Survival after curative hepatectomy for hepatocellular carcinoma in patients with and without MAFLD: a western cohort study.

Background: Evidence suggesting that hepatocellular carcinoma (HCC) arising in patients with metabolic-associated fatty liver disease (MAFLD) is associated with better outcomes than HCC related to other liver diseases has been derived largely from non-Western cohorts and has incompletely accounted for the severity of underlying liver disease. Whether MAFLD independently influences survival after hepatic resection, particularly in Western populations, remains uncertain. Methods: In this retrospective single-center cohort study, adults who underwent curative-intent hepatic resection for HCC at a Western academic center were evaluated. Patients managed without surgery were excluded. MAFLD was defined according to international consensus criteria. In the primary analysis, patients were classified as MAFLD-positive if they fulfilled MAFLD criteria and had no competing chronic liver disease etiology. Overall survival (OS) and disease-free survival (DFS) were assessed with Cox proportional-hazards models adjusted for cirrhosis, albumin-bilirubin grade, tumor burden, performance status, and alpha-fetoprotein level among other confounders. Results: Among 156 patients, 89 (57.1%) were classified as MAFLD-positive. As compared with MAFLD-negative patients, MAFLD-positive patients were older, more frequently obese and diabetic, and less likely to have cirrhosis (all P ≤ 0.043). Open or hybrid resection was more common in the MAFLD-positive group, whereas minimally invasive resection was more common in the MAFLD-negative group (67.4% vs. 44.8% and 32.6% vs. 55.2%, respectively; P = 0.006). In unadjusted analyses, MAFLD-positive status was associated with longer DFS and a trend towards longer OS; however, these associations were attenuated after multivariable adjustment. MAFLD was not independently associated with OS (adjusted hazard ratio, 0.91; 95% confidence interval [CI], 0.45 to 1.84; P = 0.785) or DFS (adjusted hazard ratio, 0.58; 95% CI, 0.28 to 1.19; P = 0.139). Cirrhosis, impaired performance status, elevated alpha-fetoprotein, and greater tumor burden were the principal predictors of postoperative outcomes. Conclusions: In this Western resection cohort, MAFLD was not independently associated with OS or DFS after curative hepatectomy once liver disease severity and tumor burden were taken into account. Prognosis was driven primarily by established hepatic and oncologic factors rather than metabolic etiology alone.