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透明质酸是同种异体移植物功能障碍的生物标志物,并可预测肝移植后1年移植物丢失情况。

Hyaluronic Acid Is a Biomarker for Allograft Dysfunction and Predicts 1-Year Graft Loss After Liver Transplantation.

作者信息

Rostved A A, Ostrowski S R, Peters L, Lundgren J D, Hillingsø J, Johansson P I, Rasmussen A

机构信息

Department of Surgical Gastroenterology and Transplantation, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

出版信息

Transplant Proc. 2018 Dec;50(10):3635-3643. doi: 10.1016/j.transproceed.2018.09.018. Epub 2018 Sep 11.

Abstract

BACKGROUND

Allograft dysfunction after liver transplantation has a profound impact on the risks of death and retransplantation within the first year. We tested whether elevated hyaluronic acid (HA; a glycosaminoglycan cleared by hepatic sinusoidal endothelium) levels may predict excess risk of graft loss.

METHODS

This was a retrospective single-center prognostic cohort study. Patients with either a plasma sample before transplantation, an early post-transplantation sample nearest day 30 (range 10-89 d, 80% within days 15-60), or both were included. Plasma HA was measured with the use of enzyme-linked immunosorbent assays. The primary end point was 1-year graft loss (all-cause mortality and retransplantation). A secondary end point was biliary stricture.

RESULTS

In this study, 169 of 196 patients who received a liver transplant in the study period were included. Pre-transplantation HA (n = 152) did not predict graft loss. Post-transplantation HA (n = 124) was higher among patients with graft loss (median, 177 μg/L [interquartile range (IQR), 89-465] vs 54 μg/L [IQR 37-93]) and was a strong predictor of this outcome (hazard ratio per 50 μg/L, 1.24 [95% confidence interval [CI], 1.14-1.34]). The discriminatory ability of HA was high (area under the receiver operating characteristic curve, 0.86 [95% CI, 0.77-0.94]) and noninferior to other liver function tests. When adjusted for known risk factors of graft loss, HA remained an independent predictor of graft loss.

CONCLUSIONS

High post-transplantation plasma HA level was a strong predictor of 1-year all-cause mortality and retransplantation, whereas pre-transplantation levels were not, despite variety in the time span of blood sampling. Prospective studies are warranted to assess the utility of HA in liver transplantation.

摘要

背景

肝移植后的同种异体移植物功能障碍对第一年的死亡风险和再次移植有深远影响。我们测试了透明质酸(HA;一种由肝窦内皮清除的糖胺聚糖)水平升高是否可预测移植物丢失的额外风险。

方法

这是一项回顾性单中心预后队列研究。纳入了在移植前有血浆样本、移植后最接近第30天(范围10 - 89天,80%在15 - 60天内)的早期样本或两者皆有的患者。使用酶联免疫吸附测定法测量血浆HA。主要终点是1年移植物丢失(全因死亡率和再次移植)。次要终点是胆道狭窄。

结果

在本研究中,纳入了研究期间接受肝移植的196例患者中的169例。移植前HA(n = 152)不能预测移植物丢失。移植物丢失患者的移植后HA(n = 124)较高(中位数,177 μg/L [四分位间距(IQR),89 - 465] 对比54 μg/L [IQR 37 - 93]),并且是这一结果的有力预测指标(每50 μg/L的风险比,1.24 [95%置信区间(CI),1.14 - 1.34])。HA的鉴别能力较高(受试者工作特征曲线下面积,0.86 [95% CI,0.77 - 0.94]),且不劣于其他肝功能检查。在对已知的移植物丢失风险因素进行校正后,HA仍然是移植物丢失的独立预测指标。

结论

尽管采血时间跨度不同,但移植后血浆HA水平高是1年全因死亡率和再次移植的有力预测指标,而移植前水平则不是。有必要进行前瞻性研究以评估HA在肝移植中的效用。

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