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血浆脂肪酸脂质组与肝移植中的肝硬化预后及移植物损伤相关。

Plasma fatty acid lipidome is associated with cirrhosis prognosis and graft damage in liver transplantation.

作者信息

Ginanni Corradini Stefano, Zerbinati Chiara, Maldarelli Federica, Palmaccio Giuseppina, Parlati Lucia, Bottaccioli Anna Giulia, Molinaro Antonio, Poli Edoardo, Boaz Mona, Serviddio Gaetano, Mennini Gianluca, Corsi Alessandro, Bianco Paolo, Rossi Massimo, Iuliano Luigi

机构信息

From the Department of Clinical Medicine, Gastroenterology Division (SGC, FM, LP, AM, and EP), the Departments of General Surgery "Paride Stefanini" (GM and MR), and the Department of Molecular Medicine (AC and PB), "Sapienza" University of Rome, Rome, Italy; the Department of Medical-Surgical Sciences and Biotechnology, Vascular Biology and Mass Spectrometry Laboratory, "Sapienza" University of Rome, Latina, Italy (CZ, GP, AGB, and LI); the School of Health Sciences, Department of Nutrition, Ariel University, Ariel, Israel (MB); and the Department of Medical Sciences, Università of Foggia, Foggia, Italy (GS).

出版信息

Am J Clin Nutr. 2014 Aug;100(2):600-8. doi: 10.3945/ajcn.113.074427. Epub 2014 Jun 25.

Abstract

BACKGROUND

Knowledge regarding the plasma fatty acid (FA) pattern in patients with liver cirrhosis is fragmentary.

OBJECTIVE

We evaluated plasma FA lipidome and its association with the prognosis of cirrhosis and severity of liver graft damage after transplantation.

DESIGN

In this observational study, plasma FA lipidome was investigated in 51 cirrhotic patients before liver transplantation and in 90 age- and sex-matched healthy control subjects. In addition, we studied ischemia-reperfusion damage in the liver of 38 patients for whom a graft biopsy was available at transplantation. With the use of logistic regression, we modeled the presence of cirrhosis, the dichotomized model for end-stage liver disease score below and above the median, and the presence of severe liver graft ischemia-reperfusion damage.

RESULTS

The FA pattern was markedly altered in cirrhotic patients, who showed, compared with healthy controls, higher monounsaturated FAs, lower n-6 and n-3 polyunsaturated FAs, and undetectable cerotic acid. Plasma di-homo-γ-linolenic acid was independently associated with the presence of cirrhosis (OR: 0.026; 95% CI: 0.004, 0.196; P < 0.0001), severity of its prognosis (OR: 0.041; 95% CI:0.005, 0.376; P = 0.006), postreperfusion graft hepatocellular necrosis (OR: 0.921; 95% CI: 0.851, 0.997; P = 0.043), and sinusoidal congestion (OR: 0.954; 95% CI: 0.912, 0.998; P = 0.039). Associations of di-homo-γ-linolenic acid with the presence of cirrhosis and severity of its prognosis were confirmed also after false discovery rate correction.

CONCLUSIONS

Cerotic and di-homo-γ-linolenic acids may serve as markers of disease and prognosis in liver cirrhosis. Dietary supplementation with di-homo-γ-linolenic acid could be a reasonable interventional strategy to delay disease progression in liver cirrhosis.

摘要

背景

关于肝硬化患者血浆脂肪酸(FA)模式的知识尚不完整。

目的

我们评估了血浆FA脂质组及其与肝硬化预后和移植后肝移植损伤严重程度的关联。

设计

在这项观察性研究中,对51例肝移植前的肝硬化患者和90例年龄及性别匹配的健康对照者的血浆FA脂质组进行了研究。此外,我们研究了38例在移植时可获得移植肝活检的患者肝脏的缺血再灌注损伤。使用逻辑回归,我们对肝硬化的存在、终末期肝病评分中位数上下的二分模型以及严重肝移植缺血再灌注损伤的存在进行了建模。

结果

肝硬化患者的FA模式明显改变,与健康对照相比,其单不饱和FA含量更高,n-6和n-3多不饱和FA含量更低,且未检测到蜡酸。血浆二高-γ-亚麻酸与肝硬化的存在(比值比:0.026;95%置信区间:0.004,0.196;P<0.0001)、其预后的严重程度(比值比:0.041;95%置信区间:0.005,0.376;P = 0.006)、再灌注后移植肝细胞坏死(比值比:0.921;95%置信区间:0.851,0.997;P = 0.043)以及窦状隙充血(比值比:0.954;95%置信区间:0.912,0.998;P = 0.039)独立相关。在进行错误发现率校正后,二高-γ-亚麻酸与肝硬化的存在及其预后严重程度的关联也得到了证实。

结论

蜡酸和二高-γ-亚麻酸可能作为肝硬化疾病和预后的标志物。补充二高-γ-亚麻酸饮食可能是延缓肝硬化疾病进展的合理干预策略。

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