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

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 chronicall y infected with the virus. Thus, this study investigated the effect of anti viral 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/J(H)) and t(14;18) translocation (MBR bcl2-J(H)) were detected in peripheral bloo d mononuclear cells by polymerase chain reaction. Fifteen of 29 patients (8 with IgH rearrangement, 6 with t(14;18) translocation, and 1 with both) we re treated with either interferon ol or by combination therapy with interfe ron 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 patie nts compared with 1 of 6 nontreated patients (P = .03). Disappearance of Ig H rearrangement or t(14;18) translocation was strongly associated with viro logic response to treatment. Two t(14;18)(+) patients developed B-cell lymp homa during follow-up. Antiviral treatment appears to be effective in elimi nating the clonal proliferation of B cells in patients with chronic HCV inf ection and may prevent the subsequent development of lymphoma. The mechanis m can be related to a direct effect of interferon-<alpha> an the proliferat ing clone or to an indirect effect by eradicating the antigenic stimulus. ( Blood. 2001; 97:1555-1559) (C) 2001 by The American Society of Hematology.