld.2014.1121.271.ald.

Abstract

BACKGROUND AND AIMS

Current management of alcoholic liver disease (ALD), especially for alcoholic hepatitis (AH) is still driven by liver biopsy. Therefore, the identification of novel and accurate noninvasive biomarkers for the diagnosis and assessment of severity is important. Metabolomics, because it unravels changes closest to the phenotype, may represent the key for novel biomarkers. The aim of this study was to identify and characterize potential metabolomic biomarkers for diagnosis, staging and severity assessment of ALD.

METHODS

30 consecutive ALD patients and 10 healthy controls were included in this proof-of-concept cross-sectional study. Baseline assessment consisted in evaluation of Maddrey's Discriminant Function, Model for End-Stage Liver Disease (MELD) and ABIC scores as well as ASH-Test (Fibromax) as a surrogate for the confirmatory diagnosis of AH in suggestive clinical and biologic settings. Additionally, SOP metabolomics and lipidomics were performed from serum samples by liquid chromatography mass-spectrometry analysis.

RESULTS

From the 127 and 135 serum/urine candidate metabolites initially identified, only 11/5 metabolites were characteristic for ALD patients. None of them correlated with alcohol intake, and only 5/1 metabolites could differentiate cirrhotic from non-cirrhotic patients. Of those, N-Lauroglycine (NLG) was the best for identifying cirrhosis (100% sensitivity and 90% negative predictive value, NPV) and decatrienoic acid (DTEA) was the best for assessing disease severity (evaluated by ABIC score) with 100% sensitivity and 100% NPV.

CONCLUSION

Due to their high NPV, NLG and DTEA could be used in conjunction in ALD patients to exclude cirrhosis or a severe disease. If further validated, they could become biomarkers for better management and risk assessment in ALD.

摘要

背景与目的

目前酒精性肝病(ALD)的管理,尤其是酒精性肝炎(AH)的管理仍依赖肝活检。因此,识别用于诊断和评估严重程度的新型、准确的非侵入性生物标志物非常重要。代谢组学能够揭示最接近表型的变化,可能是新型生物标志物的关键所在。本研究旨在识别并表征用于ALD诊断、分期及严重程度评估的潜在代谢组学生物标志物。

方法

本概念验证性横断面研究纳入了30例连续的ALD患者和10名健康对照。基线评估包括对Maddrey判别函数、终末期肝病模型(MELD)和ABIC评分的评估,以及在提示性临床和生物学背景下将ASH-Test(Fibromax)作为AH确诊诊断的替代指标。此外,通过液相色谱质谱分析对血清样本进行了标准操作规程代谢组学和脂质组学分析。

结果

在最初鉴定出的127种和135种血清/尿液候选代谢物中,只有11/5种代谢物是ALD患者的特征性代谢物。它们均与酒精摄入量无关,只有5/1种代谢物能够区分肝硬化患者和非肝硬化患者。其中,N-月桂酰甘氨酸(NLG)在识别肝硬化方面表现最佳(灵敏度100%,阴性预测值90%,NPV),而癸三烯酸(DTEA)在评估疾病严重程度(通过ABIC评分评估)方面表现最佳,灵敏度和NPV均为100%。

结论

由于其高NPV,NLG和DTEA可联合用于ALD患者以排除肝硬化或严重疾病。如果进一步验证,它们可能成为改善ALD管理和风险评估的生物标志物。

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