Background & Aims: Non-invasive biomarkers provide prognostic information for the development of major adverse liver outcomes (MALO) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the predictive value of longitudinal biomarker measurements has not been evaluated. We assessed whether changes in biomarkers could predict incident MALO in MASLD. Approach and Results: We analyzed a cohort of 1,260 patients (71.7% on biopsy) with non-cirrhotic MASLD between 1974 and 2019. Data at baseline and follow-up visits were obtained from medical charts. MALO was determined through medical charts and linkage to national registers until the end of 2020. A joint modeling approach was used to quantify the associations between the trajectory of biomarkers with the risk of MALO. MASLD was diagnosed at median age of 52 years (IQR: 39-60), and 59% were male. During a median follow-up of 12.2 years, 111 (8.8%) patients developed MALO. The joint modeling showed that an elevated FIB-4 (HR 2.60, 95% CI 1.89-3.50), AST (HR 2.69, 95% CI 2.57-3.05), and lower platelet count (HR 0.93, 95% CI 0.90-0.97) at any time point were associated with an increased risk of MALO, whereas the rate of change in these biomarkers had no association with this risk. Conclusions: In addition to baseline measurements of non-invasive biomarkers such as FIB-4 and AST, and platelets taken at MASLD diagnosis, monitoring their values over time is important, as the latest value of these biomarkers is closely associated with the risk of future MALO. The rate of change may not be as important.

中文翻译：

---

非肝硬化代谢功能障碍相关脂肪肝病患者的纵向生物标志物与主要不良肝脏结局之间的关联


背景和目的：非侵入性生物标志物为代谢功能障碍相关脂肪肝病（MASLD）患者发生主要不良肝脏结局（MALO）提供预后信息，但纵向生物标志物测量的预测价值尚未得到评估。我们评估了生物标志物的变化是否可以预测 MASLD 中的 MALO 事件。方法和结果：我们分析了 1974 年至 2019 年间 1,260 名非肝硬化 MASLD 患者（71.7% 接受活检）的队列。基线和随访数据来自医疗图表。截至 2020 年底，MALO 是通过医疗图表和与国家登记册的链接确定的。联合建模方法用于量化生物标志物轨迹与 MALO 风险之间的关联。 MASLD 的中位年龄为 52 岁（IQR：39-60），其中 59% 为男性。在中位随访 12.2 年期间，111 名患者 (8.8%) 出现 MALO。联合模型显示 FIB-4 升高（HR 2.60，95% CI 1.89-3.50）、AST（HR 2.69，95% CI 2.57-3.05），血小板计数降低（HR 0.93，95% CI 0.90-0.97）在任何时间点都与 MALO 风险增加相关，而这些生物标志物的变化率与该风险无关。结论：除了对 FIB-4 和 AST 等非侵入性生物标志物以及 MASLD 诊断时采集的血小板进行基线测量外，随着时间的推移监测其值也很重要，因为这些生物标志物的最新值与未来的风险密切相关。马洛。变化率可能没那么重要。