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Hepatocyte transplantation for metabolic liver disease: UK experience

2005; SAGE Publishing; Volume: 98; Issue: 8 Linguagem: Inglês

10.1258/jrsm.98.8.341

1758-1095

R.D. Hughes,

Liver Disease Diagnosis and Treatment

For end-stage liver disease and liver-based metabolic conditions the accepted treatment is liver transplantation. With developments in surgical techniques and immunosuppressive drug therapy the survival of patients and grafts is now good. In the conventional procedure the patient's whole liver is replaced with a liver obtained from a braindead or living donor. When the donor liver is too big it can be reduced to a compatible size; and, recently, split-liver procedures have been performed whereby the right lobe is transplanted into an adult and the smaller left lobe into a child,1 thus increasing the effective donor pool. Another important advance in surgical technique is the use of auxiliary liver transplantation for patients with acute liver failure and certain liver-based metabolic defects such as Crigler–Najjar syndrome type I, urea cycle defects, and familial hypercholesterolaemia. In this procedure, part of the patient's liver, often the left lobe, is replaced with part of a donor liver. In a patient with acute liver failure this leaves open the possibility of regeneration of the native liver, in which case immunosuppression can be stopped and the graft allowed to atrophy; and in a patient with a metabolic disorder the native liver will be available for future gene therapy. The results of auxiliary liver transplantation in man2 have supported observations in animals that small amounts of liver tissue can provide sufficient function to correct an underlying metabolic defect. This finding was a spur to work on hepatocyte transplantation for such disorders. The aim is to repopulate the liver with donor hepatocytes, injected either directly into the liver or into the spleen, from which they migrate to the liver. If the technique proves successful, hepatocyte transplantation offers several potential advantages. In terms of supply, there is the possibility of using cells from livers that are unsuitable for conventional transplantation because of steatosis or trauma. The patient does not have to undergo major surgery; moreover, in metabolic conditions the native liver provides a safety net in case of failure. One of the most important advantages is the availability of the liver as a target organ for gene therapy when this becomes a clinical reality. Experience of hepatocyte transplantation has been gained in patients with acute liver failure3,4 and metabolic liver diseases such as Crigler–Najjar syndrome type I,5 glycogen storage disease type 1a,6 and urea cycle defects.7 The background to this work has been described elsewhere.8–11 The current paper discusses the sources of hepatocytes, the isolation process, preclinical studies and clinical experience in the UK, especially in the treatment of liver-based inborn errors of metabolism.