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.
Result s: 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.
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Preclinical studies highlighted potential therapeutic applications of aspirin and statins as anticancer agents based on their pleiotropic effects. Epidemiologic studies suggested the role of aspirin and statins in the chemoprevention of hepatocellular carcinoma (HCC). However, observational data is prone to bias, and no prospective randomized trials are currently available to assess the risks and benefits of statin or aspirin therapy for chemoprevention of HCC. It is therefore important for clinicians and researchers to be aware of the quality of current evidence regarding this issue. In this review, we summarize currently available evidence to assist clinicians with their decision to use statin or aspirin and provide information for further clinical investigations.
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Background/Aims Tumor angiogenesis, a major requirement for tumor growth and metastasis, is
regulated by pro- and anti-angiogenic factors. Hepatocellular carcinoma (HCC) has become a common
malignant tumor worldwide. It is characterized by a high vascularity. Methods: We studied the
immunohistochemical expression of angiostatin, vascular endothelial cell growth factor (VEGF), matrix
metalloproteinase (MMP)-9 and MMP-12, and the relationship between these results and the microvessel
density (MVD) in 48 HCC specimens. To determine whether HCC cells express angiostatin per se, we
examined the expression of angiostatin, MMP-9 and MMP-12 by Western blotting in four HCC cell lines.
Result s: Expression of angiostatin and MMP-12 (but not MMP-9) were strongly correlated with decreased
MVD in HCCs (P=0.006, P=0.038, respectively). VEGF positive tumors showed a significantly higher MVD
than VEGF negative tumors (P=0.01). We divided the 48 cases into the following four groups: group A,
angiostatin (+), MMP-9 or -12 (+), and VEGF (-); group B, angiostatin (-) and VEGF (-); group C,
angiostatin (+), MMP-9 or -12 (+), and VEGF (+); group D, angiostatin (-) and VEGF (+). There was a
significant correlation with MVD among these groups (P<0.001). Angiostatin was detected by Western
blotting in 2 out of 4 HCC cell lines and was associated with plasminogen and MMP expression.
Conclusions These results indicate that angiogenesis in HCC is a complex process involving multiple
factors including angiostatin, VEGF, and MMP. Our results suggest that angiostatin is generated by
MMP-mediated proteolysis of plasminogen in HCC cells.(Korean J Hepatol 2004;10:62-72)
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