First Reports About Hepatitis G Virus

Article from Antiviral Agents Bulletin, September 1995, p. 263


Researchers from Genelabs Technologies, Inc. (Redwood City, CA) and the company's corporate and federal laboratory collaborators made the first substantive disclosures about hepatitis G virus (HGV) at a recent meeting in Gold Coast, Australia. As discussed in the February Bulletin (p. 38), researchers from Genelabs, the Centers for Disease Control and Prevention (CDC; Atlanta, GA) and the National Institutes of Health (NIH; Bethesda, MD) discovered HGV through a Collaborative Research and Development Agreement (CRADA) and Genelabs will exclusively license related inventions from CDC. Genelabs has nonexclusive licensing and collaborative development agreements with Boehringer Mannheim GmbH and Ortho Diagnostic Systems (subsidiary of Johnson & Johnson) for HGV diagnostics and blood screening tests. Several presentations at the conference discussed the molecular cloning and characterization of HGV and its transmission via blood transfusion. HGV was reported to be a RNA virus in the Flaviviradae family distinct from hepatitis C and other known viruses. HGV was also reported to be distributed worldwide and cases have been identified in Asia, Europe, North America and Australia. HGV-infection causes acute and chronic hepatitis and active infection has been observed to persist for up to nine years. It is transmissible via blood transfusion and blood products, and has been identified in otherwise healthy carriers among the blood donor population of the U.S. and other countries.

Dr. J. Kim, Genelabs, discussed the isolation and characterization of PNF2161, a new virus provisionally designated as HGV, isolated from a patient with chronic hepatitis. HGV has a genome of about 2,900 bases and is similar in many respects, particularly its nonstructural genes, to other Flaviviridae viruses. The 5' untranslated region is highly conserved, expected to enable development of oligonucleotide probe and immunodiagnostic assays. Dr. H.J. Alter, NIH, discussed evidence suggesting the existence of one or more hepatitis viruses other than hepatitis A, B and C. He reported that retrospective analysis of 98 patients diagnosed with non-A, non-B hepatitis following blood transfusions found 12 could be classified as non-A,B,C (presumably HGV), and HGV RNA was observed in 2 of these patients. HGV was also identified in 14% of blood transfusion recipients with minor ALT elevations that did not meet criteria for hepatitis and in 8% of those diagnosed with hepatitis C virus infection. HGV RNA was found in 13 of 769 (1.7%) healthy blood donors with normal ALT values and in 11% with elevated ALT. Dr. H.C. Thomas, Saint Mary's Hospital (London, U.K.), reported that HGV has only 26% homology with hepatitis C virus at the amino acid sequence level; that it can be transmitted by parenteral route, including intravenous drug use and blood transfusion; that many hepatitis C virus infected patients also were infected with HGV; that normal HGV carrier state(s) have not yet been characterized; and that healthy persons can be HGV-infected carriers. Regarding results of retrospective analyses of alpha-interferon treatment of patients now identified as co-infected with hepatitis G and chronic hepatitis B or C infection, he reported, "Although the virus appears to be sensitive to interferon whilst the patient is on treatment, all cases relapsed on cessation of therapy."

Available studies demonstrate that HGV-infection is a blood transfusion and parenterally transmitted disease; HGV-infection is relatively mild in most cases; among transfusion recipients, HGV-infection is about as frequent in those formally diagnosed with hepatitis as in those with only mild ALT elevations; HGV and hepatitis C virus can be transmitted simultaneously and result in persistent co-infection; HGV-infection can be persistent and cause chronic hepatitis; the prevalence of HGV is higher than that of hepatitis C virus and unrelated to the ALT status of the blood donor; and the role of HGV in fulminant hepatitis and hepatocellular carcinoma has not been delineated. Initial studies are concentrating on the development of assay methods, diagnostics and virus characterization. However, with HGV incidence apparently greater than that of hepatitis C and conventional alpha-interferon treatments apparently lacking a high degree of efficacy, there appears to be potential for commercial development of drugs and vaccines for treatment and prevention of HGV-infection.