Optimizing CEUS LI-RADS for Hepatocellular Carcinoma Diagnosis in Non-Cirrhotic Hepatitis B Virus Infection Patients: Incorporating Alpha-fetoprotein or Adjusting Washout Criteria

• CEUS LR-5 in non-cirrhotic HBV shows high HCC specificity but low sensitivity. • Adding AFP or earlier washout raises HCC sensitivity, keeping high specificity. • Revised LR-M criteria improve specificity for non-HCC malignancies. CEUS LR-5 in non-cirrhotic HBV shows high HCC specificity but low sensitivity. Adding AFP or earlier washout raises HCC sensitivity, keeping high specificity. Revised LR-M criteria improve specificity for non-HCC malignancies. To improve the diagnostic performance of CEUS LI-RADS for hepatocellular carcinoma (HCC) in non-cirrhotic hepatitis B virus (NC-HBV) patients by integrating serum AFP or adjusting washout thresholds. A retrospective analysis included 105 pathologically confirmed focal liver lesions in NC-HBV patients. The diagnostic performance of original CEUS LI-RADS (Criteria 1) was compared with three modified versions: reclassifying LR-M nodules with AFP > 200 ng/mL as LR-5 (Criteria 2), AFP > 400 ng/mL as LR-5 (Criteria 3), and reducing the early washout threshold for LR-M from 60 to 45 seconds (Criteria 4). Sensitivity, specificity, and positive predictive value (PPV) were assessed. Criteria 1 showed high specificity (93.1%) and PPV (95.2%) but low sensitivity (52.6%) for HCC. Criteria 2, 3, and 4 significantly increased sensitivity to 68.4%, 67.1%, and 63.2%, respectively (all p < 0.05), without significantly reducing specificity or PPV (all p > 0.05). For non-HCC malignancies, the specificity of revised LR-M increased to 82.8%, 81.6%, and 82.8% with Criteria 2, 3, and 4, respectively, compared to Criterion 1 (69.0%; all p < 0.01), while sensitivities remained statistically unchanged (all p > 0.05). CEUS LR-5 has high specificity for characterizing HCC in NC-HBV patients. Integrating AFP or modifying the early washout threshold can significantly improve the sensitivity of CEUS LR-5 for diagnosing HCC in NC-HBV patients, while maintaining high specificity and PPV.