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The incidence of hepatocellular carcinoma (HCC), the most common primary liver cancer, is increasing in the US and tripled during the past two decades. The reasons for such phenomenon remain poorly understood. Texas is among continental states with the highest incidence of liver cancer with an annual increment of 5.7%. Established risk factors for HCC include Hepatitis B and C (HBV, HCV) viral infection, alcohol, tobacco and suspected risk factors include obesity and diabetes. While distribution of these risk factors in the state of Texas is similar to the national data and homogeneous, the incidence of HCC in this state is exceptionally higher than the national average and appears to be dishomogeneous in various areas of the state suggesting that other non-recognized risk factors might play a role. No population-based studies are currently available investigating the effect of exposure to Hazardous Air Pollutants (HAPs) as a contributing risk factor for liver cancer. Incidence rate of liver cancer in Texas by counties for the time period between 2002 and 2012 was obtained from the Texas Cancer Registry (TCR). Through Principal Component Analysis (PCA) a subgroup of pollutants, explaining almost all the dataset variability, were identified and used to cluster Texas counties. The analysis generated 4 clusters showing liver cancer rate either higher or lower than national average in association with either high or low levels of HAPs emission in the environment. The study shows that the selected relevant HAPs, 10 among 253 analyzed, produce a significant correlation (P = 0.01-0.05) and some of these have been previously identified as carcinogens. An association between the increased production and consequent exposure to these HAPs and a higher presence of liver cancer in certain counties is suggested. This study provides a new insight on this complex multifactorial disease suggesting that environmental substances might play a role in the etiology of this cancer.

Isolation of hepatocytes from cirrhotic human livers and subsequent primary culture are important new tools for laboratory research and cell-based therapeutics in the study of hepatocellular carcinoma (HCC). Using such techniques, we have previously identified different subpopulations of human hepatocytes and among them one is showing a progressive transformation of hepatocytes in HCC-like cells. We have hypothesized that increasing the distance from the neoplastic lesion might affect hepatocyte function and transformation capacity. However, limited information is available in comparing the growth and proliferation of human hepatocytes obtained from different areas of the same cirrhotic liver in relation to their distance from the HCC lesion. In this study, hepatocytes from 10 patients with cirrhosis and HCC undergoing surgical resections from specimens obtained at a proximal (CP) and distal (CD) distance from the HCC lesion were isolated and placed in primary culture. CP hepatocytes (CP-Hep) were isolated between 1 to 3 cm (leaving at least 1cm margin to avoid cancer cells and/or satellite lesions), while CD hepatocytes (CD-Hep) were isolated from more than 5 cm or from the contralateral-lobe. A statistical model was built to analyze the proliferation rates of these cells and we evaluated expression of HCC markers (Glypican-3 (GPC3), αSmooth Muscle Actin (α-SMA) and PCNA). We observed a significant difference in proliferation and in-vitro growth showing that CP-Hep had a proliferation pattern and rate significantly different than CD-Hep. Based on these data, this model can provide information to predict growth of human hepatocytes in primary culture in relation to their pre-cancerous state with significant differences in the HCC markers expression. This model provides an important innovative tool for in-vitro analysis of HCC.