Obesity-related hepatocellular carcinoma: roles of risk factors altered in obesity

Epidemiological data have demonstrated that the prevalence of either obesity or hepatocellular carcinoma (HCC) is increasing worldwide during past decades, and obesity has been unequivocally shown to be a risk factor for HCC. It has been reported that a significant proportion of HCC in obesity develops in cryptogenic cirrhosis, which is largely associated with the progression of nonalcoholic fatty liver disease, especially nonalcoholic steatohepatitis. Since the HCC is a highly malignant tumor with a poor prognosis, a better understanding of the molecular mechanisms may help researchers to explore new approaches for preventing and treating the obesity-related HCC, and thereby facilitating a substantial reduction of morbidity and mortality. In this article, we reviewed the mechanisms underlying the relationship between obesity and HCC, with an emphasis on the roles of insulin/insulin-like growth factor axis, adipose tissue derived hormones, oxidative stress, and liver stem cells. In addition, we will discuss the impact of life-style modification on obesity-related HCC.