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Prepublished online as a Blood First Edition Paper on April 10, 2003; DOI 10.1182/blood-2002-05-1537.
Submitted May 29, 2002
Accepted February 28, 2003
Effect of antiviral treatment in patients with chronic HCV infection and t(14;18) translocation
Francesca Giannelli, Stefania Moscarella, Carlo Giannini, Patrizio Caini, Monica Monti, Laura Gragnani, Roberto Giulio Romanelli, Vera Solazzo, Giacomo Laffi, Giorgio La Villa, Paolo Gentilini, and Anna Linda Zignego*
Department of Internal Medicine, University of Florence, Florence, Italy
* Corresponding author; email: a.zignego{at}dmi.unifi.it.
Hepatitis C virus (HCV) may be associated with the mixed cryoglobulinemia syndrome and other B cell lymphoproliferative disorders (LPDs). T(14;18) may play a pathogenetic role. Limited data are available regarding the effects of antiviral therapy on rearranged B-cell clones. We evaluated the effects of interferon and ribavirin on serum, B lymphocyte HCV RNA and t(14;18) in 30 HCV-positive, t(14;18)-positive patients without either mixed cryoglobulinemia syndrome or other LPDs. T(14;18) was analyzed by both bcl-2/JH PCR and bcl-2/JH junction sequencing in peripheral blood mononuclear cells in all patients. Fifteen untreated patients with comparable characteristics served as controls. Throughout the study, the presence or absence of both t(14;18) and HCV RNA sequences were, in most cases, associated in the same cell samples. At the end of treatment, t(14;18) was no longer detected in 15 patients (50%) with complete or partial virological response, whereas it was persistently detected in non-responders (p < 0.05), as well as in 14/15 control patients. In 4 responder patients, t(14;18) and HCV RNA sequences were no longer detected in blood cells after treatment, but were again detected after viral relapse; the same B-cell clones were involved in the pre- and post-treatment periods. In conclusion, this study suggests that antiviral therapy may induce regression of the t(14;18) bearing B-cell clones in HCV-positive patients and that this phenomenon may be related, at least in part, to the antiviral effect of therapy. This in turn suggests that antiviral treatment may help prevent and/or treat HCV-related lymphoproliferative disorders.
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