B cell activating factor (BAFF) in the natural history of chronic hepatitis C virus liver disease and mixed cryoglobulinaemia.

B cell activating factor (BAFF) plays a crucial role in the process of development, maturation and activation of B lymphocytes. Chronic hepatitis C virus (HCV) infection is characterized by multiple B cell disorders. It is a major cause of type II mixed cryoglobulinaemia (MC). We measured serum BAFF levels in several clinical situations to elucidate the potential role of BAFF in chronic HCV infection. We used a commercially available solid phase enzyme-linked immunosorbent assay. We estimated serum BAFF in stored sera from uninfected controls (n = 8), patients with chronic hepatitis B virus infection HBV (n = 5) and chronic HCV infection with (n = 16) and without mixed cryoglobulinaemia (n = 14). In two patients with HCV and MC we correlated BAFF with HCV RNA after pegylated interferon (peg-I). We correlated serum BAFF levels at baseline and at 12 weeks with treatment response: sustained virological response SVR (n = 5), non-responders (n = 6) and relapsers (n = 2). Finally, we estimated BAFF levels after complete depletion of B cells with rituximab in patients with chronic HCV with MC (n = 3). Serum levels of BAFF were increased in chronic HCV with MC, but not in chronic HBV infection, suggesting an association between BAFF and cryoglobulinaemia. Peg-I increased BAFF levels in serum and this paralleled HCV RNA very closely. Serum BAFF levels at week 12 of therapy with peg-I and R were significantly higher in responders than non-responders. Finally, B cell depletion was associated with markedly increased levels of BAFF.