3.9 New hepatitis viruses

    Recently there have been reports of new hepatitis viruses which may be present in a significant proportion of blood donors, and which may be responsible for those residual cases of post-transfusion hepatitis (PTH) that cannot be shown to be due to viral hepatitis of type A, B, C, D or E. Generally NANBH can be divided into three groups based upon mode of transmission: community, acquired, parenteral and enteric. Virtually all enteric cases are identified as being caused by HEV. Most cases of parenteral and community-acquired NANBH are now known to be due to HCV, but a small number are not, and are thought to be due to another as yet unidentified viral agent or agents.

    Studies in the USA have identified putative viruses that may be responsible for such residual cases of NANBH. Essentially there have been two viruses/groups of viruses identified: the GB viruses (subdivided into three types: GBV-A, GBV-B, GBV-C) and the new hepatitis virus: hepatitis G virus (HGV). These viruses have all been identified as almost certainly members of the Flaviviridae, transmitted parenterally, and as present in a significant number of asymptomatic and symptomatic individuals although not necessarily associated with any specific disease process. The GBV-C and HGV viruses identified have been found to have greater than 90% homology at the genomic level and to be virtually identical in their structural organization, suggesting that there is a high probability that the two may be strains of the same virus.

    Unfortunately, at present, tests for these viruses depend upon molecular rather than serological principles. The polymerase chain reaction (PCR) has been used extensively to identify the presence of virus in samples from infected individuals. Liver enzyme levels, notably ALT, have also proved to have some predictive value in marking acute infection with active hepatitis. Serological tests, however, have not proved to be straightforward, with problems encountered in identifying potential antigens that are capable of detecting specific antibody in infected individuals. In a similar way to the development of anti-HCV assays, structural and nonstructural proteins have been identified from the viral genomes and expressed to produce tentative diagnostic antigens. However, little is known currently about the serology of these viruses, and those assays that have been put together and used have given some contradictory results. Prevalence figures for GBV-C and HGV, derived from PCR results and serological studies, give figures varying from 2% in volunteer blood donors to as high as 30% in some west African populations.

    The role and significance of GBV-A and GBV-B are harder to assess. Phylogenetically GBV-A and GBV-C are more closely related than GBV-B. Primate animal studies have shown that GBV-A does not cause hepatitis or establish an antibody response, while GBV-B does and a degree of protective immunity is established in those animals. Limited comparative prevalence studies have demonstrated the presence of antibodies against GBV-A and GBV-B in different patient and risk groups, but the prevalences have all been significantly less than that of GBV-C/HGV.