scholarly journals Hepatitis C Virus-Related Lymphomagenesis in a Mouse Model

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Kyoko Tsukiyama-Kohara ◽  
Satoshi Sekiguchi ◽  
Yuri Kasama ◽  
Nagla Elwy Salem ◽  
Keigo Machida ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Mouse Model ◽  
B Cell ◽  
Lymphoproliferative Disorder ◽  
Interleukin 2 ◽  
Elevated Serum ◽  
Hcv Infection ◽  
Α Subunit ◽  
Non Hodgkin Lymphoma

B cell non-Hodgkin lymphoma is a typical extrahepatic manifestation frequently associated with hepatitis C virus (HCV) infection. The mechanism by which HCV infection leads to lymphoproliferative disorder remains unclear. Our group established HCV transgenic mice that expressed the full HCV genome in B cells (RzCD19Cre mice). We observed a 25.0% incidence of diffuse large B cell non-Hodgkin lymphomas (22.2% in male and 29.6% in female mice) within 600 days of birth. Interestingly, RzCD19Cre mice with substantially elevated serum-soluble interleukin-2 receptor α-subunit (sIL-2Rα) levels (>1000 pg/mL) developed B cell lymphomas. Another mouse model of lymphoproliferative disorder was established by persistent expression of HCV structural proteins through disruption of interferon regulatory factor-1 (irf-1_/_/CN2 mice). Irf-1_/_/CN2 mice showed extremely high incidences of lymphomas and lymphoproliferative disorders. Moreover, these mice showed increased levels of interleukin (IL)-2, IL-10, and Bcl-2 as well as increased Bcl-2 expression, which promoted oncogenic transformation of lymphocytes.

scholarly journals Persistent expression of the full genome of hepatitis C virus in B cells induces spontaneous development of B-cell lymphomas in vivo

Blood ◽  
2010 ◽  
Vol 116 (23) ◽  
pp. 4926-4933 ◽  
Author(s):  
Yuri Kasama ◽  
Satoshi Sekiguchi ◽  
Makoto Saito ◽  
Kousuke Tanaka ◽  
Masaaki Satoh ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hcv Infection ◽  
Mouse Serum ◽  
B Cell Lymphomas ◽  
Α Subunit

AbstractExtrahepatic manifestations of hepatitis C virus (HCV) infection occur in 40%-70% of HCV-infected patients. B-cell non-Hodgkin lymphoma is a typical extrahepatic manifestation frequently associated with HCV infection. The mechanism by which HCV infection of B cells leads to lymphoma remains unclear. Here we established HCV transgenic mice that express the full HCV genome in B cells (RzCD19Cre mice) and observed a 25.0% incidence of diffuse large B-cell non-Hodgkin lymphomas (22.2% in males and 29.6% in females) within 600 days after birth. Expression levels of aspartate aminotransferase and alanine aminotransferase, as well as 32 different cytokines, chemokines and growth factors, were examined. The incidence of B-cell lymphoma was significantly correlated with only the level of soluble interleukin-2 receptor α subunit (sIL-2Rα) in RzCD19Cre mouse serum. All RzCD19Cre mice with substantially elevated serum sIL-2Rα levels (> 1000 pg/mL) developed B-cell lymphomas. Moreover, compared with tissues from control animals, the B-cell lymphoma tissues of RzCD19Cre mice expressed significantly higher levels of IL-2Rα. We show that the expression of HCV in B cells promotes non-Hodgkin–type diffuse B-cell lymphoma, and therefore, the RzCD19Cre mouse is a powerful model to study the mechanisms related to the development of HCV-associated B-cell lymphoma.

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 High prevalence of Hepatitis C Virus associated B-cell lymphoma in Mansoura Region (Egypt), ANRS 12263 study

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Layla M. Saleh ◽  
Danielle Canioni ◽  
Sameh Shamaa ◽  
Maha El-Zaafarany ◽  
Ziad Emarah ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Antiviral Treatment ◽  
B Cell Lymphoma ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Delta Region ◽  
Genotype 4 ◽  
Non Hodgkin Lymphoma

Abstract : Background: The prevalence of Hepatitis C virus in Egypt reaches 15%, which is considered the highest in the world. Genotype 4 represents 93 % of Egyptian HCV infections. Non-Hodgkin lymphoma (NHL) is the 5th most common cancer in Egypt. The association between HCV infection and occurrence of B-cell NHL is well known while data are scarce in Eastern countries. Objectives: We aimed to evaluate the prevalence of HCV infection among patients with B-cell NHL and the clinical characteristics of HCV associated B-cell NHL in Delta region (Mansoura-Egypt). Methods: Between March 2012 and March 2013, 110 adult patients newly diagnosed with B-cell NHL were enrolled in the current study. This study was carried out at Oncology Center, Mansoura University. Study subjects provided serum for HCV testing and for HCV RNA. Results: The prevalence of HCV infection among these patients was 61% (67/110 patients) which is the highest reported value in literature. Among them, 80% (32/40 tested patients) presented with viremia. Contrasting with the histological distribution previously described in Northern regions, the majority of HCV associated lymphomas were DLBCLs (72 %) followed by SLL/CLL (13 %), follicular lymphomas (7.5%) and 7.5% of marginal zone lymphomas. In conclusion:  B-cell lymphomas are highly associated with HCV infection in Egypt. Further developments are needed to give access to antiviral treatment for those patients in Delta region. 

Oncogenic transcriptomic profile is sustained in the liver after the eradication of the hepatitis C virus

2021 ◽  
Author(s):  
Haruhiko Takeda ◽  
Atsushi Takai ◽  
Eriko Iguchi ◽  
Masako Mishima ◽  
Soichi Arasawa ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Molecular Basis ◽  
Elevated Serum ◽  
Gene Clusters ◽  
Viral Clearance ◽  
Hcv Infection ◽  
Transcriptomic Profile ◽  
Direct Acting ◽  
Liver Tissues

Abstract Hepatocellular carcinoma (HCC) developing after hepatitis C virus (HCV) eradication is a serious clinical concern. However, molecular basis for the hepatocarcinogenesis after sustained virologic response (SVR) remains unclear. In this study, we aimed to unveil the transcriptomic profile of post-SVR liver tissues and explore the molecules associated with post-SVR carcinogenesis. We analysed 90 RNA-sequencing datasets, consisting of noncancerous liver tissues including 20 post-SVR, 40 HCV-positive and 7 normal livers, along with Huh7 cell line specimens before and after HCV infection and eradication. Comparative analysis demonstrated that cell cycle- and mitochondrial function-associated pathways were altered only in HCV-positive noncancerous liver tissues, while some cancer-related pathways were upregulated in the noncancerous liver tissues of both post-SVR and HCV-positive cases. The persistent upregulation of carcinogenesis-associated gene clusters after viral clearance was reconfirmed through in vitro experiments, of which, CYR61, associated with liver fibrosis and carcinogenesis in several cancer types, was the top enriched gene and co-expressed with cell proliferation-associated gene modules. To evaluate whether this molecule could be a predictor of hepatocarcinogenesis after cure of HCV infection, we also examined 127 sera from independent HCV-positive cohorts treated with direct-acting antivirals, including 60 post-SVR-HCC patients, and found that the elevated serum Cyr61 was significantly associated with early carcinogenesis after receiving direct-acting antiviral therapy. In conclusion, some oncogenic transcriptomic profiles are sustained in liver tissues after HCV eradication, which might be a molecular basis for the liver cancer development even after viral clearance. Among them, upregulated CYR61 could be a possible biomarker for post-SVR HCC.

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 and B-cell non-Hodgkin lymphomas: an Italian multicenter case-control study

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 996-999 ◽  
Author(s):  
Alfonso Mele ◽  
Alessandro Pulsoni ◽  
Elvira Bianco ◽  
Pellegrino Musto ◽  
Andrè Szklo ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Case Control Study ◽  
Antiviral Treatment ◽  
Case Series ◽  
Positive Association ◽  
Case Control ◽  
Hcv Infection ◽  
Control Study

Abstract The existence of an association between infection with hepatitis C virus (HCV) and B-cell non-Hodgkin lymphoma (B-NHL) remains controversial, largely because previous studies were based on prevalent case series or comparisons with less than optimal control groups. This hospital-based case-control study was conducted from January 1998 through February 2001 to evaluate the association between HCV infection and B-NHL of different types. Cases were consecutive patients with a new diagnosis of B-NHL; controls were patients from other departments of the same hospitals. Both groups were interviewed using a standardized questionnaire. The prevalence of HCV infection was calculated by histologic type of B-NHL and clinical behavior (indolent or aggressive). Adjusted odds ratio (OR) and HCV-attributable risk (AR) were estimated. HCV prevalence was 17.5% among the 400 lymphoma patients and 5.6% among the 396 controls. The OR of B-NHL (patients vs controls), adjusted by age, sex, level of education, and place of birth, was 3.1 (95% confidence interval [CI], 1.8-5.2); an OR indicative of positive association was found for indolent and aggressive B-NHL. The estimated AR was 4.6%. This study confirms an association between HCV and B-NHL. In Italy, 1 of 20 instances of B-NHL may be attributable to HCV infection and may, thus, benefit from antiviral treatment.

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