Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Minerva Foundation Institute for Medical Research, Helsinki, Finland.
J Clin Endocrinol Metab. 2022 Apr 19;107(5):e2008-e2020. doi: 10.1210/clinem/dgab933.
Guidelines recommend blood-based fibrosis biomarkers to identify advanced nonalcoholic fatty liver disease (NAFLD), which is particularly prevalent in patients with obesity.
To study whether the degree of obesity affects the performance of liver fibrosis biomarkers in NAFLD.
Cross-sectional cohort study comparing simple fibrosis scores [Fibrosis-4 Index (FIB-4); NAFLD Fibrosis Score (NFS); aspartate aminotransferase to platelet ratio index; BARD (body mass index, aspartate-to-alanine aminotransferase ratio, diabetes); Hepamet Fibrosis Score (HFS)] and newer scores incorporating neo-epitope biomarkers PRO-C3 (ADAPT, FIBC3) or cytokeratin 18 (MACK-3).
Tertiary referral center.
We recruited overweight/obese patients from endocrinology (n = 307) and hepatology (n = 71) clinics undergoing a liver biopsy [median body mass index (BMI) 40.3 (interquartile range 36.0-44.7) kg/m2]. Additionally, we studied 859 less obese patients with biopsy-proven NAFLD to derive BMI-adjusted cutoffs for NFS.
Biomarker area under the receiver operating characteristic (AUROC), sensitivity, specificity, and predictive values to identify histological stage ≥F3 fibrosis or nonalcoholic steatohepatitis with ≥F2 fibrosis [fibrotic nonalcoholic steatohepatitis (NASH)].
The scores with an AUROC ≥0.85 to identify ≥F3 fibrosis were ADAPT, FIB-4, FIBC3, and HFS. For fibrotic NASH, the best predictors were MACK-3 and ADAPT. The specificities of NFS, BARD, and FIBC3 deteriorated as a function of BMI. We derived and validated new cutoffs for NFS to rule in/out ≥F3 fibrosis in groups with BMIs <30.0, 30.0 to 39.9, and ≥40.0 kg/m2. This optimized its performance at all levels of BMI. Sequentially combining FIB-4 with ADAPT or FIBC3 increased specificity to diagnose ≥F3 fibrosis.
In obese patients, the best-performing fibrosis biomarkers are ADAPT and the inexpensive FIB-4, which are unaffected by BMI. The widely used NFS loses specificity in obese individuals, which may be corrected with BMI-adjusted cutoffs.
指南建议使用基于血液的纤维化生物标志物来识别非酒精性脂肪性肝病（NAFLD）的晚期，而肥胖患者尤其普遍患有这种疾病。
研究肥胖程度是否会影响 NAFLD 中肝纤维化生物标志物的性能。
比较简单纤维化评分[纤维化 4 指数（FIB-4）；非酒精性脂肪性肝病纤维化评分（NFS）；天门冬氨酸氨基转移酶与血小板比值指数；BARD（体重指数、天冬氨酸-丙氨酸氨基转移酶比值、糖尿病）；Hepamet 纤维化评分（HFS）]和包含新表位生物标志物 PRO-C3（ADAPT、FIBC3）或细胞角蛋白 18（MACK-3）的新型评分的横断面队列研究。
三级转诊中心。
我们从内分泌科（n=307）和肝病科（n=71）招募了超重/肥胖患者进行肝活检[中位数体重指数（BMI）40.3（四分位距 36.0-44.7）kg/m2]。此外，我们研究了 859 名肥胖程度较轻的 NAFLD 活检患者，以确定 NFS 的 BMI 调整临界值。
生物标志物接受者操作特征曲线下面积（AUROC）、敏感性、特异性和预测值，以识别组织学阶段≥F3 纤维化或非酒精性脂肪性肝炎伴≥F2 纤维化[纤维化性非酒精性脂肪性肝炎（NASH）]。
AUROC≥0.85 以识别≥F3 纤维化的评分是 ADAPT、FIB-4、FIBC3 和 HFS。对于纤维化性 NASH，最佳预测因子是 MACK-3 和 ADAPT。NFS、BARD 和 FIBC3 的特异性随 BMI 而恶化。我们为 BMI<30.0、30.0-39.9 和≥40.0 kg/m2 的组确定并验证了 NFS 的新临界值，以排除/纳入≥F3 纤维化。这优化了其在所有 BMI 水平的性能。依次将 FIB-4 与 ADAPT 或 FIBC3 结合使用可提高诊断≥F3 纤维化的特异性。
在肥胖患者中，表现最佳的纤维化生物标志物是 ADAPT 和廉价的 FIB-4，它们不受 BMI 的影响。广泛使用的 NFS 在肥胖个体中的特异性丧失，可通过 BMI 调整临界值纠正。
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