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 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-alpha 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-alpha on the proliferating clone or to an indirect effect by eradicating the antigenic stimulus.
Zuckerman
E
E
Liver Unit and the Department of Internal Medicine A, and the Institute of Hematology, Bnai Zion Medical Center, Haifa, Israel.
Zuckerman
T
T
Sahar
D
D
Streichman
S
S
Attias
D
D
Sabo
E
E
Yeshurun
D
D
Rowe
J M
JM
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D004359:Drug Therapy, Combination; D005260:Female; D015321:Gene Rearrangement / Q000187:drug effects*; D019254:Genes, bcl-2 / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000187:drug effects* / Q000235:genetics; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage / Q000494:pharmacology; D014178:Translocation, Genetic / Q000187:drug effects* / Q000235:genetics
D000998:Antiviral Agents; D007143:Immunoglobulin Heavy Chains; D016898:Interferon-alpha; D012254:Ribavirin