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The role of CD5(+) B cells in patients with HCV infection and HCV-related disorders, including mixed cryoglobulinemia (MC), has been addressed in previous reports with conflicting results. We established a correlation between CD5/CD20 expression on circulating B lymphocytes, characterizing monoclonal B cell lymphocytosis (MBL), and clinical features in a cohort of 45 patients with chronic HCV hepatitis [without MC: 23 patients (MC-group); with MC: 22 patients (MC+ group)], and 45 HCV-negative healthy subjects as controls. By flow cytometry analysis, three B cells phenotypes were singled out: 1) CD5(+) CD20(dim) (CLL-like phenotype); 2) CD5(+) CD20(bright) (atypical phenotype); and 3) CD5-CD20(+) phenotype. CD5(+) CD20(bright) cells were reduced in MC-patients (p = 0.049). CD5(+) CD20(dim) B cells were significantly higher in group B than in the control group (p = 0.003). ROC curve analysis in MC+ patients showed the highest positive likelihood ratio at >= 7.35% (p = 0.008) for CLL-like phenotype and at <= 63.6% (p = 0.03) for the CD5-CD20(+) B cell phenotype. HCV infection was associated with a higher frequency of CLL-like (odds ratio = 16, p = 0.002) and a lower frequency of atypical (odds ratio: 3.1, p = 0.02) and CD5-CD20(+) (odds ratio: 11, p = 0.01) phenotypes. The association with higher levels of CLL-like phenotype progressively increased from group of MC-patients (odds ratio: 9.3, p = 0.04) to the group of MC+ patients (odds ratio: 25.1, p = 0.0003).Conclusions: The occurrence of a CLL-like pattern may allow to identify HCV-infected patients at risk of developing MC and eventually non-Hodgkin lymphoma, who should require a closer surveillance and a longer follow-up.

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