Diabetes Mellitus and Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Diabetes Metab Res Rev. 2012 Feb;28(2):109-22. doi: 10.1002/dmrr.1291.


Studies of diabetes and hepatocellular carcinoma (HCC) yielded inconsistent findings. This meta-analysis was conducted to examine the association between diabetes and risk of HCC. Studies were identified by searching PUBMED and MEDLINE database up to February 2011. Pooled risk estimates were calculated using the random-effects model. Potential sources of heterogeneity were explored by subgroup analyses. A total of 17 case-control studies and 32 cohort studies were included in the meta-analysis. The combined risk estimate of all studies showed a statistically significant increased risk of HCC prevalence among diabetic individuals (RR = 2.31, 95% CI: 1.87-2.84). The pooled risk estimate of 17 case-control studies (OR = 2.40, 95% CI: 1.85-3.11) was slightly higher than that from 25 cohort studies (RR = 2.23, 95% CI: 1.68-2.96). Metformin treatment was potentially protective. On the contrary, long duration of diabetes and sulfonylureas or insulin treatment possibly increase HCC risk. Also meta-analysis of 7 cohort studies found a statistically significant increased risk of HCC mortality (RR = 2.43, 95% CI: 1.66-3.55) for individuals with (versus without) diabetes. This meta-analysis shows that diabetes is associated with moderately increased risk of HCC prevalence, as well as HCC mortality. Considering the rapidly increasing prevalence of diabetes mellitus, the study underlines the need for cancer prevention in diabetic individuals. Further investigation is needed to focus on the potential mechanism for the pathogenesis of HCC and the link between HCC and different types, severity, treatment and duration of diabetes.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Carcinoma, Hepatocellular / etiology*
  • Case-Control Studies
  • Cohort Studies
  • Diabetes Complications / prevention & control*
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / epidemiology*
  • Humans
  • Insulin / therapeutic use
  • Liver Neoplasms / etiology*
  • Metformin / therapeutic use
  • Risk
  • Sulfonylurea Compounds / adverse effects


  • Insulin
  • Sulfonylurea Compounds
  • Metformin