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活体肝移植供体和受体术前及术后肝脏再生相关细胞因子谱

Liver Regeneration-Related Cytokine Profiles in Donors and Recipients Before and After Living-Donor Liver Transplant.

作者信息

Fingas Christian D, Beste Mechthild, Penndorf Volker, Sydor Svenja, Nadalin Silvio, Bechmann Lars, Paul Andreas, Gerken Guido, Canbay Ali, Jochum Christoph

机构信息

From the Department of General, Visceral and Transplantation Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany.

出版信息

Exp Clin Transplant. 2018 Oct;16(5):554-561. doi: 10.6002/ect.2017.0039. Epub 2018 Apr 9.

Abstract

OBJECTIVES

The liver's capability to completely regenerate after injury is a unique phenomenon in which cytokines are of particular interest. Here, we aimed to assess the release patterns and prognostic relevance of liver regeneration-related cytokines in the setting of living-donor liver transplant.

MATERIALS AND METHODS

Eleven cytokines related to liver regeneration (hepatocyte growth factor, interleukin 6, insulin-like growth factor-1, tumor necrosis factor alpha, transforming growth factor beta, granulocyte colony-stimulating factor, stem cell factor, chemokine (C-X-C motif) ligand 12, angiogenin, fibroblast growth factor-2, and vascular endothelial growth factor) were compared in 13 living-donor liver transplant recipients and their corresponding donors before and daily (10 days) after transplant. Patients and donors were stratified by clinical outcomes (early graft loss within 4 weeks after transplant vs beneficial outcome).

RESULTS

Most cytokines tested (especially tumor necrosis factor alpha and stem cell factor) were elevated in recipients versus donors. Many cytokines were also increased in recipients with graft loss (especially CXCL12) and in donors of recipients with beneficial outcomes (especially fibroblast growth factor 2). Fibroblast growth factor 2 levels were also correlated positively with serum gamma-glutamyltransferase, and higher preoperative concentrations in donors were associated with recipients having beneficial outcomes, indicating an improved regenerative capacity. In contrast, elevated CXCL12 levels in recipients before and after LDLT predicted graft loss and were linked to ongoing liver damage.

CONCLUSIONS

In living-donor liver transplant, there are distinct differences between donors and recipients regarding the release of liver regeneration-related cytokines. Moreover, fibroblast growth factor 2 and CXCL12 may be of diagnostic value in a complementary way to describe or even predict the possible outcomes after transplant. These results may be of clinical interest not only for living-donor liver transplant but also for acute liver failure.

摘要

目的

肝脏在损伤后完全再生的能力是一种独特现象,细胞因子在其中备受关注。在此,我们旨在评估活体肝移植中肝脏再生相关细胞因子的释放模式及其预后相关性。

材料与方法

比较了13例活体肝移植受者及其相应供者在移植前及移植后每日(共10天)11种与肝脏再生相关的细胞因子(肝细胞生长因子、白细胞介素6、胰岛素样生长因子-1、肿瘤坏死因子α、转化生长因子β、粒细胞集落刺激因子、干细胞因子、趋化因子(C-X-C基序)配体12、血管生成素、成纤维细胞生长因子-2和血管内皮生长因子)。根据临床结局(移植后4周内早期移植物丢失与有益结局)对患者和供者进行分层。

结果

与供者相比,大多数检测的细胞因子(尤其是肿瘤坏死因子α和干细胞因子)在受者中升高。许多细胞因子在移植物丢失的受者(尤其是CXCL12)和有益结局受者的供者(尤其是成纤维细胞生长因子2)中也升高。成纤维细胞生长因子2水平也与血清γ-谷氨酰转移酶呈正相关,供者术前较高浓度与受者有益结局相关,表明再生能力增强。相反,活体肝移植前后受者中CXCL12水平升高预示移植物丢失,并与持续的肝损伤有关。

结论

在活体肝移植中,供者和受者在肝脏再生相关细胞因子的释放方面存在明显差异。此外,成纤维细胞生长因子2和CXCL12可能具有互补的诊断价值,用于描述甚至预测移植后的可能结局。这些结果不仅对活体肝移植,而且对急性肝衰竭可能具有临床意义。

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