Non-invasive risk-based surveillance of hepatocellular carcinoma in patients with metabolic dysfunction-associated steatotic liver disease

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 30% of the general population and is the fastest growing cause of hepatocellular carcinoma (HCC). Current guidelines recommend HCC surveillance in patients with cirrhosis when annual HCC incidence exceeds 1% without specifying the role of non-invasive tests in patient selection. Objective To define non-invasive test thresholds to select patients with MASLD for HCC surveillance. Design A multicentre longitudinal study of adults with MASLD from 16 tertiary centres in the USA, Europe and Asia between February 2004 and January 2023. Primary outcome was incident HCC. Results 12 950 patients had Fibrosis-4 index (FIB-4) and liver stiffness measurement (LSM) (mean age 51.7 years; 41.1% male). At a median follow-up of 47.7 (IQR 23.3–72.3) months, 109 (0.8%) developed HCC. FIB-4 was below the low cut-off (<1.3 if aged <65 years and <2.0 if aged ≥65 years), between the low cut-off and <2.67, 2.67 to <3.25, and ≥3.25 in 66.3%, 23.9%, 3.4% and 6.4% of patients; the corresponding annual HCC incidence was 0.07%, 0.17%, 0.77% and 1.18%. As a stand-alone test, the annual HCC incidence exceeded 0.2% for LSM ≥10 kPa and 1% for LSM ≥20 kPa. If LSM was performed as a second step only among patients with FIB-4 above the low cut-off, the annual HCC incidence exceeded 0.2% for LSM ≥10 kPa and 1% for LSM ≥15 kPa. Conclusion HCC surveillance should be offered to patients with MASLD with FIB-4 ≥3.25 or LSM ≥20 kPa. When a two-step approach is adopted, LSM ≥15 kPa in patients with increased FIB-4 predicts a high HCC risk.