Vitale A, Svegliati-Baroni G, Ortolani A, et al. - In Italy, MAFLD(metabolic dysfunction-associated fatty liver disease)-associated hepatocellular carcinoma (HCC) prevalence is swiftly growing to cover the majority of patients with HCC. A lower risk of HCC-related death exists in MAFLD HCC patients despite a less favourable cancer stage at diagnosis, this indicates decreased cancer aggressiveness.

• A total of 6882 HCC patients were analyzed to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC.

• Most HCC cases (68.4%) had MAFLD, and a significant increase over time in the proportion of both total MAFLD and S-MAFLD HCC has been observed (from 50.4% and 3.6% in 2002–2003, to 77.3% and 28.9% in 2018–2019, respectively).

• Older age, more often male gender, less often cirrhosis with clinically relevant portal hypertension and a surveillance-related diagnosis, more commonly large tumours and extrahepatic metastases, were seen in patients with S-MAFLD HCC.

• Post-weighting, and relative to patients with non-MAFLD, S-MAFLD and M-MAFLD HCC demonstrated a significantly lower overall and HCC-related risk of death.

• A significantly higher risk of non-HCC-related death was present in patients with S-MAFLD HCC.