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Acetylsalicylic acid (ASA) and pentoxifylline (PTX) have shown promise for treatment of NAFLD, but have not yet been tested in combination. Guinea pigs were fed a high\u2010fat diet for 16\u00a0weeks and then continued on the diet while being treated with ASA, PTX or ASA+PTX for 8\u00a0weeks. Chow\u2010fed animals served as healthy controls. Guinea pigs were CT scanned before intervention start and at intervention end. Animals without steatosis (ie NAFLD) at week 16 were excluded from the data analysis. ASA and PTX alone or in combination did not improve hepatic steatosis, ballooning, inflammation or fibrosis nor did the treatments affect liver enzymes (aminotransferases and alkaline phosphatase) or circulating lipids. Liver triglyceride levels, relative liver weight and hepatic mRNA expression of monocyte chemoattractant protein 1, interleukin 8 and platelet\u2010derived growth factor b were nominally decreased. 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