Over the past three decades hepatocellular carcinoma (HCC) is one of the few cancers for which incidence has increased in the United States (US) (1, 2). This is alarming because HCC has been recognized by the US Congress as a recalcitrant cancer of which the 5 year survival is less than 50%1. Consequently, it is projected that by 2030 cancers of the liver and bile duct will be the third leading cause of cancer deaths in the US (3). The increase has been primarily attributed to three risk factors leading to hepatic dysfunction: (1) Hepatitis C virus (HCV) infection; (2) obesity-related metabolic dysfunction leading to Non Alcoholic Fatty Liver Disease (NAFLD); and (3) alcohol-use disorders (AUD). While HCV infection represents the greatest individual risk among the three, what is driving the epidemic at the population level is more complex. Due to the high prevalence of metabolic syndrome (20%) and obesity (35%) in the general population, the population attributable fraction (PAF) for NAFLD is estimated at 32%, followed by HCV infection at 20.5% and AUD at 13.4% (4, 5). Consequently, it may be that the continued increase in HCC will be driven by the rising rates of obesity related metabolic disorders leading to NAFLD (6, 7).
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