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

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