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This focus led to significant breakthroughs, but it became clear in animal models that single-pathway stimulation had a ceiling effect regarding metabolic stabilization and lipid management

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2017 Dec;140(6):e20173034

In non-alcoholic fatty liver disease, several pathophysiological arguments suggest (in the absence of proof from clinical trials) that long-term methotrexate therapy worsens liver damage and the progression of liver disease