Aplastic anemia and viral hepatitis. Non-A, Non-B, Non-C?
OBJECTIVE
To test the hypothesis that the rare, often fatal, syndrome of hepatitis-associated aplasia is associated with hepatitis C virus infection.


METHODS
Case series.


METHODS
Tertiary referral centers in the United States, Japan, Italy, and Germany.


METHODS
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.


METHODS
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.
Hibbs
J R
JR
Clinical Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Md 20892.
Frickhofen
N
N
Rosenfeld
S J
SJ
Feinstone
S M
SM
Kojima
S
S
Bacigalupo
A
A
Locasciulli
A
A
Tzakis
A G
AG
Alter
H J
HJ
Young
N S
NS
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000382:microbiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis
D012367:RNA, Viral