Clinicopathological and Prognostic Significance of Preoperative Serum Zinc Status in Patients with Hepatocellular Carcinoma After Initial Hepatectomy

Imai, Katsunori; Beppu, Teruhiko; Yamao, Takanobu; Okabe, Hidetoshi; Hayashi, Hiromitsu; Nitta, Hidetoshi; Hashimoto, Daisuke; Mima, Kosuke; Nakagawa, Shigeki; Sakamoto, Keita; Chikamoto, Akira; Ishiko, Takatoshi; Baba, Hideo

doi:10.1245/s10434-014-3786-3

Cited by 25 publications

(25 citation statements)

References 27 publications

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“…However, it is not clear whether hypozincemia induces the development of HCC. Several groups have examined the relationship between serum zinc levels and hepatocarcinogenesis in retrospective studies using a mixed cohort of HCV‐related CH and C‐LC patients . However, the frequency of HCC development is significantly different in the CH cohort when compared to the LC cohort, thus the current study using only the LC cohort is valuable in exploring the relationship between serum zinc levels and the development of HCC.…”

Section: Discussionmentioning

confidence: 99%

“…Hypozincemia, a deficiency of zinc, mediates various pathological and mental disorders, including taste disorders, dermatitis, wound healing abnormalities, depressed mental function, immune dysfunction, and hypogonadism . Hypozincemia is associated with the progression of human chronic liver diseases including chronic hepatitis (CH) and liver cirrhosis (LC) . Indeed, serum zinc levels are inversely correlated with liver function and with the severity of hepatic fibrosis in patients with hepatitis C virus (HCV)‐related chronic liver diseases .…”

Section: Introductionmentioning

confidence: 99%

“…1,2 Hypozincemia is associated with the progression of human chronic liver diseases including chronic hepatitis (CH) and liver cirrhosis (LC). [3][4][5][6] Indeed, serum zinc levels are inversely correlated with liver function and with the severity of hepatic fibrosis in patients with hepatitis C virus (HCV)-related chronic liver diseases. 4 In addition, zinc supplementation enhances the response to interferon therapy, leading to an improvement of liver damage and a reduction in mortality.…”

Section: Introductionmentioning

confidence: 99%

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Hypozincemia is associated with human hepatocarcinogenesis in hepatitis C virus‐related liver cirrhosis

Shigefuku

Iwasa

Katayama

et al. 2019

Hepatology Research

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hypozincemia is associated with human hepatocarcinogenesis in hepatitis C virus‐related liver cirrhosis

Shigefuku

Iwasa

Katayama

et al. 2019

Hepatology Research

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“…A low pre-operative serum Zn level was especially predominant in patients with HCV, and this was associated with post-treatment impaired liver function and hepatic fibrosis in a large sample of 310 patients who underwent initial hepatectomy for HCC. There was a significant inverse relationship between serum Zn level and HA level (mean HA 244.1 ± 223.2 in patients with serum Zn ≤65 vs. 118.8 ± 117.9 ng/mL in patients with serum Zn >65 mg/dL, p<0.0001) (118). Table 5 describes studies in individuals with diseases to other organs that are also accompanied by liver involvement (119)(120)(121)(122)(123).…”

Section: Other Liver Disease Populationsmentioning

confidence: 99%

Hyaluronic acid as a non-invasive biomarker of liver fibrosis

Neuman

Cohen

Nanau

2016

Clinical Biochemistry

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“…Cellular internalization mechanisms of Fe-bLf have been extensively investigated, and are mainly promoted via LRP1 and -2, DMT1, and transferrin receptors. 10,24,27 Absorption of zinc can also be promoted via zinc-specific receptors 29 and DMT1. [30][31][32] Therefore, understanding the in vivo internalization mechanisms of Zn-Fe-bLf NCs is a goal for the future.…”

mentioning

confidence: 99%

Theranostic multimodular potential of zinc-doped ferrite-saturated metal-binding protein-loaded novel nanocapsules in cancers

Kamalapuram

Kanwar

Roy

et al. 2016

IJN

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The present study successfully developed orally deliverable multimodular zinc (Zn) iron oxide (Fe 3 O 4 )-saturated bovine lactoferrin (bLf)-loaded polymeric nanocapsules (NCs), and evaluated their theranostic potential (antitumor efficacy, magnetophotothermal efficacy and imaging capability) in an in vivo human xenograft CpG-island methylator phenotype (CIMP)-1 + /CIMP2 − /chromosome instability-positive colonic adenocarcinoma (Caco2) and claudin-low, triple-negative (ER − /PR − /HER2 − ; MDA-MB-231) breast cancer model. Mice fed orally on the Zn-Fe-bLf NC diet showed downregulation in tumor volume and complete regression in tumor volume after 45 days of feeding. In human xenograft colon cancer, vehicle-control NC diet-group (n=5) mice showed a tumor volume of 52.28±11.55 mm 3 , and Zn-Fe-bLf NC diet (n=5)-treated mice had a tumor-volume of 0.10±0.073 mm 3 . In the human xenograft breast cancer model, Zn-Fe-bLf NC diet (n=5)-treated mice showed a tumor volume of 0.051±0.062 mm 3 within 40 days of feeding. Live mouse imaging conducted by near-infrared fluorescence imaging of Zn-Fe-bLf NCs showed tumor site-specific localization and regression of colon and breast tumor volume. Ex vivo fluorescence-imaging analysis of the vital organs of mice exhibited sparse localization patterns of Zn-Fe-bLf NCs and also confirmed tumor-specific selective localization patterns of Zn-Fe-bLf NCs. Dual imaging using magnetic resonance imaging and computerized tomography scans revealed an unprecedented theranostic ability of the Zn-Fe-bLf NCs. These observations warrant consideration of multimodular Zn-Fe-bLf NCs for real-time cancer imaging and simultaneous cancer-targeted therapy.

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Clinicopathological and Prognostic Significance of Preoperative Serum Zinc Status in Patients with Hepatocellular Carcinoma After Initial Hepatectomy

Abstract: Serum Zn level reflects liver function and is useful for predicting the hepatic fibrosis before surgery. The prognosis of patients with HCC was found to be associated with preoperative serum Zn level, especially in patients with HCV-related chronic liver disease.

Cited by 25 publications

References 27 publications

Hypozincemia is associated with human hepatocarcinogenesis in hepatitis C virus‐related liver cirrhosis

Hypozincemia is associated with human hepatocarcinogenesis in hepatitis C virus‐related liver cirrhosis

Hyaluronic acid as a non-invasive biomarker of liver fibrosis

Theranostic multimodular potential of zinc-doped ferrite-saturated metal-binding protein-loaded novel nanocapsules in cancers

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