Ryuta Shigefuku1, Motoh Iwasa1, Kazuhiro Katayama2, Akiko Eguchi1, Takumi Kawaguchi3, Koichi Shiraishi4, Toshifumi Ito5, Kazutomo Suzuki6, Chizu Koreeda7, Takaaki Ohtake8, Yoshio Tokumoto9, Ryujin Endo10, Naohiro Kawamura11, Makoto Shiraki12, Daiki Habu13, Hironori Sakai14, Akinobu Kato15, Shuhei Nishiguchi16, Hisataka Moriwaki12, Kazuyuki Suzuki17, Yoshiyuki Takei1. 1. Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan. 2. Department of Hepato-Biliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan. 3. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. 4. Department of Gastroenterology, Tokai University School of Medicine, Isehara, Japan. 5. Department of Gastroenterology, JCHO Osaka Hospital, Osaka, Japan. 6. Department of Gastroenterology, Shuuwa General Hospital, Kasugabe, Japan. 7. Liver Disease Center, Kansai Medical University Medical Center, Moriguchi, Japan. 8. Department of Gastroenterology, International University of Health and Welfare Hospital, Nasushiobara, Japan. 9. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan. 10. Division of Medical Fundamentals for Nursing, School of Nursing, Iwate Medical University, Morioka, Japan. 11. Third Department of Internal Medicine, Kyorin University School of Medicine, Mitaka, Japan. 12. Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan. 13. Department of Nutritional Medicine, Osaka City University Graduate School of Human Life Science, Osaka, Japan. 14. Department of Gastroenterology and Hepatology, NHO Beppu Medical Center, Beppu, Japan. 15. Department of Internal Medicine, Morioka Municipal Hospital, Morioka, Japan. 16. Division of Hepatobiliary and Pancreatic Disease, Hyogo College of Medicine, Nishinomiya, Japan. 17. Department of Nutritional Science, Morioka University, Takizawa, Japan.
Abstract
AIM: Hypozincemia is associated with the progression of chronic liver diseases, but it is unknown whether hypozincemia promotes human hepatocarcinogenesis. Our aim is to evaluate the serum zinc levels in liver cirrhosis (LC) patients and clarify the relationship between the serum zinc levels and the development of hepatocellular carcinoma (HCC). METHODS: Cirrhotic patients without HCC (n = 299) were enrolled from 14 medical institutes in Japan as a multicenter prospective study (No. 2028). Of the 299 patients, 157 were included in the present study based on reliable and consistent serum zinc levels and no history of oral zinc supplementation. Clinical parameters associated with the development of HCC were determined. Furthermore, the cumulative incidence of HCC was analyzed using Kaplan-Meier methods and was calculated using the log-rank test. A Cox regression analysis was utilized for the multivariate analysis to evaluate the predictors of hepatocarcinogenesis. RESULTS: Thirty of 157 patients (19.1%) developed HCC during an observation period of 3 years. Serum zinc levels were significantly decreased in hepatitis C virus-related LC (C-LC) patients with HCC (0.0180). The risk factors for incidence of HCC were hypozincemia (0.0014), high α-fetoprotein (0.0080), low branched chain amino acids-to-tyrosine ratio (0.0128), or female sex (0.0228). Hypozincemia (hazard ratio 1.61, 0.0324) was the only significant predictor of hepatocarcinogenesis by multivariate Cox regression analysis. CONCLUSIONS: Hypozincemia is associated with hepatocarcinogenesis in C-LC patients.
AIM: Hypozincemia is associated with the progression of chronic liver diseases, but it is unknown whether hypozincemia promotes humanhepatocarcinogenesis. Our aim is to evaluate the serum zinc levels in liver cirrhosis (LC) patients and clarify the relationship between the serum zinc levels and the development of hepatocellular carcinoma (HCC). METHODS: Cirrhotic patients without HCC (n = 299) were enrolled from 14 medical institutes in Japan as a multicenter prospective study (No. 2028). Of the 299 patients, 157 were included in the present study based on reliable and consistent serum zinc levels and no history of oral zinc supplementation. Clinical parameters associated with the development of HCC were determined. Furthermore, the cumulative incidence of HCC was analyzed using Kaplan-Meier methods and was calculated using the log-rank test. A Cox regression analysis was utilized for the multivariate analysis to evaluate the predictors of hepatocarcinogenesis. RESULTS: Thirty of 157 patients (19.1%) developed HCC during an observation period of 3 years. Serum zinc levels were significantly decreased in hepatitis C virus-related LC (C-LC) patients with HCC (0.0180). The risk factors for incidence of HCC were hypozincemia (0.0014), high α-fetoprotein (0.0080), low branched chain amino acids-to-tyrosine ratio (0.0128), or female sex (0.0228). Hypozincemia (hazard ratio 1.61, 0.0324) was the only significant predictor of hepatocarcinogenesis by multivariate Cox regression analysis. CONCLUSIONS: Hypozincemia is associated with hepatocarcinogenesis in C-LC patients.