Liver and Bile

J Hepatol. 2023;78(2):281–92

Tsai PC, Kuo HT, Hung CH, Tseng KC, Lai HC, Peng CY, Wang JH, Chen JJ, Lee PL, Chien RN, Yang CC, Lo GH, Kao JH, Liu CJ, Liu CH, Yan SL, Bair MJ, Lin CY, Su WW, Chu CH, Chen CJ, Tung SY, Tai CM, Lin CW, Lo CC, Cheng PN, Chiu YC, Wang CC, Cheng JS, Tsai WL, Lin HC, Huang YH, Yeh ML, Huang CF, Hsieh MH, Huang JF, Dai CY, Chung WL, Chen CY, Yu ML; T-COACH Study Group

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.

Dr. Dr. M.-L. Yu, Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan,
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C.-Y. Chen, Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan,
E-Mail: or

DOI: DOI: 10.1016/j.jhep.2022.09.019

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