Diagnostic Performance of Non-invasive Tests for Hepatic Fibrosis Using Liver Biopsy As the Reference Standard: A Systematic Review and Meta-Analysis

Liver biopsy remains the reference standard for staging hepatic fibrosis, but its invasive nature, sampling error, cost, and possible complications have encouraged wider use of non-invasive tests. This systematic review and meta-analysis compared serum-based indices and elastography methods with liver biopsy for detecting fibrosis in chronic liver disease (CLD). A literature search was completed in March 2026 using PubMed/MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, and Google Scholar. Eligible diagnostic accuracy studies assessed serum-based markers, including aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 index (FIB-4), fibrotest/enhanced liver fibrosis (ELF) panels, and imaging-based modalities, including transient elastography (TE), shear wave elastography (SWE), and magnetic resonance elastography (MRE), using liver biopsy as the reference standard. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) area under the curve (AUC) were calculated using a random-effects model in Stata version 18.0 (StataCorp LLC, College Station, TX), and study quality was assessed with Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Forty-two studies, including 12,486 patients, were analyzed. For significant fibrosis, TE showed a pooled sensitivity of 84.6%, a specificity of 79.8%, and an area under the curve (AUC) of 0.88, while FIB-4 and APRI showed moderate accuracy with AUC values of 0.79 and 0.75, respectively. For advanced fibrosis, TE showed a sensitivity of 87.2%, a specificity of 82.6%, a DOR of 31.8, and an AUC of 0.91. Magnetic resonance elastography had the best overall performance, with AUC values of 0.92 for significant fibrosis, 0.94 for advanced fibrosis, and 0.96 for cirrhosis. Accuracy increased with fibrosis severity, although heterogeneity was seen due to differences in disease aetiology, cut-off values, and biopsy quality. Overall, elastography-based tests are reliable for advanced fibrosis and cirrhosis, while APRI and FIB-4 remain useful, low-cost first-line screening tools. A stepwise approach using serum scores followed by elastography may help reduce unnecessary biopsies without compromising diagnostic confidence.