Early nitisinone treatment reduces the need for liver transplantation in children with tyrosinaemia type 1 and improves post-transplant renal function

Background 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 in 1992. We describe the impact of nitisinone on the outcome and need for OLT in a single centre. Methods A retrospective analysis was performed of patients treated for HT1 at Birmingham Children's Hospital from 1989-2009. Results Thirty eight patients were treated during the study period. Prior to 1992 6/7 (85.7 %) underwent OLT compared to 7/31 (22.6 %) after 1992 (p = 0.004) when nitisinone treatment was available. Furthermore, nitisinone-treated patients proceeding to OLT 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. Conclusions Nitisinone reduces the need for OLT particularly when started early. For those progressing to OLT the use of prior nitisinone therapy results in a preservation of their subsequent renal function.