Influence of diabetes mellitus and effectiveness of metformin on hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers, and it is important to elucidate the carcinogenic factors and improve the recurrence and prognosis of HCC patients. Diabetes mellitus (DM) has been reported to be a risk factor for the carcinogenesis of many cancers including HCC, and the mechanism of DM for carcinogenesis is gradually being elucidated. Metformin, a drug for DM, has been reported to have anticancer effects on many cancers, including HCC. Metformin not only suppresses carcinogenesis but also improves the prognosis of recurrence after treatment, and there are many reports on the mechanism of these effects. In this review, we describe the mechanism of action of hyperglycemia and hyperinsulinemia on carcinogenesis by DM against HCC. The carcinogenic effects of DM on hepatitis B, hepatitis C, and nonalcoholic fatty liver disease by etiology are also described. In addition, the carcinogenic effect of metformin on HCC and its mechanism of action are reviewed. We also discuss the effects of metformin on recurrence after hepatectomy and radiofrequency therapy and the effects of metformin in combination with anticancer medicine, focusing on the inhibition of HCC development.