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Zinc deficiency as an independent prognostic factor for patients with early hepatocellular carcinoma due to hepatitis virus
Author(s) -
Hiraoka Atsushi,
Nagamatsu Kensuke,
Izumoto Hirofumi,
Adachi Tomoko,
Yoshino Takeaki,
Tsuruta Miho,
Aibiki Toshihiko,
Okudaira Tomonari,
Yamago Hiroka,
Iwasaki Ryuichiro,
Suga Yoshifumi,
Mori Kenichiro,
Miyata Hideki,
Tsubouchi Eiji,
Ninomiya Tomoyuki,
Kawasaki Hideki,
Hirooka Masashi,
Matsuura Bunzo,
Abe Masanori,
Hiasa Yoichi,
Michitaka Kojiro
Publication year - 2020
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.13430
Subject(s) - hepatocellular carcinoma , medicine , gastroenterology , zinc deficiency (plant disorder) , hepatitis c virus , liver disease , stage (stratigraphy) , hepatitis b virus , milan criteria , hepatitis b , hepatitis c , virus , immunology , pathology , liver transplantation , transplantation , biology , paleontology , micronutrient
Aim Although a reduced serum zinc level is often observed in patients with chronic liver disease due to hepatitis virus, its prognostic importance has not been adequately investigated. This study aimed to elucidate the association of zinc deficiency with prognosis, especially in early hepatocellular carcinoma (HCC) patients. Methods From 2005 to 2018, 466 patients with naïve HCC due to hepatitis virus were enrolled (327 men, 139 women; median age 70 years; hepatitis C virus [HCV] n = 389, hepatitis B virus [HBV] n = 69, hepatitis C virus and hepatitis B virus n = 8; Child–Pugh A n = 367, Child–Pugh B n = 82; Child–Pugh C n = 17; TNM‐LCSGJ stage I n = 150, stage II n = 181, stage III n = 91, stage IVa n = 26, state IVb n = 18). Of the 466 patients, 287 were within the Milan criteria (early HCC) and treated curatively. Zinc deficiency was defined as <60 μg/dL. Clinical records and prognostic factors were retrospectively evaluated. Results The levels of serum zinc became lower with chronic liver disease progression (Child–Pugh A, B, C: 64.3 ± 14.3, 52.3 ± 15.7, 48.4 ± 13.5 μg/dL, respectively; P < 0.001). In early HCC patients treated curatively, overall survival and recurrence rates were better in patients treated curatively and without zinc deficiency as compared with patients with zinc deficiency (3‐year overall survival 86.5% vs. 77.2%, 5‐year overall survival 73.5% vs. 43.8%, P < 0.001; 3‐year recurrence 44.8% vs. 58.3%, 5‐year recurrence 56.8% vs. 77.5%, P = 0.002). Not only infection control of hepatitis virus (sustained virological response in HCV or nucleos(t)ide analogs in HBV; HR 0.078, P < 0.001), but also zinc deficiency (HR 1.773, P = 0.041) were significant prognostic factors for death. Conclusion Serum levels of zinc were reduced in association with chronic liver disease grade progression. In addition to infection control of hepatitis virus, zinc deficiency might be a significant prognostic factor for survival in patients with early HCC due to viral hepatitis treated curatively.