The Metabolic Syndrome, Diabetes and Steatosis and Incidence of Hepatocellular

Carcinoma The incidence of hepatocellular carcinoma (HCC) is increasing, but the temporal changes of risk factors remain unclear. A significant proportion of HCC develops in cryptogenic cirrhosis, and may present the most worrisome complication of non-alcoholic

steatohepatitis. Non-alcoholic steatohepatitis is tightly linked to insulin resistance and several features of the MeS, e.g. obesity, diabetes and dyslipidemia.
A systemic review and meta-analysis of a total of 26 studies revealed that diabetes
is associated with an increased risk for HCC [50]. A population-based case-control
study in the USA documented that diabetes increases the risk of HCC two- to threefold, regardless of the presence of other major HCC risk factors. Findings from this study suggest that diabetes is an independent risk factor for HCC [51]. Databases from the Surveillance & Risk Assessment Division of Health Canada & Statistics Canada were analyzed for trends in both age-adjusted incidence of and mortality due to HCC from 1984 to 2001 [52]. The incidence of HCC in Canada has increased in the past 20 years and is associated with a rise in the incidence of hepatitis C, obesity and diabetes. Similar results are reported by two studies from Taiwan [53] and Japan [54].

It is likely that the association of HCC with obesity and diabetes represents the
progression of underlying non-alcoholic fatty liver disease to cirrhosis. The mechanisms most likely involve replicative senescence of steatotic mature hepatocytes and compensatory hyperplasia of progenitor cells as a reaction to chronic injury due to ongoing non-alcoholic steatohepatitis [55] and inflammation [56].