The stealthy saboteur: hepatic steatosis and its erosion of APRI and FIB-4 accuracy

Background and aims: Noninvasive models are increasingly important for liver fibrosis assessment. However, their accuracy can be affected by comorbidities. We aimed to evaluate the impact of concurrent hepatic steatosis (HS) on the diagnostic performance of the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) for staging liver fibrosis in patients with chronic hepatitis B (CHB). Methods: This retrospective cohort study included treatment-naïve CHB patients of Han Chinese ethnicity who underwent liver biopsy between January 2008 and December 2025. Patients were stratified into two groups: CHB without HS and CHB with HS. The diagnostic accuracy of APRI and FIB-4 for identifying advanced fibrosis (Metavir stage F3-F4) was assessed using the area under the receiver operating characteristic curve (AUROC) and at established clinical cut-offs. Results: In patients without HS, both APRI and FIB-4 demonstrated high diagnostic accuracy for advanced fibrosis, with AUROCs of 0.896 and 0.854, respectively. However, their performance was severely impaired by steatosis, with AUROCs dropping to just 0.473 for APRI and 0.468 for FIB-4 in patients with moderate-to-severe steatosis (S2-S3). This translated to a dramatic loss of clinical utility; for example, the positive predictive value (PPV) of APRI collapsed from 73.1% in the non-HS group to an unreliable 23.3% in the moderate-to-severe steatosis group. Conclusion: The presence of hepatic steatosis significantly compromises the diagnostic utility of APRI and FIB-4 for assessing advanced fibrosis in CHB patients. Clinicians should exercise caution when applying these noninvasive scores in CHB patients with known or suspected steatosis. We suggest prioritizing alternative methods, such as elastography-based techniques or newer biomarker panels, in this population. Our findings underscore the need for developing fibrosis models specifically validated or adjusted for patients with dual liver pathologies.