Hyperinsulinaemia and insulin signalling in the pathogenesis and the clinical course of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and is one of the leading causes of cancer-related death. The risk factors for HCC include cirrhosis, chronic viral hepatitis, heavy alcohol intake and metabolic diseases such as obesity, type 2 diabetes and metabolic syndrome. Insulin resistance is a common denominator of all of these conditions and is tethered to hyperinsulinaemia. Here, we give an overview of the recent advances linking hyperinsulinaemia to HCC development and progression. In particular, we summarise the underlying causes of hyperinsulinaemia in the setting of chronic liver diseases. We present epidemiological evidence linking metabolic diseases to HCC risk and HCC-related mortality, as well as the pathogenic cellular and molecular mechanisms explaining this relation. A better understanding of the mechanisms by which insulin participates in HCC biology might ultimately provide novel opportunities for prevention and treatment.