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.
Liver Unit and the Department of Internal Medicine A, and the Institute of Hematology, Bnai Zion Medical Center, Haifa, Israel.
E
E
Zuckerman
T
T
Zuckerman
D
D
Sahar
S
S
Streichman
D
D
Attias
E
E
Sabo
D
D
Yeshurun
J M
JM
Rowe
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