Cardiometabolic Signatures Drive Divergent HCC Risk Trajectories in MASLD-Associated Advanced Fibrosis

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognised as a systemic disorder driven by cardiometabolic risk factors (CMRF), including obesity, Type 2 diabetes mellitus (T2DM), hypertension, and dyslipidaemia. 1-3 While advanced fibrosis (AF) is a major determinant of hepatocellular carcinoma (HCC) risk, the impact of cumulative metabolic burden and specific CMRF combinations on HCC trajectories remains unclear. 2,3 This study aimed to evaluate how distinct metabolic profiles influence HCC risk in patients with MASLD with AF.

In this Italian cohort study, patients with MASLD-AF were stratified into clusters based on the number and combination of CMRFs (from one to four). Individual metabolic dysfunction profiles were defined through non-redundant permutations of CMRFs. 4 The primary endpoint was 5-year HCC incidence, while secondary endpoints included HCC staging at diagnosis (Milan-out criteria) 5 and identification of high-risk metabolic profiles. Multivariable competing risk models adjusted for demographic and clinical variables were applied.