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Hypozincemia is associated with human hepatocarcinogenesis in hepatitis C virus‐related liver cirrhosis
Author(s) -
Shigefuku Ryuta,
Iwasa Motoh,
Katayama Kazuhiro,
Eguchi Akiko,
Kawaguchi Takumi,
Shiraishi Koichi,
Ito Toshifumi,
Suzuki Kazutomo,
Koreeda Chizu,
Ohtake Takaaki,
Tokumoto Yoshio,
Endo Ryujin,
Kawamura Naohiro,
Shiraki Makoto,
Habu Daiki,
Sakai Hironori,
Kato Akinobu,
Nishiguchi Shuhei,
Moriwaki Hisataka,
Suzuki Kazuyuki,
Takei Yoshiyuki
Publication year - 2019
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.13388
Subject(s) - hepatocellular carcinoma , medicine , cirrhosis , gastroenterology , proportional hazards model , hepatitis c virus , cumulative incidence , hazard ratio , incidence (geometry) , liver cancer , immunology , virus , confidence interval , transplantation , physics , optics
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.