Ann Liver Transplant.  2023 Nov;3(2):80-85. 10.52604/alt.23.0019.

Pediatric liver transplantation for Wilson disease

• Park JI
• Jung BH

• KMID: 2560927
• DOI: http://doi.org/10.52604/alt.23.0019

Abstract

Wilson disease (WD) stands as an autosomal recessive disorder primarily brought about by genetic mutations affecting the ATP7B gene, yielding a prevalence rate estimated at 1:30,000 to 50,000 individuals. The ATP7B gene codes for an enzyme known as transmembrane copper-transporting ATPase, a crucial factor in the incorporation of copper into ceruloplasmin and its elimination through bile excretion. The malfunction or absence of this enzyme leads to the progressive buildup of copper within various organs, particularly the liver, nervous system, corneas, kidneys, and heart. Children afflicted with WD may manifest with asymptomatic liver issues, cirrhosis, or even acute liver failure, accompanied by or without neurological and psychiatric symptoms. Approximately 20% to 30% of WD patients experience acute liver failure, while the majority of others develop chronic progressive hepatitis or cirrhosis when left untreated. While genetic testing has gained significance in diagnosing WD, the diagnosis still relies on a combination of clinical observations and laboratory tests. In cases of liver failure and encephalopathy, liver transplantation emerges as a life-saving option for WD patients. This review addresses specific concerns pertinent to liver transplantation for pediatric WD patients.

Keyword

Wilson disease; Acute liver failure; Copper metabolism; Genetic disorder; Liver transplantation

Reference

1. Socha P, Janczyk W, Dhawan A, Baumann U, D'Antiga L, Tanner S, et al. 2018; Wilson's disease in children: a position paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 66:334–344. DOI: 10.1097/MPG.0000000000001787. PMID: 29341979.

2. Reilly M, Daly L, Hutchinson M. 1993; An epidemiological study of Wilson's disease in the Republic of Ireland. J Neurol Neurosurg Psychiatry. 56:298–300. DOI: 10.1136/jnnp.56.3.298. PMID: 8459248. PMCID: PMC1014866.

3. Poujois A, Woimant F, Samson S, Chaine P, Girardot-Tinant N, Tuppin P. 2018; Characteristics and prevalence of Wilson's disease: a 2013 observational population-based study in France. Clin Res Hepatol Gastroenterol. 42:57–63. DOI: 10.1016/j.clinre.2017.05.011. PMID: 28648494.

4. Cheung KS, Seto WK, Fung J, Mak LY, Lai CL, Yuen MF. 2017; Epidemiology and natural history of Wilson's disease in the Chinese: a territory-based study in Hong Kong between 2000 and 2016. World J Gastroenterol. 23:7716–7726. DOI: 10.3748/wjg.v23.i43.7716. PMID: 29209112. PMCID: PMC5703931.

5. Gao J, Brackley S, Mann JP. 2019; The global prevalence of Wilson disease from next-generation sequencing data. Genet Med. 21:1155–1163. DOI: 10.1038/s41436-018-0309-9. PMID: 30254379.

6. Steindl P, Ferenci P, Dienes HP, Grimm G, Pabinger I, Madl C, et al. 1997; Wilson's disease in patients presenting with liver disease: a diagnostic challenge. Gastroenterology. 113:212–218. DOI: 10.1016/S0016-5085(97)70097-0. PMID: 9207280.

7. Seo JK. 2012; Diagnosis of Wilson disease in young children: molecular genetic testing and a paradigm shift from the laboratory diagnosis. Pediatr Gastroenterol Hepatol Nutr. 15:197–209. DOI: 10.5223/pghn.2012.15.4.197. PMID: 24010089. PMCID: PMC3746050.

8. Kluska A, Kulecka M, Litwin T, Dziezyc K, Balabas A, Piatkowska M, et al. 2019; Whole-exome sequencing identifies novel pathogenic variants across the ATP7B gene and some modifiers of Wilson's disease phenotype. Liver Int. 39:177–186. DOI: 10.1111/liv.13967. PMID: 30230192.

9. Ferenci P. 2006; Regional distribution of mutations of the ATP7B gene in patients with Wilson disease: impact on genetic testing. Hum Genet. 120:151–159. DOI: 10.1007/s00439-006-0202-5. PMID: 16791614.

10. Gomes A, Dedoussis GV. 2016; Geographic distribution of ATP7B mutations in Wilson disease. Ann Hum Biol. 43:1–8. DOI: 10.3109/03014460.2015.1051492. PMID: 26207595.

11. Huster D, Kühne A, Bhattacharjee A, Raines L, Jantsch V, Noe J, et al. 2012; Diverse functional properties of Wilson disease ATP7B variants. Gastroenterology. 142:947–956.e5. DOI: 10.1053/j.gastro.2011.12.048. PMID: 22240481. PMCID: PMC3461965.

12. Ferenci P, Roberts EA. 2012; Defining Wilson disease phenotypes: from the patient to the bench and back again. Gastroenterology. 142:692–696. DOI: 10.1053/j.gastro.2012.02.035. PMID: 22480881.

13. Caca K, Ferenci P, Kühn HJ, Polli C, Willgerodt H, Kunath B, et al. 2001; High prevalence of the H1069Q mutation in East German patients with Wilson disease: rapid detection of mutations by limited sequencing and phenotype-genotype analysis. J Hepatol. 35:575–581. DOI: 10.1016/S0168-8278(01)00219-7. PMID: 11690702.

14. Ferenci P. 2014; Phenotype-genotype correlations in patients with Wilson's disease. Ann N Y Acad Sci. 1315:1–5. DOI: 10.1111/nyas.12340. PMID: 24517292.

15. Merle U, Weiss KH, Eisenbach C, Tuma S, Ferenci P, Stremmel W. 2010; Truncating mutations in the Wilson disease gene ATP7B are associated with very low serum ceruloplasmin oxidase activity and an early onset of Wilson disease. BMC Gastroenterol. 10:8. DOI: 10.1186/1471-230X-10-8. PMID: 20082719. PMCID: PMC2845088.

16. Okada T, Shiono Y, Kaneko Y, Miwa K, Hasatani K, Hayashi Y, et al. 2010; High prevalence of fulminant hepatic failure among patients with mutant alleles for truncation of ATP7B in Wilson's disease. Scand J Gastroenterol. 45:1232–1237. DOI: 10.3109/00365521.2010.492527. PMID: 20491539.

17. Członkowska A, Litwin T, Dusek P, Ferenci P, Lutsenko S, Medici V, et al. 2018; Wilson disease. Nat Rev Dis Primers. 4:21. DOI: 10.1038/s41572-018-0018-3. PMID: 30190489. PMCID: PMC6416051.

18. Gitlin D, Janeway CA. 1960; Turnover of the copper and protein moieties of ceruloplasmin. Nature. 185:693. DOI: 10.1038/185693a0. PMID: 13828220.

19. Mounajjed T, Oxentenko AS, Qureshi H, Smyrk TC. 2013; Revisiting the topic of histochemically detectable copper in various liver diseases with special focus on venous outflow impairment. Am J Clin Pathol. 139:79–86. DOI: 10.1309/AJCPDZR4OHDQNG3L. PMID: 23270902.

20. Fernando M, van Mourik I, Wassmer E, Kelly D. 2020; Wilson disease in children and adolescents. Arch Dis Child. 105:499–505. DOI: 10.1136/archdischild-2018-315705. PMID: 31974298.

21. Walshe JM. 2013; The acute haemolytic syndrome in Wilson's disease--a review of 22 patients. QJM. 106:1003–1008. DOI: 10.1093/qjmed/hct137. PMID: 23842488.

22. Lin LJ, Wang DX, Ding NN, Lin Y, Jin Y, Zheng CQ. 2014; Comprehensive analysis on clinical features of Wilson's disease: an experience over 28 years with 133 cases. Neurol Res. 36:157–163. DOI: 10.1179/1743132813Y.0000000262. PMID: 24107488.

23. Roberts EA, Schilsky ML. 2008; Diagnosis and treatment of Wilson disease: an update. Hepatology. 47:2089–2111. DOI: 10.1002/hep.22261. PMID: 18506894.

24. Roberts EA, Yap J. 2006; Nonalcoholic Fatty Liver Disease (NAFLD): approach in the adolescent patient. Curr Treat Options Gastroenterol. 9:423–431. DOI: 10.1007/BF02738532. PMID: 16942668.

25. Yener S, Akarsu M, Karacanci C, Sengul B, Topalak O, Biberoglu K, et al. 2004; Wilson's disease with coexisting autoimmune hepatitis. J Gastroenterol Hepatol. 19:114–116. DOI: 10.1111/j.1440-1746.2004.03254.x. PMID: 14675255.

26. Squires RH Jr, Shneider BL, Bucuvalas J, Alonso E, Sokol RJ, Narkewicz MR, et al. 2006; Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr. 148:652–658. DOI: 10.1016/j.jpeds.2005.12.051. PMID: 16737880. PMCID: PMC2662127.

27. Zaccherini G, Weiss E, Moreau R. 2020; Acute-on-chronic liver failure: definitions, pathophysiology and principles of treatment. JHEP Rep. 3:100176. DOI: 10.1016/j.jhepr.2020.100176. PMID: 33205036. PMCID: PMC7652714.

28. Berman DH, Leventhal RI, Gavaler JS, Cadoff EM, Van Thiel DH. 1991; Clinical differentiation of fulminant Wilsonian hepatitis from other causes of hepatic failure. Gastroenterology. 100:1129–1134. DOI: 10.1016/0016-5085(91)90294-U. PMID: 2001814.

29. Rukunuzzaman M. 2015; Wilson's disease in Bangladeshi children: analysis of 100 cases. Pediatr Gastroenterol Hepatol Nutr. 18:121–127. DOI: 10.5223/pghn.2015.18.2.121. PMID: 26157698. PMCID: PMC4493245.

30. Kim TJ, Kim IO, Kim WS, Cheon JE, Moon SG, Kwon JW, et al. 2006; MR imaging of the brain in Wilson disease of childhood: findings before and after treatment with clinical correlation. AJNR Am J Neuroradiol. 27:1373–1378.

31. Zhong W, Huang Z, Tang X. 2019; A study of brain MRI characteristics and clinical features in 76 cases of Wilson's disease. J Clin Neurosci. 59:167–174. DOI: 10.1016/j.jocn.2018.10.096. PMID: 30385165.

32. Ferenci P, Caca K, Loudianos G, Mieli-Vergani G, Tanner S, Sternlieb I, et al. 2003; Diagnosis and phenotypic classification of Wilson disease. Liver Int. 23:139–142. DOI: 10.1034/j.1600-0676.2003.00824.x. PMID: 12955875.

33. Nicastro E, Ranucci G, Vajro P, Vegnente A, Iorio R. 2010; Re-evaluation of the diagnostic criteria for Wilson disease in children with mild liver disease. Hepatology. 52:1948–1956. DOI: 10.1002/hep.23910. PMID: 20967755.

34. Koppikar S, Dhawan A. 2005; Evaluation of the scoring system for the diagnosis of Wilson's disease in children. Liver Int. 25:680–681. Erratum in: Liver Int 2005;25:1078. DOI: 10.1111/j.1478-3231.2005.01072.x. PMID: 15910506.

35. Espinós C, Ferenci P. 2020; Are the new genetic tools for diagnosis of Wilson disease helpful in clinical practice? JHEP Rep. 2:100114. DOI: 10.1016/j.jhepr.2020.100114. PMID: 32613181. PMCID: PMC7322184.

36. Ferenci P, Stremmel W, Członkowska A, Szalay F, Viveiros A, Stättermayer AF, et al. 2019; Age and sex but not ATP7B genotype effectively influence the clinical phenotype of Wilson disease. Hepatology. 69:1464–1476. DOI: 10.1002/hep.30280. PMID: 30232804.

37. Mukherjee S, Dutta S, Majumdar S, Biswas T, Jaiswal P, Sengupta M, et al. 2014; Genetic defects in Indian Wilson disease patients and genotype-phenotype correlation. Parkinsonism Relat Disord. 20:75–81. DOI: 10.1016/j.parkreldis.2013.09.021. PMID: 24094725.

38. Collins CJ, Yi F, Dayuha R, Duong P, Horslen S, Camarata M, et al. 2021; Direct measurement of ATP7B peptides is highly effective in the diagnosis of Wilson disease. Gastroenterology. 160:2367–2382.e1. DOI: 10.1053/j.gastro.2021.02.052. PMID: 33640437. PMCID: PMC8243898.

39. European Association for Study of Liver. 2012; EASL clinical practice guidelines: Wilson's disease. J Hepatol. 56:671–685. DOI: 10.1016/j.jhep.2011.11.007. PMID: 22340672.

40. Santos Silva EE, Sarles J, Buts JP, Sokal EM. 1996; Successful medical treatment of severely decompensated Wilson disease. J Pediatr. 128:285–287. DOI: 10.1016/S0022-3476(96)70412-2. PMID: 8636833.

41. Dhawan A, Taylor RM, Cheeseman P, De Silva P, Katsiyiannakis L, Mieli-Vergani G. 2005; Wilson's disease in children: 37-year experience and revised King's score for liver transplantation. Liver Transpl. 11:441–448. DOI: 10.1002/lt.20352. PMID: 15776453.

42. Chanpong A, Dhawan A. 2021; Long-term urinary copper excretion on chelation therapy in children with Wilson disease. J Pediatr Gastroenterol Nutr. 72:210–215. DOI: 10.1097/MPG.0000000000002982. PMID: 33369596.

43. Chanpong A, Dhawan A. 2022; Wilson disease in children and young adults - state of the art. Saudi J Gastroenterol. 28:21–31. DOI: 10.4103/sjg.sjg_501_21. PMID: 35042319. PMCID: PMC8919932.

44. Dal MB, Alim A, Acarli K. 2021; The advantage of early liver transplantation for Wilson's disease using living donors. Prz Gastroenterol. 16:213–218. DOI: 10.5114/pg.2021.108990. PMID: 34584582. PMCID: PMC8456762.

45. Catana AM, Medici V. 2012; Liver transplantation for Wilson disease. World J Hepatol. 4:5–10. DOI: 10.4254/wjh.v4.i1.5. PMID: 22312450. PMCID: PMC3272077.

46. Guillaud O, Dumortier J, Sobesky R, Debray D, Wolf P, Vanlemmens C, et al. 2014; Long term results of liver transplantation for Wilson's disease: experience in France. J Hepatol. 60:579–589. DOI: 10.1016/j.jhep.2013.10.025. PMID: 24211743.

47. McCullough AJ, Fleming CR, Thistle JL, Baldus WP, Ludwig J, McCall JT, et al. 1983; Diagnosis of Wilson's disease presenting as fulminant hepatic failure. Gastroenterology. 84:161–167. DOI: 10.1016/S0016-5085(83)80181-4. PMID: 6847842.

48. Schilsky ML, Sternlieb I. 1997; Overcoming obstacles to the diagnosis of Wilson's disease. Gastroenterology. 113:350–353.

49. Sen S, Felldin M, Steiner C, Larsson B, Gillett GT, Olausson M, et al. 2002; Albumin dialysis and Molecular Adsorbents Recirculating System (MARS) for acute Wilson's disease. Liver Transpl. 8:962–967. DOI: 10.1053/jlts.2002.35546. PMID: 12360442.

50. Collins KL, Roberts EA, Adeli K, Bohn D, Harvey EA. 2008; Single pass albumin dialysis (SPAD) in fulminant Wilsonian liver failure: a case report. Pediatr Nephrol. 23:1013–1016. DOI: 10.1007/s00467-008-0761-x. PMID: 18299897.

51. Jhang JS, Schilsky ML, Lefkowitch JH, Schwartz J. 2007; Therapeutic plasmapheresis as a bridge to liver transplantation in fulminant Wilson disease. J Clin Apher. 22:10–14. DOI: 10.1002/jca.20118. PMID: 17285615.

52. Walker G, Hussaini T, Stowe R, Cresswell S, Yoshida EM. 2018; Liver transplant can resolve severe neuropsychiatric manifestations of Wilson disease: a case report. Exp Clin Transplant. 16:620–624.

53. Stracciari A, Tempestini A, Borghi A, Guarino M. 2000; Effect of liver transplantation on neurological manifestations in Wilson disease. Arch Neurol. 57:384–386. DOI: 10.1001/archneur.57.3.384. PMID: 10714666.

54. Ostapowicz G, Fontana RJ, Schiødt FV, Larson A, Davern TJ, Han SH, et al. 2002; Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 137:947–954. DOI: 10.7326/0003-4819-137-12-200212170-00007. PMID: 12484709.