Children’s Hospital Pittsburgh - North American Hospitals Supplement

Liver transplantation: A pathway to cure for paediatric metabolic disorders

An 8-year-old boy from Qatar with propionic acidemia (PA) was transferred in serious condition to Children’s Hospital of Pittsburgh of UPMC in the United States for evaluation and care. A team of specialists determined that his metabolic disease was causing his heart to fail, and liver transplant was identified as a solution. His mother, a viable candidate, stepped forward as a living donor, providing a segment of her liver to be transplanted into her son. Today, the mother’s liver function is fully recovered as her son continues to recuperate. His cardiac condition is significantly improved.

This example illustrates two significant developments with regard to liver transplantation – the ability for liver transplants to be used as a treatment for metabolic disorders, such as PA, and the growing impact of living donor transplants to help resolve critical medical situations in a timely fashion.

Liver transplants have been successfully performed in humans since the 1980s and were initially developed as a therapy for liver diseases that had a high risk of near-term mortality, such as biliary atresia, tumours, or acute liver failure.

Today, however, liver transplantation is finding an expanding role as treatment for a growing number of inborn metabolic diseases. Rather than viewing liver transplants exclusively as a life-saving procedure, it can now be seen as a “life-improving” therapy, providing a new pathway to health by dramatically reducing symptoms of primary disorders and, in some cases, even providing a complete cure. Concurrent with this is the greater reliance on and positive outcomes derived from transplanted liver tissue from living donors.

The use of tissue from living donors, in particular, helps achieve success in multiple ways, including: reduced wait times; more positive outcomes, which may be related to genetic matching from healthy living related donors; and providing an alternative to use of tissue from deceased donors, which are a scarce resource.

Metabolic conditions treated by liver transplant
Metabolic diseases are generally caused by a defect in a single or multiple genes that are supposed to instruct enzymes to convert one substance into another. Here, liver transplantation can help for disorders that are liver-specific as well as for systemic disorders, where liver replacement can result in sufficient metabolic support to normalize metabolism.

Known examples where liver transplants can provide a therapeutic option include methylmalonic acidemia (MMA), Maple Syrup Urine Disease (MSUD), urea cycle disorders (UCDs), Crigler-Najjar Syndrome, selected mitochondrial disease, alpha-1 antitrypsin disease, as well as PA. Additionally, certain glycogen storage diseases (GSD) and phenylketonuria (PKU) show potential for improvement through liver transplantation.

Many of these conditions can be medically managed, but they can have serious and sometimes fatal consequences if not treated. In some cases, medical management may be done through a very carefully controlled low-protein diet that includes special supplements required for the rest of the patient’s life. Such medical therapy can mean life-limiting compromises for the patient, including vigilant blood monitoring, dietary restrictions, travel limitations, and ongoing concerns that a misstep in therapeutic adherence may have dire health consequences.

With a history of paediatric liver transplants, spanning back to 1981, Children’s Hospital of Pittsburgh of UPMC has conducted more than 320 liver transplants for metabolic disease alone and more than 1,700 paediatric liver transplants in all, more than any other paediatric centre in the United States. Building on its experience with liver transplants for metabolic disorders, Children’s collaborated with the Clinic for Special Children in Strasburg, Pennsylvania, to create the first elective liver transplantation protocol for patients with MSUD in 2004, and has since conducted more than 65 transplants for MSUD patients with 100 percent graft and patient survival rates.

Today as the risks of liver transplant have decreased and post-operative outcomes have improved, the procedure has evolved into an attractive approach for improving life for patients with a growing number of metabolic diseases. The range of disorders suitable for this approach continues to evolve as the medical community, patients, and their families balance traditional medical management versus surgical intervention that may favourably impact their disease. And, while living-donor transplants can help overcome the ongoing demand shortfall for traditional cadaveric organs, their greater role may ultimately be in helping to provide better longterm outcomes for the patients who receive them.


Date of upload: 20th Nov 2016

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