A new agent that may be responsible for acute and chronic hepatitis was recently identified [1, 2] and named hepatitis G virus (HGV). It is a single-stranded RNA virus that can be categorized as a member of the Flaviridiae family on the basis of its structure. It resembles hepatitis C virus (HCV), but its nucleotide sequence is too divergent to allow it to be classified as an HCV genotype. The estimated prevalence of HGV RNA, determined using reverse transcription polymerase chain reaction (PCR), is about 1% in healthy blood donors, 3% to 5% in patients receiving maintenance hemodialysis, and as great as 24% in patients infected with HCV [3]. As many as 55% to 85% of patients with chronic HCV infection have mixed cryoglobulinemia [4]. The underlying mechanisms leading to this production of mixed cryoglobulinemia are unknown, although a long duration of HCV infection, older age, and the presence of cirrhosis seem to be predictive factors [5].

To determine the role of HGV infection in the production of mixed cryoglobulinemia, we conducted a study in 49 consecutive patients. Eleven patients had symptomatic essential mixed cryoglobulinemia without such underlying diseases as autoimmune, infectious, or malignant hematologic disorders. Thirty-eight patients had chronic HCV infection (defined by the presence of alanine aminotransferase levels more than twice the upper limit of normal), antibodies to HCV detected on a third-generation enzyme-linked immunosorbent assay, liver biopsy findings compatible with chronic hepatitis C, and no other cause of liver dysfunction. All HCV-positive patients were positive for viremia on PCR. Of these 38 HCV-positive patients, 18 had symptomatic mixed cryoglobulinemia and 20 did not have mixed cryoglobulinemia on repeated tests. Cryoglobulins were isolated from the patients' serum specimens and were purified and characterized by immunoblotting at 37 °C, as described elsewhere [4]. Patients were considered to have significant cryoglobulin if they had a serum cryoglobulin level of 0.05 g/L or more on two determinations. All patients with cryoglobulinemia had type II or type III mixed cryoglobulinemia. A nested-PCR method using primers located in the NS3 and NS5 regions was used to search HGV RNA [1, 2]. The main results are summarized in Table 1.

In conclusion, HGV infection does not seem to be a risk factor for the production of essential mixed cryoglobulinemia or an HCV cofactor for the production of HCV-related mixed cryoglobulinemia.