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.

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.

scholarly journals Occult hepatitis C virus infection in patients with malignant lymphoproliferative disorders

2020 ◽  
Vol 34 ◽  
pp. 205873842096120
Author(s):  
Abeya A Lotfi ◽  
Asmaa E Mohamed ◽  
Nahela A Shalaby ◽  
Deena S Eissa ◽  
Ehab El-Dabaa ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Treatment Protocol ◽  
Lymphoproliferative Disorders ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Hepatitis C Virus Infection ◽  
Occult Hepatitis ◽  
Occult Hepatitis C

Despite the link between HCV and malignant lymphoproliferative disorders has been established, the association between occult hepatitis C virus infection and malignant lymphoproliferative disorders remains obscure. The present study intended to identify the possible association between occult HCV infection and malignant lymphoproliferative disorders. Newly diagnosed patients with LPDs were screened for the presence of HCV-RNA in both plasma and PBMCs. PBMCs of the subjects were also, examined by transmission and immuno-electron microscopy. LPD patients showed a high percentage of HCV infection (71.9%): OCI-HCV (37.5%) and HCV (34.38%). Meanwhile, 28.13% of LPD patients did not show any evidence of HCV infection. Ultrastructural examination of PBMCs revealed the presence of intracytoplasmic vacuoles enclosing viral like particles, which were less prominent in occult HCV patients. The possibility of occult HCV should be considered in patients with LPDs which can be helpful in the management of the treatment protocol in order to set up a balance between the control of the tumor progression and minimizing post chemotherapy complications related to HCV infection.

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 Characterization of Overt B-Cell Lymphomas in Patients With Hepatitis C Virus Infection

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 776-782 ◽  
Author(s):  
Salvatore De Vita ◽  
Cosimo Sacco ◽  
Domenico Sansonno ◽  
Annunziata Gloghini ◽  
Franco Dammacco ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Hcv Infection ◽  
Low Grade ◽  
B Cell Malignancy ◽  
Hodgkin's Lymphomas ◽  
Cell Malignancy

Abstract A pathogenetic role of the hepatitis C virus (HCV) has been hypothesized for a subset of B-cell non-Hodgkin's lymphomas (NHLs). However, the preliminary characterization of B-cell NHLs in HCV-infected individuals has been poorly addressed. In the present study, we report detailed information on 35 consecutive patients with overt B-cell NHL of recent onset and HCV infection; all patients referred to a single oncological center in Northeast Italy. Histopathologic evaluation was performed by a single reference hemopathologist, and the link with the two relevant autoimmune diseases predisposing to B-cell NHL and in which HCV has been implied, ie, “essential” mixed cryoglobulinemia (EMC) and Sjögren's syndrome, was investigated. Control groups included 122 consecutive HCV-negative patients with B-cell NHL and 464 consecutive histopathologic cases of B-cell NHL referred to the same center, as well as 127 consecutive patients with HCV infection and without lymphoma referred to a different center in the same geographical area. B-cell NHLs in HCV-infected patients frequently presented at onset (1) an extranodal localization with peculiar target organs of HCV infection (ie, the liver and major salivary glands) being significantly overrepresented; (2) a diffuse large cell histotype without any prior history of low-grade B-cell malignancy or bone marrow involvement; and (3) a weak association with a full-blown predisposing autoimmune disease, although serum autoimmune features were common and cryoglobulins were always present. Therefore, the HCV-related B-cell NHLs in this oncological series presented distinctive features compared with B-cell NHLs in HCV-negative patients, and they differed from bone marrow low-grade NHLs frequently diagnosed in HCV-positive patients with EMC. Such novel information may be relevant for future research aimed at clarifying the possible link between HCV infection, autoimmunity, nonmalignant B-cell lymphoproliferation, and overt B-cell malignancy.

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 Molecular Assay and Genotyping of Hepatitis C Virus among Infected Egyptian and Saudi Arabian Patients

2015 ◽  
Vol 6 ◽  
pp. VRT.S32016 ◽  
Author(s):  
Mohamed M.S. Farag ◽  
Ahmed R. Sofy ◽  
Adel A. Mousa ◽  
Mohamed A. Ahmed ◽  
Mohamed R. Alganzory
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Saudi Arabian ◽  
Molecular Techniques ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Rt Pcr ◽  
Chronic Patients ◽  
Genotype 2 ◽  
Hcv Genotyping

Hepatitis C virus (HCV) infection is a major health problem recognized globally. HCV is a common cause of liver fibrosis that may lead to liver cirrhosis or hepatocellular carcinoma. The aim of this study was to estimate the prevalence of HCV infection and genotyping among Egyptian and Saudi Arabian chronic patients using different molecular techniques. HCV RNA viral load was assessed by real-time polymerase chain reaction (RT-PCR) technology. For HCV genotyping, RT-PCR hybridization fluorescence-based method and reverse hybridization line probe assay (INNO-LiPA) were used. A total of 40 anti-HCV-positive patients with chronic hepatitis C were examined for HCV RNA, genotyping, and different laboratory investigations. In the present study, HCV genotypes 4, mixed 4.1b, and 1 were detected in patients of both countries, while genotype 2 was only detected in Saudi Arabian patients. Genotyping methods for HCV showed no difference in the classification at the genotype level. With regard to HCV subtypes, INNO-LiPA assay was a reliable test in HCV genotyping for the detection of major genotypes and subtypes, while RT-PCR-based assay was a good test at the genotype level only. HCV genotype 4 was found to be the predominant genotype among Egyptian and Saudi Arabian chronic patients. In conclusion, data analysis for detecting and genotyping HCV was an important factor for understanding the epidemiology and treatment strategies of HCV among Egyptian and Saudi Arabian chronic patients.

The B-cell receptor of a hepatitis C virus (HCV)–associated non-Hodgkin lymphoma binds the viral E2 envelope protein, implicating HCV in lymphomagenesis

Blood ◽  
2001 ◽  
Vol 98 (13) ◽  
pp. 3745-3749 ◽  
Author(s):  
Elizabeth R. Quinn ◽  
Chunghuang Hubert Chan ◽  
Kenneth G. Hadlock ◽  
Steven K. H. Foung ◽  
Mike Flint ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Cell Receptor ◽  
Lymphoproliferative Disorders ◽  
Hcv Infection ◽  
Test Cases ◽  
E2 Protein ◽  
Non Hodgkin Lymphoma ◽  
Bona Fide

Abstract Hepatitis C virus (HCV) infection is associated with extrahepatic B-cell lymphoproliferative disorders. To determine whether a viral antigen drives this B-cell expansion, the B-cell receptors were cloned from HCV-associated lymphomas and were expressed as soluble immunoglobulins. The rescued immunoglobulins were then tested for their ability to bind the HCV-E2 envelope glycoprotein, an antigen that was previously implicated in the pathogenesis of HCV-associated B-cell diseases. One of 2 lymphoma immunoglobulin test cases bound the E2 protein in a manner identical to a bona fide human anti-E2 antibody. Moreover, it bound E2 from multiple viral genotypes, suggesting reactivity with a conserved E2 epitope. These findings support the hypothesis that some HCV-associated lymphomas originate from B cells that were initially activated by the HCV-E2 protein and might explain the association between HCV infection and some B-cell lymphoproliferative disorders.

scholarly journals Characterization of Overt B-Cell Lymphomas in Patients With Hepatitis C Virus Infection

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 776-782 ◽  
Author(s):  
Salvatore De Vita ◽  
Cosimo Sacco ◽  
Domenico Sansonno ◽  
Annunziata Gloghini ◽  
Franco Dammacco ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Hcv Infection ◽  
Low Grade ◽  
B Cell Malignancy ◽  
Hodgkin's Lymphomas ◽  
Cell Malignancy

A pathogenetic role of the hepatitis C virus (HCV) has been hypothesized for a subset of B-cell non-Hodgkin's lymphomas (NHLs). However, the preliminary characterization of B-cell NHLs in HCV-infected individuals has been poorly addressed. In the present study, we report detailed information on 35 consecutive patients with overt B-cell NHL of recent onset and HCV infection; all patients referred to a single oncological center in Northeast Italy. Histopathologic evaluation was performed by a single reference hemopathologist, and the link with the two relevant autoimmune diseases predisposing to B-cell NHL and in which HCV has been implied, ie, “essential” mixed cryoglobulinemia (EMC) and Sjögren's syndrome, was investigated. Control groups included 122 consecutive HCV-negative patients with B-cell NHL and 464 consecutive histopathologic cases of B-cell NHL referred to the same center, as well as 127 consecutive patients with HCV infection and without lymphoma referred to a different center in the same geographical area. B-cell NHLs in HCV-infected patients frequently presented at onset (1) an extranodal localization with peculiar target organs of HCV infection (ie, the liver and major salivary glands) being significantly overrepresented; (2) a diffuse large cell histotype without any prior history of low-grade B-cell malignancy or bone marrow involvement; and (3) a weak association with a full-blown predisposing autoimmune disease, although serum autoimmune features were common and cryoglobulins were always present. Therefore, the HCV-related B-cell NHLs in this oncological series presented distinctive features compared with B-cell NHLs in HCV-negative patients, and they differed from bone marrow low-grade NHLs frequently diagnosed in HCV-positive patients with EMC. Such novel information may be relevant for future research aimed at clarifying the possible link between HCV infection, autoimmunity, nonmalignant B-cell lymphoproliferation, and overt B-cell malignancy.

scholarly journals Pathogenetic Mechanisms of Hepatitis C Virus-Induced B-Cell Lymphomagenesis

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Fabio Forghieri ◽  
Mario Luppi ◽  
Patrizia Barozzi ◽  
Rossana Maffei ◽  
Leonardo Potenza ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Epidemiological Studies ◽  
Hcv Infection ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Hodgkin's Lymphomas ◽  
Affinity Interaction ◽  
Global Population

Hepatitis C virus (HCV) infection is probably the most common chronic viral infection and affects an estimated 180 million people worldwide, accounting for 3% of the global population. Although the liver is considered to be the primary target, extrahepatic manifestations are well recognized among patients with chronic HCV infection. Epidemiological studies have clearly demonstrated a correlation between chronic HCV infection and occurrence of B-cell non-Hodgkin's lymphomas (B-NHL). The clinical evidence that antiviral therapy has a significant role in the treatment at least of some HCV-associated lymphoproliferative disorders, especially indolent B-NHL, further supports the existence of an etiopathogenetic link. However, the mechanisms exploited by HCV to induce B-cell lymphoproliferation have so far not completely clarified. It is conceivable that different biological mechanisms, namely, chronic antigen stimulation, high-affinity interaction between HCV-E2 protein and its cellular receptors, direct HCV infection of B-cells, and “hit and run” transforming events, may be combined themselves and cooperate in a multifactorial model of HCV-associated lymphomagenesis.

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.

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