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Blood, Vol. 93 No. 5 (March 1), 1999:
pp. 1778-1779
CORRESPONDENCE
Hepatitis C Virus Infection in Patients With Overt B-Cell
Non-Hodgkin's Lymphoma in a French Center
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LETTER |
To the Editor:
Hepatitis C virus (HCV) has been shown to be the main etiologic agent
of type II mixed cryoglobulinemia (MC),1,2 a disease associated with an underlying B-cell clonal proliferation, predisposing to B-cell malignancy, in 2% to 11% of the cases.3 Italian
studies have recently reported a 9% to 35% prevalence of chronic HCV
infection in patients with B-cell non-Hodgkin's lymphomas (B-NHL),
compared with a 2% to 13% prevalence in patients with other blood
malignancies, and a 1% to 5.4% prevalence in healthy
controls.4-9 In addition, a recent American controlled
study10 showed a 22% prevalence of HCV infection markers
in patients with B-NHL versus 5% in age-matched controls. However,
studies from other countries, including the United Kingdom and
Germany,11-14 did not confirm such an association. The aim
of the present study was to determine the prevalence of chronic HCV
infection in a large cohort of unselected patients with B-NHL in a
French center.
Between January 1994 and July 1997, 201 patients with B-NHL (109 men,
92 women; mean age, 56.0 years; range, 18 to 90) were seen at the
hematology clinic of our hospital. During the same period, 94 patients
with Hodgkin's disease were seen (54 men, 40 women; mean age, 37.5 years; range, 18 to 75) and served as a control group for this study.
Lymphoma was diagnosed on the basis of morphologic evaluation of lymph
node tissue or extranodal tissues, including bone marrow specimens.
Immunophenotypic analysis of B- and T-lymphocytic markers was performed
and B-NHL was histologically classified using the Revised European
American Lymphoma (R.E.A.L.) classification.15
Anti-HCV antibodies were prospectively sought in all patients using
second-generation enzyme-linked immunosorbent assay (ELISA), confirmed
by second-generation recombinant immunoblot assay (RIBA)
(Ortho Clinical Diagnostics, Raritan, NJ).
The overall prevalence of HCV markers in the B-NHL patients was 4/201
(2.0%; 95% confidence interval: 0.1% to 3.9%). Table 1 shows the prevalence of HCV markers
according to B-NHL histotypes. The 4 HCV+ patients were
HCV-RNA+ by polymerase chain reaction (PCR).
HCV+ patients had a lymphoplasmatocytoid lymphoma in 1 case, a mucosa-associated lymphoid tissue (MALT) lymphoma
in 1 case, and a diffuse large B-cell lymphoma in 2 cases. The
prevalence of HCV infection in the patients with Hodgkin's disease
(control group) was 1/94 (1.1%; 95% confidence interval: 0.0% to
3.2%). It was not significantly different from the prevalence in
patients with B-NHL.
Overall, the present results do not support the existence of a
significant relationship between HCV infection and B-NHL in France. The
marked discrepancies among studies from different geographic areas
might be explained by the following: (1) the studies4-10 in
favor of a relationship between HCV infection and B-NHL originated from
areas with high endemicity for HCV. However, because of the higher HCV
prevalence in older subjects in these areas, age-matched control groups
should have been used systematically for comparison.5,8 (2)
in contrast, the studies suggesting a lack of
association11-14 originated from countries with a lower prevalence of HCV infection. Thus, HCV appears to be associated with
B-NHL only in areas where HCV is highly prevalent, suggesting that HCV
is not essentially involved in the pathogenesis of B-NHL. However, some
specific B-NHL histotypes could be preferentially associated with HCV
infection. It is noteworthy that, in three studies,6-8 HCV
was principally found in patients with lymphoplasmacytoid lymphoma/immunocytoma associated with type II MC, with 30% to 45% of
these patients being HCV-RNA+.6-8 The
lymphoplasmatocytoid lymphoma/immunocytoma originates from a
CD5-peripheral B lymphocyte able to differentiate into a plasma cell.
Sites involved include bone marrow, lymph nodes, spleen and, less
frequently, peripheral blood or extranodal sites. This condition is
commonly associated with type II MC.16 In the United States
study,10 monocytoid nodal B-cell lymphoma accounted for
23% of all lymphomas and 67% of all low-grade lymphomas among the
HCV+ patients. Furthermore, another Italian
report17 pointed out an additional subset of overt B-NHL in
HCV-infected individuals, diffuse large B-cell lymphoma (23 of 83, 27.7% of cases were HCV+).
The overrepresentation of lymphoplasmatocytoid lymphoma in several
Italian studies (14% to 33%)6,7 might result from a
selection bias of the patients, due to the follow-up of a significant number of patients with MC in these centers. This could account for the
high prevalence of HCV infection in B-NHL patients in these series. The
lower prevalence of lymphoplasmatocytoid lymphoma in our series of
unselected patients with B-NHL (4.5%) is in agreement with the 1.2%
prevalence, as estimated by R.E.A.L.,15 and could explain
the low prevalence of HCV markers observed. Furthermore, the low
prevalence of HCV infection (2 of 118, 1.7%) in the large cohort of
our patients with diffuse large B-cell lymphoma does not confirm the
recently suggested association between HCV and diffuse large B-cell
lymphoma.17 Prospective case-control studies of the
prevalence of HCV in B-NHL patients from different countries, including
all R.E.A.L. histological subtypes in sufficient numbers, are now
mandated to confirm such an association.
Georgios Germanidis
Corinne Haioun
Jérôme Pourquier
Philippe Gaulard
Jean-Michel Pawlotsky
Daniel Dhumeaux
Félix Reyes
Hôpital
Henri Mondor
Université Paris XII
Créteil,
France
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