Metabolic Liver Diseases
Metabolic liver diseases refer to a heterogenous group of diseases that are due to genetic abnormalities that usually affect a single gene and result in inability of liver to synthesize a particular gene product. The gene product is usually a protein which performs a unique, vital function either in the liver itself or in other organs. The liver itself may or may not be affected by the disease. Typical examples of metabolic liver disease are Criggler-Najjar syndrome, primary hyperoxaluria, urea cycle disorders, tyrosinemia, haemochromatosis and Wilson’s disease. Some of them like Wilson’s disease, tyrosinemia and haemochromatosis affect the liver and present as liver failure. The liver itself is normal in few other metabolic diseases like Criggler-Najjar syndrome and urea cycle disorders. In the latter diseases, the problem is caused by lack of the protein product of the genetic defect which affects some body function or another organ, other than the liver itself.
Most of these diseases are currently being treated by orthotopic liver transplantation where defective, native liver is completely removed and a new liver from a donor without the genetic defect is transplanted into the recipient. Though the metabolic liver disease is cured by orthotopic liver transplantation, patients will have to be on life long immunosuppression. This is required as the new liver is foreign to the patient and without immunosuppression, patient’s body will destroy the new liver by a process called “rejection”. Problems with immunosuppression are susceptibility to infections, tumours and possibility of irreversible kidney injury.
Auxiliary liver transplantation is a type of liver transplantation in which only part of the genetically defective liver is removed. The healthy donor liver is implanted into the recipient in the space thus created. After this type of transplantation, both the genetically defective, but otherwise well functioning liver and the new liver, which doesn’t have the genetic defect exist simultaneously in the patient. Immunosuppresive drugs have to be given here as well. But, the advantage here is, when gene therapy becomes available for these diseases in future, we may gradually withdraw the immunosuppressive drugs for the patient. Gene therapy would have cured the underlying disease, whereas withdrawal of immunosuppression would result in gradual rejection of transplanted liver, which will eventually disappear. The possibility of avoiding life long immunosuppression, the holy grail of transplantation is exiting when auxiliary liver transplantation is done.
Only a few centers in the world do “Auxiliary liver transplantation”. Prof. Mohamed Rela has one of the largest personal experiences in performing auxiliary liver transplantation and performed the first auxiliary liver transplantation in India. Performing auxiliary liver transplantation successfully in metabolic liver diseases gives a huge research opportunity, especially when gene therapy becomes available.