Background & Aims

Primary nonfunction (PNF) is a rare complication after liver transplantation that requires urgent retransplantation. PNF is associated with livers from extended criteria donors. Clinical and biochemical factors have not been identified that reliably associate with graft function after liver transplantation. Serum patterns of N-glycans associate with changes in the liver. We analyzed perfusate from grafted liver to identify protein glycosylation patterns associated with PNF.

Methods

We performed a prospective study of consecutive patients who underwent liver transplantation (66 patients, from 1 center, in the derivation set, and 56 patients, from 2 centers, in the validation set) in Belgium, from October 1, 2011, through April 30, 2017. All donor grafts were transported using cold static storage, and perfusate samples were collected from the livers by flushing of hepatic veins before transplantation. Protein-linked N-glycans were isolated from perfusate samples and analyzed with a multicapillary electrophoresis-based ABI3130 sequencer.

We compared glycan patterns between patients with vs without PNF of transplanted livers. PNF was defined as the need for urgent retransplantation when a graft had no evidence of function, after exclusion of other causes, such as hepatic artery thrombosis or acute cellular rejection.

Results

The relative abundance of a single glycan, agalacto core-alpha-1,6-fucosylated biantennary glycan (NGA2F) was significantly increased in perfusate of livers given to 4 patients who developed PNF after liver transplantation compared with livers given to patients who did not develop PNF. Level of NGA2F identified patients with PNF with 100% accuracy. This glycomarker was the only factor associated with PNF in multivariate analysis in the derivation and the validation sets (P < .0001).

Conclusions

In an analysis of patients who underwent liver transplantation, we associated graft perfusate level of glycan NGA2F present on perfusate proteins with development of PNF with 100% accuracy, and validated this finding in a separate cohort of patients. This biomarker might be used to assess grafts before transplantation, especially when high-risk organs are under consideration.

中文翻译：

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肝灌注液的糖液模式在移植前与原发性无功能相关

背景与目标

原发性非功能性（PNF）是肝移植后罕见的并发症，需要紧急再移植。PNF与来自扩展标准供体的肝脏相关。尚未确定与肝移植后的移植物功能可靠相关的临床和生化因素。N-聚糖的血清模式与肝脏变化有关。我们分析了移植肝的灌注液，以确定与PNF相关的蛋白质糖基化模式。

方法

我们对比利时自2011年10月1日至4月30日接受肝移植的连续患者（在衍生组中的1个中心有66例患者，在验证组中的2个中心中有56例患者）进行了前瞻性研究。 ，2017年。所有供体移植物均使用静态冷库运输，并在移植前通过冲洗肝静脉从肝脏中收集灌注液样品。从灌流液样品中分离出与蛋白质连接的N-聚糖，并使用基于多毛细管电泳的ABI3130测序仪进行分析。

我们比较了有和没有PNF的移植肝患者之间的糖模式。PNF被定义为在排除其他原因（例如肝动脉血栓形成或急性细胞排斥）后，当移植物无功能证据时，需要进行紧急再移植。

结果

与4例未移植肝的患者相比，在4例肝移植后发生PNF的患者的肝脏灌注液中，单聚糖，半乳糖核心-α-1,6-岩藻糖基化双触角聚糖（NGA2F）的相对丰度显着增加。 PNF。NGA2F的水平以100％的准确性确定了PNF患者。该糖标记物是派生和验证集中多变量分析中与PNF相关的唯一因素（P <.0001）。

结论

在对接受肝移植的患者进行的分析中，我们将灌流蛋白上存在的聚糖NGA2F的嫁接灌流水平与PNF的发生以100％的准确性相关联，并在另一组患者中验证了这一发现。该生物标志物可用于评估移植前的移植物，特别是在考虑高危器官时。