FIB-4 和 NAFLD 纤维化评分在人群中筛查肝纤维化的准确性低 202

StephenW

FIB-4 和 NAFLD 纤维化评分在人群中筛查肝纤维化的准确性低
2022 年 11 月 1 日

背景与目标
Fibrosis-4 (FIB-4) 和非酒精性脂肪性肝病纤维化评分 (NFS) 是建议用于广泛纤维化筛查的两种最流行的非侵入性血液血清检测。因此，我们旨在描述 FIB-4 和 NFS 检测肝硬度升高作为低流行人群肝纤维化指标的准确性。
方法
这项研究包括来自西班牙、香港、丹麦、英国和英国的 5 个独立人群队列的 5129 名患者，同时通过 Fibroscan（Echosens，法国）测量 FIB-4、NFS 和肝硬度测量（LSM）。法国; 3979 名来自普通人群的参与者和 1150 名来自酒精、糖尿病或肥胖高危人群的参与者。我们将 LSM 与 FIB-4 和 NFS 相关联，并计算 FIB-4 和 NFS 的测试前和测试后预测值，以检测在 8 kPa 和 12 kPa 截止时 LSM 升高。平均年龄为 53 ± 12 岁，平均体重指数为 27 ± 5 kg/m2，2439 (5​​7%) 为女性。十分之一的患者（552 人；11%）的肝硬度≥8 kPa，但其中 239 人（43%）的 FIB-4 正常，171 人（31%）的 NFS 正常。高危患者的假阴性比例高于一般人群。 FIB-4 在 11% 的糖尿病受试者中为假阴性，而 NFS 为 2.5% 的假阴性。在一般人群中检测 LSM ≥8 kPa 时，腰围优于 FIB-4 和 NFS。在普通人群和高危人群中，几乎三分之一 (28%–29%) 的 FIB-4/NFS 升高为假阳性。
结论
由于过度诊断的高风险和不可忽略的假阴性百分比，FIB-4 和 NFS 不适合筛查目的，尤其是在具有慢性肝病危险因素的患者中。腰围成为识别普通人群中肝纤维化风险患者的潜在第一步。

如图 2 所示，大多数 LSM <8 kPa 的患者都被 NIT 很好地分类。然而，FIB-4 <1.3 的 3308 名患者中有 239 名 (7.2%) 的 LSM ≥8 kPa。 NFS 也有类似的情况，我们观察到 5.7% 的假阴性（3019 名 NFS 低的人中有 171 名 LSM ≥8 kPa）。高危人群队列的假阴性患者比例（8%–9%）高于具有两种 NIT 评分的普通人群队列（2%–4%）。表 2 和表 3 显示了 LSM ≥8 和 ≥12 kPa 在 2 类人群中的频率和分布。

我们还观察到，在普通人群和高危人群中，非侵入性评分的假阳性比例很大。在普通人群中，FIB-4 ≥1.3 和 LSM <8 kPa 的 1179 名参与者（29%）和 NFS ≥-1.45 的 1130 名参与者（28%），329 名患者（28% ) 用于 FIB-4 和 225 (28%) 用于 NFS。

补充表 1、补充表 2、补充表 3 显示了 FIB-4 和 NFS 检测肝硬度特定临界值以上患者的敏感性、特异性、NPV 和 PPV。在一般人群中，NFS 的表现优于 FIB-4，对检测高于 8 kPa 的患者具有更高的灵敏度。然而，在高危人群中，NFS 和 FIB-4 在检测肝脏硬度增加方面没有差异。在一般人群中，FIB-4 通常用于排除纤维化的临界值（LSM <8 kPa）的敏感性和特异性分别为 37% 和 69%，而 NFS 的敏感性和特异性分别为 52% 和 69%。在高危人群中，FIB-4 和 NFS 排除纤维化的敏感性分别为 70% 和 77%，而排除纤维化的特异性分别为 60% 和 55%。
由于 NITs（FIB-4 和 NFS）的假阴性结果而被错误分类的患者的基线特征与分类良好的患者（补充表 4）的比较表明，NITs 的假阴性结果与肥胖、糖尿病、动脉高血压、有害饮酒、腰围较高和 ALT 值较高。我们还发现年龄较小可以预测 FIB-4 的假阴性结果。在 341 名年龄 <35 岁的患者中，16 名患者中有 14 名 (87%) 的 FIB-4 <1.30，尽管 LSM ≥8 kPa。相比之下，年龄较大的预测 FIB-4 假阳性。在 1118 名 >65 岁的患者中，782 名中的 658 名（84%）尽管 LSM <8 kPa，但 FIB-4 ≥1.30。排除 ALT > 2 × ULN 的参与者没有改变结果，也没有排除 BMI > 35 kg/m2 的肥胖患者。

社论 2022 年 11 月 1 日

StephenW

Low Accuracy of FIB-4 and NAFLD Fibrosis Scores for Screening for Liver Fibrosis in the Population
November 01, 2022

Background & Aims
Fibrosis-4 (FIB-4) and the nonalcoholic fatty liver disease fibrosis score (NFS) are the 2 most popular noninvasive blood-based serum tests proposed for widespread fibrosis screening. We therefore aimed to describe the accuracy of FIB-4 and NFS to detect elevated liver stiffness as an indicator of hepatic fibrosis in low-prevalence populations.
Methods
This study included a total of 5129 patients with concomitant measurement of FIB-4, NFS, and liver stiffness measurement (LSM) by Fibroscan (Echosens, France) from 5 independent population-based cohorts from Spain, Hong Kong, Denmark, England, and France; 3979 participants from the general population and 1150 from at-risk cohorts due to alcohol, diabetes, or obesity. We correlated LSM with FIB-4 and NFS, and calculated pre- and post-test predictive values of FIB-4 and NFS to detect elevated LSM at 8 kPa and 12 kPa cutoffs. The mean age was 53 ± 12 years, the mean body mass index was 27 ± 5 kg/m2, and 2439 (57%) were women. One in 10 patients (552; 11%) had liver stiffness ≥8 kPa, but 239 of those (43%) had a normal FIB-4, and 171 (31%) had normal NFS. The proportion of false-negatives was higher in at-risk patients than the general population. FIB-4 was false-negative in 11% of diabetic subjects, compared with 2.5% false-negatives with NFS. Waist circumference outperformed FIB-4 and NFS for detecting LSM ≥8 kPa in the general population. Almost one-third (28%–29%) of elevated FIB-4/NFS were false-positive in both the general population and at-risk cohorts.
Conclusions
FIB-4 and NFS are suboptimal for screening purposes due to a high risk of overdiagnosis and a non-negligible percentage of false-negatives, especially in patients with risk factors for chronic liver disease. Waist circumference emerged as a potential first step to identify patients at risk for liver fibrosis in the general population.

As seen in Figure 2, the majority of patients with LSM <8 kPa were well-classified by NITs. However, 239 of 3308 patients (7.2%) with FIB-4 <1.3 had LSM ≥8 kPa. Something similar was seen with NFS, where we observed 5.7% false-negatives (171 of 3019 with low NFS had LSM ≥8 kPa). At-risk population cohorts exhibited a higher proportion of false-negative patients (8%–9%) than the general population cohorts (2%–4%) with both NIT scores. Tables 2 and 3 display the frequencies and distributions of LSM ≥8 and ≥12 kPa in the 2 types of population cohorts.

We also observed a significant proportion of false-positives with both noninvasive scores in the general population and at-risk population cohorts. There were 1179 participants (29%) with FIB-4 ≥1.3 and LSM <8 kPa and 1130 participants (28%) with NFS ≥−1.45 among the general population, and similar percentages in at-risk cohorts with 329 patients (28%) for FIB-4 and 225 (28%) for NFS.

Supplementary Table 1, Supplementary Table 2, Supplemental Table 3 show the sensitivity, specificity, NPV, and PPV of FIB-4 and NFS to detect patients above specific cutoffs of liver stiffness. In the general population, NFS performed better than FIB-4, with higher sensitivity to detect patients above 8 kPa. However, in at risk-populations, there were no differences between NFS and FIB-4 performances for detection of increased liver stiffness. The sensitivity and specificity for the cutoff commonly used to rule out fibrosis (LSM <8 kPa) with FIB-4 in the general population was 37% and 69%, respectively, whereas NFS had a sensitivity of 52% and specificity of 69%. In at-risk populations, FIB-4 and NFS sensitivity to rule out fibrosis was 70% and 77%, and specificity to rule in was 60% and 55%.
The comparison of the baseline characteristics of patients misclassified due to false-negative results in NITs (FIB-4 and NFS) with those well-classified (Supplementary Table 4) showed that false-negative results of NITs were associated to obesity, diabetes, arterial hypertension, hazardous alcohol consumption, higher waist circumference, and higher values of ALT. We also found younger age to predict false negative results by FIB-4. In 341 patients aged <35 years, 14 of 16 (87%) had FIB-4 <1.30 despite having LSM ≥8 kPa. In contrast, older age predicted FIB-4 false-positives. In 1118 patients >65 years, 658 of 782 (84%) had FIB-4 ≥1.30 despite having LSM <8 kPa. Excluding participants with ALT >2 × ULN did not change results, nor did excluding obese patients with BMI >35 kg/m2.

Editorial November 01, 2022