纤维化-4指数对脓毒症患者院内死亡率的预测价值：来自MIMIC-IV和eICU数据库的证据

摘要(中文译文)

脓毒症诱导的肝功能障碍显著导致不良临床结局。尽管Fibrosis-4（FIB-4）指数已确立用于评估慢性肝纤维化，但其作为急性脓毒症死亡率预后标志物的价值——尤其是在无既往肝病的患者中——仍不明确。我们旨在利用两个大型多中心数据库评估FIB-4在脓毒症中的预测价值。我们使用两个大型重症监护数据库开展了一项多中心回顾性研究：MIMIC-IV（n = 13,983）和eICU（n = 9,976）。脓毒症依据既定临床标准定义。缺失值采用多重插补处理以保持数据完整性。通过基于结局的分层确定FIB-4的最佳截断值（1.25）。据此将患者分为高FIB-4组和低FIB-4组。我们应用限制性立方样条（RCS）模型评估非线性趋势，随后采用加权Cox回归确定与院内死亡率的独立关联。Kaplan-Meier生存曲线评估事件发生时间差异，同时通过亚组分析、ROC曲线和敏感性分析探讨效应一致性及潜在生物学通路。在来自MIMIC-IV和eICU数据库的23,959例脓毒症患者中，FIB-4水平升高与院内死亡率显著相关（P < 0.001）。FIB-4指数 > 1.25为死亡的独立危险因素（校正HR：1.38-1.55），且在预后判别方面优于传统SOFA和APACHE评分。Kaplan-Meier曲线显示高FIB-4组生存率显著降低。重要的是，排除已知肝病、疑似MASLD或心脏相关入院患者的敏感性分析证实了这些发现的稳健性。FIB-4指数是脓毒症患者院内死亡率的稳健、独立预后标志物，在预测准确性方面优于SOFA和APACHE II等传统评分。至关重要的是，即使在排除既往肝病或急性心源性肝淤血患者后，其预后价值仍然存在，提示其反映的是更广泛的脓毒症诱导的生理紊乱，而非仅为基础肝纤维化。鉴于其简便性及依赖常规可获取的实验室参数，FIB-4为重症监护环境中的早期风险分层提供了一种实用、可及的工具。

Abstract

Sepsis-induced hepatic dysfunction contributes significantly to poor clinical outcomes. Although the Fibrosis-4 (FIB-4) index is established for assessing chronic liver fibrosis, its utility as a prognostic marker for acute sepsis mortality-particularly in patients without pre-existing liver disease-remains unclear. We aimed to evaluate the predictive value of FIB-4 in sepsis using two large, multi-center databases.We conducted a multicenter retrospective study using two large critical care databases: MIMIC-IV (n = 13,983) and eICU (n = 9,976). Sepsis was defined based on established clinical criteria. Missing values were handled using multiple imputation to preserve data integrity. The optimal FIB-4 cutoff points were determined via outcome-based stratification (1.25). Patients were categorized into high and low FIB-4 groups accordingly. We applied restricted cubic spline (RCS) modeling to evaluate nonlinear trends, followed by weighted Cox regression to determine independent associations with in-hospital mortality. Kaplan-Meier survival curves assessed time-to-event differences, while subgroup analyses, ROC curves, and sensitivity analyses explored effect consistency and underlying biological pathways. Across 23,959 sepsis patients from the MIMIC-IV and eICU databases, elevated FIB-4 levels were significantly associated with in-hospital mortality (P < 0.001). An FIB-4 index > 1.25 served as an independent risk factor for mortality (adjusted HRs: 1.38-1.55) and outperformed traditional SOFA and APACHE scores in prognostic discrimination. Kaplan-Meier curves showed significantly reduced survival in the high FIB-4 group. Importantly, sensitivity analyses excluding patients with known liver disease, suspected MASLD, or cardiac admissions confirmed the robustness of these findings. The FIB-4 index serves as a robust, independent prognostic marker for in-hospital mortality in sepsis patients, outperforming traditional scores such as SOFA and APACHE II in predictive accuracy. Crucially, its prognostic value persists even after excluding patients with pre-existing liver disease or acute cardiogenic hepatic congestion, suggesting it reflects broader sepsis-induced physiological derangements rather than solely baseline hepatic fibrosis. Given its simplicity and reliance on routinely available laboratory parameters, FIB-4 offers a practical, accessible tool for early risk stratification in the intensive care setting.

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