Ryosuke Tateishi1, Takeshi Matsumura2, Takeshi Okanoue3, Toshihide Shima3, Koji Uchino4, Naoto Fujiwara4, Takafumi Senokuchi2, Kazuyoshi Kon5, Takayoshi Sasako6,7, Makiko Taniai8, Takumi Kawaguchi9, Hiroshi Inoue10, Hirotaka Watada11, Naoto Kubota6, Hitoshi Shimano12, Shuichi Kaneko13, Etsuko Hashimoto8, Sumio Watanabe5, Goshi Shiota14, Kohjiro Ueki15, Kosuke Kashiwabara16, Yutaka Matsuyama16, Hideo Tanaka17, Masato Kasuga18, Eiichi Araki2, Kazuhiko Koike4. 1. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. tateishi-tky@umin.ac.jp. 2. Department of Metabolic Medicine, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan. 3. Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan. 4. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. 5. Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan. 6. Department of Diabetes and Metabolic Diseases, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. 7. Department of Molecular Sciences on Diabetes, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 8. Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan. 9. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. 10. Metabolism and Nutrition Research Unit, Kanazawa University Institute for Frontier Science Initiative, Kanazawa, Japan. 11. Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan. 12. Department of Internal Medicine, Metabolism and Endocrinology, Tsukuba University, Tsukuba, Japan. 13. Department of Gastroenterology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. 14. Division of Molecular and Genetic Medicine, Institute of Regenerative Medicine and Biofunction, Graduate School of Medicine, Tottori University, Yonago, Japan. 15. Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. 16. Department of Biostatistics, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. 17. Fujiidera Public Health Center, Fujiidera, Japan. 18. The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan.
Abstract
BACKGROUND: Although type 2 diabetes mellitus (T2DM) is a known risk factor for hepatocellular carcinoma (HCC) development, the annual incidence in diabetes patients is far below the threshold of efficient surveillance. This study aimed to elucidate the risk factors for HCC in diabetic patients and to determine the best criteria to identify surveillance candidates. METHODS: The study included 239 patients with T2DM who were diagnosed with non-viral HCC between 2010 and 2015, with ≥ 5 years of follow-up at diabetes clinics of 81 teaching hospitals in Japan before HCC diagnosis, and 3277 non-HCC T2DM patients from a prospective cohort study, as controls. Clinical data at the time of and 5 years before HCC diagnosis were collected. RESULTS: The mean patient age at HCC diagnosis was approximately 73 years, and 80% of the patients were male. The proportion of patients with insulin use increased, whereas the body mass index (BMI), proportion of patients with fatty liver, fasting glucose levels, and hemoglobin A1c (HbA1c) levels decreased significantly in 5 years. In the cohort study, 18 patients developed HCC during the mean follow-up period of 4.7 years with an annual incidence of 0.11%. Multivariate logistic regression analyses showed that the FIB-4 index was an outstanding predictor of HCC development along with male sex, presence of hypertension, lower HbA1c and albumin levels, and higher BMI and gamma-glutamyl transpeptidase levels. Receiver-operating characteristic analyses showed that a FIB-4 cut-off value of 3.61 could help identify high-risk patients, with a corresponding annual HCC incidence rate of 1.1%. CONCLUSION: A simple calculation of the FIB-4 index in diabetes clinics can be the first step toward surveillance of HCC with a non-viral etiology.
BACKGROUND: Although type 2 diabetes mellitus (T2DM) is a known risk factor for hepatocellular carcinoma (HCC) development, the annual incidence in diabetes patients is far below the threshold of efficient surveillance. This study aimed to elucidate the risk factors for HCC in diabetic patients and to determine the best criteria to identify surveillance candidates. METHODS: The study included 239 patients with T2DM who were diagnosed with non-viral HCC between 2010 and 2015, with ≥ 5 years of follow-up at diabetes clinics of 81 teaching hospitals in Japan before HCC diagnosis, and 3277 non-HCC T2DM patients from a prospective cohort study, as controls. Clinical data at the time of and 5 years before HCC diagnosis were collected. RESULTS: The mean patient age at HCC diagnosis was approximately 73 years, and 80% of the patients were male. The proportion of patients with insulin use increased, whereas the body mass index (BMI), proportion of patients with fatty liver, fasting glucose levels, and hemoglobin A1c (HbA1c) levels decreased significantly in 5 years. In the cohort study, 18 patients developed HCC during the mean follow-up period of 4.7 years with an annual incidence of 0.11%. Multivariate logistic regression analyses showed that the FIB-4 index was an outstanding predictor of HCC development along with male sex, presence of hypertension, lower HbA1c and albumin levels, and higher BMI and gamma-glutamyl transpeptidase levels. Receiver-operating characteristic analyses showed that a FIB-4 cut-off value of 3.61 could help identify high-risk patients, with a corresponding annual HCC incidence rate of 1.1%. CONCLUSION: A simple calculation of the FIB-4 index in diabetes clinics can be the first step toward surveillance of HCC with a non-viral etiology.
Entities:
Keywords:
FIB-4 index; Hepatocellular carcinoma; Type 2 diabetes mellitus
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