Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy

Clin Mol Hepatol. 2024 Jul;30(3):468-486. doi: 10.3350/cmh.2024.0038. Epub 2024 Apr 19.

Abstract

Background/aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients.

Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development.

Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients.

Conclusion: Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Keywords: Hepacivirus; Hepatitis C; Hepatocellular carcinoma; Metformin; Statins.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents* / therapeutic use
  • Carcinoma, Hepatocellular* / epidemiology
  • Carcinoma, Hepatocellular* / etiology
  • Carcinoma, Hepatocellular* / prevention & control
  • Diabetes Mellitus
  • Female
  • Hepatitis C, Chronic* / complications
  • Hepatitis C, Chronic* / drug therapy
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Incidence
  • Liver Neoplasms* / epidemiology
  • Liver Neoplasms* / etiology
  • Liver Neoplasms* / prevention & control
  • Male
  • Metformin* / therapeutic use
  • Middle Aged
  • Proportional Hazards Models
  • Risk Factors
  • Taiwan / epidemiology

Substances

  • Metformin
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Antiviral Agents