Background Hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) has a high short-term mortality. This study aimed to determine the diagnostic and prognostic role of MER tyrosine kinase (MERTK) in HBV-ACLF patients. Methods Transcriptomics analysis evaluated MERTK expression and function during disease progression. The diagnostic and prognostic significance of MERTK for HBV-ACLF patients were verified by ELISA, the area under the receiver operating characteristic curve (AUROC) analysis, and immunohistochemistry (IHC) of liver tissues. Results MERTK mRNA was highly expressed in the HBV-ACLF compared to the liver cirrhosis (LC), chronic hepatitis B (CHB) and normal controls (NC) groups. Elevated MERTK mRNA predicted poor prognosis for HBV-ACLF at 28/90 days (AUROCs=0.814/0.731). Functional analysis showed MERTK was significantly associated with TLR and inflammatory signaling, and several key biological processes. External validation with 285 plasma subjects confirmed the high diagnostic accuracy of plasma MERTK for HBV-ACLF (AUROC=0.859) and potential prognostic value for 28/90-day mortality rates (AUROC=0.673 and 0.644, respectively). Risk stratification analysis indicated higher mortality risk for patients with plasma MERTK level above the cut-off value. Moreover, IHC staining showed increasing MERTK expression from NC, CHB and LC to HBV-ACLF patients. Conclusions MERTK shows promise as a candidate biomarker for early diagnosis and prognosis of HBV-ACLF.

中文翻译：

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血浆 MERTK 是一种有前途的生物标志物，可用于 HBV 相关慢加急性肝衰竭的诊断和预后

背景乙型肝炎相关的慢性肝衰竭（HBV-ACLF）具有较高的短期死亡率。本研究旨在确定 MER 酪氨酸激酶 (MERTK) 在 HBV-ACLF 患者中的诊断和预后作用。方法 转录组学分析评估疾病进展过程中 MERTK 的表达和功能。通过ELISA、受试者工作特征曲线下面积（AUROC）分析和肝组织免疫组织化学（IHC）验证MERTK对HBV-ACLF患者的诊断和预后意义。结果 与肝硬化（LC）组、慢性乙型肝炎（CHB）组和正常对照（NC）组相比，MERTK mRNA在HBV-ACLF中高表达。MERTK mRNA 升高预示 28/90 天时 HBV-ACLF 的预后不良（AUROC=0.814/0.731）。功能分析显示 MERTK 与 TLR 和炎症信号传导以及几个关键的生物过程显着相关。对 285 名血浆受试者的外部验证证实了血浆 MERTK 对 HBV-ACLF 的高诊断准确性（AUROC = 0.859）以及 28/90 天死亡率的潜在预后价值（AUROC 分别 = 0.673 和 0.644）。风险分层分析表明，血浆 MERTK 水平高于临界值的患者死亡风险较高。此外，IHC 染色显示，从 NC、CHB 和 LC 到 HBV-ACLF 患者，MERTK 表达增加。结论 MERTK 作为 HBV-ACLF 早期诊断和预后的候选生物标志物具有前景。