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Keywords: Liver, MASLD, MASH, Fibrosis, HCC, Sexual dimorphism, Animal models Highlights The liver exhibits pronounced sexual dimorphism, influenced by sex hormones, sex chromosomes, ageing, and circadian regulation Estrogen signaling is protective for liver metabolism, while postmenopausal hormonal decline increases disease vulnerability Sex-dependent differences in lipid handling, xenobiotic metabolism, and immune responses shape the course of liver diseases Generating and weighing alternative hypotheses for apparent sex differences found in data can reveal the important role of gender-related social factors in shaping human biology Limited inclusion of both sexes in preclinical and clinical studies hampers biomarker discovery and therapeutic optimisation

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