Development and validation of a novel non-invasive test for diagnosing fibrotic non-alcoholic steatohepatitis in patients with biopsy-proven non-alcoholic fatty liver disease

Authors

• Feng Gao
• Jiao-Feng Huang
• Kenneth I. Zheng
• Xiao-Yan Pan
• Hong-Lei Ma
• Wen-Yue Liu
• Christopher D. Byrne
• Giovanni Targher
• Yang-Yang Li
• Yong-Ping Chen
• Wah-Kheong ChanFollow
• Ming-Hua Zheng

Document Type

Article

Publication Date

10-1-2020

Abstract

Background and Aim 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. Methods 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. Results 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. Conclusions 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.

Keywords

Diagnostic tests, Liver biopsy, Liver fibrosis, NAFLD, Clinical, NASH

Publication Title

Journal of Gastroenterology and Hepatology

Divisions

fac_med,medicinedept

Volume

35

Issue

10

Publisher

Blackwell Publishing

Publisher Location

111 RIVER ST, HOBOKEN 07030-5774, NJ USA