Performance of Serum-Based Non-Invasive Fibrosis Scores Compared with Liver Biopsy in Patients with Chronic Hepatitis B

Background and Objectives: Accurate assessment of liver fibrosis is essential for treatment decisions in patients with chronic hepatitis B (CHB). Although liver biopsy is considered the reference standard, its invasive nature limits routine use. Serum-based non-invasive fibrosis scores have been proposed as alternatives; however, their diagnostic performance in CHB remains variable. This study aimed to compare multiple serum-based non-invasive fibrosis scores with liver biopsy findings and to evaluate their association with histological activity. Materials and Methods: This retrospective cross-sectional study included 219 adult patients with CHB who underwent liver biopsy with simultaneous laboratory evaluation. Patients with viral co-infections (HIV, HCV, or HDV), metabolic syndrome, diabetes mellitus, hepatic steatosis, or incomplete data were excluded. Non-invasive fibrosis scores—including APRI, FIB-4, AST/ALT ratio (AAR), age–platelet index (API), GGT-to-platelet ratio (GPR), Lok index, modified Forns index, Albumin–Bilirubin (ALBI) score, and red cell distribution width (RDW)-based indices—were calculated using routine laboratory parameters. Histopathological fibrosis staging served as the reference standard. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis, and areas under the curve (AUC) were compared using the DeLong test. Associations with histological activity index (HAI) were assessed using Spearman correlation. Results: For the prediction of significant fibrosis (≥F2), FIB-4 demonstrated the highest AUC, followed by ALBI and APRI. For advanced fibrosis (≥F3), FIB-4 again showed the highest AUC, followed by APRI and GPR. For significant fibrosis (≥F2), DeLong analysis revealed no statistically significant differences between FIB-4 and the other serum-based scores (p > 0.05). APRI (r = 0.556, p < 0.001) and FIB-4 (r = 0.463, p < 0.001) showed the strongest correlations with HAI. In ROC analysis for moderate-to-severe histological activity (HAI ≥ 4), APRI demonstrated the highest diagnostic accuracy (AUC = 0.677). Conclusions: Serum-based non-invasive fibrosis scores demonstrate comparable but overall modest diagnostic performance for biopsy-confirmed fibrosis in patients with chronic hepatitis B. Indices such as FIB-4 and APRI demonstrated relatively better discrimination and may be considered as screening or rule-out tools in selected clinical contexts. APRI and FIB-4 also show associations with histological activity; however, their clinical application should be interpreted with caution, given their moderate discriminatory capacity. © 2026 by the authors.