Bcl-2 rearrangement [t(14;18)] occurs in most patients with HCV-related mixed cryoglobulinemia (MC). MC patients are generally resistant to antiviral therapy. To evaluate whether t(14;18) influences the response in HCV chronic infection, we treated 64 HCV+ patients: 32 (21 m; mean age 49 yrs, group A) with t(14;18) and 32 (19 m; mean age 51 yrs, group B) without t(14;18) with interferon alpha (5MU twice/weekly) plus ribavirin (1-1.2 g/die). Patients did not differ with respect to HCV genotype distribution, viral titer or severity of liver disease. T(14;18) was detected in peripheral B lymphocytes (BL) by bcl-2/JH PCR and sequencing. At the end of treatment, HCV viremia was determined in 19 (59%) group A and 10 (31%) group B patients (p < 0.05). HCV RNA was also detectable in BL from most of non-responder patients. Six months later, HCV viremia was detected in 30 Group A (93%) and 22 Group B (68%) patients. In conclusion, this study indicates that presence of rearranged BL clones is associated with a poorer end-of-treatment response to antiviral therapy, and a trend towards a reduced sustained response. A tentative explanation for this phenomenon may be that abnormally prolonged life of rearranged BL may represent a persistent reservoir of viral infection.
Bcl-2 rearranged B cell clones in chronic HCV infection: a possible factor negatively influencing the virological response to treatment
ROMANELLI, ROBERTO GIULIO;GRAGNANI, LAURA;
2002-01-01
Abstract
Bcl-2 rearrangement [t(14;18)] occurs in most patients with HCV-related mixed cryoglobulinemia (MC). MC patients are generally resistant to antiviral therapy. To evaluate whether t(14;18) influences the response in HCV chronic infection, we treated 64 HCV+ patients: 32 (21 m; mean age 49 yrs, group A) with t(14;18) and 32 (19 m; mean age 51 yrs, group B) without t(14;18) with interferon alpha (5MU twice/weekly) plus ribavirin (1-1.2 g/die). Patients did not differ with respect to HCV genotype distribution, viral titer or severity of liver disease. T(14;18) was detected in peripheral B lymphocytes (BL) by bcl-2/JH PCR and sequencing. At the end of treatment, HCV viremia was determined in 19 (59%) group A and 10 (31%) group B patients (p < 0.05). HCV RNA was also detectable in BL from most of non-responder patients. Six months later, HCV viremia was detected in 30 Group A (93%) and 22 Group B (68%) patients. In conclusion, this study indicates that presence of rearranged BL clones is associated with a poorer end-of-treatment response to antiviral therapy, and a trend towards a reduced sustained response. A tentative explanation for this phenomenon may be that abnormally prolonged life of rearranged BL may represent a persistent reservoir of viral infection.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
