Metformin-associated Chemopreventive Effects on Recurrence After Hepatic Resection of Hepatocellular Carcinoma: From In Vitro to a Clinical Study

Abstract

We investigated metformin-induced cytotoxic effects in vitro and assessed the chemopreventive effects of metformin in patients undergoing hepatic resection (HR) for hepatocellular carcinoma (HCC). This study consisted of laboratory and clinical studies. In vitro study using HCC cell lines revealed noticeable cytotoxic effects of metformin, that were largely weaker than those of sorafenib. In the clinical study, no statistical differences were found in tumor recurrence or overall survival between metformin and control groups. In contrast, there was a non-significant difference in tumor recurrence between metformin and propensity score-matched control groups, but there was a significant difference in overall patient survival. Metformin administration was an independent risk factor for patient survival. In conclusion, our in vitro laboratory study demonstrated the presence of cytotoxic effects of metformin. Metformin administration was associated with reduced tumor recurrence and helped induce significant improvements in overall patient survival in patients who underwent HR for HCC.