Abstract
Background & aims:
Diabetes mellitus (DM) has increased the risk of hepatocellular carcinoma (HCC) among chronic hepatitis C (CHC) patients. We aimed to evaluate whether metformin reduces HCC risk among diabetic CHC patients after successful antiviral therapy.
Methods:
CHC patients who achieved a sustained virological response (SVR) after interferon-based therapy were enrolled in a large-scale, multicenter cohort in Taiwan (T-COACH). HCC one-year after SVR were identified by linking to the catastrophic illness and cancer registry databases.
Results:
Of 7,249 CHC patients enrolled in the study, 781 (10.8%) patients had diabetes with 647 (82.8%) metformin users. During a median follow-up of 4.4 years, 227 patients developed new-onset HCC. The 5-year cumulative HCC incidence were 10.9% in DM non-metformin users and 2.6% in DM metformin users, compared to 3.0% in non-DM patients (adjusted hazard ratio [aHR], 95% confidence interval [95% CI]: 2.83, 1.57-5.08 and 1.46, 0.98-2.19, respectively). Cirrhosis was the most important factors significantly associated with higher HCC risk in Cox regression analysis, followed by DM non-metformin use, older age, male, and obesity; whereas hyperlipidemia with statin use was associated with a lower HCC risk. Risk stratification with the two most crucial risk factors, LC and DM non-metformin use, found significant effects of the two risks in predicting HCC risk among CHC patients after SVR. The benefits of metformin use were consistently observed in reducing risk of all liver-related complications.
Conclusions:
Metformin use greatly reduced the HCC risk after successful antiviral therapy in diabetic CHC patients. A simple risk stratification composed of cirrhosis and DM non-metformin use could predict the long-term outcomes of CHC patients after SVR.
Lay summary:
Diabetes mellitus (DM) is associated with an increased risk of HCC among CHC patients. Linking a large-scale nationwide T-COACH cohort in Taiwan to the National Health Insurance Research Database, we confirmed that DM increased the risk of HCC among CHC patients after successful antiviral therapy (achievement of sustained virological response, SVR). However, the use of metformin among DM patients could significantly reduce the HCC risk in diabetic CHC patients achieving an SVR. A simple risk stratification by using two crucial unfavorable factors, liver cirrhosis and DM non-metformin use, could predict the long-term outcomes of CHC patients after HCV eradication.
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