PRIMARY PREVENTION OF HEPATOCELLULAR CARCINOMA BY METFORMIN IN PATIENTS WITH VIRAL C CIRRHOSIS : PROSPECTIVE MULTICENTER STUDY, RANDOMIZED CONTROL TRIAL. Ancillary Study of the ANRS CO12 CirVir Cohort

Hepatocellular carcinoma (HCC) is currently the first cause of death of patients with compensated HCV cirrhosis.Despite progresses,existing therapies are limited in their ability to prevent recurrences. Even diagnosed at early stage, long-term prognosis remains poor due to the high rate of recurrence after local treatments. Liver transplantation the only long-term curative treatment is limited by advanced age, comorbidities or the shortage of the graft It concerns less than 5 % of HCC patients . Therefore, the best approach to reduce mortality remains the reduction of HCC incidence.

Abundant observational studies have related a relation between insulinoresistance occurrence and outcome of many cancers. The level of IR assessed by the HOMA index have been recognized as an independent predictive factor of HCC occurrence in patients with compensated viral C cirrhosis. Metformin, a Type 2 diabetic treatment drug, inhibits hepatic gluconeogenesis and increases the stimulation of the glucose uptake in muscle.

Independently of its' anti diabetic effects, Metformin is credited of anti tumoral, anti oxidant, anti inflammatory, and anti angiogenic properties.

Amount epidemiological and experimental data have demonstrated the anti tumoral and chemopreventive effect of metformin in certain cancers.

From our cohort of patients with compensated HCV cirrhosis and not treated by insulin, we have observed that the level of IR assessed by the HOMA was a strong and independent risk factor of HCC occurrence and liver related death. We have also observed in our cohort of diabetic patients with compensated HCV cirrhosis, that treatment by Metformin was associated with a decreased risk of HCC occurrence and liver related death.