Rare diseases Xagena

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Children with tyrosinaemia type 1: early Nitisinone treatment reduces the need for liver transplantation and improves post-transplant renal function

Tyrosinaemia type 1 ( HT1 ) is a rare disorder of tyrosine metabolism leading to liver failure and hepatocellular carcinoma. Treatment previously consisted of dietary restriction and orthotopic liver transplantation ( OLT ) but was transformed by the introduction of Nitisinone ( Orfadin ) in 1992.

Researchers have described the impact of Nitisinone on the outcome and need for orthotopic liver transplantation in a single Centre.

A retrospective analysis was performed of patients treated for HT1 at Birmingham Children's Hospital from 1989-2009.

Thirty eight patients were treated during the study period. Prior to 1992 6/7 ( 85.7 % ) underwent orthotopic liver transplantation compared to 7/31 ( 22.6 % ) after 1992 ( p = 0.004 ) when Nitisinone treatment was available.

Furthermore, Nitisinone-treated patients proceeding to orthotopic liver transplantation started treatment at a median age of 428 ( 86-821 ) days compared to 52 ( 2-990 ) days in those who did not ( p = 0.004 ).

Pre-OLT calculated glomerular filtration rate ( cGFR ) was similar in both groups but Nitisinone prevented early decline after OLT ( pre-Nitisinone median 99.8 to 45.8 ml/min/1.73 m2, p = 0.02 versus Nitisinone-treated group median 104.3 to 89.9 ml/min/1.73 m2, p = 0.5 ).

Urinary protein:creatinine ratio ( PCR ) fell post-OLT to within the normal range for those treated with Nitisinone but remained elevated in those not treated with Nitisinone.

Tubular reabsorption of phosphate ( TRP ) was normal or near normal in both groups pre-OLT and post-OLT.

Hypertension was commoner and more severe in those not treated with Nitisinone.

In conclusion. Nitisinone has reduced the need for orthotopic liver transplantation particularly when started early.
For those progressing to orthotopic liver transplantation the use of prior Nitisinone therapy results in a preservation of their subsequent renal function. ( Xagena )

Bartlett DC et al, J Inherit Metab Dis 2014; 37:745-752