A clinical and virological study of hepatitis C virus-related cryoglobulinemia in Germany

Background/Aims: Several reports, especially from Southern Europe, have demonstrated a close association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia. In this study we have analyzed the significance of HCV-related cryoglobulinemia in Germany. Methods: Sera from 79 patients with cryoglobulinemia of type I (n=21), II (n=28) or III (n=30) were investigated for HCV markers. Furthermore, 132 consecutive patients with chronic hepatitis C were studied for the presence of cryoglobulins. Genotypes of HCV were determined according to Simmonds, and HCV-RNA concentrations were measured in patients with and without cryoglobulinemia. Results: In 79 patients with cryoglobulinemia we found anti-HCV antibodies in 17 (22%) and HCV-RNA in 11 patients (14%), HCV antibodies were more frequent in essential (44%) compared to secondary mixed cryoglobulinemia (15%), In 132 patients with chronic HCV infection cryoglobulins were detected in 37 patients (28%), in 21 of them at low levels. Clinical symptoms due to cryoglobulinemia were observed in eight of the 37 patients, severe vasculitis in three patients with high cryocrit-levels and cryoprecipitation at room temperature. HCV genotype 1 and subtype Ib were most prevalent, both in patients with and without cryoglobulinemia, and mean HCV-RNA levels were not different between the two groups. Comparison of HCV-RNA levels in cryoprecipitates, supernatant and native serum suggests binding of HCV-RNA to the cryoprecipitate with different affinity in individual patients. Conclusions: The lower prevalence of HCV-related cryoglobulinemia in our study compared with data from Italy and France suggests a south-north gradient in the prevalence of HCV-associated cryoglobulinemia in Europe.