Abstract / Summary
Background: Liver fibrosis is a key determinant of prognosis and management in chronic liver diseases. Although liver biopsy is considered the gold standard for fibrosis assessment, its invasiveness, sampling variability, and associated risks have prompted increasing reliance on non-invasive tests. This systematic review evaluates the diagnostic accuracy and clinical applicability of non-invasive modalities for diagnosing liver fibrosis in adult patients with chronic liver diseases.
Aim: To systematically evaluate the diagnostic accuracy, clinical utility, and applicability of non-invasive tests for detecting and staging liver fibrosis in adult patients with chronic liver diseases, using liver biopsy as the reference standard.
Methods: A systematic literature search was conducted using predefined search terms combining liver fibrosis, chronic liver disease, non-invasive diagnostic tests, and diagnostic accuracy measures, with liver biopsy as the reference standard. Studies were selected based on a PICO (Population, Intervention, Comparison, Outcome) framework including adults (≥ 18 years) with chronic liver diseases such as hepatitis B, hepatitis C, non-alcoholic fatty liver disease, and alcohol-related liver disease. Eligible interventions included serum biomarkers (e.g., aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index, enhanced liver fibrosis), imaging-based techniques (e.g., transient elastography, acoustic radiation force impulse, magnetic resonance imaging elastography), and combined diagnostic algorithms. Diagnostic accuracy outcomes including sensitivity, specificity, positive predictive value, and negative predictive value were extracted. Two independent reviewers performed abstract and full-text screening according to predefined inclusion and exclusion criteria, with disagreements resolved by consensus or a third reviewer.
Results: The included studies comprised prospective and retrospective cohort studies, randomized controlled trials, and cross-sectional studies. Elastography-based techniques consistently demonstrated high diagnostic accuracy for detecting significant and advanced fibrosis across multiple chronic liver disease etiologies. Serum biomarker panels showed variable performance but were effective as first-line screening tools due to their accessibility and cost-effectiveness. Heterogeneity was observed in study design, fibrosis staging systems, and cut-off values.
Conclusion: Non-invasive tests represent reliable and clinically applicable alternatives to liver biopsy for fibrosis assessment in chronic liver diseases. Elastography-based modalities, particularly transient elastography and two-dimensional shear wave elastography, demonstrated consistently high diagnostic accuracy for advanced fibrosis across included studies. Serum biomarker panels such as fibrosis-4 index and enhanced liver fibrosis showed variable performance but are effective as first-line screening tools due to their accessibility and cost-effectiveness. A sequential diagnostic approach integrating serum biomarkers followed by imaging modalities improves overall diagnostic accuracy and reduces the need for invasive procedures. However, significant heterogeneity in study design, patient populations, and cut-off values limits standardization and highlights the need for larger multicentric validation studies.