Recurrence of inhibitor after orthotopic liver transplantation in severe haemophilia A

Abstract

Objective: Orthotopic liver transplantation (OLT) treats both hepatitis C‐associated cirrhosis and haemophilia A with factor VIII activity increasing into the normal range in most patients. However, the results of OLT in haemophilia patients with inhibitors have been mixed. We report the follow‐up factor VIII values after OLT in an inhibitor patent.Methods: A middle‐aged white male with severe haemophilia A, who had been on immune tolerance for >10 years for a high‐responding factor VIII inhibitor underwent OLT. Factor VIII activity and inhibitor titres were followed over the next 9 months.Summary: The patient had received factor VIII 40 u kg−1 three times/week for many years, which suppressed inhibitor titres to <2 BU. Higher doses of factor had been used to support him through surgery with good results. At the time of OLT, his inhibitor titre was 0.7BU. He was treated prior to transplant surgery with 116 u kg−1 with smaller doses every 2–4 h with monitoring during the operation. In the next 24 h he required another 300 u kg−1 of factor VIII to maintain activity between 61–122%. On postop days 1 and 2 he received 46 and 35 u kg−1 to maintain mean activity of about 50%. Around Day 6 his requirement for factor VIII increased to 70 u kg−1 daily to maintain the same levels. He was treated for possible acute liver rejection with high dose Solu–Medrol and his requirements for factor VIII decreased so that it was discontinued on day 13 postop. Over the next month, his factor VIII activity increased from 57–91% and he had no bleeding complications. Immune suppression was achieved with tacrolimus, mycophenolate and prednisone, the latter being discontinued about 1 month post OLT. After a peak of factor VIII activity at one month, his level decreased so that it was 52% and 37% at 4 and 6 months, respectively, despite the continuous use of immunosuppression for the OLT. Seven months after transplant, the patient underwent a procedure with a prefactor VIII infusion activity of 25% and a 2 h postinfusion activity of 71% after receiving 50 u kg−1. The Bethesda titre for the inhibitor was 0.9 units at this time. The most recent factor activity has dropped to 19% at 9 months. The patient has not had any bleeds post‐transplantation, however.Conclusions: 1. An inhibitor patient on long‐term immune tolerance underwent successful orthotopic liver transplantation with initial normalization of factor VIII activity.2. Beginning 2 months after OLT and continuing to the present, factor VIII activity gradually decreased associated with detection of a low titre recurrent factor VIII inhibitor.Synthesis of factor VIII by the donor liver is not sufficient for total suppression of the long‐standing inhibitor.