Aplastic anemia after transplantation for non-A, non-B, non-C fulminant hepatic failure: case report and review of the literature.
Aplastic anemia is a rare complication of liver transplantation (<1%). However, an increasing number of cases of aplastic anemia have been recently reported when liver transplantation is performed for non-A, non-B, non-C fulminant hepatic failure. The aim of this study is to reevaluate the importance and the incidence of aplastic anemia after liver transplantation for non-A, non-B, non-C fulminant hepatic failure, and to propose preventive measures, diagnostic and management guidelines to try to reduce the incidence, morbidity and mortality associated with this complication. In this report a case of aplastic anemia after liver transplantation for non-A, non-B, non-C fulminant hepatic failure is described. In addition, the pertinent literature on aplastic anemia after liver transplantation, since the first description of that complication in 1987, is reviewed. A 20-year-old woman developed aplastic anemia 14 weeks after liver transplantation for fulminant non-A, non-B, non-C hepatitis. After failure of G-CSF treatment, she was treated with intensive immunosuppression (FK 506, ATG, high-dose steroids). She is well 1 year post-transplantation, with normal liver tests and with bone marrow recovery. Through a Medline literature search (1988-1999), we identified 30 additional cases of aplastic anemia following liver transplantation for non-A, non-B, non-C fulminant hepatic failure. Of all liver transplantations performed for that indication at five participating centers, the mean incidence of aplastic anemia was 23.2%. Mean age was 10 years (1.2-29) and the male/female ratio was 4.6. For treating aplastic anemia, different modalities were used: ATG ( n=12), ALG ( n=1), OKT 3 ( n=1), G-CSF ( n=6), a 6-HLA-compatible bone marrow transplantation ( n=3), and none ( n=12). The mortality rate remains high (39%), with infections and bleeding as the two most frequent causes of death. Based on this literature review, we conclude that aplastic anemia is a relatively common complication of liver transplantation for non-A, non-B, non-C fulminant hepatic failure in children and young adults. An unknown viral agent operating through immune-mediated mechanisms is probably responsible. The myelotoxic environment inherent to transplantation (e.g. azathioprine, trimethoprim) probably has a cumulative effect. Preventive measures (e.g. not using myelotoxic drugs) should be adopted in high-risk children and young adults transplanted for non-A, non-B, non-C fulminant hepatic failure. Early detection of bone marrow depression, a low threshold for performing a bone marrow biopsy, and prompt treatment are pivotal. Intensive standard supportive care with broad-spectrum antibiotics and anti-fungal agents is essential during phases of pancytopenia. Although spontaneous recovery has been described under maintenance immunosuppression, increased immunosuppression, in particular with ATG, may reverse the aplastic anemia and promote bone marrow recovery. In unresponsive patients, six-HLA-identical bone marrow transplantation has been successful.
Itterbeek
Patrick
P
Abdominal Transplant Surgery Department, University Hospitals Leuven, Belgium.
Vandenberghe
Peter
P
Nevens
Frederik
F
Fevery
Johan
J
Aerts
Raymond
R
Yap
Sing Hiem
SH
Demuynck
Hilde
H
Fourneau
Inge
I
Koshiba
Takaaki
T
Emonds
Marie-Paule
MP
Roskams
Tania
T
Boogaerts
Marc
M
Pirenne
Jacques
J
D000328:Adult; D000741:Anemia, Aplastic / Q000209:etiology*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006526:Hepatitis C / Q000601:surgery*; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D011183:Postoperative Complications; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents