Emerging Biomarkers in Non-Alcoholic Fatty Liver Disease: A Comprehensive Narrative Review of Mirna, Lipidomics, and Metabolomics for Early Detection and Diagnosis

Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is one of the most common chronic liver diseases globally, affecting about 25% of the population. It ranges from simple steatosis to more severe stages like non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Early detection is crucial to prevent disease progression, but traditional diagnostic tools like liver function tests (LFTs) and biopsies have limitations, including low sensitivity and invasiveness. Recent advancements in non-invasive biomarkers, such as microRNAs (miRNAs), lipidomics, and metabolomics, offer a promising solution for early detection and staging of NAFLD. This review explores the diagnostic accuracy and clinical utility of these emerging biomarkers. Objectives: To provide a comprehensive overview of the emerging biomarkers—specifically miRNAs, lipidomics, and metabolomics—for the early detection and diagnosis of NAFLD, evaluating their diagnostic accuracy and clinical utility in identifying stages of NAFLD (simple steatosis, NASH, and fibrosis) in comparison to traditional liver function tests. Methodology: A comprehensive literature search was conducted in PubMed and Google Scholar for studies published between 2021 and 2024. The search focused on emerging biomarkers for liver injury detection in NAFLD, using terms like "NAFLD biomarkers," "miRNA profiles," "lipidomics," and "metabolomics." The review included original research, cohort, case-control, and diagnostic accuracy studies on miRNAs, lipidomics, and metabolomics in NAFLD. A total of 250 articles were screened, with 8 studies selected based on relevance, methodology, and diagnostic potential. These studies were analyzed for their diagnostic accuracy in distinguishing between different NAFLD stages. Results: The selected studies demonstrated that miRNAs, lipidomics, and metabolomics are promising non-invasive biomarkers for early detection of NAFLD. MiR-122, miR-21, and miR-29 emerged as reliable miRNA markers for distinguishing between simple steatosis, NASH, and fibrosis, with diagnostic accuracy (AUC) values ranging from 0.79 to 0.82. Lipidomic studies highlighted ceramides, diacylglycerols (DAGs), and lysophosphatidylcholine (LPC)(16:0) as key biomarkers, with AUC values of 0.85 to 0.88 in predicting NASH and liver inflammation. Metabolomic profiling identified amino acids, such as glycine, and bile acids as markers of advanced fibrosis and NASH, with diagnostic accuracy values up to 0.81. These biomarkers significantly improve the ability to detect and stage NAFLD compared to traditional tests. Conclusion: The integration of miRNAs, lipidomics, and metabolomics into NAFLD diagnostics offers a promising non-invasive approach for early detection and staging of the disease. These biomarkers not only provide high diagnostic accuracy but also offer a more comprehensive understanding of disease progression. Further large-scale validation studies are needed to standardize their clinical application and refine diagnostic models for routine use, potentially improving NAFLD management and patient outcomes. Keywords: Biomarkers, Non-Alcoholic Fatty Liver Disease, miRNA, Lipidomics, and Metabolomics