Study: NCT01465100

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: Preparative Radiation Therapy
Description: Subjects will undergo CT-based simulation and treatment planning for radiation therapy. Once a suitable hepatocyte donor is found and the cell count and viability is acceptable for transplantation, patients will receive Intensity-Modulated Radiation Therapy (IMRT) in one fraction(10 Gy)to the right lobe of the liver (but not exceeding 50% of the liver mass).

Intervention type: PROCEDURE
Group type: EXPERIMENTAL
Intervention: Hepatocyte Transplant
Description: Transplantation of hepatocytes into the liver will be through the portal vein, either accessed transhepatically, or by umbilical vein. After cell transplantation, measures will be taken to provide chronic access to the portal venous circulation system. If chronic access is achieved, patients will be seen in the PCTRC once a week to assess the site.~Hepatocytes from more than one donor may be required to provide sufficient numbers of cells for transplantation to correct the disease process and to optimize Phe tolerance. Hepatocytes will be infused until the goal number of hepatocytes is infused. If viable hepatocytes remain after the goal number has been infused, the remaining cells will also be infused, as tolerated by the patient.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Immunosuppression
Description: Following transplantation, patients will be treated with conventional immune suppression, as is used following whole organ liver transplantation. Patients will be followed as routinely performed following organ transplantation and also followed as would normally be performed for their PKU.

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Liver Evaluation
Description: Prior to the hepatocyte transplant subjects will undergo a liver evaluation which is standard for all patients who have whole organ transplants at Children's Hospital of Pittsburgh of UPMC. The evaluation includes immunosuppression medication education, psychological assessment, bloodwork to assess blood count, blood and tissue type, blood chemistries, immune system function and certain infectious diseases, EKG, chest x-ray, and abdominal ultrasound to assess blood flow to the blood vessels in the liver. A liver biopsy may be performed if, in the clinical judgment of the investigators, the subject shows clinical signs of liver failure, or is at increased risk for liver fibrosis.

Intervention type: BEHAVIORAL
Group type: EXPERIMENTAL
Intervention: Neuro-psychological Assessment
Description: Subjects will undergo a repeat neuropsychological assessment at 6, 12 and 24 months post-transplant (Visits 4 and 6 and the End of Study Visit) which will be compared to results obtained pre-transplant to determine whether an improvement in assessment scoring is associated with the transplant procedure.

Intervention type: DIAGNOSTIC_TEST
Group type: EXPERIMENTAL
Intervention: Whole body Phe oxidation testing
Description: Patient will again be asked to not eat or drink for at least four hours prior to testing. Isotopic monitoring of whole body Phe oxidation will be performed pre-transplant and at every follow-up visit following the final hepatocyte infusion. An additional Phe oxidation test may also be completed in the event of suspected graft rejection.

Intervention type: PROCEDURE
Group type: EXPERIMENTAL
Intervention: Liver Biopsy
Description: Liver biopsies will be performed at 3 and 12 months post-transplant to assess for the presence of donor hepatocytes, and may be completed in the event of suspected graft rejection.