Risk of Non-Hodgkin Lymphoma and Lymphoproliferative Precursor Diseases in US Veterans With Hepatitis C Virus

Giordano, Thomas P.; Henderson, Louise M.; Landgren, Ola; Chiao, Elizabeth Y.; Kramer, Jennifer R.; El–Serag, Hashem B.; Engels, Eric A.

doi:10.1001/jama.297.18.2010

Cited by 304 publications

(246 citation statements)

References 29 publications

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“…More recently, we conducted two large nationwide studies based on U.S. veterans. In a large study including 146,394 patients infected with hepatitis C virus (HCV) and 572,293 controls, 58 HCV infection was found to confer a 20-30% increased risk of NHL overall and a 3-fold higher risk of WM. In another large study based on 4 million U.S. veterans, we assessed WM risk in relation to a variety of chronic immune stimulatory conditions.…”

Section: Lymphomamentioning

confidence: 99%

Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies

Kristinsson

Goldin²,

Björkholm³

et al. 2009

Haematologica

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Section: Lymphomamentioning

confidence: 99%

Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies

Kristinsson

Goldin²,

Björkholm³

et al. 2009

Haematologica

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“…HCV infection is associated with an increase incidence of B-cell non-Hodgkin lymphoma (NHL) of approximately 20 to 30 % [1]. DLBCL and marginal zone B-cell lymphoma are the common histologic sub-types of NHL in HCV infected patients [2].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and Therapeutic Quandaries in a Patient with Primary Hepatic Lymphoma and Concurrent Hepatitis C Infection

Mohamed

Fernando

2014

Indian J Hematol Blood Transfus

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Primary hepatic lymphoma (PHL) is a very rare sub-type of non-Hodgkin's lymphoma and hepatitis C infection may be a contributory factor. The association of hepatitis C infection and PHL causes difficulties in management since safety of rituximab in such situations is unclear due to lack of evidence. The role of anti-viral therapy in combination with chemotherapy is also uncertain. We describe the diagnostic and therapeutic challenges posed by a patient who was diagnosed with PHL and concurrent hepatitis C infection.

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“…Of note, a large retrospective cohort study of 146,394 patients of Veterans Affairs health care facilities in the United States, in which 97% of the patients were male, also demonstrated an increased risk of cryoglobulinemia for HCV-infected men. 8 …”

Section: Reply: B-cell Frequency In Hcv-related Mixed Cryoglobulinemiamentioning

confidence: 99%

Reply: B-cell frequency in HCV-related mixed cryoglobulinemia

et al. 2013

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We read with great interest the article by Holz et al. 1 published in HEPATOLOGY. The authors provide information on immunophenotypic changes of peripheral B cells (PBLs) in 17 chronically hepatitis C virus (HCV)-infected patients with mixed cryoglobulinemia (MC). They underlined the primary role of B cells in the pathogenesis of MC. The occurrence of B-cell subpopulations biased toward anergy and/or apoptosis was demonstrated. As unexpected findings, they reported a significant reduction of total circulating B-cell number in MC patients as compared with control populations. They concluded that, naive B cells being more prone to apoptosis and representing the largest fraction of the major B-cell compartment, their reduced frequency may contribute to the observed reduction in CD19 þ Bcell number in these patients.These data, indeed, contradict many previously published observations showing an expanded number of PBLs in MC populations. 2,3 Stirred by these observations, we reassessed the results of immunophenotypic analyses of PBLs assessed in 100 HCV-related MC and in 100 HCV-infected patients without MC and in 50 healthy controls. In all patients, PBLs were obtained on the same day of liver biopsy and in no case were cells thawed after cryopreservation. All had histological diagnosis of chronic hepatitis without cirrhosis. The patient groups had a comparable total lymphocyte frequency of 1,435 6 277 cells/lL in cryoglobulinemic and 1,280 6 196 cells/lL in noncryoglobulinemic patients. As shown in Fig. 1, the results demonstrate a significant enrichment of circulating B cells in MC patients.As a measure of range values, MC patients showed a CD19 þ B-cell frequency higher than 20% in almost 80%. These results are not in line with data reported by Holz et al., whose observations may support the notion of compartmentalization of lymphocyte subpopulations. An altered trafficking of B cells with an increased number of naive phenotype in circulation may be proposed, in that activated B cells are selectively retained. HCV induces changes regulating lymphocyte homing, migration, or adhesion to the extracellular matrix. Furthermore, the sharp prevalence of male sex in Holz et al.'s population accounts for a distinct subgroup of cryoglobulinemic patients. They found a 2.4 male/female ratio, which is a very unusual finding. The high prevalence of females in cryoglobulinemic patients is a long-standing observation. In this context remarkable differences in sex distribution within the patients considered by Holz et al. may suggest that hormone patterns may contribute to the modification of characteristics of the B-cell immune response. Reply: B-cell Frequency in HCV-Related Mixed CryoglobulinemiaWe appreciate the interest of Sansonno et al. in our recent article. 1 Sansonno et al. correctly state that we observed a reduction in the total number of B cells and in the size of the naïve B cell subset in patients with mixed cryoglobulinemia (MC) compared with hepatitis C virus (HCV)-infected patients without MC and healthy cont...

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Risk of Non-Hodgkin Lymphoma and Lymphoproliferative Precursor Diseases in US Veterans With Hepatitis C Virus

Cited by 304 publications

References 29 publications

Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies

Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies

Diagnostic and Therapeutic Quandaries in a Patient with Primary Hepatic Lymphoma and Concurrent Hepatitis C Infection

Reply: B-cell frequency in HCV-related mixed cryoglobulinemia

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