Identification of serum biomarkers associated with hepatitis B virus-related hepatocellular carcinoma and liver cirrhosis using mass-spectrometry-based metabolomics

Hepatitis B virus (HBV) infection is a major risk factor for deaths from liver cirrhosis and hepatocellular carcinoma (HCC). With a long-term goal of improving early diagnosis, we aimed to identify specific biomarkers associated with the development of HCC and liver cirrhosis in patients with HBV infection. Serum samples from 46 HBV infected patients with HCC and liver cirrhosis and 24 age-gender matched healthy subjects were profiled by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. It was found that fatty acids and long-chain acylcarnitines were significantly elevated in HBV-related HCC patients, whereas most of the carbohydrates, amino acids, short- and medium-chain acylcarnitines, and glycerophospholipids were decreased, when compared to healthy subjects. The up-regulation of fatty acids and long-chain acylcarnitines in HCC was positively correlated with liver cirrhosis state. Logistic regression analysis indicated that palmitoylcarnitine together with arginine was an effective combined marker for diagnosing HBV-related HCC with 97.3 % sensitivity and 100 % specificity. Linoleic acid plus glucose was useful for discrimination of liver cirrhosis in HCC patients with 79.2 % sensitivity and 75 % specificity. These findings demonstrate that mass-spectrometry-based metabolomics is a promising tool that could provide special insights into tumor metabolism and identify novel biomarkers for detection of HCC and liver cirrhosis from HBV infected patients.