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Our objective was to comparatively profile the metabolite composition of primary hepatocellular carcinoma (HCC) tumors from alcoholic liver disease (ALD), hepatitis B virus (HBV)-infected, and hepatitis C virus (HCV)-infected cirrhotic patients. Primary HCC tumors were collected from ALD, HBV-infected, and HCV-infected cirrhotic patients (n=20 each). High-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and metabonomic data analysis were performed to compare HCC tumors from the three groups. Sensitivity analyses were performed to determine the effects of diabetes, high body mass index, and smoking status. Metabonomic pathway analyses were conducted to identify dysregulated pathways. Three metabolites were significantly differentiated between ALD and HBV-infected patients, which were distinguishable by changes in ketone body, glycerolipid, and phenylalanine metabolism. Five metabolites were significantly differentiated between ALD and HCV-infected patients, which were distinguishable by changes in ketone body, alanine/aspartate/glutamate, and phenylalanine metabolism. Six metabolites were significantly differentiated between HBV-infected and HCV-infected patients, which were distinguishable by changes in ketone body, tyrosine, and alanine/aspartate/glutamate metabolism. In conclusion, this is the first study to demonstrate that the metabolic phenotypes of primary HCC tumors vary significantly across ALD, HBV-infected, and HCV-infected cirrhotic patients.

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Differential metabonomic profiles of primary hepatocellular carcinoma tumors from alcoholic liver disease, HBV-infected, and HCV-infected cirrhotic patients