Skip to main content
SpringerLink
Log in

Liver Cirrhosis with Inherited Liver Diseases: Wilson Disease

  • Chapter
  • First Online:
The Evolving Landscape of Liver Cirrhosis Management

  • 465 Accesses

Abstract

Wilson disease is a genetic disorder of copper metabolism. Wilson disease is treatable by several pharmacological agents. If untreated, this disease results in severe disability and death. Therefore, early diagnosis and adequate treatments are important for this disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Oe S, Miyagawa K, Honma Y, Harada M. Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease. Exp Cell Res. 2016;347:192–200.

    Article  CAS  Google Scholar 

  2. Roberts EA, Schilsky ML. Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47:2089–111.

    Article  CAS  Google Scholar 

  3. European Association for the Study of the Liver. EASL clinical practice guidelines: Wilson’s disease. J Hepatol. 2012;56:671–85.

    Article  Google Scholar 

  4. Harada M. Pathogenesis and management of Wilson disease. Hepatol Res. 2014;44:395–402.

    Article  Google Scholar 

  5. Kim BE, Turski ML, Nose Y, Casad M, Rockman HA, Thiele DJ. Cardiac copper deficiency activates a systemic signaling mechanism that communicates with the copper acquisition and storage organs. Cell Metab. 2010;11:353–63.

    Article  CAS  Google Scholar 

  6. Lönnerdal B. Intestinal regulation of copper homeostasis: a developmental perspective. Am J Clin Nutr. 2008;88:846S–50S.

    Article  Google Scholar 

  7. Nose Y, Wood LK, Kim BE, Prohaska JR, Fry RS, Spears JW, et al. Ctr1 is an apical copper transporter in mammalian intestinal epithelial cells in vivo that is controlled at the level of protein stability. J Biol Chem. 2010;285:32385–92.

    Article  CAS  Google Scholar 

  8. Lutsenko S, Barnes NL, Bartee MY, Dmitriev OY. Function and regulation of human copper-transporting ATPases. Physiol Rev. 2007;87:1011–46.

    Article  CAS  Google Scholar 

  9. Nyasae L, Bustos R, Braiterman L, Eipper B, Hubbard A. Dynamics of endogenous ATP7A (Menkes protein) in intestinal epithelial cells: copper-dependent redistribution between two intracellular sites. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1181–94.

    Article  CAS  Google Scholar 

  10. Linder MC, Hazegh-Azam M. Copper biochemistry and molecular biology. Am J Clin Nutr. 1996;63:797S–811S.

    CAS  PubMed  Google Scholar 

  11. Wijmenga C, Klomp LW. Molecular regulation of copper excretion in the liver. Proc Nutr Soc. 2004;63:31–9.

    Article  CAS  Google Scholar 

  12. Zhou B, Gitschier J. hCTR1: a human gene for copper uptake identified by complementation in yeast. Proc Natl Acad Sci U S A. 1997;94:7481–6.

    Article  CAS  Google Scholar 

  13. Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet. 1993;5:327–37.

    Article  CAS  Google Scholar 

  14. Petrukhin K, Fischer SG, Pirastu M, Tanzi RE, Chernov I, Devoto M, et al. Mapping, cloning and genetic characterization of the region containing the Wilson disease. Gene. 1993;5(4):338–43.

    CAS  Google Scholar 

  15. Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, Wasco W, Ross B, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet. 1993;5:344–50.

    Article  CAS  Google Scholar 

  16. Terada K, Nakako T, Yang XL, Iida M, Aiba N, Minamiya Y, et al. Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA. J Biol Chem. 1998;273:1815–20.

    Article  CAS  Google Scholar 

  17. Terada K, Aiba N, Yang XL, Iida M, Nakai M, Miura N, et al. Biliary excretion of copper in LEC rat after introduction of copper transporting P-type ATPase, ATP7B. FEBS Lett. 1999;448:53–6.

    Article  CAS  Google Scholar 

  18. Yamaguchi Y, Heiny ME, Shimizu N, Aoki T, Gitlin JD. Expression of the Wilson disease gene is deficient in the long-Evans cinnamon rat. Biochem J. 1994;301:1–4.

    Article  CAS  Google Scholar 

  19. Hung IH, Suzuki M, Yamaguchi Y, Yuan DS, Klausner RD, Gitlin JD. Biochemical characterization of the Wilson disease protein and functional expression in the yeast Saccharomyces cerevisiae. J Biol Chem. 1997;272:21461–6.

    Article  CAS  Google Scholar 

  20. Yang XL, Miura N, Kawarada Y, Terada K, Petrukhin K, Gilliam T, et al. Two forms of Wilson disease protein produced by alternative splicing are localized in distinct cellular compartments. Biochem J. 1997;326:897–902.

    Article  CAS  Google Scholar 

  21. Harada M, Sakisaka S, Terada K, Kimura R, Kawaguchi T, Koga H, et al. Role of ATP7B in biliary copper excretion in a human hepatoma cell line and normal rat hepatocytes. Gastroenterology. 2000;118:921–8.

    Article  CAS  Google Scholar 

  22. Harada M, Sakisaka S, Kawaguchi T, Kimura R, Taniguchi E, Koga H, et al. Copper does not alter the intracellular distribution of ATP7B, a copper-transporting ATPase. Biochem Biophys Res Commun. 2000;275:871–6.

    Article  CAS  Google Scholar 

  23. Harada M, Sakisaka S, Terada K, Kimura R, Kawaguchi T, Koga H, et al. A mutation of the Wilson disease protein, ATP7B, is degraded in the proteasomes and forms protein aggregates. Gastroenterology. 2001;120:967–74.

    Article  CAS  Google Scholar 

  24. Harada M, Kumemura H, Sakisaka S, Shishido S, Taniguchi E, Kawaguchi T, et al. Wilson disease protein ATP7B is localized in the late endosomes in a polarized human hepatocyte cell line. Int J Mol Med. 2003;11:293–8.

    CAS  PubMed  Google Scholar 

  25. Harada M, Kawaguchi T, Kumemura H, Terada K, Ninomiya H, Taniguchi E, et al. The Wilson disease protein ATP7B resides in the late endosomes with Rab7 and the Niemann-Pick C1 protein. Am J Pathol. 2005;166:499–510.

    Article  CAS  Google Scholar 

  26. Yanagimoto C, Harada M, Kumemura H, Koga H, Kawaguchi T, Terada K, et al. Niemann-Pick C1 protein transports copper to the secretory compartment from late endosomes where ATP7B resides. Exp Cell Res. 2009;315:119–26.

    Article  CAS  Google Scholar 

  27. Yanagimoto C, Harada M, Kumemura H, Abe M, Koga H, Sakata M, et al. Copper incorporation into ceruloplasmin is regulated by Niemann-Pick C1 protein. Hepatol Res. 2011;41:484–91.

    Article  CAS  Google Scholar 

  28. Polishchuk EV, Concilli M, Iacobacci S, Chesi G, Pastore N, Piccolo P, et al. Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. Dev Cell. 2014;29:686–700.

    Article  CAS  Google Scholar 

  29. Lalioti V, Peiró R, Pérez-Berlanga M, Tsuchiya Y, Muñoz A, Villalba T, et al. Basolateral sorting and transcytosis define the Cu+-regulated translocation of ATP7B to the bile canaliculus. J Cell Sci. 2016;129:2190–201.

    Article  CAS  Google Scholar 

  30. Connemann BJ, Gahr M, Schmid M, Runz H, Freudenmann RW. Low ceruloplasmin in a patient with Niemann-Pick type C disease. J Clin Neurosci. 2012;19:620–1.

    Article  Google Scholar 

  31. Vázquez MC, Martínez P, Alvarez AR, González M, Zanlungo S. Increased copper levels in in vitro and in vivo models of Niemann-Pick C disease. Biometals. 2012;25:777–86. https://doi.org/10.1007/s10534-012-9546-6.

    Article  CAS  PubMed  Google Scholar 

  32. Wilson SAK. Progressive lenticular degeneration: a familial nervous disease associated with cirrhosis of the liver. Brain. 1912;34:295–507.

    Article  Google Scholar 

  33. Cumings JN. The copper and iron content of brain and liver in the normal and in hepato-lenticular degeneration. Brain. 1948;71:410–5.

    Article  CAS  Google Scholar 

  34. Scheinberg IH, Gitlin D. Deficiency of ceruloplasmin in patients with hepatolenticular degeneration (Wilson’s disease). Science. 1952;116:484–5.

    Article  CAS  Google Scholar 

  35. Ferenci P, Członkowska A, Merle U, et al. Late-onset Wilson’s disease. Gastroenterology. 2007;132:1294–8.

    Article  CAS  Google Scholar 

  36. Scheinberg IH, Sternlieb I. Pregnancy in penicillamine-treated patients with Wilson’s disease. N Engl J Med. 1975;293:1300–2.

    Article  CAS  Google Scholar 

  37. Sinha S, Taly AB, Prashanth LK, Arunodaya GR, Swamy HS. Successful pregnancies and abortions in symptomatic and asymptomatic Wilson’s disease. J Neurol Sci. 2004;217:37–40.

    Article  Google Scholar 

  38. Brewer GJ, Johnson VD, Dick RD, Hedera P, Fink JK, Kluin KJ. Treatment of Wilson’s disease with zinc. Hepatology. 2000;31:364–70.

    Article  CAS  Google Scholar 

  39. Sternlieb I. Wilson’s disease and pregnancy. Hepatology. 2000;31:531–2.

    Article  CAS  Google Scholar 

  40. Ferenci P, Caca K, Loudianos G, Mieli-Vergani G, Tanner S, Sternlieb I, et al. Diagnosis and phenotypic classification of Wilson disease. Liver Int. 2003;23:139–42.

    Article  Google Scholar 

  41. Walshe JM. Wilson’s disease. New oral therapy. Lancet. 1956;1:25–6.

    Article  Google Scholar 

  42. Weiss KH, Thurik F, Gotthardt DN, Schäfer M, Teufel U, Wiegand F, et al. Efficacy and safety of oral chelators in treatment of patients with Wilson disease. Clin Gastroenterol Hepatol. 2013;11:1028–35.

    Article  CAS  Google Scholar 

  43. Walshe JM. Treatment of Wilson’s disease with trientine dihydrochloride. Lancet. 1982;1:643–7.

    Article  CAS  Google Scholar 

  44. Weiss KH, Askari FK, Czlonkowska A, Ferenci P, Bronstein JM, Bega D, et al. Bis-choline tetrathiomolybdate in patients with Wilson’s disease: an open-label, multicentre, phase 2 study. Lancet Gastroenterol Hepatol. 2017;2:869–76.

    Article  Google Scholar 

  45. Brewer GJ, Terry CA, Aisen AM, Hill GM. Treatment of Wilson’s disease. Semin Neurol. 1987;7:209–20.

    Article  CAS  Google Scholar 

  46. Shimizu N, Fujiwara J, Ohnishi S, Sato M, Kodama H, Kohsaka T, et al. Effects of long-term zinc treatment in Japanese patients with Wilson disease: efficacy, stability, and copper metabolism. Transl Res. 2010;156:350–7.

    Article  CAS  Google Scholar 

  47. Weiss KH, Gotthardt DN, Klemm D, Merle U, Ferenci-Foerster D, Schaefer M, et al. Zinc monotherapy is not as effective as chelating agents in treatment of Wilson disease. Gastroenterology. 2011;140:1189–98.

    Article  CAS  Google Scholar 

  48. Askari FK, Greenson J, Dick RD, Johnson VD, Brewer GJ. Treatment of Wilson’s disease with zinc. J Lab Clin Med. 2003;142:385–90.

    Article  CAS  Google Scholar 

  49. Sini M, Sorbello O, Sanna F, Battolu F, Civolani A, Fanni D, et al. Histologic evolution and long-term outcome of Wilson’s disease: results of a single-center experience. Eur J Gastroenterol Hepatol. 2013;25:111–7.

    Article  Google Scholar 

  50. Yoshitoshi EY, Takada Y, Oike F, Sakamoto S, Ogawa K, Kanazawa H, et al. Long-term outcomes for 32 cases of Wilson’s disease after living-donor liver transplantation. Transplantation. 2009;87:261–7.

    Article  Google Scholar 

  51. Petrasek J, Jirsa M, Sperl J, Kozak L, Taimr P, Spicak J, et al. Revised King’s College score for liver transplantation in adult patients with Wilson’s disease. Liver Transpl. 2007;13:55–61.

    Article  Google Scholar 

  52. Harada M. Management for acute liver failure of Wilson disease: indication for liver transplantation. Hepatol Res. 2017;47:281–2.

    Article  Google Scholar 

  53. Merle U, Schaefer M, Ferenci P, Stremmel W. Clinical presentation, diagnosis and long-term outcome of Wilson’s disease: a cohort study. Gut. 2007;56:115–20.

    Article  CAS  Google Scholar 

  54. Beinhardt S, Leiss W, Stättermayer AF, Graziadei I, Zoller H, Stauber R, et al. Long-term outcomes of patients with Wilson disease in a large Austrian cohort. Clin Gastroenterol Hepatol. 2014;12:683–9.

    Article  Google Scholar 

  55. Walshe JM, Dixon AK. Dangers of non-compliance in Wilson’s disease. Lancet. 1986;327:845–7.

    Article  Google Scholar 

  56. Tatsumi Y, Hattori A, Hayashi H, Ikoma J, Kaito M, Imoto M, et al. Current state of Wilson disease patients in central Japan. Intern Med. 2010;49:809–15.

    Article  CAS  Google Scholar 

  57. Harada M. Wilson disease and its current problems. Intern Med. 2010;49:807–8.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Masaru Harada

Authors
  1. Masaru Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masaru Harada .

Editor information

Editors and Affiliations

  1. Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan

    Hitoshi Yoshiji

  2. Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan

    Kosuke Kaji

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Harada, M. (2019). Liver Cirrhosis with Inherited Liver Diseases: Wilson Disease. In: Yoshiji, H., Kaji, K. (eds) The Evolving Landscape of Liver Cirrhosis Management. Springer, Singapore. https://doi.org/10.1007/978-981-13-7979-6_5

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-7979-6_5

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-7663-4

  • Online ISBN: 978-981-13-7979-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation