title: Effect of antiviral treatment in patients with chronic HCV infection and t(14;18) translocation.
abstract: Hepatitis C virus (HCV) may be associated with the mixed cryoglobulinemia syndrome and other B-cell lymphoproliferative disorders (LPDs). The t(14;18) translocation 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+, t(14;18)+ patients without either mixed cryoglobulinemia syndrome or other LPDs. The t(14;18) translocation was analyzed by both bcl-2/JH polymerase chain reaction 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 virologic response, whereas it was persistently detected in nonresponders (P <.05), as well as in 14 of 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 pretreatment and posttreatment periods. In conclusion, this study suggests that antiviral therapy may induce regression of t(14;18)-bearing B-cell clones in HCV+ 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 or treat HCV-related LPDs.
authors.affiliation: Department of Internal Medicine, University of Florence, School of Medicine, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Giannelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Moscarella
authors.forename: Carlo
authors.initials: C
authors.lastname: Giannini
authors.forename: Patrizio
authors.initials: P
authors.lastname: Caini
authors.forename: Monica
authors.initials: M
authors.lastname: Monti
authors.forename: Laura
authors.initials: L
authors.lastname: Gragnani
authors.forename: Roberto Giulio
authors.initials: RG
authors.lastname: Romanelli
authors.forename: Vera
authors.initials: V
authors.lastname: Solazzo
authors.forename: Giacomo
authors.initials: G
authors.lastname: Laffi
authors.forename: Giorgio
authors.initials: G
authors.lastname: La Villa
authors.forename: Paolo
authors.initials: P
authors.lastname: Gentilini
authors.forename: Anna Linda
authors.initials: AL
authors.lastname: Zignego
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D001483:Base Sequence; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D019254:Genes, bcl-2 / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D012254:Ribavirin / Q000627:therapeutic use*; D014178:Translocation, Genetic / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D012254:Ribavirin; D007372:Interferons; D000410:Alanine Transaminase