Institute of Liver Studies, King's College Hospital, London, UK.
Division of Gastroenterology and Department of Critical Care Medicine, University of Alberta, Edmonton, Canada.
J Hepatol. 2021 Aug;75(2):424-434. doi: 10.1016/j.jhep.2021.03.013. Epub 2021 Apr 12.
BACKGROUND & AIMS: Acetaminophen (APAP)-induced acute liver failure (ALF) remains the most common cause of ALF in the Western world. Conventional prognostic models, utilising markers of liver injury and organ failure, lack sensitivity for mortality prediction. We previously identified a microRNA signature that is associated with successful regeneration post-auxiliary liver transplant and with recovery from APAP-ALF. Herein, we aimed to use this microRNA signature to develop outcome prediction models for APAP-ALF.
We undertook a nested, case-control study using serum samples from 194 patients with APAP-ALF enrolled in the US ALF Study Group registry (1998-2014) at early (day 1-2) and late (day 3-5) time-points. A microRNA qPCR panel of 22 microRNAs was utilised to assess microRNA expression at both time-points. Multiple logistic regression was used to develop models which were compared to conventional prognostic models using the DeLong method.
Individual microRNAs confer limited prognostic value when utilised in isolation. However, incorporating them within microRNA-based outcome prediction models increases their clinical utility. Our early time-point model (AUC = 0.78, 95% CI 0.71-0.84) contained a microRNA signature associated with liver regeneration and our late time-point model (AUC = 0.83, 95% CI 0.76-0.89) contained a microRNA signature associated with cell-death. Both models were enhanced when combined with model for end-stage liver disease (MELD) score and vasopressor use and both outperformed the King's College criteria. The early time-point model combined with clinical parameters outperformed the ALF Study Group prognostic index and the MELD score.
Our findings demonstrate that a regeneration-linked microRNA signature combined with readily available clinical parameters can outperform existing prognostic models for ALF in identifying patients with poor prognosis who may benefit from transplantation.
While acute liver failure can be reversible, some patients will die without a liver transplant. We show that blood test markers that measure the potential for liver recovery may help improve identification of patients unlikely to survive acute liver failure who may benefit from a liver transplant.
对乙酰氨基酚（APAP）诱导的急性肝衰竭（ALF）仍然是西方世界 ALF 的最常见原因。利用肝损伤和器官衰竭标志物的传统预后模型缺乏对死亡率预测的敏感性。我们之前确定了一个与辅助肝移植后成功再生以及从 APAP-ALF 中恢复相关的 microRNA 特征。在此，我们旨在使用该 microRNA 特征为 APAP-ALF 开发预后预测模型。
我们对 194 名接受 APAP-ALF 治疗的患者的血清样本进行了嵌套病例对照研究，这些患者于 1998-2014 年期间在美国 ALF 研究组注册中心（US ALF Study Group registry）接受治疗，时间点分别为早期（第 1-2 天）和晚期（第 3-5 天）。利用 microRNA qPCR 面板对 22 个 microRNA 进行检测，以评估两个时间点的 microRNA 表达情况。使用多变量逻辑回归建立模型，并使用 DeLong 方法与传统预后模型进行比较。
单独使用单个 microRNA 时，其预后价值有限。然而，将它们纳入基于 microRNA 的预后预测模型中可以提高其临床应用价值。我们的早期时间点模型（AUC=0.78，95%CI 0.71-0.84）包含与肝再生相关的 microRNA 特征，而我们的晚期时间点模型（AUC=0.83，95%CI 0.76-0.89）包含与细胞死亡相关的 microRNA 特征。当与终末期肝病模型（MELD）评分和血管加压药的使用结合使用时，这两个模型都得到了增强，并且都优于 King's College 标准。结合临床参数的早期时间点模型优于 ALF 研究组预后指数和 MELD 评分。
我们的研究结果表明，与肝再生相关的 microRNA 特征与现有临床参数相结合，可以提高现有 ALF 预后模型识别预后不良的患者的能力，这些患者可能受益于肝移植。
虽然急性肝衰竭可能是可逆的，但有些患者如果没有进行肝移植将会死亡。我们的研究表明，血液测试标记物可以测量肝恢复的潜力，这可能有助于改善对那些不太可能存活急性肝衰竭但可能受益于肝移植的患者的识别。
