The effect of antiviral therapy on t(14;18) translocation and immunoglobulin gene rearrangement in patients with chronic hepatitis C virus infection

• Published in: Blood Vol. 97; no. 6; pp. 1555 - 1559
• Main Authors: Zuckerman, Eli, Zuckerman, Tsila, Sahar, Dvora, Streichman, Sara, Attias, Dina, Sabo, Edmond, Yeshurun, Daniel, Rowe, Jacob M.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 15.03.2001
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V97.6.1555.h8001555_1555_1559

The mechanism of lymphomagenesis of hepatitis C virus (HCV)–related B-cell lymphoma is unknown. Recently, it has been suggested that HCV may induce B-cell clonal proliferation and t(14;18) translocation in patients chronically infected with the virus. Thus, this study investigated the effect of antiviral treatment on immunoglobulin heavy-chain gene (IgH) rearrangement and t(14;18) translocation in HCV infected patients. Twenty-nine patients with chronic HCV infection were studied in whom IgH rearrangement and/or t(14;18) translocation were previously detected. The IgH rearrangement (FR3/JH) and t(14;18) translocation (MBR bcl2-JH) were detected in peripheral blood mononuclear cells by polymerase chain reaction. Fifteen of 29 patients (8 with IgH rearrangement, 6 with t(14;18) translocation, and 1 with both) were treated with either interferon-α or by combination therapy with interferon and ribavirin for 6 to 12 months. IgH rearrangement became negative in 7 of 9 treated patients compared with only 1 of 8 of nontreated patients (P < .02). The t(14;18) translocation became negative in 6 of 7 treated patients compared with 1 of 6 nontreated patients (P = .03). Disappearance of IgH rearrangement or t(14;18) translocation was strongly associated with virologic response to treatment. Two t(14;18)+patients developed B-cell lymphoma during follow-up. Antiviral treatment appears to be effective in eliminating the clonal proliferation of B cells in patients with chronic HCV infection and may prevent the subsequent development of lymphoma. The mechanism can be related to a direct effect of interferon-α on the proliferating clone or to an indirect effect by eradicating the antigenic stimulus.