Hepatitis G-associated aplastic anaemia
Authors: John J Byrnes, A Theresa Banks, Michael Piatack, Jungsuh P Kim
Journal: The Lancet (1996)

Aplastic anaemia is sometimes preceded by hepatitis, an association recognised as hepatitis-associated aplastic anaemia. The responsible agent has not been identified; hepatitis A (HAV), hepatitis B (HBV), and hepatitis C (HCV) viruses, however, have been excluded.1Zeldis JB Dienstag JL Gale RP Aplastic anemia and non-A, non-B hepatitis.Am J Med. 1988; 74: 64-68Summary Full Text PDF Scopus (101) Google Scholar, 2Hibbs JR Frickhofen N Rosenfeld SJ et al.Aplastic anemia and viral hepatitis non-A, non-B, non-C.JAMA. 1992; 267: 2051-2054Crossref PubMed Scopus (115) Google Scholar We report evidence implicating hepatitis G (HGV),3Linnen J Wages J Jr Zhang-Keck ZY et al.Molecular cloning and disease association of hepatitis G virus: a transfusion transmissible agent.Science. 1996; 271: 505-508Crossref PubMed Scopus (1384) Google Scholar a newly discovered flavivirus. A 26-year-old man developed anorexia, fatigue, and jaundice. There were no prior medication use, blood transfusions, intravenous drug abuse, chronic alcohol consumption, or family history of liver disease. The serum bilirubin was 194 (lmol/L (direct 89 (lmol/L), aspartate aminotransferase 1540 U/L, and alanine aminotransferase 2565 U/L. His white-cell count (WBC) was 4200·107L, haematocrit reading 0·47, and platelet count 170 000×106/L. Serological markers for HAV, HBV (surface antigen and core IgM), and HCV were repeatedly negative. HCV testing by PCR did not detect HCV-RNA. Cytomegalovirus, antinuclear antibody, antimitochondrial antibody, heterophile antibody, and HIV-1 serology were negative; parvovirus B19 serology indicated remote infection. On day 34, he developed petechiae and epistaxis; WBC was 1300·107L, haematocrit reading 0·27, and platelet count 4000·107L; serum bilirubin was 612 (lmol/L, serum aspartate aminotransferase 1220 U/L, and alanine aminotransferase 1262 U/L. On day 37 the WBC was 300·106/L and a bone-marrow biopsy specimen was severely hypoplastic. Numerous transfusions of red cells and platelets were required. The course was complicated by infections, haemorrhage, and cyclosporin toxicity. After the liver function tests returned to normal, severe pancytopenia persisted. Granulocytes reappeared on day 161, and after day 195 he received blood-product transfusions as an outpatient. Hypersplenism necessitated a splenectomy on day 265. Transfusions were not required after day 326 and filgrastim was unnecessary after day 425. The platelets gradually increased to above 130 000×109/L (day 590). The patient is now in good general health. Serum obtained on day 1 before any blood products were given and throughout the clinical course, were positive for HGV. HGV was detected with PCR; two separate primer sets specific for conserved regions of the genome were used in a common reaction (multiplex PCR assay). HGV-specific products were detected by probe hybridisation for electrochemiluminescence measurement and, separately, for autoradiography of 32P-labelled products. Positive specimens had a second round of extraction and assay for confirmation. The presence of HGV in a patient with hepatitis-associated aplastic anaemia suggests examination of other cases for its presence. HGV is distantly related to HCV and GBV-A. Of note, HGV virus was first identified in a patient with aplastic anaemia.4Simons JN Leary TP Dawson GJ et al.Isolation of novel virus-like sequences associated with human hepatitis.Nature Med. 1995; 1: 564-569Crossref PubMed Scopus (1163) Google Scholar Although HGV appears not to be a major cause of significant hepatic injury, responsibility for aplastic anaemia would add a new dimension to its public-health profile. We thank Lennox J Jeffers, Rajender Reddy, and Eugene R Schriff.