Sung Shuen, Al-Karaghouli Mustafa, Tam Matthew, Wong Yu Jun, Jayakumar Saumya, Davyduke Tracy, Ma Mang, Abraldes Juan G
Faculty of Medicine and Dentistry, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Division of Gastroenterology, Department of Medicine, Liver Unit, University of Alberta, Edmonton, Alberta, Canada.
Hepatol Commun. 2024 Dec 11;9(1). doi: 10.1097/HC9.0000000000000609. eCollection 2025 Jan 1.
Fibrosis 4 (FIB-4) is widely used to triage patients with metabolic dysfunction-associated steatotic liver disease. Given that age is part of FIB-4, higher scores may be expected in the elderly population. This led to the proposal of using a higher threshold of FIB-4 to triage patients aged ≥65. Our main objective is to evaluate how age modifies the association between the FIB-4 index and disease severity based on the vibration-controlled transient elastography (VCTE) "rule of 5s."
In this cross-sectional study, we prospectively analyzed data from a primary care referral pathway. We used liver stiffness measurement by VCTE as a reference standard for liver risk. We modeled with ordinal regression the exceedance probabilities of finding different liver stiffness measurement thresholds according to FIB-4, and how age modifies FIB-4 predictions.
Nine hundred eighty-five participants with complete data were used for modeling. Participants aged ≥65 had a higher prevalence of advanced liver disease estimated by VCTE and higher FIB-4 values than those <65 (85.9% vs. 20.2% for FIB-4 ≥1.3, and 46.5% vs. 6.5% for FIB-4 ≥2.0). In participants age ≥65, the negative predictive value for VCTE ≥10 kPa of FIB-4 <1.3 was 100% versus FIB-4 <2.0 was 83%. Age significantly modified FIB-4-based prediction of fibrosis, but predictions at a threshold of 1.3 or 2 were only minimally altered. For higher FIB-4 threshold (ie, 2.7), age strongly modified FIB-4 predictions of liver stiffness measurement.
Age does not relevantly modify FIB-4 predictions when using the common threshold of 1.3. Our data suggest no rationale for increasing the FIB-4 threshold to 2 for undergoing further testing in patients aged ≥65. However, the meaning of a FIB-4 of 2.7 strongly changes with age. This cutoff for ages over 65 is not enough to define high-risk and would not warrant direct referral.
纤维化4（FIB-4）广泛用于对代谢功能障碍相关脂肪性肝病患者进行分类。鉴于年龄是FIB-4的一部分，老年人群中FIB-4评分可能更高。这导致有人提议使用更高的FIB-4阈值对年龄≥65岁的患者进行分类。我们的主要目标是根据振动控制瞬时弹性成像（VCTE）的“5法则”评估年龄如何改变FIB-4指数与疾病严重程度之间的关联。
在这项横断面研究中，我们前瞻性地分析了来自初级保健转诊途径的数据。我们将通过VCTE测量的肝脏硬度作为肝脏风险的参考标准。我们使用有序回归模型根据FIB-4对不同肝脏硬度测量阈值的超过概率进行建模，以及年龄如何改变FIB-4的预测。
985名具有完整数据的参与者用于建模。年龄≥65岁的参与者中，根据VCTE估计的晚期肝病患病率以及FIB-4值高于年龄<65岁的参与者（FIB-4≥1.3时分别为85.9%对20.2%，FIB-4≥2.0时分别为46.5%对6.5%）。在年龄≥65岁的参与者中，FIB-4<1.3时对VCTE≥10 kPa的阴性预测值为100%，而FIB-4<2.0时为83%。年龄显著改变了基于FIB-4的纤维化预测，但在阈值为1.3或2时预测仅略有改变。对于更高的FIB-4阈值（即2.7），年龄强烈改变了FIB-4对肝脏硬度测量的预测。
使用1.3的常见阈值时，年龄对FIB-4预测没有显著影响。我们的数据表明，对于年龄≥65岁的患者，没有理由将FIB-4阈值提高到2以进行进一步检测。然而，FIB-4为2.7的意义随年龄变化很大。65岁以上人群的这个临界值不足以定义高风险，也不值得直接转诊。
