Zehender and colleagues report on a series of patients in whom the prevalence of HGV infection is much lower than that found in our study. We share their opinion that this discrepancy may be ascribed primarily to the different methods used to detect GB virus C and HGV RNA. Indeed, the high sensitivity of our assay is suggested by the elevated prevalence of GB virus C RNA not only in cryoglobulinemic patients with or without HCV infection but also in anti-HCV-positive blood donors. Furthermore, in another study using the same method, the GB virus C genome was detected in 39% of patients with chronic hepatitis of unknown cause [1]. Unfortunately, reverse transcriptase PCR assays for GB virus C and HGV RNA are generally not well standardized, especially with regard to the amplification of various genomic regions. Thus, large differences in results may be expected.

The possibility that the high prevalence of GB virus C infection in cryoglobulinemic patients reflects widespread circulation of this agent in the general population of our geographic area is unlikely if one considers the low frequency of GB virus C positivity in our blood donors. Another possible explanation of the discrepancy between our results and those of Zehender and colleagues is differences in patient characteristics. First, we studied a more homogenous sample formed only by patients with type II cryoglobulinemia. Second, in contrast to the series reported by Zehender and colleagues, only 33% of our patients had obvious signs of hepatitis; mean alanine aminotransferase values for the group as a whole were 53.2 ± 47.8 U/L (0.89 ± 0.80 µkat/L). Finally, we found that 76% of GB virus C RNA-positive patients were infected with HCV genotype 2a. Most of our patients (66%), in contrast to data reported in the literature [2], had genotype 2a; thus, the high prevalence of GB virus C infection may be at least partly explained.

Although many epidemiologic and biological characteristics of HGV and GB virus C remain unknown, our study clearly indicates that an infection with this agent has little, if any, pathogenic or clinical relevance in patients with type II cryoglobulinemia.