Biomarkers of NAFLD progression: a lipidomics approach to an epidemic

TLDR

NAFLD ranges from steatosis to NASH and cirrhosis, and early, accurate diagnosis—particularly of NASH—is critical, yet liver biopsy remains the gold standard, underscoring the need for non‑invasive diagnostic tools. The study applies an omics strategy to identify a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts across NAFLD stages using a double‑blinded cohort with liver biopsies, plasma, and urine samples. Linear discriminant analysis of 20 plasma metabolites—including glycerophospholipids, sphingolipids, sterols, and small aqueous molecules—distinguishes NASH from steatosis. These differential biomolecular signatures could enhance NAFLD diagnosis and support therapeutic interventions.

Abstract

The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an "omics" approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD.