Hepatocellular Carcinoma in Obesity: Finding a Needle in the Haystack?

Obesity has been implicated in the development of hepatocellular carcinoma (HCC), one of the most common malignancies worldwide with an increasing incidence in the United States. Obesity and associated metabolic disorders such as type II diabetes and the metabolic syndrome are key factors in the development of nonalcoholic fatty liver disease (NAFLD) and promote several molecular mechanisms that may contribute to hepatocarcinogenesis. The vast majority of HCC occur in cirrhotic livers, but a subgroup of patients may develop HCC in non-advanced NAFLD. While the incidence rate for noncirrhotic HCC is low, the population-attributable fraction is still significant due to the extraordinary prevalence of obesity-associated liver disease. This is a challenge since HCC surveillance cannot be provided to the large population of non-advanced NAFLD in a cost-efficient way and requires enhanced risk stratification strategies. Recent advances may offer new clinical, laboratory, and genetic biomarkers and help us meet this important public health need.