锌缺乏作为肝炎病毒所致早期肝细胞癌患者的独立预后因素。
Zinc deficiency as an independent prognostic factor for patients with early hepatocellular carcinoma due to hepatitis virus.
作者信息
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
机构信息
Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
Department of Surgery, Ehime Prefectural Central Hospital, Matsuyama, Japan.
出版信息
Hepatol Res. 2020 Jan;50(1):92-100. doi: 10.1111/hepr.13430. Epub 2019 Nov 24.
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.
目的
尽管在因肝炎病毒导致的慢性肝病患者中经常观察到血清锌水平降低，但其预后重要性尚未得到充分研究。本研究旨在阐明锌缺乏与预后的关联，尤其是在早期肝细胞癌（HCC）患者中。
方法
2005年至2018年，纳入466例因肝炎病毒导致的初治HCC患者（男性327例，女性139例；中位年龄70岁；丙型肝炎病毒[HCV]389例，乙型肝炎病毒[HBV]69例，丙型肝炎病毒和乙型肝炎病毒8例；Child-Pugh A级367例，Child-Pugh B级82例；Child-Pugh C级17例；TNM-LCSGJ分期I期150例，II期181例，III期91例，IVa期26例，IVb期18例）。466例患者中，287例符合米兰标准（早期HCC）并接受了根治性治疗。锌缺乏定义为<60μg/dL。对临床记录和预后因素进行回顾性评估。
结果
血清锌水平随着慢性肝病进展而降低（Child-Pugh A级、B级、C级分别为64.3±14.3、52.3±15.7、48.4±13.5μg/dL；P<0.001）。在接受根治性治疗的早期HCC患者中，与锌缺乏患者相比，接受根治性治疗且无锌缺乏的患者总生存率和复发率更高（3年总生存率86.5%对77.2%，5年总生存率73.5%对43.8%，P<0.001；3年复发率44.8%对58.3%，5年复发率56.8%对77.5%，P=0.002）。不仅肝炎病毒的感染控制（HCV的持续病毒学应答或HBV的核苷（酸）类似物；HR 0.078，P<0.001），而且锌缺乏（HR 1.773，P=0.041）都是死亡的重要预后因素。
结论
血清锌水平随着慢性肝病分级进展而降低。除了肝炎病毒的感染控制外，锌缺乏可能是接受根治性治疗的病毒性肝炎所致早期HCC患者生存的重要预后因素。
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