Omics-based biomarkers as useful tools in metabolic dysfunction-associated steatotic liver disease clinical practice: How far are we?

Abstract

Unmet needs exist in metabolic dysfunction-associated steatotic liver disease (MASLD) risk stratification. Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited. Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors. With this aim, omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades. While the research in this field is thriving, much of the publication has been haphazard, often using single-omics data and specimen sets of convenience, with many identified candidate biomarkers but lacking clinical validation and utility. If we incorporate these biomarkers to direct patients' management, it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual, analytically valid test useful in MASLD clinical practice is rigorous and, therefore, not easily accomplished. This article presents an overview of this area's current state, the conceivable opportunities and challenges of omics-based laboratory diagnostics, and a roadmap for improving MASLD biomarker research.

Keywords: Biomarker; Metabolic dysfunction-associated steatotic liver disease; Non-alcoholic steatohepatitis; Omics; Risk stratification.

Figure 1

Characterization of omics literature based on a systematic screen of PubMed indexed research articles on metabolic dysfunction-associated steatotic liver disease biomarker (up to December 2023). A: Plot representing the rapidly increasing number of omics articles indexed in PubMed indicating the use of single-omic (red) or multi-omic technologies (blue); the dip in 2023 can be attributed to indexing delay which was not accounted for in the current plot; B: Proportion of omics and combinations of omics (grouped by the characterized entities) commonly used in the analyzed articles; C: Distribution of sample types used in the analyzed articles. The details of articles included in the analysis are listed in Supplementary Table 1.

Figure 2

A roadmap for the improvement of biomarker research in metabolic dysfunction-associated steatotic liver disease: Discovery of a biologically, and perhaps clinically, interesting omics-based biomarker; analytical, biological/clinical validation of the discovered biomarker; and finally, the evaluation for its clinical utility and use, and the evaluation for its economic benefits (cost-effectiveness or cost-utility studies). A summary of the criteria for the development path of omics-based predictors proposed by the United States National Cancer Institute are also included in the roadmap. Modified from freepik.com.