Effect of antiviral treatment in patients with chronic HCV infection and t(14;18) translocation.
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.
Giannelli
Francesca
F
Department of Internal Medicine, University of Florence, School of Medicine, Italy.
Moscarella
Stefania
S
Giannini
Carlo
C
Caini
Patrizio
P
Monti
Monica
M
Gragnani
Laura
L
Romanelli
Roberto Giulio
RG
Solazzo
Vera
V
Laffi
Giacomo
G
La Villa
Giorgio
G
Gentilini
Paolo
P
Zignego
Anna Linda
AL
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
D000998:Antiviral Agents; D012367:RNA, Viral; D012254:Ribavirin; D007372:Interferons; D000410:Alanine Transaminase