Ethnic difference in the prevalence of monoclonal B-cell proliferation in patients affected by hepatitis C virus chronic liver disease

Background/Aim: In previous studies we demonstrated that all patients affected by HCV-positive type II mixed cryoglobulinaemia have a monoclonal B-cell population in peripheral blood mononuclear cells, and that a large fraction of HCV-infected patients develop a monoclonal B-cell expansion, even in the absence of dosable serum cryoglobulins. However, the prevalence of Type II mixed cryoglobulinaemia in HCV-infected individuals seems to be high in Italy, whereas it is very low in Japan. This study was performed to investigate whether there are ethnic differences in the prevalence of asymptomatic HCV-associated monoclonal B-cell expansions. Methods: Forty-four Japanese patients affected by HCV-positive chronic liver disease (two healthy carriers, 31 chronic hepatitis and 11 cirrhosis) were compared with a group of 60 Italian patients (one healthy carrier, 49 chronic hepatitis, and 10 cirrhosis) without dosable levels of cryoglobulins. The monoclonality of peripheral blood mononuclear cells was investigated by RT/PCR analysis of Immunoglobulin gene rearrangements. Liver function tests, rheumatoid factor, cryocrit level, anti-HCV antibodies, HCV-RNA, and HCV genotype were performed according to standard methodology. Results: A B-cell monoclonal population was found in 26% of Italian patients, whereas all Japanese patients were negative. No correlation was found between B-cell monoclonality and severity of liver disease, length or source of the infection, HCV genotype, sex, clinical and biochemical parameters. Conclusions: This study indicates that a monoclonal B-cell proliferation in peripheral blood mononuclear cells is common in HCV infection, but only in Italy, whereas it is absent in Japan. This explains the very low prevalence of Type II mixed cryoglobulinaemia in HCV-positive Japanese subjects, and suggests that HCV is able to determine a B-cell expansiononly in the presence of, presently undetermined, host factors.