Liver Transplantation 27 Years after Bone Marrow Transplantation from the Same Living Donor
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《新英格兰医药杂志》
To the Editor: We present a case of bone marrow transplantation and liver transplantation from the same living donor for cirrhosis due to infection with the hepatitis C virus (HCV). In North America, cirrhosis due to HCV infection is the most common diagnosis leading to end-stage liver disease. Recurrence of HCV infection in a liver graft is virtually assured. Reports of decreased graft survival due to recurrence less than a decade after transplantation are increasing in frequency.1,2,3,4,5
The patient, a 42-year-old woman, presented with end-stage liver disease from HCV infection. At the age of 15 years, she had had aplastic anemia and had received numerous blood transfusions, to which the HCV infection was attributed. In 1974, at the age of 16 years, she received a bone marrow transplant from her HLA-identical sister. The same sister donated her right liver lobe in March 2001. Analysis of tetranucleotide markers on chromosomes 3, 7, and 12 showed complete engraftment of the transplanted bone marrow.
After the liver transplantation, the donor's course was unremarkable, and she was discharged home on postoperative day 8. The recipient had an uneventful operation and was discharged while receiving tacrolimus and prednisone, tapered according to a standard protocol. Within three months, the prednisone was discontinued; low-dose tacrolimus (trough goal, 3 to 6 ng per milliliter) was continued as maintenance therapy.
After six months of immunosuppression to provide protection against graft-versus-host disease, the results of the patient's liver-function tests normalized. Examination of a liver-biopsy specimen revealed no evidence of rejection but did show mild (grade 1, stage 1) HCV infection (Figure 1A). The immunosuppressive therapy was tapered and was stopped one year after the liver transplantation.
Figure 1. Liver-Biopsy Specimens.
At six months, the portal area was expanded by a lymphocytic infiltrate (arrow), with focal piecemeal (or interface) hepatitis (arrowhead) (Panel A, x100). At two years, the lymphocytic infiltrate in the portal areas was significantly reduced (Panel B, x100), and the piecemeal necrosis was absent (inset, x400).
A liver biopsy two years after the transplantation (one year after the cessation of immunosuppression) showed a decrease in the portal inflammation as compared with that observed in the six-month specimen, with no signs of rejection (Figure 1B). Evidence of the mild HCV infection included a few necrotic hepatocytes and a few mononuclear cells within the lobule, with no periportal inflammation. The fibrosis had lessened and was interpreted as consistent with grade 1, stage 0 HCV infection. Currently, the patient's viral load remains between 200,000 and 450,000 IU per milliliter, and she is considering combination antiviral therapy.
Use of grafts from living donors for adult liver transplantation is currently a matter of debate. The risk to the donor is real, although so is the advantage to the recipient of undergoing transplantation before severe decompensation, development of a hepatocellular carcinoma, and (in this unusual case), receipt of an "isograft" after a previous bone marrow transplantation. As our understanding of the immune response improves, the potential for developing "operational tolerance" may widen the recipient's benefits from living donor transplantation.
Kenneth A. Andreoni, M.D.
Jennifer I. Lin, M.D.
Pamela A. Groben, M.D.
University of North Carolina at Chapel Hill
Chapel Hill, NC 27599
References
Gane EJ, Portmann BC, Naoumov NV, et al. Long-term outcome of hepatitis C infection after liver transplantation. N Engl J Med 1996;334:815-820.
Sanchez-Fueyo A, Restrepo JC, Quinto L, et al. Impact of the recurrence of hepatitis C virus infection after liver transplantation on the long-term viability of the graft. Transplantation 2002;73:56-63.
Prieto M, Berenguer M, Rayon JM, et al. High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: relationship with rejection episodes. Hepatology 1999;29:250-256.
Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology 2002;122:889-896.
Berenguer M. Host and donor risk factors before and after liver transplantation that impact HCV recurrence. Liver Transpl 2003;9:S44-S47.
The patient, a 42-year-old woman, presented with end-stage liver disease from HCV infection. At the age of 15 years, she had had aplastic anemia and had received numerous blood transfusions, to which the HCV infection was attributed. In 1974, at the age of 16 years, she received a bone marrow transplant from her HLA-identical sister. The same sister donated her right liver lobe in March 2001. Analysis of tetranucleotide markers on chromosomes 3, 7, and 12 showed complete engraftment of the transplanted bone marrow.
After the liver transplantation, the donor's course was unremarkable, and she was discharged home on postoperative day 8. The recipient had an uneventful operation and was discharged while receiving tacrolimus and prednisone, tapered according to a standard protocol. Within three months, the prednisone was discontinued; low-dose tacrolimus (trough goal, 3 to 6 ng per milliliter) was continued as maintenance therapy.
After six months of immunosuppression to provide protection against graft-versus-host disease, the results of the patient's liver-function tests normalized. Examination of a liver-biopsy specimen revealed no evidence of rejection but did show mild (grade 1, stage 1) HCV infection (Figure 1A). The immunosuppressive therapy was tapered and was stopped one year after the liver transplantation.
Figure 1. Liver-Biopsy Specimens.
At six months, the portal area was expanded by a lymphocytic infiltrate (arrow), with focal piecemeal (or interface) hepatitis (arrowhead) (Panel A, x100). At two years, the lymphocytic infiltrate in the portal areas was significantly reduced (Panel B, x100), and the piecemeal necrosis was absent (inset, x400).
A liver biopsy two years after the transplantation (one year after the cessation of immunosuppression) showed a decrease in the portal inflammation as compared with that observed in the six-month specimen, with no signs of rejection (Figure 1B). Evidence of the mild HCV infection included a few necrotic hepatocytes and a few mononuclear cells within the lobule, with no periportal inflammation. The fibrosis had lessened and was interpreted as consistent with grade 1, stage 0 HCV infection. Currently, the patient's viral load remains between 200,000 and 450,000 IU per milliliter, and she is considering combination antiviral therapy.
Use of grafts from living donors for adult liver transplantation is currently a matter of debate. The risk to the donor is real, although so is the advantage to the recipient of undergoing transplantation before severe decompensation, development of a hepatocellular carcinoma, and (in this unusual case), receipt of an "isograft" after a previous bone marrow transplantation. As our understanding of the immune response improves, the potential for developing "operational tolerance" may widen the recipient's benefits from living donor transplantation.
Kenneth A. Andreoni, M.D.
Jennifer I. Lin, M.D.
Pamela A. Groben, M.D.
University of North Carolina at Chapel Hill
Chapel Hill, NC 27599
References
Gane EJ, Portmann BC, Naoumov NV, et al. Long-term outcome of hepatitis C infection after liver transplantation. N Engl J Med 1996;334:815-820.
Sanchez-Fueyo A, Restrepo JC, Quinto L, et al. Impact of the recurrence of hepatitis C virus infection after liver transplantation on the long-term viability of the graft. Transplantation 2002;73:56-63.
Prieto M, Berenguer M, Rayon JM, et al. High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: relationship with rejection episodes. Hepatology 1999;29:250-256.
Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology 2002;122:889-896.
Berenguer M. Host and donor risk factors before and after liver transplantation that impact HCV recurrence. Liver Transpl 2003;9:S44-S47.