Blood-based biomarker panel aids noninvasive diagnosis of MASH

Noninvasive diagnosis of metabolic dysfunction–associated steatohepatitis (MASH) may become a possibility with a robust blood-based biomarker panel developed by researchers from the Chinese University of Hong Kong (CUHK) and their collaborators in mainland China and the US, which demonstrated high diagnostic accuracy in Asian and American validation cohorts.

Known as N3-MASH, the blood-based biomarker panel comprises C-X-C motif chemokine ligand 10 (CXCL10), cytokeratin 18 fragments M30 (CK-18), and adjusted body mass index. It was developed in a discovery cohort of 184 individuals from Hong Kong (metabolic dysfunction–associated steatotic liver disease [MASLD], n=112; healthy controls, n=72), and validated in three independent cohorts involving a total of 516 patients with MASLD from San Diego, US (n=173), Wenzhou, mainland China (n=240), and Hong Kong (n=103). [Cell Metab 2024;doi:10.1016/j.cmet.2024.10.008]

N3-MASH demonstrated high accuracy in differentiating patients with MASLD from healthy controls, with an area under the receiver operating characteristic curve (AUROC) of 0.954 (95 percent confidence interval [CI], 0.927–0.981). At a cut-off value of 0.720, the specificity was 94.4 percent and sensitivity was 83.9 percent. Diagnostic accuracy was maintained in the ethnically diverse validation cohort of patients from San Diego, with an AUROC of 0.946 (95 percent CI, 0.899–0.993).

N3-MASH also distinguished MASH in patients with MASLD, with an AUROC of 0.823 (95 percent CI, 0.747–0.898), outperforming alanine aminotransferase (ALT), aspartate aminotransferase (AST) and other biomarker panels. At a cut-off value of 0.664, the specificity was 90.0 percent, sensitivity was 62.9 percent, and positive predictive value (PPV) was 88.6 percent.

“The diagnostic performance of N3-MASH in distinguishing MASH from patients with MASLD was consistent in the three validation cohorts, with AUROC of 0.802 [95 percent CI, 0.729–0.876] in the San Diego cohort, 0.805 [95 percent CI, 0.729–0.881] in the Wenzhou cohort, and 0.823 [95 percent CI, 0.743–0.903] in the Hong Kong cohort,” the researchers reported. “Its performance in MASH diagnosis was not affected by age, gender, ALT, diabetes and hypertension.”

“N3-MASH can also assess MASH improvement and monitor treatment effectiveness,” said lead author Professor Jun Yu of the State Key Laboratory of Digestive Disease, CUHK.

The ability of N3-MASH in assessing MASH improvement over time was analyzed using serum samples from 48 patients with MASH from Hong Kong and Wenzhou, who underwent a second liver biopsy ≥6 months after the initial biopsy. Results showed significant decrease in N3-MASH index in patients with histological improvement over time (p<0.001), as well as an AUROC of 0.857 (95 percent CI, 0.751–0.963) in identifying patients with MASH improvement.

“Given the US FDA’s recent approval of the first drug for MASH, this finding holds significant implications for monitoring treatment efficacy,” the researchers suggested.

“N3-MASH’s ability to effectively identify patients with a high likelihood of MASH is particularly valuable in a primary care setting, where the easy-to-use N3-MASH panel can help rule in MASH diagnosis for referral to specialists for liver stiffness measurement with transient elastography and consideration of pharmacotherapeutic interventions,” they noted. “The components of N3-MASH can be measured using widely accepted and commonly used methods, making it easily applicable in clinical practice.”

“N3-MASH can also help reduce unnecessary liver biopsies,” added corresponding author Professor Vincent Wong of CUHK’s Division of Gastroenterology and Hepatology.