Validation of the blood test MACK-3 for the noninvasive diagnosis of fibrotic NASH: an international study with 1,924 patients.

Canivet, Clémence M; Zheng, Ming-Hua; Qadri, Sami; Vonghia, Luisa; Chuah, Kee-Huat; Costentin, Charlotte; George, Jacob; Armandi, Angelo; Adams, Leon A; Lange, Naomi F; Blanchet, Odile; Moal, Valérie; Younes, Ramy; Roux, Marine; Chan, Wah-Kheong; Sturm, Nathalie; Eslam, Mohammed; Bugianesi, Elisabetta; Wang, Zhengyi; Dufour, Jean-François; ... (2023). Validation of the blood test MACK-3 for the noninvasive diagnosis of fibrotic NASH: an international study with 1,924 patients. Clinical gastroenterology and hepatology, 21(12), 3097-3106.e10. Elsevier 10.1016/j.cgh.2023.03.032

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BACKGROUND AND AIMS

Drug development in NASH is hampered by a high screening failure rate that reaches 60-80% in therapeutic trials, mainly because of the absence of fibrotic NASH on baseline liver histology. MACK-3, a blood test including three biomarkers (aspartate aminotransferase, homeostasis model assessment and cytokeratin 18), was recently developed for the noninvasive diagnosis of fibrotic NASH. We aimed to validate the diagnostic accuracy of this noninvasive test in an international multicenter study.

METHODS

1,924 patients with biopsy-proven NAFLD from 10 centers in Asia, Australia, and Europe were included. The blood test MACK-3 was calculated for all patients. FAST, an elastography-based test for fibrotic NASH, was also available in a subset of 655 patients. Fibrotic NASH was defined as the presence of NASH on liver biopsy with NAFLD Activity Score ≥4 and fibrosis stage F≥2 according to the NASH CRN scoring system.

RESULTS

AUROC of MACK-3 for fibrotic NASH was 0.791 [0.768-0.814]. Sensitivity at the previously published MACK-3 threshold of <0.135 was 91% and specificity at its >0.549 threshold was 85%. The MACK-3 AUROC was not affected by age, sex, diabetes, or BMI. MACK-3 and FAST results were well correlated (Rs=0.781, P < .001). Except an 8% higher rate of patients included in the grey zone, MACK-3 provided similar accuracy to that of FAST. Both tests included 27% of patients in their rule-in zone, with 85% specificity and 35% false positives (screen failure rate).

CONCLUSION

The blood test MACK-3 is an accurate tool to improve patient selection in NASH therapeutic trials.

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