Steatosis grade and cardiometabolic burden as determinants of hepatocellular carcinoma risk after hepatitis C cure in patients with metabolic dysfunction-associated steatotic liver disease.

[BACKGROUND] Coexistence of metabolic dysfunction-associated steatotic liver disease (MASLD) increases hepatocellular carcinoma (HCC) risk after HCV cure.

[OBJECTIVE] The specific impacts of steatosis grade and cardiometabolic burden on HCC risk among patients with MASLD remain unclear.

[DESIGN] We enrolled 700 patients who underwent biannual HCC surveillance after HCV cure. Steatosis was graded by vibration-controlled transient elastography using controlled attenuation parameter cut-offs of 248-267, 268-279 and ≥280 dB/m, corresponding to S1, S2 and S3, respectively. Cardiometabolic risk factors (CMRFs) were assessed at the time of viral cure. Cumulative HCC incidence was compared across steatosis grades and cardiometabolic burdens using the log-rank test. Multivariable Cox proportional hazards models with Akaike Information Criterion-based selection evaluated the effects of steatosis grade, cardiometabolic burden and individual CMRFs on HCC risk, expressed as adjusted HRs (aHRs) with 95% CIs. Fine-Gray subdistribution hazard models were used for sensitivity analyses.

[RESULTS] Cumulative HCC incidence differed significantly across steatosis grades (p=0.035) but not across cardiometabolic burdens (p=0.62). In multivariable analysis adjusted for age, sex, liver stiffness and alpha-fetoprotein, advanced steatosis remained independently associated with HCC risk (S3 vs S1: aHR 2.15, 95% CI 1.25 to 3.69, p=0.005). Among individual CMRFs, pre-diabetes or type 2 diabetes was significantly associated with HCC risk (aHR 2.33, 95% CI 1.38 to 3.94, p=0.002). Fine-Gray analyses confirmed these associations.

[CONCLUSION] Advanced hepatic steatosis and glycaemic abnormalities, rather than overall cardiometabolic burden, are independently associated with increased HCC risk after HCV cure.