Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Hepatology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
J Gastroenterol Hepatol. 2020 Oct;35(10):1804-1812. doi: 10.1111/jgh.15055. Epub 2020 Apr 28.
There is an immediate need for non-invasive accurate tests for diagnosing liver fibrosis in patients with non-alcoholic steatohepatitis (NASH). Previously, it has been suggested that MACK-3 (a formula that combines homeostasis model assessment-insulin resistance with serum serum aspartate aminotransferase and cytokeratin [CK]18-M30 levels) accurately identifies patients with fibrotic NASH. Our aim was to assess the performance of MACK-3 and develop a novel, non-invasive algorithm for diagnosing fibrotic NASH.
Six hundred and thirty-six adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from two independent Asian cohorts were enrolled in our study. Liver stiffness measurement (LSM) was assessed by vibration-controlled transient elastography (Fibroscan). Fibrotic NASH was defined as NASH with a NAFLD activity score (NAS) ≥ 4 and F ≥ 2 fibrosis.
Metabolic syndrome (MetS), platelet count and MACK-3 were independent predictors of fibrotic NASH. On the basis of their regression coefficients, we developed a novel nomogram showing a good discriminatory ability (area under receiver operating characteristic curve [AUROC]: 0.79, 95% confidence interval [CI 0.75-0.83]) and a high negative predictive value (NPV: 94.7%) to rule out fibrotic NASH. In the validation set, this nomogram had a higher AUROC (0.81, 95%CI 0.74-0.87) than that of MACK-3 (AUROC: 0.75, 95%CI 0.68-0.82; P < 0.05) with a NPV of 93.2%. The sequential combination of this nomogram with LSM data avoided the need for liver biopsy in 56.9% of patients.
Our novel nomogram (combining MACK-3, platelet count and MetS) shows promising utility for diagnosing fibrotic NASH. The sequential combination of this nomogram and vibration-controlled transient elastography limits indeterminate results and reduces the number of unnecessary liver biopsies.
目前迫切需要一种非侵入性的准确方法来诊断非酒精性脂肪性肝炎（NASH）患者的肝纤维化。此前有研究表明，MACK-3（一种将稳态模型评估-胰岛素抵抗与血清天门冬氨酸氨基转移酶和细胞角蛋白 18-M30 水平相结合的公式）能够准确识别纤维化 NASH 患者。我们的目的是评估 MACK-3 的性能，并开发一种新的、非侵入性的诊断纤维化 NASH 的算法。
本研究纳入了来自两个独立亚洲队列的 636 名经肝活检证实的非酒精性脂肪性肝病（NAFLD）成人患者。通过振动控制瞬态弹性成像（Fibroscan）评估肝硬度测量（LSM）。纤维化 NASH 的定义为 NASH 伴有 NAFLD 活动评分（NAS）≥4 分和 F≥2 纤维化。
代谢综合征（MetS）、血小板计数和 MACK-3 是纤维化 NASH 的独立预测因子。根据它们的回归系数，我们开发了一种新的列线图，显示出良好的区分能力（接受者操作特征曲线下面积 [AUROC]：0.79，95%置信区间 [CI 0.75-0.83]）和高阴性预测值（NPV：94.7%），可排除纤维化 NASH。在验证集中，该列线图的 AUROC 高于 MACK-3（AUROC：0.75，95%CI 0.68-0.82；P<0.05），NPV 为 93.2%。该列线图与 LSM 数据的序贯组合使 56.9%的患者避免了肝活检的需要。
我们的新列线图（结合 MACK-3、血小板计数和 MetS）显示出在诊断纤维化 NASH 方面有很好的应用前景。该列线图与振动控制瞬态弹性成像的序贯组合可以限制不确定结果的出现，并减少不必要的肝活检数量。
