Fibrosis‐4 Index as a Robust Long‐Term Predictor of Cancers in Metabolic Dysfunction–Associated Steatotic Liver Disease

ABSTRACT Aim We investigated whether the baseline fibrosis‐4 (FIB‐4) index stratifies long‐term cancer risk in patients with biopsy‐proven MASLD and compared its discrimination for HCC and extrahepatic malignancies against other noninvasive fibrosis markers. Methods In this single‐center retrospective cohort study, 417 adults with biopsy‐proven MASLD (2001–2024) were followed for incident malignancy (median follow‐up, 4.75 years). Patients were categorized using standard FIB‐4 thresholds (< 1.3, 1.3–2.67, ≥ 2.67). Cause‐specific Cox models and Fine–Gray competing‐risk models were used to estimate adjusted hazard ratios (HRs) for HCC and extrahepatic cancer. Discriminative performance was evaluated using Harrell's C‐index and time‐dependent area under the curve (AUC) values at 3, 5, and 10 years. Results During followup, 24 patients (5.8%) developed HCC, whereas 40 (9.6%) developed extrahepatic cancer. The ≥ 2.67 category was associated with markedly increased risks of HCC (adjusted HR 35.31) and extrahepatic cancer (adjusted HR 13.10) compared with < 1.3. Associations remained robust in competing‐risk and age‐adjusted sensitivity analyses. FIB‐4 showed the highest and most consistent discriminative performance among the evaluated indices (C‐indices of 0.83 for HCC and 0.78 for extrahepatic cancer). Time‐dependent AUCs improved over time and exceeded 0.80 for HCC after 5 years. Conclusion The FIB‐4 index provides consistent long‐term risk stratification for HCC and shows an association with extrahepatic cancer among commonly used noninvasive fibrosis markers. Its strong time‐dependent discrimination for HCC and moderate discrimination for extrahepatic cancer support its potential role as a simple, widely accessible tool for long‐term risk stratification in MASLD.