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.