BACKGROUND: Hepatitis C virus (HCV) infection is strictly associated with mixed cryoglobulinemia, a benign B-cell lymphoproliferative disorder that may evolve to lymphoma. An increased prevalence of bcl-2 rearrangement (the t(14;18) translocation) has been shown in patients infected with HCV.OBJECTIVE: To evaluate the prevalence of bcl-2 rearrangement in patients with HCV-related mixed cryoglobulinemia and patients with chronic hepatitis but no cryoglobulinemia.DESIGN: Prospective study.SETTING: Two university hospitals.PATIENTS: 37 consecutively recruited patients with HCV-related mixed cryoglobulinemia and 101 patients with chronic HCV infection but without mixed cryoglobulinemia.MEASUREMENTS: Clinical and serologic characteristics; liver biopsy; bcl-2 rearrangement, Bcl-2 expression, and the ratio of Bcl-2 to Bax in total peripheral blood mononuclear cells and cell subgroups; and sequence analysis of the junction of bcl-2 and IgH joining segments in positive samples.RESULTS: Rearrangement of bcl-2 was observed in 28 of 37 (75.7%) patients with mixed cryoglobulinemia (65% of those with type III disease and 85% of those with type II disease, including 3 of 4 patients with lymphoma) and in 38 of 101 (37.6%) patients with chronic HCV infection but not mixed cryoglobulinemia (P < 0.001). Overexpression of Bcl-2 protein and a high ratio of Bcl-2 to Bax were observed in samples from patients with bcl-2 rearrangement. In 2 patients followed over time, peripheral blood cells bearing the t(14;18) translocation disappeared after antiviral therapy.CONCLUSIONS: Rearrangement of bcl-2 was found with increased frequency in patients with chronic HCV infection and mixed cryoglobulinemia. The frequency was greatest in patients with type II mixed cryoglobulinemia. The high ratio of Bcl-2 to Bax in patients with bcl-2 rearrangement and disappearance of the rearrangement with antiviral therapy suggest that the translocation is associated with the antiapoptotic function of Bcl-2 and that HCV infection is linked to inhibition of B-cell apoptosis.
Prevalence of bcl-2 rearrangement in patients with hepatitis C virus-related mixed cryoglobulinemia with or without B-cell lymphomas / Zignego, Al; Ferri, Clodoveo; Giannelli, F.; Giannini, C.; Caini, P.; Monti, M.; Marrocchi, Me; Di Pietro, E.; La Villa, G.; Laffi, G.; Gentilini, P.. - In: ANNALS OF INTERNAL MEDICINE. - ISSN 0003-4819. - STAMPA. - 137:7(2002), pp. 571-580. [10.7326/0003-4819-137-7-200210010-00008]
Prevalence of bcl-2 rearrangement in patients with hepatitis C virus-related mixed cryoglobulinemia with or without B-cell lymphomas
FERRI, Clodoveo;
2002
Abstract
BACKGROUND: Hepatitis C virus (HCV) infection is strictly associated with mixed cryoglobulinemia, a benign B-cell lymphoproliferative disorder that may evolve to lymphoma. An increased prevalence of bcl-2 rearrangement (the t(14;18) translocation) has been shown in patients infected with HCV.OBJECTIVE: To evaluate the prevalence of bcl-2 rearrangement in patients with HCV-related mixed cryoglobulinemia and patients with chronic hepatitis but no cryoglobulinemia.DESIGN: Prospective study.SETTING: Two university hospitals.PATIENTS: 37 consecutively recruited patients with HCV-related mixed cryoglobulinemia and 101 patients with chronic HCV infection but without mixed cryoglobulinemia.MEASUREMENTS: Clinical and serologic characteristics; liver biopsy; bcl-2 rearrangement, Bcl-2 expression, and the ratio of Bcl-2 to Bax in total peripheral blood mononuclear cells and cell subgroups; and sequence analysis of the junction of bcl-2 and IgH joining segments in positive samples.RESULTS: Rearrangement of bcl-2 was observed in 28 of 37 (75.7%) patients with mixed cryoglobulinemia (65% of those with type III disease and 85% of those with type II disease, including 3 of 4 patients with lymphoma) and in 38 of 101 (37.6%) patients with chronic HCV infection but not mixed cryoglobulinemia (P < 0.001). Overexpression of Bcl-2 protein and a high ratio of Bcl-2 to Bax were observed in samples from patients with bcl-2 rearrangement. In 2 patients followed over time, peripheral blood cells bearing the t(14;18) translocation disappeared after antiviral therapy.CONCLUSIONS: Rearrangement of bcl-2 was found with increased frequency in patients with chronic HCV infection and mixed cryoglobulinemia. The frequency was greatest in patients with type II mixed cryoglobulinemia. The high ratio of Bcl-2 to Bax in patients with bcl-2 rearrangement and disappearance of the rearrangement with antiviral therapy suggest that the translocation is associated with the antiapoptotic function of Bcl-2 and that HCV infection is linked to inhibition of B-cell apoptosis.
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