oa Mechanisms of Liver Carcinogenesis: Studies of Co-morbidity Factors Using Animal Models

Hepatocellular carcinoma (HCC) is the most common type of primary malignancy in the liver. Main risk factors of HCC are well-defined and include hepatitis B virus (HBV); lifestyle, diet and environmental factors (e.g., alcoholic beverages, aflatoxin B1 (AFB1), and tobacco smoking); and metabolic diseases (e.g., obesity, diabetes and non-alcoholic steatohepatitis). Importantly, the rise in incidence of HCC in the developed countries has been attributed, at least in part, to an increase in hepatitis C virus (HCV) infections and non-alcoholic steatohepatitis, pathological states whose prevalence is growing in the US and Europe. In addition, liver fibrosis and cirrhosis are well known precursor liver disease states for hepatocellular HCC in humans. While animal model studies of HCC have contributed much of the understanding of the molecular events leading to disease initiation, progression and promotion, few publications examined co-morbidity factors that are known to contribute to HCC in humans. This presentation will describe two examples of experimental animal models of HCC where co-morbidity factors (HCV+AFB1, or genotoxic carcinogen diethylnitrosamine+liver fibrosis) were explored. These studies afford an opportunity to examine the molecular mechanisms that are crucial for the synergy between co-morbidity factors.