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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
N Engl J Med. Author manuscript; available in PMC 2010 October 28.
Published in final edited form as:
PMCID: PMC2965446


To the Editor: A cure rather than a treatment has long been the goal of those caring for and those suffering from hemophilia. Encouraging results were obtained some years ago with the transplantation of normal livers into a dog with mild hemophilia 1,2 and into four others with severe hemophilia.3 Two dogs given transplants survived more than 100 days and produced coagulation factor VIII in quantities sufficient to maintain normal levels.

The first “cure” in a human being appears to have been achieved, at least temporarily, in a 15-year-old boy with hemophilia and severe chronic active hepatitis, who received a liver from a 9-year-old “normal” donor on March 5, 1985. The patient was given the diagnosis of hemophilia A in early childhood and has been followed at the Hemophilia Center, Children’s Memorial Hospital, Northwestern School of Medicine, Chicago, by Dr. John Paul Scott. In 1969 he had severe hepatitis B; positivity for hepatitis B surface antigen and antibody to hepatitis B e has persisted. In addition, therapy-related non A,non B hepatitis may have contributed to his liver disease. About four months before liver transplantation, a splenectomy was performed for chronic thrombocytopenia, which resolved postoperatively, but a residual pancreaticogastrocutaneous fistula remained. Liver transplantation and repair of the fistula were accomplished with less than the average blood loss. Before, during, and for 18 hours after liver transplantation, the patient’s factor VIII level was maintained at 0.54 to 1.60 U per milliliter by intermittent infusions of heat-treated factor VIII concentrate. From 18 hours after operation to the time of this writing (April 17), his level has been sustained at 1.0 to 3.0 U per milliliter without exogenous treatment. The high postoperative levels of factor VIII are similar to those seen after transplantation in patients without hemophilia. Eight days after operation the patient underwent repair of a bile duct. There was no increased hemorrhage, and he required no factor VIII treatment.

Although in this case, at least temporarily, internal production of factor VIII has been achieved by the implanted liver, liver transplantation cannot be recommended as a “cure” for hemophilia. This drastic operation is justified only for end-stage liver disease because of the risks of lifelong immunosuppressive therapy, rejection, infection, and recurrence of disease. The duration of production of factor VIII is unknown. This case suggests that the antihemophilic activity (factor VIII:C) of the large factor VIII complex, synthesized in endothelium.4,5 is acquired in the liver.


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