Introduction Tyrosinaemia Type 1 (TT1) is a disorder of tyrosine metabolism which may lead to liver failure and a high risk of hepatocellular carcinoma (HCC). Treatment previously consisted of dietary restriction and orthotopic liver transplantation (OLT) but was transformed by the introduction of Nitisinone in 1992. Here we report how Nitisione has altered the outcome of and need for OLT in patients with TT1 in our centre.
Method A retrospective analysis was performed of patients treated for TT1 at Birmingham Children's Hospital from 1989 to 2009.
Results 38 patients were treated with no significant difference in the annual number of patients seen before and after 1992 (p=0.47). 6/7 (85.7%) seen prior to 1992 and 7/31 (22.6%) initially treated with Nitisinone underwent OLT. The primary indication for OLT prior to 1992 was hepatic dysplasia in all with rising α-fetoprotein in 4. Post 1992 indications were suspected/high risk of HCC in five patients, proven HCC in 1 and failure to respond to Nitisinone in 1. In patients treated with Nitisinone who subsequently required OLT, treatment was started at a median age of 428 days compared to 52 days in those who have not required OLT (p=0.03). Survival following OLT was 4/6 (66.7%) pre- and 7/7 (100%) post-Nitisione. Early complications included acute rejection in 4, hepatic artery thrombosis in 1, biliary reconstruction in 1, redo portal vein anastomoses in 1, burst abdomen in 1 and primary non function in 1 patient. Late complications included chronic rejection in 3, hypertension in 3, post transplant lymphoproliferative disease in 2, de novo hepatitis in 2, pulmonary metastasis in 1 and renal failure in 1 patient. 3 patients required a second transplant. Mean calculated glomerular filtration rate decreased post OLT with no significant difference between the pre- and post-Nitisinone groups. Mean tubular reabsorption of phosphate remained within the normal range for both groups up to 5 years post OLT. With the non-responder to Nitisinone excluded, mean urinary protein:creatinine ratio normalised post OLT in the Nitisinone group and was significantly lower than the non-treated group in which it remained raised up to 5 years post OLT (p=0.0046). Quality of life following transplant is good with unrestricted diet in all.
Conclusion OLT remains an effective treatment for TT1 but since the introduction of Nitisinone the need for OLT has been reduced and the likelihood of requiring OLT is minimised if Nitisinone therapy is instigated early. Although mean cGFR remains reduced post OLT, prior treatment with Nitisinone may improve tubular function as evidenced by normal protein:creatinine ratios.
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