Association of metabolic dysfunction-associated steatotic liver disease trajectories with incident liver cancer: a UK Biobank cohort study

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a contributor to hepatocellular carcinoma. Whether repeated assessment of MASLD provides additional prognostic information for liver cancer risk remains unclear. Methods: Using the UK Biobank, we included 12,111 participants who underwent both baseline and follow-up health screenings. MASLD was defined at each assessment as fatty liver index ≥60 plus at least one cardiometabolic risk criterion. Four trajectory groups were defined: no MASLD → no MASLD, no MASLD → MASLD, MASLD → no MASLD, and MASLD → MASLD. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: At baseline, 4,008 participants (33.1%) had MASLD. MASLD at period 1 was associated with a higher risk of incident liver cancer compared with no MASLD (aHR, 2.81; 95% CI, 1.20-6.58). A similar association was observed for MASLD at period 2 (aHR, 2.61; 95% CI, 1.12-6.06). In trajectory analyses, MASLD → no MASLD (aHR, 4.00; 95% CI, 1.01-15.80) and MASLD → MASLD (aHR, 3.51; 95% CI, 1.31-9.44) were associated with higher liver cancer risk than no MASLD → no MASLD. Conclusions: MASLD at either assessment was associated with higher incident liver cancer risk. Trajectory analyses suggest that persistent MASLD and prior MASLD exposure may both carry prognostic importance.