Corey KE, Pitts R, Lai M, et al. - The ADAMTSL2 (A disintegrin and metalloproteinase with thrombospondin motifs like 2) protein and an 8-protein soluble biomarker panel are highly linked to at-risk non-alcoholic steatohepatitis (NASH) and significant fibrosis, outperforming standard-of-care fibrosis scores.

• In cohorts A (n = 62) and B (n = 98), multiplex profiling revealed that 16 proteins differed substantially by fibrosis.

• SPMS assays that are quantitative and resilient were designed and validated in Cohorts C (n = 71) and D (n = 84).

• With an AUROC of 0.83 and 0.86 in Cohorts C and D, respectively, the protein ADAMTSL2 precisely distinguished NAFL/NASH with fibrosis stage 0-1 (F0-1) from at-risk NASH with fibrosis stage 2-4, and from NASH with significant fibrosis (F2-3).

• NAFL/NASH F0-1 was separated from at-risk NASH (AUROC 0.90 and 0.87 in Cohort C and D, respectively) and NASH F2-3 (AUROC 0.89 and 0.83 in Cohorts C and D, respectively) using an 8-protein panel.

• The 8-protein panel and the ADAMTSL2 protein outperformed the NAFLD fibrosis score and the Fibrosis-4 score.