Aplastic anemia and viral hepatitis. Non-A, Non-B, Non-C?
J. R. Hibbs, N. Frickhofen, S. J. Rosenfeld, S. M. Feinstone, S. Kojima, A. Bacigalupo, A. Locasciulli, A. G. Tzakis, H. J. Alter and N. S. Young
Clinical Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Md 20892.
OBJECTIVE--To test the hypothesis that the rare, often fatal, syndrome of
hepatitis-associated aplasia is associated with hepatitis C virus
infection. DESIGN--Case series. SETTING--Tertiary referral centers in the
United States, Japan, Italy, and Germany. PATIENTS--Twenty-eight patients
with onset of aplastic anemia within 90 days after seeking medical
attention for jaundice, or having serum transaminase levels 150% or more of
normal (hepatitis-associated aplasia patients) and three patients who
developed aplastic anemia following liver transplantation for non-A, non-B
hepatitis. OUTCOME MEASURES--Presence of hepatitis C in serum, bone marrow,
and liver samples, detected by the polymerase chain reaction; antibody
testing; and percentage of activated peripheral cytotoxic T lymphocytes
determined by immunophenotyping. RESULTS--Hepatitis ribonucleic acid was
present in the serum samples of 10 (36%) patients with hepatitis-associated
aplasia. However, hepatitis C virus viremia was associated with
transfusions received after the onset of aplasia: seven (58%) of 12
patients with hepatitis-associated aplasia who had received 21 or more
units of blood products at the time of serum sampling were viremic,
compared with only three (19%) of 16 patients with hepatitis-associated
aplasia who had received 20 or less units of blood products (P less than
.05). Hepatitis C virus was not found in blood and bone marrow samples of
three National Institutes of Health case patients tested at the time of
diagnosis. None of three livers from non-A, non-B hepatitis patients who
developed aplastic anemia after liver transplantation contained hepatitis C
virus ribonucleic acid. Activated CD8+ T lymphocytes were elevated three-
to 20-fold early in the course of hepatitis-associated aplasia.
CONCLUSIONS--Our results implicate a novel, non-A, non-B, and non-C agent
in both hepatitis-associated aplasia and fulminant hepatitis.
