Liver Transplantation Review

These results indicate that liver transplantation can cure not only genetic disorders that present in the liver, but also liver disorders associated with extrahepatic pathology. Furthermore, a genetic defect present in all body cells such as familial hypercholesterolemia can be compensated by the mass of normal cells provided by liver transplantation.

Cholesterol Ester Storage Disease

 Cirrhosis is a possible complication and was successfully treated by liver transplantation in a 14-year-old child. Neonatal Hemochromatosis. A few infants received liver transplantation with success. The recent availability of medical antioxidant therapy may limit the need for transplantation in the future.

Type IV Glycogen Storage Disease

Liver transplantation eliminates cirrhosis and may even improve the degree of amylopectin storage in the heart. Careful follow-up is, however, necessary in this respec.

Type IA and IB Glycogen Storage Diseases

Beside severe hypoglycemia, growth failure, and acidosis, they also carry a risk of liver adenoma, possibly complicated by intratumoral hemorrhage or liver cell carcinoma.

Wilson's Disease

This is usually treated successfully with copper-chelating agents; in a few cases, howover (e.g., acure liver failure with or without hemolysis, acute relapse after discontinuation of therapy),

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.

Early Postoperative Period at Liver Transplantation

This lasts an average of 10 days and takes place in the intensive care unit. Supportive measures are taken as after any major surgical procedure; it is especially important to monitor adequate diuresis, as a good renal function will ease the use of cyclosporine. An attempt at lowering the incidence or severity of cytomegalovirus {CMV} infections is made by specific anti-CMV immunoglobulin infusions or with acyclovir. In high-risk situations, heparin is used to prevent hepatic artery thrombosis. Immunosuppression is started with i.v. methylprednisolone {10 mg/kg} and azathioprine {2 mg/kg} during the operation; i.v. cyclosporine is started postoperatively at increasing doses as soon as the hemodynamics and diuresis are satisfactory; azathioprine is discontinued when stable blood levels of cyclosporine are reached; methylprednisolone is progressively decreased down to 1 mg/kg per day at the end of the first week.

Liver Transplantation

Current results of liver transplantation indicate that 70%-80% of children treated are alive, most of them leading normal. Liver transplantation is carried out for liver diseases {inborn or acquired} wich result in death through liver cell failure and for inherited disorders exclusively or mostly in the liver without the risk of liver cell failure, but with the risk of severe extrahepatic damage.This chapter reviews briefly the main surgical and postsurgical aspects of liver transplantation performed so far in patients with inborn errors of metabolism.