Metformin reduces hepatocellular carcinoma incidence after successful antiviral therapy in patients with diabetes and chronic hepatitis C in Taiwan
Abstract
Background & aims Diabetes mellitus (DM) is known to increase the risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis C (CHC). We aimed 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 7,249 individuals with CHC enrolled in the study, 781 (10.8%) had diabetes 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% 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 two most crucial risk factors, cirrhosis and DM non-metformin use, we 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 HCC risk after successful antiviral therapy in individuals with diabetes and CHC. A simple risk stratification model comprising cirrhosis and DM non-metformin use could predict long-term outcomes in individuals with CHC after SVR.Impact and implications The current study provides evidence that metformin could reduce hepatocellular carcinoma (HCC) incidence after successful antiviral therapy among those with diabetes and chronic hepatitis C in a large-scale nationwide cohort study. Although successful antiviral therapy greatly reduces HCC risk in individuals with chronic hepatitis C, those with cirrhosis, diabetes, obesity, and the elderly remain at high risk of HCC development. We demonstrated that a simple risk model composed of two crucial unfavorable factors, cirrhosis and diabetes without metformin use, predicts the risk of HCC and major liver-related complications after successful antiviral therapy in individuals with chronic hepatitis C. Metformin use is highly recommended for individuals with diabetes and chronic hepatitis C after viral eradication to reduce the risk of HCC.
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Observational data suggest a potential protective effect of metformin against HCC.
“However, observational data suggest a potential protective effect against HCC.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [462]
Cites
A Proportional Hazards Model for the Subdistribution of a Competing Risk
Fine, J. P., & Gray, R. J. (1999) · Journal of the American Statistical Association · doi:10.1080/01621459.1999.10474144 · Cited by 14,290 · see citing works
Austin, P. C. (2011) · Multivariate Behavioral Research · doi:10.1080/00273171.2011.568786 · Cited by 12,242 · see citing works
EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma
Galle, P. R., Forner, A., Llovet, J. M., Mazzaferro, V., Piscaglia, F., Raoul, J.-L., Schirmacher, P., & Vilgrain, V. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.03.019 · Cited by 11,406 · see citing works
Sterling, R. K., Lissen, E., Clumeck, N., Sola, R., Correa, M. C., Montaner, J., S. Sulkowski, M., Torriani, F. J., Dieterich, D. T., Thomas, D. L., et al. (2006) · Hepatology · doi:10.1002/hep.21178 · Cited by 5,021 · see citing works
A Class of $K$-Sample Tests for Comparing the Cumulative Incidence of a Competing Risk
Gray, R. J. (1988) · The Annals of Statistics · doi:10.1214/aos/1176350951 · Cited by 4,957 · see citing works
Castéra, L., Vergniol, J., Foucher, J., Bail, B. L., Chanteloup, E., Haaser, M., Darriet, M., Couzigou, P., & de Lédinghen, V. (2005) · Gastroenterology · doi:10.1053/j.gastro.2004.11.018 · Cited by 2,480 · see citing works
Akinyemiju, T., Abera, S. F., Ahmed, M. B., Alam, N., Alemayohu, M. A., Allen, C., Al-Raddadi, R. M., Alvis‐Guzmán, N., Amoako, Y. A., Artaman, A., et al. (2017) · JAMA Oncology · doi:10.1001/jamaoncol.2017.3055 · Cited by 1,985 · see citing works
Classification of chronic viral hepatitis: a need for reassessment
Scheuer, P. J. (1991) · Journal of Hepatology · doi:10.1016/0168-8278(91)90084-o · Cited by 1,588 · see citing works
From NASH to HCC: current concepts and future challenges
Anstee, Q. M., Reeves, H. L., Kotsiliti, E., Govaere, O., & Heikenwalder, M. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0145-7 · Cited by 1,392 · see citing works
Davila, J. A., Morgan, R. O., Shaib, Y. H., McGlynn, K. A., & El‐Serag, H. B. (2005) · Gut · doi:10.1136/gut.2004.052167 · Cited by 703 · see citing works
Chen, H.-P., Shieh, J., Chang, C., Chen, T.-T., Lin, J., Wu, M., Lin, J.-H., & Wu, C. (2012) · Gut · doi:10.1136/gutjnl-2011-301708 · Cited by 392 · see citing works
Incidence and Predictors of Hepatocellular Carcinoma in Patients With Cirrhosis
Ioannou, G. N., Splan, M. F., Weiss, N. S., McDonald, G. B., Beretta, L., & Lee, S. P. (2007) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2007.02.039 · Cited by 363 · see citing works
Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma
Hassan, M. M., Curley, S. A., Li, D., Kaseb, A. O., Davila, M. L., Abdalla, E. K., Javle, M. M., Moghazy, D. M., Lozano, R. D., Abbruzzese, J. L., et al. (2010) · Cancer · doi:10.1002/cncr.24982 · Cited by 309 · see citing works
Kanwal, F., Kramer, J. R., Asch, S. M., Cao, Y., Li, L., & El‐Serag, H. B. (2019) · Hepatology · doi:10.1002/hep.30823 · Cited by 277 · see citing works
Statins and the Risk of Hepatocellular Carcinoma in Patients With Hepatitis C Virus Infection
Tsan, Y., Lee, C., Ho, W., Lin, M., Wang, J., & Chen, P. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.44.6831 · Cited by 210 · see citing works
Self-citationSimon, T. G., Bonilla, H. F., Yan, P., Chung, R. T., & Butt, A. A. (2016) · Hepatology · doi:10.1002/hep.28506 · Cited by 179 · see citing works
Lin, C.-W., Lin, C.-C., Mo, L.-R., Chang, C.-Y., Perng, D.-S., Hsu, C.-C., Lo, G.-H., Chen, Y.-S., Yen, Y.-C., Hu, J.-T., et al. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2012.11.045 · Cited by 174 · see citing works
Self-citationHepatitis C virus leaves an epigenetic signature post cure of infection by direct-acting antivirals
Perez, S., Kaspi, A., Domovitz, T., Davidovich, A., Lavi-Itzkovitz, A., Meirson, T., Holmes, J. A., Dai, C., Huang, C., Chung, R. T., et al. (2019) · PLoS Genetics · doi:10.1371/journal.pgen.1008181 · Cited by 173 · see citing works
Self-citationImpact of Metformin on the Prognosis of Cirrhosis Induced by Viral Hepatitis C in Diabetic Patients
Nkontchou, G., Cosson, E., Aout, M., Mahmoudi, A., Bourcier, V., Charif, I., Ganne‐Carrié, N., Grando–Lemaire, V., Vicaut, É., Trinchet, J., et al. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2415 · Cited by 165 · see citing works
Matsuura, K., Sawai, H., Ikeo, K., Ogawa, S., Iio, E., Isogawa, M., Shimada, N., Komori, A., Toyoda, H., Kumada, T., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.01.041 · Cited by 154 · see citing works
Huang, C., Yeh, M., Tsai, P., Hsieh, M., Yang, H., Hsieh, M., Yang, J., Lin, Z., Chen, S., Wang, L., et al. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.02.022 · Cited by 129 · see citing works
Self-citationKramer, J. R., Natarajan, Y., Dai, J., Yu, X., Li, L., El‐Serag, H. B., & Kanwal, F. (2021) · Hepatology · doi:10.1002/hep.32244 · Cited by 113 · see citing works
Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review
Cunha, V., Cotrim, H. P., Rocha, R., Carvalho, K. S. D., & Lins-Kusterer, L. (2019) · Annals of Hepatology · doi:10.1016/j.aohep.2019.10.005 · Cited by 106 · see citing works
Cancer Risk in HBV Patients With Statin and Metformin Use
Chen, C.-I., Kuan, C.-F., Fang, Y.-A., Liu, S., Liu, J., Wu, L., Chang, C.-J., Yang, H., Hwang, J., Miser, J. S., et al. (2015) · Medicine · doi:10.1097/md.0000000000000462 · Cited by 76 · see citing works
Self-citationZhou, J., Ke, Y., Lei, X., Wu, T., Li, Y., Bao, T., Tang, H., Zhang, C., Wu, X., Wang, G., et al. (2019) · Annals of Hepatology · doi:10.1016/j.aohep.2019.11.008 · Cited by 62 · see citing works
Chen, C.-Y., Huang, C., Cheng, P., Tseng, K., Lo, G., Kuo, H., Huang, Y., Tai, C., Peng, C., Bair, M., et al. (2021) · Liver International · doi:10.1111/liv.14849 · Cited by 58 · see citing works
Self-citationHuang, J., Yu, M., Dai, C., Hsieh, M., Hwang, S., Hsiao, P., Lee, L., Lin, Z., Chen, S., Hsieh, M., et al. (2008) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2008.01996.x · Cited by 53 · see citing works
Self-citationWang, C., Liu, C., Lin, C., Wang, P., Tseng, T., Lin, H. H., & Kao, J. (2015) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2015.07.004 · Cited by 40 · see citing works
Self-citationLiao, Y.-H., Hsu, R., Wang, T.-H., Wu, C., Huang, S.-Y., Hsu, C. Y., Su, Y., Hsu, W.-L., & Liu, D.-W. (2020) · BMC Gastroenterology · doi:10.1186/s12876-020-1158-y · Cited by 40 · see citing works
Huang, J., Huang, C., Yeh, M., Dai, C., Hsieh, M., Yang, J., Huang, C., Lin, Y., Liang, P., Lin, Z., et al. (2017) · The Kaohsiung Journal of Medical Sciences · doi:10.1016/j.kjms.2017.07.003 · Cited by 38 · see citing works
Self-citationHuang, C., Dai, C., Yeh, M., Huang, C., Lee, H., Lai, W., Liang, P., Lin, Y., Hsieh, M., Hou, N., et al. (2020) · The Kaohsiung Journal of Medical Sciences · doi:10.1002/kjm2.12275 · Cited by 37 · see citing works
Self-citationHuang, C., Yeh, M., Huang, C.-Y., Tsai, P., Ko, Y., Chen, K., Lin, Z., Chen, S., Dai, C., Chuang, W., et al. (2016) · Medicine · doi:10.1097/md.0000000000004157 · Cited by 36 · see citing works
Self-citationLin, Y., Yeh, M., Huang, C., Yang, J., Liang, P., Huang, C., Dai, C., Lin, Z., Chen, S., Huang, J., et al. (2016) · The Kaohsiung Journal of Medical Sciences · doi:10.1016/j.kjms.2016.05.008 · Cited by 34 · see citing works
Self-citationLiu, M., Tseng, T., Jun, D. W., Yeh, M., Trinh, H. N., Wong, G. L., Chen, C., Peng, C., Kim, S. E., Oh, H., et al. (2021) · Hepatology International · doi:10.1007/s12072-020-10113-2 · Cited by 34 · see citing works
Self-citationThe Impact of Steatosis on Chronic Hepatitis C Progression and Response to Antiviral Treatments
Siphepho, P. Y., Liu, Y., Shabangu, C. S., Huang, J., Huang, C., Yeh, M., Yu, M., & Wang, S. (2021) · Biomedicines · doi:10.3390/biomedicines9101491 · Cited by 34 · see citing works
Self-citationChen, V. L., Yeh, M., Yang, J. D., Leong, J., Huang, D. Q., Toyoda, H., Chen, Y., Guy, J. E., Maeda, M., Tsai, P., et al. (2020) · Hepatology Communications · doi:10.1002/hep4.1606 · Cited by 29 · see citing works
Self-citationHuang, C., Lai, H., Chen, C.-Y., Tseng, K., Kuo, H., Hung, C., Wang, J., Chen, J.-J., Lee, P.-L., Chien, R., et al. (2020) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000000606 · Cited by 28 · see citing works
Self-citationCiancio, A., Ribaldone, D. G., Dotta, A., Giordanino, C., SACCO, M., Fagoonee, S., Pellicano, R., & Saracco, G. M. (2020) · Liver International · doi:10.1111/liv.14676 · Cited by 24 · see citing works
Hsu, W., Tsai, P., Chen, C.-Y., Tseng, K., Lai, H., Kuo, H., Hung, C., Tung, S., Wang, J., Chen, J.-J., et al. (2021) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15538 · Cited by 23 · see citing works
Self-citationHuang, C., Yeh, M., Huang, C., Liang, P., Lin, Y., Lin, Z., Chen, S., Huang, J., Dai, C., Chuang, W., et al. (2018) · Hepatology International · doi:10.1007/s12072-018-9908-4 · Cited by 21 · see citing works
Self-citationBenhammou, J. N., Lin, J., Aby, E. S., Markovic, D., Raman, S. S., Lu, D., & Tong, M. J. (2021) · Hepatoma Research · doi:10.20517/2394-5079.2021.74 · Cited by 15 · see citing works
Wang, C., Kuhn, J. G., Shah, D. P., Schmidt, S., Lam, Y.-W. F., MacCarthy, D., Tenner, L. L., & Ramírez, A. G. (2019) · Cancer Medicine · doi:10.1002/cam4.2142 · Cited by 10 · see citing works
Self-citationHsu, W., Chen, C.-Y., Tseng, K., Lai, H., Kuo, H., Hung, C., Tung, S., Wang, J., Chen, J.-J., Lee, P.-L., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-61991-3 · Cited by 6 · see citing works
Self-citationAssociation between Aspirin and Hepatocellular Carcinoma
Liao, R., Zhou, B.-Y., & Wu, Z. (2020) · New England Journal of Medicine · doi:10.1056/nejmc2009497 · Cited by 6 · see citing works
Tsai, P., Chen, C.-Y., Kuo, H., Hung, C., Tseng, K., Lai, H., Peng, C., Wang, J., Chen, J.-J., Lee, P., et al. (2020) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofaa397 · Cited by 5 · see citing works
Self-citationYang, Q., Fung, W. K., & Li, G. (2017) · Statistics in Medicine · doi:10.1002/sim.7590 · Cited by 3 · see citing works
Hsieh, M., Bair, M., Tsai, P., Tseng, K., Lo, G., Chen, C.-Y., Kuo, H., Hung, C., Lai, H., Peng, C., et al. (2021) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15469 · Cited by 3 · see citing works
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Tacke, F., Horn, P., Wai-Sun Wong, V., Ratziu, V., Bugianesi, E., Francque, S., Zelber-Sagi, S., Valenti, L., Roden, M., Schick, F., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.031 · Cited by 2,210 · see citing works
(2024) · Obesity Facts · doi:10.1159/000539371 · Cited by 510 · see citing works
Eslam, M., Fan, J., Yu, M., Wong, V. W., Cua, I. H., Liu, C., Tanwandee, T., Gani, R. A., Seto, W., Alam, S., et al. (2025) · Hepatology International · doi:10.1007/s12072-024-10774-3 · Cited by 186 · see citing works
Self-citationCurrent and emerging strategies for the prevention of hepatocellular carcinoma
Yeo, Y. H., Abdelmalek, M. F., Khan, S. A., Moylan, C. A., Rodriquez, L. M., Villanueva, A., & Yang, J. D. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-01021-z · Cited by 99 · see citing works
Perspectives on the Underlying Etiology of HCC and Its Effects on Treatment Outcomes
Ito, T., & Nguyen, M. H. (2023) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s347959 · Cited by 61 · see citing works
Fiehn, F., Beisel, C., & Binder, M. (2024) · Current Opinion in Virology · doi:10.1016/j.coviro.2024.101423 · Cited by 44 · see citing works
Liu, C., Cheng, P., Fang, Y., Chen, C.-Y., Kao, W., Lin, C., Yang, S., Shih, Y., Peng, C., Chang, Y., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.09.038 · Cited by 36 · see citing works
Self-citationMetabolic primary liver cancer in adults: risk factors and pathogenic mechanisms
Lugari, S., Baldelli, E., & Lonardo, A. (2023) · Metabolism and Target Organ Damage · doi:10.20517/mtod.2022.38 · Cited by 33 · see citing works
Metformin in Antiviral Therapy: Evidence and Perspectives
Halabitska, I., Petakh, P., Lushchak, O. V., Kamyshna, I. I., Oksenych, V., & Kamyshnyi, O. (2024) · Viruses · doi:10.3390/v16121938 · Cited by 33 · see citing works
Papadakos, S. P., Ferraro, D., Carbone, G., Frampton, A. E., Vennarecci, G., Kykalos, S., Schizas, D., Theocharis, S. E., & Machairas, N. (2023) · Cancers · doi:10.3390/cancers15123161 · Cited by 30 · see citing works
Lu, M., Huang, C., Hung, C., Tai, C., Mo, L., Kuo, H., Tseng, K., Lo, G., Bair, M., Wang, S., et al. (2023) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2023.0287 · Cited by 30 · see citing works
Self-citationDu, Y., Zhu, J., Guo, Z., Wang, Z., Wang, Y., Hu, M., Zhang, L., Yang, Y., Wang, J., Huang, Y., et al. (2024) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2024.2306223 · Cited by 30 · see citing works
Self-citationHu, N., Li, H., Tao, C., Xiao, T., & Rong, W. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115584 · Cited by 23 · see citing works
Beyond the Liver: A Comprehensive Review of Strategies to Prevent Hepatocellular Carcinoma
Polpichai, N., Saowapa, S., Danpanichkul, P., Chan, S., Sierra, L., Blagoie, J., Rattananukrom, C., Sripongpun, P., & Kaewdech, A. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13226770 · Cited by 22 · see citing works
Huang, C., Awad, M. H., Gal-Tanamy, M., & Yu, M. (2024) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2024.0155 · Cited by 20 · see citing works
Self-citationTsai, P., Huang, C., Yeh, M., Hsieh, M., Kuo, H., Hung, C., Tseng, K., Lai, H., Peng, C., Wang, J., et al. (2024) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2024.0038 · Cited by 19 · see citing works
Self-citationLv, G.-J., Ji, D., Yu, L., Chen, H.-Y., Chen, J., He, M. L., Wang, W., Wang, H., Tsang, C., Wang, J., et al. (2024) · Hepatology International · doi:10.1007/s12072-024-10700-7 · Cited by 18 · see citing works
Self-citationAdvances in the Use of Metformin for Liver Disease
Bao, J., Zhao, Y., Xu, X., & Ling, S. (2024) · Current Medicinal Chemistry · doi:10.2174/0109298673274268231215110330 · Cited by 16 · see citing works
Yeh, M., Huang, J., Dai, C., Huang, C., Yu, M., & Chuang, W. (2024) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2024.2388790 · Cited by 16 · see citing works
Self-citationWatanabe, T., Tokumoto, Y., Joko, K., Michitaka, K., Horiike, N., Tanaka, Y., Hiraoka, A., Tada, F., Ochi, H., Kisaka, Y., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-36052-0 · Cited by 15 · see citing works
Huang, J., Chang, T., Yeh, M., Shen, F., Tai, C., Chen, J., Huang, Y., Hsu, C., Cheng, P., Lin, C., et al. (2024) · Hepatology Communications · doi:10.1097/hc9.0000000000000571 · Cited by 15 · see citing works
Self-citationGonzález-Aldaco, K., Torres-Reyes, L. A., Ojeda‐Granados, C., Leal-Mercado, L., Román, S., & Panduro, A. (2024) · Clinics and Practice · doi:10.3390/clinpract14060200 · Cited by 15 · see citing works
Alhusayen, R. O., Dienes, S., Lam, M., Alavi, A., Alikhan, A., Aleshin, M. A., Bahashwan, E., Daveluy, S. D., Goldfarb, N. I., Garg, A., et al. (2024) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2024.11.071 · Cited by 16 · see citing works
Zandavi, S. M., Kim, C., Goodwin, T., Thilakanathan, C., Bostanara, M., Akon, A. C., Mouiee, D. A., Barisic, S., Majeed, A., Kemp, W. W., et al. (2024) · Liver International · doi:10.1111/liv.16050 · Cited by 14 · see citing works
Lu, M., Liu, T.-W., Liang, P., Huang, C., Tsai, Y., Tsai, P., Ko, Y., Wang, W.-H., Lin, C., Chen, K., et al. (2023) · PubMed Central · Cited by 13 · see citing works
Self-citationPelusi, S., Bianco, C., Colombo, M., Cologni, G., Poggio, P. D., Pugliese, N., Prati, D., Pigozzi, M. G., D’Ambrosio, R., Lampertico, P., et al. (2023) · Liver International · doi:10.1111/liv.15577 · Cited by 13 · see citing works
Mezzacappa, C., Mahmud, N., Serper, M., John, B. V., Taddei, T. H., & Kaplan, D. E. (2023) · Hepatology Communications · doi:10.1097/hc9.0000000000000344 · Cited by 12 · see citing works
Prevention of liver cancer in the era of next-generation antivirals and obesity epidemic
Suzuki, H., Fujiwara, N., Singal, A. G., Baumert, T. F., Chung, R. T., Kawaguchi, T., & Hoshida, Y. (2025) · Hepatology · doi:10.1097/hep.0000000000001227 · Cited by 11 · see citing works
Chang, Y.-P., Chen, Y.-C., Cheng, P., Fang, Y., Chen, C.-Y., Kao, W., Lin, C., Yang, S.-S., Shih, Y. L., Peng, C., et al. (2026) · Gut · doi:10.1136/gutjnl-2025-337275 · Cited by 9 · see citing works
Self-citationInsulin resistance: mechanisms and therapeutic interventions
Yu, L., Qian, J., Li, X., Tian, M., Bai, X., Yang, J., Deng, R., Lu, C., He, X., Lü, A., et al. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00408-5 · Cited by 9 · see citing works
Zhang, J., Ma, X., Liu, F., Zhang, D., Ling, J., Zhu, Z., Chen, Y., Yang, P., Yang, Y., Liu, X., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1203389 · Cited by 9 · see citing works
SACCO, M., Ribaldone, D. G., & Saracco, G. M. (2023) · Viruses · doi:10.3390/v15122451 · Cited by 8 · see citing works
Lo, G., Lei, W., Huang, Y., Hwang, J.-J., Lo, C., Lin, C., Cheng, H.-S., Liao, Y.-T., Liang, P., Chiou, M.-J., et al. (2023) · Journal of Microbiology Immunology and Infection · doi:10.1016/j.jmii.2023.01.014 · Cited by 8 · see citing works
Self-citationMino, M., Kakazu, E., & Kanto, T. (2025) · Gut and Liver · doi:10.5009/gnl250187 · Cited by 6 · see citing works
Zang, Y., Xu, W., Qiu, Y., Jiang, X., & Fan, Y. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e18425 · Cited by 6 · see citing works
Yang, S.-H., He, Y.-S., Zheng, S., Zhang, X.-J., Dai, H., & Xue, Y. (2024) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s454037 · Cited by 6 · see citing works
Ho, C.-T., Fu, C., Tan, E. C., Kao, W., Lee, P., Huang, Y., Huo, T., Hou, M., Wu, J., & Su, C. (2024) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16640 · Cited by 6 · see citing works
Self-citationBrunetto, M. R., & Bonino, F. (2025) · Viruses · doi:10.3390/v17030319 · Cited by 5 · see citing works
Chemoprevention of hepatocellular carcinoma
Schwenk, S., & Kaplan, D. E. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000836 · Cited by 5 · see citing works
Tsai, P., Huang, C., Yeh, M., Wei, Y., Wang, C., Jang, T., Liang, P., Lin, Y., Dai, C., Huang, J., et al. (2025) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.70500 · Cited by 5 · see citing works
Self-citationMisceo, D., Mocciaro, G., D’Amore, S., & Vacca, M. (2024) · Nutrition & Metabolism · doi:10.1186/s12986-024-00871-3 · Cited by 6 · see citing works
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Asadalizadeh, M., Rahbar, M. K. M., Mahmoudie, T., Abbasi, M., Akbari, M., Shakiba, D., Shabestari, A. M., & Ebrahimifar, M. (2026) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-026-01411-x · Cited by 4 · see citing works
Lee, T., Yang, S., Tsai, P., Huang, C., Chen, C.-Y., Hung, C., Chen, C., Tai, C., Cheng, P., Kuo, H., et al. (2025) · European Journal of Cancer · doi:10.1016/j.ejca.2025.116109 · Cited by 4 · see citing works
Self-citationIshido, S., Tamaki, N., Kurosaki, M., Mori, N., Tsuji, K., Hasebe, C., Mashiba, T., Ochi, H., Yasui, Y., Akahane, T., et al. (2023) · JGH Open · doi:10.1002/jgh3.12914 · Cited by 4 · see citing works
Chen, Y., Tsai, P., Huang, C., Chen, C.-Y., Hung, C., Chen, C.-H., Tai, C., Cheng, P., Kuo, H., Mo, L., et al. (2025) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2025.01.026 · Cited by 4 · see citing works
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Baker, F. A., Davidov, Y., Israel, A., Green, I., Taher, R., Ben‐Ari, Z., & Mouch, S. A. (2023) · Minerva Medica · doi:10.23736/s0026-4806.23.08428-8 · Cited by 4 · see citing works
Huang, C., Yeh, M., Dai, C., Huang, J., Chuang, W., & Yu, M. (2024) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2024.0638 · Cited by 4 · see citing works
Self-citationOgawa, E., Kawano, A., Kohjima, M., Koyanagi, T., Dohmen, K., Ooho, A., Satoh, T., Takahashi, K., Furusyo, N., Kajiwara, E., et al. (2025) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16892 · Cited by 3 · see citing works
Hsu, W. (2024) · American Journal of Cancer Research · doi:10.62347/eqir8735 · Cited by 3 · see citing works
Metformin as adjuvant treatment in hepatitis C virus infections and associated complications
Landis, D. M., Sutter, A., Khemka, S., Songtanin, B., Nichols, J., & NUGENT, K. M. (2024) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2024.04.019 · Cited by 3 · see citing works
Li, M., Li, T., Li, K.-J., & Zhou, C. (2023) · World Journal of Clinical Cases · doi:10.12998/wjcc.v11.i5.1009 · Cited by 3 · see citing works
Masaoka, R., Gyotoku, Y., Shirahashi, R., Suda, T., & Tamano, M. (2023) · World Journal of Clinical Cases · doi:10.12998/wjcc.v11.i22.5204 · Cited by 3 · see citing works
Elbahrawy, A., Atalla, H., Mahmoud, A. A., Eliwa, A., Alsawak, A., Alboraie, M. A. A., Madian, A., Alashker, A., Mostafa, S., Alwassief, A., et al. (2023) · Frontiers in Virology · doi:10.3389/fviro.2023.1227317 · Cited by 3 · see citing works
Shojaeian, A., Nakhaie, M., Amjad, Z. S., Boroujeni, A. K., Shokri, S., & Mahmoudvand, S. (2024) · Journal of Cancer Metastasis and Treatment · doi:10.20517/2394-4722.2023.147 · Cited by 3 · see citing works
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Chang, C.-W., Hsu, W., Tseng, K., Chen, C.-Y., Cheng, P., Hung, C., Lo, G., Bair, M., Chen, C., Lee, P., et al. (2024) · Digestive Diseases and Sciences · doi:10.1007/s10620-024-08512-8 · Cited by 3 · see citing works
Self-citationChen, Y., & Yu, M. (2025) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2025.06.034 · Cited by 3 · see citing works
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Chang, S., Liu, C., Chan, S., & Lin, L. (2026) · Journal of Medical Virology · doi:10.1002/jmv.70952 · Cited by 2 · see citing works
Self-citationChida, T., Ohta, K., Noritake, H., Matsushita, M., Murohisa, G., Kageyama, F., Sasada, Y., Oyaizu, T., Tsugiki, M., Tamakoshi, K., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-61366-y · Cited by 2 · see citing works
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Lv, R., Lu, Y., Xiang, W., Meng, M., & Li, S. (2024) · Journal of Viral Hepatitis · doi:10.1111/jvh.13922 · Cited by 2 · see citing works
Kwo, P. Y. (2024) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2024.0425 · Cited by 2 · see citing works
Zhang, H. B., Yan, Y., Pang, J. P., Kong, M. T., & Zhu, Q. (2026) · OncoTargets and Therapy · doi:10.2147/ott.s572872 · Cited by 1 · see citing works
Chemoprevention in hepatocellular carcinoma
Suzuki, H., Ng, C. H., Tan, D. J. H., Teng, M. L. P., Kawaguchi, T., & Huang, D. Q. (2023) · Current Hepatology Reports · doi:10.1007/s11901-023-00614-7 · Cited by 1 · see citing works
Carvalho‐Gomes, Â., Valcheva, T. V. V., Sahuco, I., Vidal, E., Martínez‐Arenas, L., Vinaixa, C., Aguilera, V., García, S. G., & Berenguer, M. (2024) · United European Gastroenterology Journal · doi:10.1002/ueg2.12571 · Cited by 1 · see citing works
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Luhmann, N., & Wedemeyer, H. H. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.03.029 · Cited by 1 · see citing works
Masaoka, R., Gyotoku, Y., Shirahashi, R., Suda, T., & Tamano, M. (2023) · World Journal of Clinical Cases · doi:10.12998/wjcc.v11.i22.5198
The benefits of hepatitis C viral eradication: a real-world nationwide cohort study in TaiwanPreprint
Chang, C.-W., Hsu, W., Tseng, K., Chen, C.-Y., Cheng, P., Hung, C., Lo, G., Bair, M., Chen, C., Lee, P., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-4205349/v1
Self-citationLopez-Canovas, J. L., Naranjo-Martínez, B., & Díaz‐Ruiz, A. (2024) · Cellular Oncology · doi:10.1007/s13402-024-00966-2
Lee, C. H., Lin, C., Yen, T., & Hsieh, S. (2024) · International Journal of General Medicine · doi:10.2147/ijgm.s472260
Self-citationGetu, M. A., Zhang, X., Wang, J., Xu, K., Ying, Y., Ma, L., & Gong, P. (2025) · Current Cancer Drug Targets · doi:10.2174/0115680096345507241030224210
Self-citationHsu, W., Lai, H., Wang, H., Chen, S., Su, W., Chen, H., Huang, G., & Peng, C. (2025) · Journal of Microbiology Immunology and Infection · doi:10.1016/j.jmii.2025.07.011
Self-citationTsai, P., Huang, J., & Yu, M. (2026) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.70567
Self-citationMetformin enhances TRAIL-mediated antitumor activity of liver natural killer cells in mice
Bekki, T., Ohira, M., Imaoka, Y., Imaoka, K., Niitsu, H., Tanaka, Y., Kobayashi, T., & Ohdan, H. (2026) · Scientific Reports · doi:10.1038/s41598-026-45613-y
Huang, C., Lin, Y., Tsai, P., Yeh, M., Wang, C., Jang, T., Liang, P., Wei, Y., Hou, N., Hsieh, M., et al. (2026) · The Kaohsiung Journal of Medical Sciences · doi:10.1002/kjm2.70214
Self-citationSánchez, H. C., Jara, L., Heredia, R. E., Villarino, I., Alvarado, R., Calvo, M. Q., García, M. L. G., Miquel, J., Torralba, M., Catalá, M., et al. (2026) · Liver International · doi:10.1111/liv.70798
Pharmacological chemoprevention of hepatocellular carcinoma: hype, hope, or reality?
Weiskirchen, R., & Lonardo, A. (2026) · Hepatoma Research · doi:10.20517/2394-5079.2026.62
Jang, T., Huang, C., & Yu, M. (2026) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2026.08.027
Self-citationVillani, R., & Serviddio, G. (2026) · Annals of Hepatology · doi:10.1016/j.aohep.2026.102434
Quang, E. V., Lemoine, M., & Pawlotsky, J. (2026) · Journal of Hepatology · doi:10.1016/j.jhep.2026.08.032
Extrahepatic endocrine manifestations of chronic HCV infection
Stefanaki, K., Kaltsounis, E. –. L., Syrigou, R., Karakousis, N. D., Tsiodras, S., & Karagiannakis, D. S. (2026) · Annals of Hepatology · doi:10.1016/j.aohep.2026.102440
El‐Kassas, M., Awad, A., AlNaamani, K. M., Alswat, K., & Elzouki, A.-N. (2026) · Hepatoma Research · doi:10.20517/2394-5079.2026.57
Ogawa, E., Kawano, A., Kohjima, M., Koyanagi, T., Dohmen, K., Ooho, A., Satoh, T., Takahashi, K., Furusyo, N., Kajiwara, E., et al. (2026) · Annals of Hepatology · doi:10.1016/j.aohep.2026.102455
- Authors
- Tsai, P.-C., Kuo, H.-T., Hung, C.-H., Tseng, K.-C., Lai, H.-C., Peng, C.-Y., Wang, J.-H., Chen, J.-J., Lee, P.-L., Chien, R.-N., Yang, C.-C., Lo, G.-H., Kao, J.-H., Liu, C.-J., Liu, C.-H., Yan, S.-L., Bair, M.-J., Lin, C.-Y., Su, W.-W., Chu, C.-H., Chen, C.-J., Tung, S.-Y., Tai, C.-M., Lin, C.-W., Lo, C.-C., Cheng, P.-N., Chiu, Y.-C., Wang, C.-C., Cheng, J.-S., Tsai, W.-L., Lin, H.-C., Huang, Y.-H., Yeh, M.-L., Huang, C.-F., Hsieh, M.-H., Huang, J.-F., Dai, C.-Y., Chung, W.-L., Chen, C.-Y., & Yu, M.-L.
- Affiliations
- Kaohsiung Medical University (TW)
- National Sun Yat-sen University (TW)
- Chiayi Chang Gung Memorial Hospital (TW)
- Dalin Tzu Chi Hospital (TW)
- China Medical University Hospital (TW)
- Chang Gung University (TW)
- Chi Mei Medical Center (TW)
- Chang Gung Memorial Hospital (TW)
- Chang Bing Show Chwan Memorial Hospital (TW)
- E-Da Hospital (TW)
- National Taiwan University (TW)
- Mackay Memorial Hospital (TW)
- Changhua Christian Hospital (TW)
- St. Martin de Porres Hospital (TW)
- National Cheng Kung University Hospital (TW)
- Tzu Chi University (TW)
- Kaohsiung Veterans General Hospital (TW)
- Taipei Veterans General Hospital (TW)
- National Yang Ming Chiao Tung University (TW)
- Corresponding author
- Chen, Chi-Yi
- Yu, Ming-Lung
- ORCID
- Tsai, Pei-Chien
- Kuo, Hsing-Tao
- Hung, Chao-Hung
- Tseng, Kuo-Chih
- Lai, Hsueh-Chou
- Wang, Jing-Houng
- Chen, Jyh-Jou
- Lee, Pei-Lun
- Chien, Rong-Nan
- Lo, Gin-Ho
- Kao, Jia-Horng
- Liu, Chun-Jen
- Liu, Chen-Hua
- Yan, Sheng-Lei
- Bair, Ming-Jong
- Lin, Chun-Yen
- Su, Wei-Wen
- Chen, Chih-Jen
- Tai, Chi-Ming
- Lo, Ching-Chu
- Cheng, Pin-Nan
- Chiu, Yen-Cheng
- Wang, Chia-Chi
- Tsai, Wei-Lun
- Lin, Han-Chieh
- Huang, Yi-Hsiang
- Yeh, Ming-Lun
- Huang, Chung-Feng
- Hsieh, Meng-Hsuan
- Huang, Jee-Fu
- Dai, Chia-Yen
- Chung, Wan-Long
- Chen, Chi-Yi
- Yu, Ming-Lung
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2023-02
- Volume
- 78
- Issue
- 2
- Pages
- 281-292
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W4302024129
- Cited by
- 82
- References
- 47
- Citations by year
- 2026: 16 · 2025: 14 · 2024: 33 · 2023: 19
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kaohsiung Medical University (MOHW111-TDU-B-221-114007, KMU-MOST 111-2314-B-037-069-MY2, KMU-NSTC 111-2314-B-037-017, KMU111-2314-B-037-082)
- Health and Welfare Data Science Center
- Kaohsiung Medical University Chung Ho Memorial Hospital
- Mackay Memorial Hospital (TTMMH-111-06)
- National Cancer Institute (KMU-TC111A04)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- metformin, hepatocellular carcinoma, chronic hepatitis C, diabetes mellitus, antiviral therapy, sustained virological response, liver cirrhosis, statin use, hyperlipidemia, liver cancer prevention, Taiwan, obesity, age and sex risk factors, liver complications
- MeSH terms
- Sustained Virologic Response, Aged, Antiviral Agents, Diabetes Mellitus, Carcinoma, Hepatocellular, Humans, Liver Cirrhosis, Liver Neoplasms, Male, Metformin, Obesity, Retrospective Studies, Taiwan, Cohort Studies, Incidence, Hepatitis C, Chronic
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