Hepatitis GBV-C sequences in patients infected with HCV contaminated anti-D immunoglobulin and among i.v. drug users in Germany

Background/Aims: A novel virus, GB virus-C (GBV-C), with a genome organization similar to those of the Flaviviridae family was identified in sera of patients diagnosed with hepatitis. Up to now little has been known about the prevalence of GBV-C sequences in German hepatitis C virus infected patients. Methods: We investigated two groups of patients chronically infected with hepatitis C virus: (i) Women infected in 1978/79 with HCV-contaminated anti-D immunoglobulin batches in former Eastern Germany, and (ii) I.v. drug users infected with different HCV subtypes. Nested polymerase chain reaction products amplified with GBV-C specific primer pairs within the helicase region were sequenced directly and compared with the GBV-C sequences reported recently. Results: GBV-C sequences of the putative NS 3 gene region were shown to occur in two randomly selected anti-D immunoglobulin batches of 1978 (GI and GII) and two sera of HCV-infected women drawn in 1979. In patient 3, the HCV-infected erythrocyte donor in 1978, specific GBV-C sequences were also evident in serum drawn in 1990. In the high-risk group of i.v. drug users, 49% were GBV-C RNA positive. Among the 21 GBV-C positive samples, 11 were coinfected with HCV subtype 3a and 10 with subtype 1 b. All isolates showed an overall homology to the GBV-C sequence reported by Simons of 75–81% at the nucleotide level and 94–100% at the amino acid level. Conclusion: GBV-C sequences are detectable in the anti-D immunoglobulin batches which caused a hepatitis C virus outbreak in 1979, and a first hint of its transmission to recipients was shown. The detection of GBV-C in patient serum drawn 12 years after the onset of chronic liver disease confirms the persistence of the novel virus described here. In the group of i.v. drug users a high frequency of GBV-C sequences (49%) was shown, and the considerable variability of the nucleotide sequences indicates the existence of different GBV-C genotypes/subtypes.