MACK-3 (combination of hoMa, Ast and CK18): A promising novel biomarker for fibrotic non-alcoholic steatohepatitis

Introduction: MACK-3 (combination of hoMa, Ast and CK18) was reported to be a good biomarker for the diagnosis of fibrotic non-alcoholic steatohepatitis (NASH). However, there is no external validation to date.

Aim: To evaluate the accuracy of MACK-3 for the diagnosis of fibrotic NASH.

Methodology: Consecutive adult non-alcoholic fatty liver disease (NAFLD) patients who had liver biopsy in a university hospital were included. MACK-3 was calculated using the online calculator using the following variables: fasting glucose, fasting insulin, aspartate aminotransferase (AST) and cytokeratin 18 (CK18). MACK-3 cut-offs ≤0.134 and ≥0.550 were used to predict absence and presence of fibrotic NASH, respectively. Histopathological examination of liver biopsy specimen was reported according to the NASH Clinical Research Network Scoring System.

Results: Data for 196 subjects were analysed. MACK-3 was good for diagnosis of fibrotic NASH (area under receiver-operating characteristics curve [AUROC] 0.80), comparable to the Fibrosis-4 index (FIB4) and the NAFLD fibrosis score (NFS) and superior to the BARD score and CK18. MACK-3 was good for diagnosis of active NASH (AUROC 0.81) and was superior to other blood fibrosis tests. The overall accuracy, percentage of subjects in grey zone, sensitivity, specificity, positive predictive value and negative predictive value of MACK-3 for diagnosis of fibrotic NASH was 79.1%, 46.9%, 100%, 43.8%, 43.1% and 100%, respectively, while for diagnosis of active NASH was 90.0%, 39.3%, 84.2%, 81.4%, 88.9% and 74.5%, respectively.

Conclusion: MACK-3 is promising as a non-invasive test for active NASH and fibrotic NASH and may be useful to identify patients who need more aggressive intervention.