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The Relationship Between Zinc Deficiency and Hepatocellular Carcinoma Associated with Hepatitis B Liver Cirrhosis: A 10-year Follow-up Study

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Abstract

Our aim is to evaluate the serum zinc levels in Hepatitis B liver cirrhosis patients and clarify the relationship between the serum zinc levels and the development of hepatocellular carcinoma (HCC). From January 2009 to December 2019, 295 included patients diagnosed with Hepatitis B liver cirrhosis received nucleos(t)ide analogues (NUCs) therapy at China-Japan Union Hospital of Jilin University. Their comprehensive medical records were retrospectively analyzed, and to analyze the relationship between hypozincemia and hepatitis B-related HCC. Twenty-eight of 295 patients (9.49%) developed HCC during an observation period of the median follow-up time was 42 months. Compared with the non-zinc deficiency group, the zinc deficiency group is older, has a higher proportion of hepatic encephalopathy, higher levels of aspartate aminotransferase(AST), international normalized ratio(INR) and TB, and lower levels of cholinesterase (CHE), creatinine, and platelet counts (P< 0.05). Multivariate analysis showed that zine (HR=0.854, 95%CI 0.725–1.007; P=0.061), zinc is not significant for reducing the incidence of HCC, as liver disease progresses, the proportion of zinc deficiency is getting higher and higher, Child-Pugh C. The proportion of grade zinc deficiency accounted for 64.86%. Child-Pugh grade C was more than Child-Pugh grade B and A, p<0.001. Zinc deficiency is associated with hepatic encephalopathy, and other complications related to hepatitis B and liver cirrhosis. But the relationship with hepatocellular carcinoma still needs further study.

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References

  1. Vallee BL, Falchuk KH (1993) The biochemical basis of zinc physiology. Physiol Rev 73(1):79–118

    Article  CAS  Google Scholar 

  2. Wessels I, Maywald M, Rink L (2017) Zinc as a gatekeeper of immune function. Nutrients 9(12):1286

    Article  Google Scholar 

  3. Leoni G, Rosato A, Perozzi G et al (2014) Zinc proteome interaction network as a model to identify nutrient-affected pathways in human pathologies. Genes Nutr 9(6):436

    Article  Google Scholar 

  4. Wastney ME, Aamodt RL, Rumble WF et al (1986) Kinetic analysis of zinc metabolism and its regulation in normal humans. Am J Physiol 251(2):398–408

    Google Scholar 

  5. Alker W, Haase H (2018) Zinc and Sepsis[J]. Nutrients 10(8):976

    Article  Google Scholar 

  6. Nishikawa H, Enomoto H, Yoh K et al (2019) Serum Zinc Concentration and Sarcopenia: A Close Linkage in Chronic Liver Diseases. J Clin Med 8(3):336

    Article  CAS  Google Scholar 

  7. Stamoulis I, Kouraklis G, Theocharis S (2007) Zinc and the liver: An active interaction. Dig Dis Sci 52(7):1595–1612

    Article  CAS  Google Scholar 

  8. Livingstone C (2015) Zine: Physiology, deficiency, and parenteral nutrition. Nutr Clin Pract 30(3):371–382

    Article  CAS  Google Scholar 

  9. Prasad AS (2013) Discovery of human zinc deficiency: Its impact on human health and disease. Adv Nutr 4(2):176–190

    Article  CAS  Google Scholar 

  10. Farooq M (2019) Zinc Defificiency is Associated with Poor Glycemic Control. J Coll Physicians Surg Pak 29(3):253–257

    Article  Google Scholar 

  11. Sullivan JF, Jetton MM, Burch RE (1979) A zinc tolerance test. J Lab Clin Med 93(3):485–492

    CAS  Google Scholar 

  12. Chiba M, Katayama K, Takeda R et al (2013) Diuretics aggravate zinc deficiency in patients with liver cirrhosis by increasing zinc excretion in urine. Hepatol Res 43(4):365–373

    Article  CAS  Google Scholar 

  13. Shigefuku R, Iwasa M, Katayama K et al (2019) Hypozincemia is associated with human hepatocarcinogenesis in hepatitis C virus-related liver cirrhosis. Hepatol Res 49(10):1127–1135

    Article  CAS  Google Scholar 

  14. Chavez-Tapia NC, Cesar-Arce A, Barrientos-Gutiérrez T et al (2013) A systematic review and meta-analysis of the use of oral zinc in the treatment of hepatic encephalopathy. Nutr J 12:74

    Article  CAS  Google Scholar 

  15. Hosui A, Kimura E, Abe S et al (2018) Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma. Nutrients 10(12):1955

    Article  Google Scholar 

  16. JiDong J, LanJuan L (2011) The guideline of prevention and treatment for chronic hepatitis B (2010 version). J Clin Hepatol 27(1):113–128

    Google Scholar 

  17. GuiQiang W, FuSheng W, Jun C et al (2015) The guideline of prevention and treatment for chronic hepatitis B (2015 version). J Clin Hepatol 31(12):1941–1960

    Google Scholar 

  18. Ministry of Health of the People’s Republic of China (2011) Standards for diagnosis and treatment of primary liver cancer (2011 edition). J Clin Hepatol 27(11):1141–1159

    Google Scholar 

  19. National Health and Family Planning Commission of the People’s Republic of China (2011) Standards for diagnosis and treatment of primary liver cancer. J Clin Hepatol, 2017 33(8):1419–1431

    Google Scholar 

  20. Chinese Society of Gastroenterology and Chinese Society of Hepatology, Chinese Medical Association (2013) Consensus on the diagnosis and treatment of hepatic encephalopathy in China (Chongqing 2013). J Clin Hepatol 21(9):641–645

    Google Scholar 

  21. Chinese Society of Hepatology, Chinese Medical Association (2018) Guidelines on the management of hepatic encephalopathy in cirrhosis. J Clin Hepatol 34(10):2076–2089

    Google Scholar 

  22. McClain CJ, Antonow DR, Cohen DA et al (1986) Zinc metabolism in alcoholic liver disease. Alcohol Clin Exp Res 10(6):582–589

    Article  CAS  Google Scholar 

  23. Grüngreiff K, Presser HJ, Franke D et al (1989) Correlations between zinc, amino acids and ammonia in liver cirrhosis. Z Gastroenteriol 27(12):731–735

    Google Scholar 

  24. Miatto O, Casaril M, Gabrielli BG et al (1985) Diagnostic and prognostic value of serum copper and plasma fibrinogen in hepatic carcinoma. Cancer 55(4):774–778

    Article  CAS  Google Scholar 

  25. Sharma P, Sharma BC (2013) Disaccharides in the treatment of hepatic encephalopathy. Metab Brain Dis 28(2):313–320

    Article  CAS  Google Scholar 

  26. Shen YC, Chang YH, Fang CJ et al (2019) Zinc supplementation in patients with cirrhosis and hepatic encephalopathy: a systematic review and meta-analysis. Nutr J 18(1):34

    Article  Google Scholar 

  27. Franklin RB, Costello LC (2009) The important role of the apoptotic effects of zinc in the development of cancers. J Cell Biochem 106(5):750–757

    Article  CAS  Google Scholar 

  28. Nardinocci L, Pantisano V, Puca R et al (2010) Zinc downregulates HIF-1 and inhibits its activity in tumor cells in vitro and in vivo. PLoS One 5(12):e15048

    Article  Google Scholar 

  29. Poo JL, Rosas-Romero R, Montemayor AC et al (2003) Diagnostic value of the copper/zinc ratio in hepatocellular carcinoma: A case control study. J Gastroenterol 38(1):45–51

    Article  Google Scholar 

  30. Hogstrand C, Kille P, Nicholson RI, Taylor et al (2009) Zinc transporters and cancer: A potential role for ZIP7as a hub for tyrosine kinase activation. Trends Mol Med 15(3):101–111

    Article  CAS  Google Scholar 

  31. Takahashi M, Saito H, Higashimoto M et al (2007) Possible inhibitory effect of oral zinc supplementation on hepatic fibrosis through downregulation of TIMP-1: A pilot study. Hepatol Res 37(6):405–409

    Article  CAS  Google Scholar 

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Author notes

  1. Shuai Wang and Xuemei Fan contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  1. Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China

    Shuai Wang, Yang Gao, Lijuan Zuo, Mingqi Hong & Yan Xu

  2. Department of Neurology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Xuemei Fan

Authors
  1. Shuai Wang
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  2. Xuemei Fan
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  3. Yang Gao
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  4. Lijuan Zuo
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  5. Mingqi Hong
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  6. Yan Xu
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Shuai Wang, Xuemei Fan, Yang Gao, Mingqi Hong, and Lijuan Zuo. The first draft of the manuscript was written by Shuai Wang, Yan Xu and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yan Xu.

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Ethics Approval

The present study was implemented following the Declaration of Helsinki and was approved by the Ethics Committee of China-Japan Union Hospital of Jilin University.

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Since it was a retrospective study, the informed consent of the participants was waived.

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The authors declare no competing interests.

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Wang, S., Fan, X., Gao, Y. et al. The Relationship Between Zinc Deficiency and Hepatocellular Carcinoma Associated with Hepatitis B Liver Cirrhosis: A 10-year Follow-up Study. Biol Trace Elem Res 201, 114–120 (2023). https://doi.org/10.1007/s12011-022-03156-z

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  • DOI: https://doi.org/10.1007/s12011-022-03156-z

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