Non-invasive tests to guide hepatocellular carcinoma surveillance

Background & Aims Current guidelines recommend hepatocellular carcinoma (HCC) surveillance for patients with cirrhosis, though guidance on the use of non-invasive tests is lacking. Patients with compensated advanced chronic liver disease, defined non-invasively by liver stiffness measurement (LSM) ≥10 kPa, are at increased risk of hepatic decompensation and HCC. Although a fibrosis-4 (FIB-4) score ≥1.75 aligns with LSM ≥10 kPa in tertiary care, its utility for guiding HCC surveillance remains unclear. This study assessed the accuracy of FIB-4 vs. LSM in predicting HCC risk. Methods We retrospectively analyzed 6,143 patients with suspected chronic liver disease undergoing FIB-4 and LSM between 2007 and 2020 in Vienna. External validation was performed in participants from the UK Biobank with pre-existing liver disease. Patients were stratified by FIB-4 cut-offs (1.75 and 2.67) and corresponding LSM thresholds (10 kPa and 15 kPa). Results FIB-4 predicted de novo HCC with AUROCs of 0.79 (95% CI 0.65–0.94) at 1 year and 0.85 (95% CI 0.76–0.94) at 2 years, comparable to LSM. Two-year HCC incidence was 0.10% vs. 1.05% (0.05 vs. 0.53/100 person-years) for FIB-4 2.67. Among UK Biobank participants with pre-existing liver disease, the 5 year cumulative incidence of HCC was 3.7% vs. 0% for FIB-4 ≥1.75 vs. 2.67 vs. ≤2.67. Conclusions FIB-4 (≥1.75 and >2.67) shows similar ability to predict HCC development as LSM (≥10 kPa and ≥15 kPa) in tertiary care and population-based cohorts. FIB-4 may serve as a practical tool to guide HCC surveillance. Impact and implications This study addresses the need for easily accessible non-invasive tools to stratify hepatocellular carcinoma risk in patients with (suspected) chronic liver disease and shows that the universally available fibrosis-4 (FIB-4) score performs comparably to liver stiffness measurement (LSM) across clinically relevant thresholds. FIB-4 ≥1.75 or LSM ≥10 kPa identify patients at risk, although thresholds of >2.67 or ≥15 kPa may be required for cost-effectiveness beyond a specialist setting. In clinical practice, physicians may use FIB-4 to guide hepatocellular carcinoma surveillance where LSM is unavailable. Researchers and policymakers can leverage these findings to develop risk-adapted surveillance strategies.