Skip to main content

Advertisement

SpringerLink
Log in

Liver Transplantation: A Safe and Definitive Alternative to Lifelong Nitisinone for Tyrosinemia Type 1

  • Original Article
  • Published:
Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Objectives

To report the experience of liver transplantation (LT) for tyrosinemia type 1 (TT-1).

Methods

Clinical data of children with TT-1 who underwent living donor LT between July 2009 and May 2020 were retrospectively analyzed. Data included pre-LT nitisinone therapy, graft type, post-LT complications, HCC incidence, and graft/patient survival.

Results

Nine children were diagnosed with TT-1 at a median age of 12 mo (6–54 mo). Nitisinone was started in 6 patients at a median age of 15 mo (6–42 mo), but all had frequent interruption of therapy due to logistics with drug procurement including its cost. Median age at transplantation was 5 y (2–11 y). Explant liver showed HCC in 5 patients (55% of total cohort). The graft and patient survival are 100% with median follow-up of 58 mo (24–84 mo).

Conclusion

LT is curative for TT-1 and excellent results can be obtained in experienced centers. This is especially favorable in countries with limited resources where the cost of medical therapy is highly prohibitive, with lifelong diet restrictions and unclear long-term risk of HCC.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Chinsky JM, Singh R, Ficicioglu C, et al. Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations. Genet Med. 2017;19.https://doi.org/10.1038/gim.2017.101.

  2. Arnon R, Kerkar N, Davis MK, et al. Liver transplantation in children with metabolic diseases: the studies of pediatric liver transplantation experience: liver transplantation in childhood metabolic disease. Pediatr Transplant. 2010;14:796–805.

    Article  Google Scholar 

  3. Arnon R, Annunziato R, Miloh T, et al. Liver transplantation for hereditary tyrosinemia type I: analysis of the UNOS database: liver transplantation for tyrosinemia. Pediatr Transplant. 2011;15:400–5.

    Article  Google Scholar 

  4. Couce ML, Dalmau J, del Toro M, et al. Spanish working group on tyrosinemia type 1yrosinemia type 1 in Spain: mutational analysis, treatment and long-term outcome. Pediatr Int. 2011;53:985–9.

    Article  CAS  Google Scholar 

  5. Larochelle J, Alvarez F, Bussières JF, et al. Effect of nitisinone (NTBC) treatment on the clinical course of hepatorenal tyrosinemia in Québec. Mol Genet Metab. 2012;107:49–54.

    Article  CAS  Google Scholar 

  6. Neto JS, Leite KM, Porta A, et al. HCC prevalence and histopathological findings in liver explants of patients with hereditary tyrosinemia type 1. Pediatr Blood Cancer. 2014;61:1584–9.

    Article  Google Scholar 

  7. Masurel-Paulet A, Poggi-Bach J, Rolland MO, et al. NTBC treatment in tyrosinaemia type I: long-term outcome in French patients. J Inherit Metab Dis. 2008;31:81–7.

    Article  CAS  Google Scholar 

  8. Onenli Mungan N, Yildizdas D, Kor D, et al. Tyrosinemia type 1 and irreversible neuro- logic crisis after one month discontinuation of nitisone. Metab Brain Dis. 2016;31:1181–3.

    Article  CAS  Google Scholar 

  9. Angileri F, Bergeron A, Morrow G, et al. Geographical and ethnic distribution of mutations of the fumarylacetoacetate hydrolase gene in hereditary tyrosinemia type 1. JIMD Rep. 2015;19:43–58.

    Article  Google Scholar 

  10. Mieles LA, Esquivel CO, Van Thiel DH, et al. Liver transplantation for tyrosinemia: a review of 10 cases from the university of Pittsburgh. Digest Dis Sci. 1990;35:153–7.

    Article  CAS  Google Scholar 

  11. McKiernan P. Liver Transplantation for Hereditary Tyrosinaemia Type 1 in the United Kingdom. In: Tanguay RM, editor. Hereditary Tyrosinemia. Cham: Springer International Publishing; 2017. Available at: http://link.springer.com/10.1007/978-3-319-55780-9_7.  Accessed on 8 May 2020.

  12. Van Spronsen FJ, Thomasse Y, Smit GP, et al. Hereditary tyrosinemia type I: a new clinical classification with difference in prognosis on dietary treatment. Hepatol. 1994;20:1187–91.

    Article  Google Scholar 

  13. Hostetter MK, Levy HL, Winter HS, et al. Evidence for liver disease preceding amino acid abnormalities in hereditary tyrosinemia. N Engl J Med. 1983;308:1265–7.

    Article  CAS  Google Scholar 

  14. Koelink CJ, van Hasselt P, van der Ploeg A, et al. Tyrosinemia type I treated by NTBC: how does AFP predict liver cancer? Mol Genet Metab. 2006;89:310–5.

    Article  CAS  Google Scholar 

  15. Van Spronsen FJ, Bijleveld CM, van Maldegem BT, et al. Hepatocellular carcinoma in hereditary tyrosinemia type I despite 2-(2 nitro-4-3 trifluoro- methylbenzoyl)-1, 3-cyclohexanedione treatment. J Pediatr Gastroenterol Nutr. 2005;40:90–3.

    Article  Google Scholar 

  16. Karaca CA, Yilmaz C, Farajov R, et al. Live donor liver transplantation for type 1 tyrosinemia: an analysis of 15 patients. Pediatr Transplant. 2019;23:e13498.

    Article  Google Scholar 

  17. Büyükpamukçu M, Varan A, Haberal M, et al. The efficacy of liver transplantation in malignant liver tumors associated with tyrosinemia: clinical and laboratory findings of five cases. Pediatr Transplant. 2006;10:517–20.

    Article  Google Scholar 

  18. Esquivel CO, Mieles L, Marino IR, et al. Liver transplantation for hereditary tyrosinemia in the presence of hepatocellular carcinoma. Transplant Proc. 1989;21:2445–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Fagiuoli S, Daina E, D’Antiga L, et al. Monogenic diseases that can be cured by liver transplantation. J Hepatol. 2013;59:595–612.

    Article  Google Scholar 

  20. Québec NTBC Study Group, Alvarez F, Atkinson S, Bouchard M, et al. The Québec NTBC study. Adv Exp Med Biol. 2017;959:187–95.

  21. Liu Y, Luo Y, Xia L, et al. Living-donor liver transplantation for children with tyrosinemia type I. J Dig Dis. 2020;21:189–94.

    Article  CAS  Google Scholar 

  22. Freese DK, Tuchman M, Schwarzenberg SJ, et al. Early liver transplantation is indicated for tyrosinemia type I. J Pediatr Gastroenterol Nutr. 1991;13:10–5.

    Article  CAS  Google Scholar 

  23. Wijburg FA, Reitsma WChC, Slooff MJH, et al. Liver transplantation in tyrosinaemia type I: the Groningen experience. J Inherit Metab Dis. 1995;18:115–8.

    Article  CAS  Google Scholar 

  24. Laine J, Salo M, Krogerus L, et al. The Nephropathy of type I tyrosinemia after liver transplantation. Pediatr Res. 1995;37:640–5.

    Article  CAS  Google Scholar 

  25. Mohan N, McKiernan P, Kelly D, et al. Indications and outcome of liver transplantation in tyrosinemia type 1. Eur J Pediatr. 1999;158:S049–54.

    Article  Google Scholar 

  26. Van Ginkel WG, Rodenburg IL, Harding CO, et al. Long-term outcomes and practical considerations in the pharmacological management of tyrosinemia type 1. Pediatr Drugs. 2019;21:413–26.

    Article  Google Scholar 

  27. Thimm E, Richter-Werkle R, Kamp G, et al. Neurocognitive outcome in patients with hypertyrosinemia type I after long-term treatment with NTBC. J Inherit Metab Dis. 2012;35:263–8.

    Article  CAS  Google Scholar 

  28. García MI, de la Parra A, Arias C, et al. Long-term cognitive functioning in individuals with tyrosinemia type 1 treated with nitisinone and protein-restricted diet. Mol Genet Metab Rep. 2017;11:12–6.

    Article  Google Scholar 

  29. Malik S, NiMhurchadha S, Jackson C, et al. Treatment Adherence in Type 1 Hereditary Tyrosinemia (HT1): A mixed-method investigation into the beliefs, attitudes and behaviour of adolescent patients, their families and their health-care team. JIMD Rep. 2015;18:13–22.

    Article  Google Scholar 

  30. Simoncelli M, Samson J, Bussières JF, et al. Cost-consequence analysis of nitisinone for treatment of tyrosinemia type I. Can J Hosp Pharm. 2015;68:210–7.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatric Gastroenterology & Hepatology, Dr Rela Institute & Medical Centre, Bharat Institute of Higher Education and Research, Chennai, Tamil Nadu, 600044, India

    Jagadeesh Menon, Naresh Shanmugam & Joseph J. Valamparampil

  2. Department of Hepatobiliary surgery & liver transplantation, Dr Rela Institute & Medical Centre, Bharat Institute of Higher Education and Research, Chennai, Tamil Nadu, India

    Abdul Hakeem, Mettu Srinivas Reddy & Mohamed Rela

  3. Department of Histopathology, Dr Rela Institute & Medical Centre, Bharat Institute of Higher Education and Research, Chennai, Tamil Nadu, India

    Mukul Vij

  4. Department of Pediatric Genetics, NIRMAN, Mumbai, Maharashtra, India

    Anil Jalan

  5. Liver Transplant Unit, Kings College Hospital, London, UK

    Mohamed Rela

Authors
  1. Jagadeesh Menon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naresh Shanmugam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph J. Valamparampil
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abdul Hakeem
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mukul Vij
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anil Jalan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mettu Srinivas Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohamed Rela
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JM, Collection of patient data and preparation of manuscript, NS, Preparation of manuscript and proofreading, JJV, Collection of patient data and preparation of manuscript, AH, Editing and proofreading of the manuscript, MV, Reported and edited the histopathology section of the manuscript, AJ, Reported and edited the biochemical investigation section of the manuscript, MSR, Editing and proofreading of the manuscript, MR, Final proofreading and approval for publication of the manuscript, MR, is the guarantor for this paper.

Corresponding author

Correspondence to Naresh Shanmugam.

Ethics declarations

Ethics Committee Approval

The study was approved by the institute ethics committee (ECR/1276/Inst/TN2019/081).

Conflict of Interest

None.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Menon, J., Shanmugam, N., Valamparampil, J.J. et al. Liver Transplantation: A Safe and Definitive Alternative to Lifelong Nitisinone for Tyrosinemia Type 1. Indian J Pediatr 89, 438–444 (2022). https://doi.org/10.1007/s12098-021-03826-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12098-021-03826-1

Keywords

Search

Navigation