Sunday, November 28, 2010

Hereditary Tyrosinemia

For several years, liver transplantation has proven extremely useful in children with this otherwise lethal disease. The recenr introduction of the enzyme inhibitor NTBC (see chapter by Kvitington, Clayton, and Leonard, this volume), may diminish the need for liver transplantation.

Inborn Metabolic Disorders Treated by Liver Transplantation

In the European Liver Transplant Registry issued in October 1993 a metabolic disorder was recorder as a indication for transplantation in 18% of 1248 children treated by liver transplantation from May 1988 to June 1993. Two groups can be distinguished, as discussed below.

Long-Term Follow-Up at Liver Transplantation

In the majority of cases the children can resume a life close to normal when they leave the hospital and can atted school within 2-3 months of surgery. Clinical and biochemical monitorings are carried out in outpatient clinics; a salt-restricted diet is recommended, at least initially, because of the hipertensive effect of cyclosporine. Since the risk of rejection persists, immunosuppression must be pursued indefinitely, with the goal of reaching the lowest possible doses compatible with normal liver function tests in order to lower the risk of kidney damage due to cyclosporin. Prednisone is given on an alternate day basis, allowing normal growth and a significant increase in height velocity in most children who displayed growth retardation prior to tranplantation. Complications at this stage include late biliary stenosis, opportunistic infections, anemia and gastrointestinal bleeding due to portal vein stenosis, and Epstein Barr Virus (EBV) related lymphoproliferative syndrom. The latter seems in part related to the cumulative degree of immunosuppression, with early diagnosis, lowering or interruption of immunosupression, resection of the proliferative zones when limited and solitary, and careful supervision, regression may occur, but retransplantation may later be necessary because of chronic rejection.

Intermediary Folllow-Up at Liver Transplantation

The second period of follow-up takes place in conventional hospital settings and lasts an average of 6 weeks, Monitoring of liver and kidney function tests and blood cyclosporine trough levels is carried out daily. Prednisone is given orally and its dosage diminished to 0,5mg/kg per day at 1 month, cyclosperine is progressively switched from i.v. to oral.Three main complications are observed in this period :
1. Rejections is always possible and is managed as described above.
2. CMV infection must be searched for by repeated blood and urine cultures; the combination of prevention with specific immunoglobulins, early detection, and DHPG (dehydrosyphenylguanine, Gancyclovir) treatment of the symptomatic forms has made the severe forms of CMV infections vey rare.