Correspondence

Living-Donor Liver Transplantation for Chronic Hepatic Graft-versus-Host Disease

N Engl J Med 2006; 354:1536-1537April 6, 2006

Article

To the Editor:

In 2002, a four-year-old boy who had been diagnosed with acute lymphoblastic leukemia in 1999 received a bone marrow transplant from his mother, who had three HLA-antigen mismatches and an incompatible blood type. After engraftment, an erythematous rash, diarrhea, and hepatomegaly, accompanied by elevated liver-enzyme levels, developed in the boy. The findings were indicative of acute graft-versus-host disease (GVHD) and led to intensified immunosuppressive therapy with mycophenolate mofetil and corticosteroids. Although the gut and skin GVHD improved, the hepatic GVHD persisted and was confirmed as chronic hepatic GVHD on liver biopsy (Figure 1AFigure 1Liver-Biopsy Specimens from a Patient with Chronic Graft-versus-Host Disease (GVHD). and Figure 1B). The chronic GVHD was managed with low-dose corticosteroids, because of persistent hyperbilirubinemia, elevated liver-enzyme levels, thrombocytopenia, and coagulopathy. After transplantation, the patient showed complete engraftment of the transplanted bone marrow (99 percent). Bone marrow biopsy and other investigations showed no evidence of the relapse of leukemia. In March 2005, the boy underwent living-donor liver transplantation from his mother, because no other donor candidate was available.1 The left-lobe graft weighed 270 g, and the graft-to-recipient weight ratio was 1.0 percent. Both the portal vein and hepatic artery of the graft were flushed with muromonab-CD3 (Orthoclone OKT3, Ortho Pharmaceutical) that was contained in a histidine–tryptophan–ketoglutarate solution to wash out and eliminate donor lymphocytes. Histopathological examination of the boy's explanted liver revealed the presence of ductopenia with foam-cell arteriopathy, which was consistent with chronic hepatic GVHD (Figure 1C and Figure 1D).

Postoperative immunosuppression consisted of low-dose tacrolimus and corticosteroids to prevent GVHD. The patient was discharged on postoperative day 31 without complications. Protocol liver biopsy on postoperative day 60 revealed no evidence of rejection or GVHD (Figure 1E). During eight months of follow-up, the patient has been doing well with normal liver function.

GVHD, a major cause of liver dysfunction after bone marrow transplantation, occurs in 60 to 80 percent of patients when marrow from a partially HLA-matched family donor or unrelated donor is used.2 Because the patient showed no involvement of gut or skin in the GVHD and GVHD treatment had failed, he was considered a candidate for replacement of the liver. Given host immunosuppression related to bone marrow transplantation, the risk for passenger lymphocyte–associated GVHD may be an additional complication.3,4 Additional measures were required to avoid allogeneic reactions arising from passenger lymphocytes in the graft. We used a left-lobe graft, which provided the minimum graft-to-recipient weight ratio (1.0 percent) needed to sustain metabolic demand in the recipient5 and muromonab-CD3 to reduce the number of donor-derived passenger lymphocytes. This case offers evidence that a living-donor liver transplant can be harvested from the same donor who provided bone marrow for transplantation and that the recipient can be successfully treated with surgical and immunologic innovations.

Tetsunosuke Shimizu, M.D.
Mureo Kasahara, M.D.
Koichi Tanaka, M.D.
Kyoto University, Kyoto 606-8507, Japan
sur116@poh.osaka-med.ac.jp

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Citing Articles (8)

Citing Articles

1. 1

   Aiko Kida, George B. McDonald. (2012) Gastrointestinal, Hepatobiliary, Pancreatic, and Iron-Related Diseases in Long-Term Survivors of Allogeneic Hematopoietic Cell Transplantation. Seminars in Hematology 49:1, 43-58
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2. 2

   Josh Levitsky, Natasha Walzer. 2011. Hepatobiliary Complications of Hematopoietic Cell Transplantation. , 255-270.
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3. 3

   Nancy Bunin, Virginia Guzikowski, Elizabeth R. Rand, Samuel Goldfarb, Jorge Baluarte, Kevin Meyers, Kim M. Olthoff. (2010) Solid organ transplants following hematopoietic stem cell transplant in children. Pediatric Transplantation 14:8, 1030-1035
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4. 4

   Amer Beitinjaneh, Linda J. Burns, Navneet S. Majhail. (2010) Solid organ transplantation in survivors of hematopoietic cell transplantation: a single institution case series and literature review. Clinical Transplantation 24:4, E94-E102
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5. 5

   Minako Mori, Sumie Tabata, Hisako Hashimoto, Daichi Inoue, Takaharu Kimura, Sonoko Shimoji, Yuya Nagai, Katsuhiro Togami, Kiminari Itoh, Akiko Matsushita, Kenichi Nagai, Eiji Ikeda, Naoya Kimoto, Kenji Uryuhara, Satoru Kaihara, Yukihiro Imai, Masafumi Itoh, Takayuki Takahashi. (2010) Successful living donor liver transplantation for severe hepatic GVHD histologically resembling autoimmune hepatitis after bone marrow transplantation from the same sibling donor. Transplant International 23:5, e1-e4
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6. 6

   George B. McDonald. (2010) Hepatobiliary Complications of Hematopoietic Cell Transplantation, 40 Years On. Hepatology 51:4, 1450-1460
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7. 7

   Satoshi Yokoyama, Mureo Kasahara, Akinari Fukuda, Shuichi Sato, Tetsuya Mori, Atsuko Nakagawa, Akira Matsui. (2008) Successful Living-Donor Liver Transplantation for Chronic Hepatic Graft-Versus-Host Disease After Bone Marrow Transplantation for Chronic Granulomatous Disease. Transplantation 86:2, 367-368
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8. 8

   G. B. McDONALD. (2006) Review article: management of hepatic disease following haematopoietic cell transplant. Alimentary Pharmacology and Therapeutics 24:3, 441-452
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