Nature Communications, Published online: 22 August 2026; doi:10.1038/s41467-026-77089-9 Alcohol consumption and high fat diet can drive liver cancer through distinct pathways. Here, the authors characterize three murine models of steatohepatitis-associated hepatocarcinogenesis that recapitulate metabolic dysfunction-associated steatohepatitis (MASH), alcohol-related liver disease (ALD), and their overlapped condition, MetALD, showing that alcohol reshapes liver zonal plasticity and β-catenin-AhR signaling to alter tumor origin and increase immunotherapy sensitivity.