Non-Invasive Serum and Elastography-Based Markers of Fibrosis Staging in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Review

Abstract

Fibrosis stage is what determines outcome in steatotic liver disease, and the disease is far too common for biopsy to be the route to establishing it. Non-invasive tests have therefore become the pathway rather than an adjunct to it, and their thresholds now decide who is reassured, who is referred and who is treated. Objectives: To review the published evidence on serum scores and elastography for staging fibrosis in metabolic dysfunction-associated steatotic liver disease: how each performs against histology, how performance changes with the threshold chosen, how the modalities compare, and where sequential testing strategies leave the patient. Material and Methods: Narrative review of diagnostic accuracy studies, individual patient data analyses, meta-analyses, guidelines and care pathway trials indexed in PubMed and the major hepatology journals. Studies were eligible if they reported the accuracy of a serum score or an elastography modality against liver histology in a defined population, compared modalities directly, or evaluated a sequential testing pathway. No new patient data were generated; every accuracy estimate and threshold quoted is one published by the original investigators. Results: Pooling 207 studies covering more than 80,000 patient investigations, FIB-4 at the conventional 1.3 threshold detected advanced fibrosis with 71 per cent sensitivity, rising to 88 per cent at a threshold below 0.75; at 2.67 its specificity was 96 per cent. Elastography performed better and improved with stage: pooling 63 studies covering 19,199 patients, transient elastography achieved areas under the curve of 0.83 for significant fibrosis, 0.87 for advanced fibrosis and 0.94 for cirrhosis, with optimal cut-offs of 7.1 to 7.9 kilopascals against 3.62 to 3.8 for magnetic resonance elastography. Thresholds achieving roughly 90 per cent sensitivity differed by modality, at 2.32 kilopascals for magnetic resonance elastography and 7.18 for transient elastography. A sequential strategy combining FIB-4 with a serum panel excluded most patients from biopsy while retaining 90.4 per cent specificity.
Conclusion: No single test stages fibrosis adequately across the range. Serum scores are cheap and reasonable for exclusion, though the widely used FIB-4 threshold of 1.3 misses close to three in ten patients with advanced fibrosis. Elastography is more accurate but least discriminating at exactly the early stages where intervention has most to offer. Sequential pathways, rather than any individual test, are what the evidence supports. Abbreviations: MASLD – Metabolic Dysfunction-Associated Steatotic Liver Disease, MASH – Metabolic Dysfunction-Associated Steatohepatitis, NAFLD – Non-Alcoholic Fatty Liver Disease, NIT – Non-Invasive Test, FIB-4 – Fibrosis-4 Index, NFS – NAFLD Fibrosis Score, ELF – Enhanced Liver Fibrosis, APRI – Aspartate Aminotransferase to Platelet Ratio Index, VCTE – Vibration-Controlled Transient Elastography, LSM – Liver Stiffness Measurement, MRE – Magnetic Resonance Elastography, SWE – Shear Wave Elastography, AUROC – Area Under the Receiver Operating Characteristic Curve, NPV – Negative Predictive Value.