title: Clonal B cell populations in the blood and liver of patients with chronic hepatitis C virus infection.
abstract: OBJECTIVE
  The association of hepatitis C virus (HCV) infection with type II mixed cryoglobulinemia is well established, but the role of HCV in B cell lymphoma remains controversial. The objective of this study was to determine the frequency of circulating and liver-infiltrating monoclonal B cells in patients with HCV infection.
  
  
  METHODS
  One hundred sixty patients were studied prospectively, including 115 HCV-positive patients and 45 HCV-negative patients with other nonimmune chronic liver disease(s). B cell clonality was determined by DNA amplification of the IgH rearrangements, followed by polyacrylamide gel electrophoresis.
  
  
  RESULTS
  A clonal B cell population was detected in the blood of 21 (26%) of 81 HCV-positive patients whose cryoglobulin status was known, including 12 of 25 patients with type II cryoglobulinemia, 2 of 12 patients with type III cryoglobulinemia, and 7 of 44 patients without cryoglobulins. A clonal IgH rearrangement was detected in 26 (32%) of 81 liver biopsy specimens from HCV- infected patients, including 16 patients with a circulating clonal population. A clonal B cell population was not observed in the blood of 40 patients with non-HCV liver diseases and was present in only 1 (3%) of 30 liver biopsy specimens. Logistic regression analysis showed that HCV-infected patients with clonal B cell proliferation in both the blood and liver were older (P = 0.004) and had longer duration of HCV infection (P = 0.009), higher serum cryoglobulin levels (P = 0.001) that were more frequently symptomatic (P < 0.03), and liver disease that was more severe than that in patients without a clonal B cell population in the blood or liver (P = 0.05). In 4 of 16 patients with a clonal B cell population in both the blood and liver, a definite B cell malignancy was finally diagnosed.
  
  
  CONCLUSIONS
  Clonal B lymphocytes are frequently detected in the blood and liver of patients with chronic HCV infection, in the absence of overt B cell malignancy. These clones are usually, but not always, associated with the presence of type II cryoglobulins. A high percentage of patients with B cell clonality in both the blood and liver were finally diagnosed as having a definite B cell malignancy.
authors.affiliation: Department of Hematology, Assistance Publique Hopitaux, Hôpital La Pitié-Salpêtrière, 83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Vallat
authors.forename: Yves
authors.initials: Y
authors.lastname: Benhamou
authors.forename: Maya
authors.initials: M
authors.lastname: Gutierrez
authors.forename: Pascale
authors.initials: P
authors.lastname: Ghillani
authors.forename: Christel
authors.initials: C
authors.lastname: Hercher
authors.forename: Vincent
authors.initials: V
authors.lastname: Thibault
authors.forename: Frédéric
authors.initials: F
authors.lastname: Charlotte
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Piette
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.forename: Hélène
authors.initials: H
authors.lastname: Merle-Béral
authors.forename: Frédéric
authors.initials: F
authors.lastname: Davi
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000473:pathology*; D016022:Case-Control Studies; D002455:Cell Division; D002999:Clone Cells / Q000473:pathology; D003449:Cryoglobulinemia / Q000150:complications; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies