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

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

Affiliations
  • 1Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
  • 2Hepatitis Research Centre, School of Medicine and Centre for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
  • 3Health Management Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
  • 4Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Centre, Tainan, Taiwan
  • 5Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
  • 6Department of Gastroenterology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
  • 7Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
  • 8Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
  • 9Division of Gastroenterology and Hepatology, Chi-Mei Medical Centre, Liouying, Tainan, Taiwan
  • 10Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Centre, Chang Gung Memorial Hospital, Keelung, Taiwan
  • 11Division of Gastroenterology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
  • 12Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital and School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
  • 13Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
  • 14Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
  • 155Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan
  • 16Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
  • 17Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
  • 18Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital-Daya, Chiayi, Taiwan
  • 19Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  • 20Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, New Taipei, Taiwan
  • 21Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
  • 22Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
  • 23Institute of Clinical Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  • 24Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan
  • 25Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung; Mackay Medical College, Taipei, Taiwan
  • 26School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Centre of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan

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.
Conclusions
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.

Keyword

Hepatitis C; Hepacivirus; Hepatocellular carcinoma; Metformin; Statins
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