Aplastic Anemia and Viral Hepatitis: Title and subTitle BreakNon-A, Non-B, Non-C? FREE

Jonathan R. Hibbs, MD; Norbert Frickhofen, MD; Stephen J. Rosenfeld, MD; Stephen M. Feinstone, MD; Seiji Kojima, MD; Andrea Bacigalupo, MD; Anna Locasciulli, MD; Andreas G. Tzakis, MD; Harvey J. Alter, MD; Neal S. Young, MD

[+] Author Affiliations

Reprint requests to 10/7C103, Clinical Hematology Branch, National Heart, Lung, and Blood Institute, 9000 Rockville Pike, Bethesda, MD 20892 (Dr Hibbs).

JAMA. 1992;267(15):2051-2054. doi:10.1001/jama.1992.03480150057037

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ABSTRACT

ABSTRACT | REFERENCES

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<.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.(JAMA. 1992;267:2051-2054)

REFERENCES

ABSTRACT | REFERENCES

International Agranulocytosis and Aplastic Anemia Study. Incidence of aplastic anemia: the relevance of diagnostic criteria. Blood . 1987;;70:1718-1721.

Young NS. Aplastic anemia and related bone marrow failure syndromes. In: Wyngaarden JB, Smith LH, Bennett JC, eds. Cecil's Textbook of Medicine . Philadelphia, Pa: Harcourt Brace Jovanovich; 1992;:831-837.

Linet MS, Markowitz JA, Sensenbrenner LL, et al. A case-control study of aplastic anemia. Leuk Res . 1989;;13:3-11.

Young NS, Issaragrasil S, Chieh CW, Takaku F. Aplastic anemia in the Orient. Br J Haematol . 1986;;62:1-6.

Issaragrisil S, Sriratanasatavorn C, Piankijagum A, et al. Incidence of aplastic anemia in Bangkok. Blood . 1991;;77:2166-2168.

Linet MS, Tielsch JM, Markowitz JA, et al. An apparent cluster of aplastic anemia in a small population of teenagers. Arch Intern Med . 1985;;145:635-640.

Kurtzman GJ, Platanias L, Lustig L, Frickhofen N, Young NS. Feline parvovirus propagates in cat bone marrow cultures and inhibits hematopoietic colony formation in vitro. Blood . 1989;;74:71-81.

Hardy WD Jr, Essex M, McClelland AJ. Feline Leukemia Virus . New York, NY: Elsevier Science Publishing Co Inc; 1980;.

Foon KA, Mitsuyasu RT, Schroff RW, McIntyre RE, Champlin R, Gale RP. Immunologic defects in young male patients with hepatitis-associated aplastic anemia. Ann Intern Med . 1984;;100:657-662.

Wang WC, Herrod HG, Presbury GJ. Lymphocyte subsets in children with aplastic anemia. Am J Med Sci . 1986;;291:304-309.

Zoumbos NC, Gascón P, Djeu JY, Trost SR, Young NS. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med . 1985;;312:257-265.

Hagler L, Pastore RA, Bergin JJ, Wrensch MR. Aplastic anemia following viral hepatitis: report of two fatal cases and literature review. Medicine . 1975;;54:139-162.

Perrillo RP, Pohl DA, Roodman ST, Tsai CC. Acute non-A, non-B hepatitis with serum sickness-like syndrome and aplastic anemia. JAMA . 1981;;245:494-496.

Zeldis JB, Dienstag JL, Gale RP. Aplastic anemia and non-A, non-B hepatitis. Am J Med . 1983;;74:64-68.

Tzakis AG, Arditi M, Whitington PF, et al. Aplastic anemia complicating orthotopic liver transplantation for non-A, non-B hepatitis. N Engl J Med . 1988;;319:393-396.

Young NS. Flaviviruses and bone marrow failure. JAMA . 1990;;263:3065-3068.

Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science . 1989;;244:359-362.

Nakao S, Lai CJ, Young NS. Dengue virus, a flavivirus, propagates in human bone marrow progenitors and hematopoietic cell lines. Blood . 1989;;74:1235-1240.

Ulrich PP, Romeo JM, Lane PK, Kelly I, Daniel LJ, Vyas GN. Detection, semiquantitation, and genetic variation in hepatitis C virus sequences amplified from the plasma of blood donors with elevated alanine aminotransferase. J Clin Invest . 1990;;86:1609-1614.

Garson JA, Tuke PW, Makris M, et al. Demonstration of viraemia patterns in haemophiliacs treated with hepatitis C virus-contaminated factor VIII concentrates. Lancet . 1990;;336:1022-1025.

Simmonds P, Zhang LQ, Watson HG, et al. Hepatitis C quantification and sequantification and sequencing in blood products, haemophiliacs, and drug users. Lancet . 1990;;336:1469-1472.

Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidium-thiocyanate-phenol-chloroform extraction. Anal Biochem . 1987;;162:156-159.

Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning: A Laboratory Manual . Cold Spring Harbor, NY: Cold Spring Harbor Press; 1989;.

Kuo G, Choo Q, Alter HJ, et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science . 1989;;244:362-364.

Kato N, Yokosuka O, Omata M, Hosoda K, Ohto M. Detection of hepatitis C virus ribonucleic acid in the serum by amplification with polymerase chain reaction. J Clin Invest . 1990;;86:1764-1767.

Alter HJ, Purcell RH, Shih JW, et al. Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med . 1989;;321:1494-1500.

Farci P, Alter HJ, Wong D, et al. A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med . 1991;;325:98-104.

Pol S, Driss F, Devergie A, Brechot C, Berthelot P, Gluckman E. Is hepatitis C virus involved in hepatitis-associated aplastic anemia? Ann Intern Med . 1990;;113:435-437.

Feinstone SM, Kapikian AZ, Purcell RH, Alter HJ, Holland PV. Transfusion-associated hepatitis not due to viral hepatitis type A or B. N Engl J Med . 1975;;292:767-770.

Bradley DW. Enterically transmitted non-A, non-B hepatitis. Br Med Bull . 1990;;46:442-461.

Phillips MJ, Blendis LM, Poucell S, et al. Syncytial giant-cell hepatitis: sporadic hepatits with distinctive pathological features, a severe clinical course, and paramyxoviral features. N Engl J Med . 1991;;324:455-460.

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Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal