High Cardiometabolic Risk Burden Predicts Adverse Outcomes in Patients with MASLD-Related Hepatocellular Carcinoma

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a rapidly growing cause of hepatocellular carcinoma (HCC); however, the prognostic implications of the cumulative cardiometabolic risk factor (CMRF) burden remain unclear. Methods: In this single-center retrospective cohort, we identified 94 patients with MASLD-related HCC after excluding other etiologies of liver disease. The modified CMRF count (based on eight routinely available variables) was calculated, and the patients were stratified according to the count (<5 or ≥5). In addition to baseline data, survival was assessed by the Kaplan-Meier log-rank test, and prognostic factors were evaluated by Cox regression. Results: A higher CMRF burden was associated with older age, a greater cumulative tumor diameter, and a higher level of protein induced by vitamin K absence or antagonist-II (PIVKA-II), but not with the level of alpha-fetoprotein. Patients with a CMRF count ≥5 had significantly worse overall survival (OS) and recurrence-free survival (RFS). In the Cox models, a CMRF count ≥5 was associated with poor OS; the association with RFS was evident in univariate analysis but was attenuated after adjustment. Among individual factors, hypertension was independently associated with OS, whereas diabetes lost significance after adjustment. The level of triglycerides was not a prognostic factor, while higher high-density lipoprotein cholesterol levels were associated with better OS and RFS by the Kaplan-Meier method. Conclusions: The cumulative metabolic burden, represented by a modified CMRF count, was associated with larger tumors, a higher PIVKA-II level, and inferior survival in patients with MASLD-related HCC.