Liver and Bile
J Hepatol. 2023;78(2):281–92
Metformin reduces hepatocellular carcinoma incidence after successful antiviral therapy in patients with diabetes and chronic hepatitis C in Taiwan
Background and aims: Diabetes mellitus (DM) is known to increase the risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis C (CHC). The aim of this study was to evaluate whether metformin reduces HCC risk among individuals with DM and CHC after successful antiviral therapy.
Methods: Individuals with CHC who achieved a sustained virological response (SVR) after interferon-based therapy were enrolled in a large-scale, multicenter cohort in Taiwan (T-COACH). Cases of HCC at least 1 year after SVR were identified through linkage to the catastrophic illness and cancer registry databases.
Results: Of 7249 individuals with CHC enrolled in the study, 781 (10.8%) had DM and 647 (82.8%) were metformin users. During a median follow-up of 4.4 years, 227 patients developed new-onset HCC. The 5-year cumulative HCC incidence was 10.9% in non-metformin users and 2.6% in metformin users, compared to 3.0% in individuals without DM (adjusted hazard ratio [aHR] = 2.83; 95% confidence interval [CI]: 1.57–5.08, and aHR = 1.46; 95% CI: 0.98–2.19, respectively). Cirrhosis was the most important factor significantly associated with higher HCC risk in Cox regression analysis, followed by DM non-metformin use, older age, male sex, and obesity; whereas hyperlipidemia with statin use was associated with a lower HCC risk. Using the 2 most crucial risk factors, cirrhosis and DM non-metformin use, the authors constructed a simple risk model that could predict HCC risk among individuals with CHC after SVR. Metformin use was shown to reduce the risk of all liver-related complications.
Conclusions: Metformin use greatly reduced the risk of hepatocellular carcinoma (HCC) after successful antiviral therapy in individuals with diabetes mellitus (DM) and chronic hepatitis C (CHC). A simple risk stratification model comprising cirrhosis and DM non-metformin use could predict long-term outcomes in individuals with CHC after sustained virological response.