BACKGROUND AND AIMS Patients with acetaminophen-induced acute liver failure (APAP-ALF) are more likely to die while on the liver transplant waiting list than those with other causes of ALF. Therefore, there is an urgent need for prognostic biomarkers that can predict the need for liver transplantation early after an APAP overdose. APPROACH AND RESULTS We evaluated the prognostic potential of plasma chemokine CXCL14 concentrations in APAP overdose patients (n=50) and found CXCL14 is significantly higher in non-surviving patients compared to survivors with ALF (p<0.001). Logistic regression and AUROC analyses revealed that CXCL14 outperformed the MELD score better discriminating between non-survivors and survivors. We validated these data in a separate cohort of samples obtained from the Acute Liver Failure Study Group (n=80), where MELD and CXCL14 had similar AUC (0.778), but CXCL14 demonstrated higher specificity (81.2 vs. 52.6) and positive predictive value (82.4 vs. 65.4) for death or need for liver transplantation. Next, combining the patient cohorts and using a machine learning training/testing scheme to mimic the clinic scenario, we found that CXCL14 outperformed MELD based on AUC (0.821 vs. 0.787), however combining MELD and CXCL14 yielded the best AUC (0.860). CONCLUSIONS We find in two independent cohorts of APAP overdose patients that circulating CXCL14 concentration is a novel early prognostic biomarker for poor outcome which may aid in guiding decisions regarding patient management. Moreover, our findings reveal that CXCL14 performs best when measured soon after patient presentation to the clinic, highlighting its importance for early warning of poor prognosis.

中文翻译：

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趋化因子 CXCL14 是一种新型早期预后生物标志物，可用于治疗对乙酰氨基酚引起的急性肝衰竭的不良预后。

背景和目的 与其他原因引起的 ALF 患者相比，对乙酰氨基酚诱发的急性肝衰竭 (APAP-ALF) 患者在肝移植等待名单上更有可能死亡。因此，迫切需要能够预测 APAP 过量后早期是否需要肝移植的预后生物标志物。方法和结果 我们评估了 APAP 过量患者 (n=50) 中血浆趋化因子 CXCL14 浓度的预后潜力，发现与 ALF 幸存者相比，非存活患者中的 CXCL14 显着较高 (p<0.001)。Logistic 回归和 AUROC 分析显示，CXCL14 在区分非幸存者和幸存者方面优于 MELD 评分。我们在从急性肝衰竭研究组 (n=80) 获得的单独样本队列中验证了这些数据，其中 MELD 和 CXCL14 具有相似的 AUC (0.778)，但 CXCL14 表现出更高的特异性（81.2 比 52.6）和阳性预测值（82.4 vs. 65.4）死亡或需要肝移植。接下来，结合患者队列并使用机器学习训练/测试方案来模拟临床场景，我们发现基于 AUC（0.821 与 0.787），CXCL14 优于 MELD，但是将 MELD 和 CXCL14 结合产生了最佳 AUC（0.860）。结论 我们在两个独立的 APAP 过量患者队列中发现，循环 CXCL14 浓度是一种新的预后不良的早期预后生物标志物，可能有助于指导患者管理决策。此外，我们的研究结果表明，在患者就诊后不久进行测量时，CXCL14 表现最佳，这凸显了其对于不良预后早期预警的重要性。