Impact of Metformin on the Prognosis of Cirrhosis Induced by Viral Hepatitis C in Diabetic Patients

CONTEXT: Insulin resistance plays a role in hepatocarcinogenesis and is decreased by metformin treatment. OBJECTIVE: The aim of the study was to assess the influence of metformin treatment on the prognosis of compensated hepatitis C virus (HCV) cirrhosis in patients with type 2 diabetes. DESIGN AND SETTING: We studied an observational prospective cohort (1988-2007) at a university hospital referral center. PATIENTS: A total of 100 consecutive diabetic patients (53 men, age 61 ± 11 yr) with ongoing HCV cirrhosis and no contraindication for metformin were included in a screening program for hepatocellular carcinoma (HCC). MAIN OUTCOMES: The patients were prospectively followed up for HCC incidence, liver-related death, or hepatic transplantation. RESULTS: The level of platelet count was significantly lower in patients treated with metformin (n = 26) compared with those not treated with metformin (n = 74) [117 (interquartile range, 83-166) vs. 149 (105-192) Giga/liter, P = 0.045]. During a median follow-up of 5.7 (3.8-9.5) yr, one patient was lost to follow-up, 39 developed a HCC, and 33 died from liver causes or were transplanted. The 5-yr incidence of HCC was 9.5 and 31.2% (P = 0.001) and of liver-related death/transplantation, 5.9 and 17.4% (P = 0.013), in patients who received metformin treatment and in those who did not, respectively. In multivariate analysis, metformin treatment was independently associated with a decrease in HCC occurrence [hazard ratio, 0.19 (95% confidence interval, 0.04-0.79); P = 0.023] and liver-related death or transplantation [hazard ratio, 0.22 (95% confidence interval, 0.05-0.99); P = 0.049]. CONCLUSIONS: In patients with type 2 diabetes and HCV cirrhosis, use of metformin is independently associated with reduced incidence of HCC and liver-related death/transplantation.