scholarly journals Hepatitis C virus within a malignant lymphoma lesion in the course of type II mixed cryoglobulinemia

Blood ◽  
1995 ◽  
Vol 86 (5) ◽  
pp. 1887-1892 ◽  
Author(s):  
S De Vita ◽  
D Sansonno ◽  
R Dolcetti ◽  
G Ferraccioli ◽  
A Carbone ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Human Herpesvirus ◽  
Mixed Cryoglobulinemia ◽  
Hcv Infection ◽  
Etiologic Factor ◽  
Type Ii ◽  
B Cell Malignancies

Hepatitis C virus (HCV) has been implicated as the major etiologic factor sustaining B-cell clonal expansion in type II mixed cryoglobulinemia (MC). A putative pathogenetic role of HCV in the development of MC-associated B-cell malignancies has also been speculated. We report for the first time the localization of HCV within a parotid non-Hodgkin's lymphoma (NHL) lesion in the course of HCV- related type II essential MC, an important step to implicate any infectious agent in the lymphomagenesis. Plus and minus strand HCV RNA was first demonstrated by polymerase chain reaction on the whole RNA from the lesion. Further immunohistochemical studies localized HCV c22 proteins in the residual ductal or acinar parotid structures, which also abnormally expressed HLA-DR antigens. Weak c22 signals were inconstantly detected in cells strictly confined around the residual epithelium, while all the remaining infiltrating cells in the parotid lesion stained c-22-negative. Staining for c33 and c100 HCV antigens was negative. In situ hybridization (ISH) studies again identified the residual parotid epithelial cells as the site of HCV infection and replication in the NHL lesion. Sialotropic viruses previously involved in lymphoproliferation, ie, Epstein-Barr virus and human herpesvirus-6, were absent in the same tissue lesion. According to the current models of B-cell lymphomagenesis, a role of HCV as an exogenous antigenic stimulus should be considered for NHL development in the present case, whereas malignant B cells do not appear permissive of active HCV replication. Further efforts would be worthwhile to clarify a role of HCV infection in the development of some B-cell malignancies.

scholarly journals Detection and distribution of hepatitis C virus-related proteins in lymph nodes of patients with type II mixed cryoglobulinemia and neoplastic or non-neoplastic lymphoproliferation

Blood ◽  
1996 ◽  
Vol 88 (12) ◽  
pp. 4638-4645 ◽  
Author(s):  
D Sansonno ◽  
S De Vita ◽  
V Cornacchiulo ◽  
A Carbone ◽  
M Boiocchi ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Mixed Cryoglobulinemia ◽  
Hcv Infection ◽  
Lymphoid Cells ◽  
Small Cells ◽  
Low Grade ◽  
Type Ii ◽  
Related Proteins

The role of hepatitis C virus (HCV) in the pathogenesis of type II mixed cryoglobulinemia (MC) has been strongly emphasized in the last few years. Although MC is a benign lymphoproliferative disorder, the risk of overt B-cell malignancy greatly increases during its course. The occurrence of HCV infection in 10% to 30% of patients with non-Hodgkin's lymphoma (NHL) suggests that this virus may have a role in the development of MC-associated B-cell malignancies. We identified 2 patients with hyperplastic reactive lymphadenopathy (HRL) and 12 with NHL in two series of MC patients chronically infected with HCV collected over a 5-year period. Structural and nonstructural HCV-related proteins were investigated in lymph node sections by immunohistochemistry and their location and distribution were correlated with clinical and histologic findings, viremic state, and HCV genotypes. In HRL, HCV proteins were found in the cytoplasm of lymphoid cells, mainly in interfollicular areas. However, occasional positive cells were found in the mantle zone and in the germinal centers of follicles. In addition, strong reactivity was found in the circulating mononuclear cells of capsular blood vessels. HCV immunodeposits were found in 3 of 12 (25%) NHL cases. Positive cells were frequently restricted to the cortex; if not, they were randomly diffused in the neoplastic tissue. Positivity was related to the low-grade type of NHL; in the 2 composite cases, HCV immunodetection was found in the small cells, whereas large anaplastic cells were regularly negative. Other viruses previously involved in lymphoproliferation, ie, human herpes virus-6 and Epstein-Barr virus, were absent in all tissues. These data emphasize that lymphoid organs may be a site of HCV infection. The demonstration of HCV-related proteins in a nonmalignant condition, namely HRL, indicates that HCV infection precedes the neoplastic transformation and possibly plays a major role in lymphomagenesis in MC.

scholarly journals Hepatitis C Virus Infection and Mixed Cryoglobulinemia

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Gianfranco Lauletta ◽  
Sabino Russi ◽  
Vincenza Conteduca ◽  
Loredana Sansonno
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Clonal Selection ◽  
Biological Activities ◽  
Clinical Manifestations ◽  
Mixed Cryoglobulinemia ◽  
Hcv Infection ◽  
Host Immune System ◽  
Inflammatory Infiltrates

Hepatitis C virus (HCV) chronic infection is recognized as the major cause of mixed cryoglobulinemia (MC). Its persistence represents a continuous stimulus for host immune system with production of circulating immune complexes (ICs), one-third of them with cryoprecipitate property. Several factors contribute to the biological activities of ICs, many of which are not completely known. Among them, complement factors play a crucial role in the cold-insoluble ICs-mediated vasculitis, involving primarily small blood vessels in different tissues including skin, kidney, peripheral, and central nervous system. Liver represents the major target of HCV infection with inflammatory infiltrates, resembling secondary lymphoid follicles. Cytokine like CXCL13 contribute to B-cell homing in intraportal lymphoid aggregates, in which B-cell clonal selection may arise. B-cell clonal expansion starts as an antigen-driven event and expands towards indolent and malignant B-cell proliferation. Occurrence of intrahepatic B-cell clonalities correlates with extrahepatic clinical manifestations of HCV infection. In this context, cryoglobulinemic patients should be considered a peculiar HCV-infected population that needs a clinical multidisciplinary approach and more articulated therapeutic measures.

Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4296-4301 ◽  
Author(s):  
F Silvestri ◽  
C Pipan ◽  
G Barillari ◽  
F Zaja ◽  
R Fanin ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Close Association ◽  
Mixed Cryoglobulinemia ◽  
Lymphoproliferative Disorders ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Hodgkin's Lymphomas ◽  
Hcv Genotyping

It has been recently hypothesized that the hepatitis C virus (HCV) might be involved in the pathogenesis of malignant B-cell non-Hodgkin's lymphomas (NHL). On the basis of this observation we sought to determine the prevalence of HCV infection in the patients affected by B- cell NHL and extended our analysis to all the patients affected by lymphoproliferation disorders seen at our institution in the last 30 months. Five hundred and thirty-seven unselected, consecutive patients were studied. HCV infection was investigated through detection of anti- HCV antibodies and HCV-RNA. HCV genotyping was performed on HCV-RNA positive specimens. The risk of being infected by HCV was compared with that of the general population of our area. Among all lymphoproliferative disorders, the prevalence and the relative risk (RR) of being infected by HCV were increased only among B-cell NHL (9%; RR 3.24; p < .0001). Among these, a strong prevalence of HCV was found only in the subgroup of immunocytomas (30%; RR 10.27; P < .0001), while other histotypes were associated with it only occasionally. Because HCV- positive lymphomas clinically behave as essential mixed cryoglobulinemia (EMC), the close association between HCV infection and EMC is confirmed, and evidence is provided that the pathological substrate of EMC corresponds to the immunocytoma. HCV genomic sequences were found in 84% of patients analyzed. Viral genotypes were those more frequent in our area.

Hepatitis C Virus Infection and B-Cell Non-Hodgkin’s Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4668-4668
Author(s):  
Janet G. Grudeva
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Hcv Infection ◽  
Control Group ◽  
Cell Infection ◽  
Serum Samples ◽  
Pathogenetic Role ◽  
Significant Difference

Backgroud: An increasing number of bacterial and viral infections have been linked with specific subtypes of lymphoma. Preliminary evidence suggests that hepatitis C virus (HCV) might play a pathogenetic role in autoimmune-related, non-malignant B-cell lymphoproliferation, as well as a subset of B-cell non-Hodgkin, s lymphomas (B-NHL), often with extranodal localization. Design and methods: The study was conducted in the Department of Hematology and consisted 149 (86 male, 63 female) untreated patients with a new diagnosis of B-NHL for 5-years period (2000–2004). HCV infection was investigated by testing for HCV antibodies in serum samples. The controls were 587 patients (without intravenous drug users) in other departments of the same hospital. Results: HCV infection was documented in 13 cases (8,4%) with NHL. The infected patients were not clinically relevant cryoglobulinemic activity, increased rate of autoimmune disorders and extranodal localizations prevalence. There was statistically significant difference between the NHL and control group (p<0,01) and no statistically significant difference between man/women carriers (p>0,05) into the NHL group. Overall, the clinical outcome of HCV-positive NHL does not seem to be different from that of NHL patients without HCV infection. However, the evidence of a significant liver injury may predict a worse prognosis in these cases. Conclusions: Our date suggest that HCV infection may be associated with B-NHL. With regard to the mechanism(s) by which HCV might favor B-cell expansion and malignant transformation, most date support an indirect pathogenetic role of the virus as an exogenous trigger. A direct oncogenetic role of HCV by direct cell infection and deregulation has only been hypothesized on the basis of the lymphotropism of the virus.

Role of Anti-Hepatitis C Virus (HCV) Treatment in HCV-Related, Low-Grade, B-Cell, Non-Hodgkin's Lymphoma: A Multicenter Italian Experience

2005 ◽  
Vol 23 (3) ◽  
pp. 468-473 ◽  
Author(s):  
Daniele Vallisa ◽  
Patrizia Bernuzzi ◽  
Luca Arcaini ◽  
Stefano Sacchi ◽  
Vittorio Callea ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Antiviral Treatment ◽  
Complete Response ◽  
Hcv Infection ◽  
Low Grade ◽  
Hcv Treatment ◽  
Hematologic Response

Purpose Hepatitis C virus (HCV) is endemic in some areas of Northwestern Europe and the United States. HCV has been shown to play a role in the development of both hepatocellular carcinoma and B-cell non-Hodgkin's lymphoma (B-NHL). The biologic mechanisms underlying the lymphomagenic activity of the virus so far are under investigation. In this study, the role of antiviral (anti-HCV) treatment in B-NHL associated with HCV infection is evaluated. Patients and Methods Thirteen patients with histologically proven low-grade B-NHL characterized by an indolent course (ie, doubling time no less than 1 year, no bulky disease) and carrying HCV infection were enrolled on the study. All patients underwent antiviral treatment alone with pegilated interferon and ribavirin. Response assessment took place at 6 and 12 months. Results Of the twelve assessable patients, seven (58%) achieved complete response and two (16%) partial hematologic response at 14.1 ± 9.7 months (range, 2 to 24 months, median follow-up, 14 months), while two had stable disease with only one patient experiencing progression of disease. Hematologic responses (complete and partial, 75%) were highly significantly associated to clearance or decrease in serum HCV viral load following treatment (P = .005). Virologic response was more likely to be seen in HCV genotype 2 (P = .035), while hematologic response did not correlate with the viral genotype. Treatment-related toxicity did not cause discontinuation of therapy in all but two patients, one of whom, however, achieved complete response. Conclusion This experience strongly provides a role for antiviral treatment in patients affected by HCV-related, low-grade, B-cell NHL.

scholarly journals Hepatitis C virus and non-Hodgkin’s lymphoma: biology, epidemiology and therapy

2011 ◽  
Author(s):  
Gabriele Pozzato ◽  
Francesca Zorat ◽  
Stefania Bonetto ◽  
Cesare Mazzaro
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Regional Differences ◽  
Mixed Cryoglobulinemia ◽  
Point Of View ◽  
Therapeutic Approaches ◽  
Biological Mechanisms ◽  
Hodgkin's Lymphomas

Although the association between the hepatitis C virus and B-cell non-Hodgkin’s lymphomas is still controversial, there is increasing evidence of the role of this virus in several B-cell lymphoproliferative disorders, whose prototype is mixed cryoglobulinemia. The aim of the present paper was to provide an overview of the biological mechanisms involved in the development of B-cell disorders in the course of chronic hepatitis C virus infection. The link between this virus and non-Hodgkin’s lymphomas is also considered from an epidemiological point of view, and the great regional differences in the prevalence of hepatitis C-associated lymphomas are discussed. Finally, the role of antiviral therapy and suggestions about the most appropriate, currently available, therapeutic approaches are also discussed.

scholarly journals Hepatitis C virus and non-Hodgkin’s lymphoma: biology, epidemiology and therapy

2011 ◽  
Vol 5 (4) ◽  
pp. 249 ◽  
Author(s):  
Gabriele Pozzato ◽  
Francesca Zorat ◽  
Stefania Bonetto ◽  
Cesare Mazzaro
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Regional Differences ◽  
Mixed Cryoglobulinemia ◽  
Point Of View ◽  
Therapeutic Approaches ◽  
Biological Mechanisms ◽  
Hodgkin's Lymphomas

Although the association between the hepatitis C virus and B-cell non-Hodgkin’s lymphomas is still controversial, there is increasing evidence of the role of this virus in several B-cell lymphoproliferative disorders, whose prototype is mixed cryoglobulinemia. The aim of the present paper was to provide an overview of the biological mechanisms involved in the development of B-cell disorders in the course of chronic hepatitis C virus infection. The link between this virus and non-Hodgkin’s lymphomas is also considered from an epidemiological point of view, and the great regional differences in the prevalence of hepatitis C-associated lymphomas are discussed. Finally, the role of antiviral therapy and suggestions about the most appropriate, currently available, therapeutic approaches are also discussed.

Regression of lymphoproliferative disorder after treatment for hepatitis C virus infection in a patient with partial trisomy 3, Bcl-2 overexpression, and type II cryoglobulinemia

Blood ◽  
2002 ◽  
Vol 99 (6) ◽  
pp. 2259-2261 ◽  
Author(s):  
Milvia Casato ◽  
Cristina Mecucci ◽  
Vincent Agnello ◽  
Massimo Fiorilli ◽  
Glenn B. Knight ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cells ◽  
B Cell ◽  
Partial Trisomy ◽  
Hcv Infection ◽  
Interferon Α ◽  
Cryoglobulinemic Vasculitis ◽  
Type Ii ◽  
Trisomy 3

Abstract A patient with type II cryoglobulinemic vasculitis and hepatitis C virus (HCV) infection presented with a leukemiclike proliferation of B cells bearing marginal zone B-cell phenotypic markers. A partial trisomy 3 (bands 3q11–29) and overexpression of Bcl-2 without t(14;18) translocation was detected in the monoclonal B cells that were classic rheumatoid factor–producing B cells bearing the WA cross-idiotype. Treatment with interferon-α produced a complete clinical remission and synchronous marked decreases in viremia and monoclonal B-cell prevalence. This is the first report of partial trisomy 3 and Bcl-2 overexpression in type II cryoglobulinemic vasculitis associated with HCV infection. Further studies of HCV-infected patients with and without type II cryoglobulinemia are required to determine the prevalence and possible physiologic and/or pathophysiologic significance of these findings.

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