Efficacy of Non-invasive Biomarkers in Diagnosing Non-alcoholic Fatty Liver Disease (NAFLD) and Predicting Disease Progression: A Systematic Review.

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease, with significant global prevalence and a strong association with metabolic syndrome, obesity, and diabetes. Early diagnosis and prediction of disease progression are critical for effective management. Non-invasive biomarkers have emerged as promising alternatives to liver biopsy, offering safer and more accessible diagnostic and prognostic options. This systematic review evaluates the efficacy of non-invasive biomarkers in diagnosing NAFLD and predicting disease progression, focusing on diagnostic accuracy, clinical utility, and limitations. A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including studies published between 2010 and 2024. Databases such as PubMed, Embase, and Scopus were searched using relevant keywords and Boolean operators. Inclusion criteria comprised studies evaluating adults (18+) with NAFLD using non-invasive biomarkers, compared to liver biopsy or other standards, and reporting diagnostic metrics such as sensitivity, specificity, and area under the curve (AUC). Data were extracted systematically, and study quality was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) and the Newcastle-Ottawa Scale. The nine studies include a range of biomarkers such as serum markers (Pro-C3, NIS4), imaging techniques (MRI-PDFF, cT1), and composite scores (cTAG, NFS). Diagnostic accuracy was high, with area under the curve (AUC) values ranging from 0.81 to 0.90 for detecting significant fibrosis and at-risk non-alcoholic steatohepatitis (NASH). Imaging tools such as MRI-PDFF offered superior reproducibility and whole-liver assessments, while composite biomarkers such as NIS4 demonstrated robust sensitivity but moderate specificity. Notable heterogeneity in populations and methodologies was observed. Non-invasive biomarkers show comparable diagnostic performance to liver biopsy while offering significant advantages in safety, scalability, and patient adherence. However, gaps remain, including the need for validation in diverse populations and improved specificity for advanced fibrosis. Integrating non-invasive biomarkers into clinical practice could revolutionize NAFLD management by enabling early diagnosis, guiding treatment, and reducing reliance on invasive methods. Future research should focus on validating these tools across diverse cohorts and developing novel biomarkers to address existing limitations.