Abstract
The cumulative effects of hepatic injury due to hepatitis B virus (HBV) infections and aflatoxin-B1 (AFB1) exposure are the major risk factors of HCC. Understanding early metabolic changes involving these risk factors in an animal model closely resembling human hepatocellular carcinoma (HCC) is critical for biomarker discovery and disease therapeutics. We have used the hepatitis B surface antigen (HBsAg) transgenic mouse model that mimics HBV carriers with and without AFB1 treatment. We investigated early metabolic changes from preneoplastic state to HCC by non-invasive longitudinal imaging in three HCC groups of mice: HBsAg + AFB1(Gp-I), AFB1 alone (Gp-II), HBsAg alone (Gp-III) and a control group (wild-type untreated; Gp-IV). For the first time, we have identified acylcarnitine signals in vivo in the liver prior to the histological manifestation of the tumors in all three groups. Acylcarnitine concentration increased with increase in tumor growth in all HCC mouse models, indicating elevated metabolic activity and increased cell turnover. This was confirmed in a pilot study using human serum from HCC patients, which revealed a higher concentration of acylcarnitine compared with normal subjects. Translational clinical studies can be designed to detect acylcarnitine in patients with high risk factors for HCC.
Highlights
The cumulative effects of hepatic injury due to hepatitis B virus (HBV) infections and aflatoxin-B1 (AFB1) exposure are the major risk factors of Hepatocellular carcinoma (HCC)
The cumulative effect of risk factors hepatitis B surface antigen (HBsAg) and AFB1 contributed to highly aggressive and proliferative tumor growth in Group I (Gp-I) HCC compared with Gp-II and III HCC models
Understanding the independent risk factors and early metabolic changes involving HBV, and AFB1 is essential for biomarker discovery and disease therapeutics
Summary
The cumulative effects of hepatic injury due to hepatitis B virus (HBV) infections and aflatoxin-B1 (AFB1) exposure are the major risk factors of HCC. Understanding early metabolic changes involving these risk factors in an animal model closely resembling human hepatocellular carcinoma (HCC) is critical for biomarker discovery and disease therapeutics. Acylcarnitine concentration increased with increase in tumor growth in all HCC mouse models, indicating elevated metabolic activity and increased cell turnover. This was confirmed in a pilot study using human serum from HCC patients, which revealed a higher concentration of acylcarnitine compared with normal subjects. The risk factors associated with HCC include hepatitis B (HBV) and hepatitis C (HCV) viral infections, and aflatoxin-B1 (AFB1) exposure[2]. We investigated the early metabolic changes from normal liver to malignant stage involving independent and cumulative risk factors of hepatitis B, and AFB1 exposure. Longitudinal MRI and MRS were performed to characterize the HCC and studied the changes in lipid composition, and their correlation to tumor malignancy
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