Previous data demonstrated that an elevated percentage of hepatitis C virus (HCV) infected patients are endotoxemic. Endotoxemic patients are poor responders to the interferon (IFN)- alpha/ribavirin (RIB) treatment and exhibit lower serum levels of IFN-gamma and interleukin (IL)-10 than the responder counterpart. Here we provide evidence that in endotoxemic HCV+ patients absolute numbers of CD19(+) cells (B cells) are higher than those observed in the non-endotoxemic counterpart at the end of the combined treatment. Moreover, anti lactoferrin (LF) antibodies are more elevated in non-responder HCV+ patients than in the responders. In turn, these autoantibodies may affect the antiviral activity of LF, on the one hand, and, on the other hand abrogate the LF binding to lipopolysaccharides (LPS). Such an interaction hampers the binding of LPS to LPS binding protein, thus inhibiting LPS fixation to CD14(+) cells and, ultimately, leading to a decreased release of proinflammatory cytokines.