Infection of B cells with hepatitis C virus for the development of lymphoproliferative disorders in patients with chronic hepatitis C.
Infection with hepatitis C virus (HCV) is associated with lymphoproliferative disorders, represented by essential mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma, but the pathogenic mechanism remains obscure. HCV may infect B cells or interact with their cell surface receptors, and induce lymphoproliferation. The influence of HCV infection of B cells on the development of lymphoproliferative disorders was evaluated in 75 patients with persistent HCV infection. HCV infection was more prevalent (63% vs. 16%, 14%, or 17% P < 0.05 for each), and HCV RNA levels were higher (3.35 +/- 3.85 vs. 1.75 +/- 2.52, 2.15 +/- 2.94 or 2.10 +/- 2.90 log copies/100 ng, P < 0.01 for each) in B cells than CD4(+), CD8(+) T cells or other cells. Negative-strand HCV RNA, as a marker of viral replication, was detected in B cells from four of the 75 (5%) patients. Markers for lymphoproliferative disorders were more frequent in the 50 patients with chronic hepatitis C than the 32 with chronic hepatitis B, including cryoglobulinemia (26% vs. 0%, P < 0.001), low CH(50) levels (48% vs. 3%, P = 0.012), and the clonality of B cells (12% vs. 0%, P < 0.01). By multivariate analysis, HCV RNA in B cells was an independent factor associated with the presence of at least one marker for lymphoproliferation (odds ratio: 1.98 [95% confidence interval: 1.36-7.24], P = 0.027). Based on the results obtained, the infection of B cells with HCV would play an important role in the development of lymphoproliferative disorders.
Inokuchi
Momoko
M
Department of Gastroenterology, Showa University School of Medicine, Tokyo, Japan.
Ito
Takayoshi
T
Uchikoshi
Manabu
M
Shimozuma
Yuu
Y
Morikawa
Kenichi
K
Nozawa
Hisako
H
Shimazaki
Tomoe
T
Hiroishi
Kazumasa
K
Miyakawa
Yuzo
Y
Imawari
Michio
M
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000473:pathology / Q000821:virology*; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics; D016174:Hepacivirus / Q000472:pathogenicity* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000453:epidemiology / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood; D014779:Virus Replication
D012367:RNA, Viral