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This review differentiates between low-dose methotrexate used in autoimmune diseases and high-dose methotrexate used in oncology, emphasizing mechanistic differences in hepatotoxicity pathways, integrating MASLD-related risk factors, and summarizing current non-invasive diagnostic strategies

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Special emphasis is placed on the crosstalk between mTOR signaling and mitochondrial regulation, highlighting the mechanisms by which these two metabolic hubs co-regulate cellular adaptation, survival, and disease progression