Metabolic Dysfunction‐Associated Steatotic Liver Disease (MASLD) Impacts Long‐Term Outcomes After Curative‐Intent Surgery for Hepatocellular Carcinoma

ABSTRACT Background Curative surgery for hepatocellular carcinoma (HCC) includes liver resection (LR) and orthotopic liver transplantation (OLT). Due to the obesity epidemic, metabolic dysfunction‐associated steatotic liver disease (MASLD) is a frequent HCC aetiology that often coincides with increased alcohol consumption, termed MetALD, or even alcohol‐associated liver disease (ALD). Methods Patients undergoing LR or OLT for HCC at Charité—Universitätsmedizin Berlin (2010–2020) were included in this retrospective cohort study investigating disease aetiology, time to recurrence (TTR), overall survival (OS) and CT‐based body composition. Results Out of 579 patients with HCC, 417 underwent LR and 162 OLT. Tumour aetiologies were viral n = 191 (33.0%), MASLD n = 158 (27.3%), MetALD n = 51 (8.8%), ALD n = 68 (11.7%) and other/cryptogenic n = 111 (19.2%). Patients with MASLD and MetALD had more intramuscular ( p < 0.001, p = 0.015) and visceral fat (both p < 0.001) than patients with non‐metabolic dysfunction aetiologies. Patients with MASLD‐HCC had comparable TTR (median 26 months, [95% CI: 23–31] vs. 30 months [95% CI: 4–57], p = 0.425) but shorter OS than patients with other HCC aetiologies (63 months [95% CI: 42–84] vs. 80 months [95% CI: 60–100], hazard ratio: 1.53 [95% CI: 1.050–2.229], p = 0.026) after LR. Multivariate analysis confirmed MASLD aetiology, portal vein thrombosis and MELD score ≥ 10 as independent prognostic factors for OS in LR (adjusted p = 0.021, p < 0.001, p = 0.003), even after excluding in‐hospital mortality (adjusted p = 0.016, p = 0.002, p = 0.002). Causes of death were similar in MASLD and non‐MASLD aetiology. Conclusions Patients with HCC undergoing LR and meeting the new MASLD criteria have significantly shorter OS. This study provides empirical prognostic evidence for the novel MASLD/MetALD classification in a large European cohort of patients undergoing curative‐intent HCC therapy.