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.

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 High Anti-HCV Seroprevalence and Low Performance of ICT Strip in Diagnosing Hepatitis C Virus Infection in Children in Enugu Metropolis

2018 ◽  
Vol 12 (1) ◽  
pp. 149-156
Author(s):  
Maryann C. Ezeilo ◽  
Godwill A. Engwa ◽  
Romanus I. Iroha ◽  
Damian N. Odimegwu
Keyword(s):  
Risk Factors ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Test Performance ◽  
Clinical Manifestations ◽  
Signs And Symptoms ◽  
Cross Sectional Study ◽  
Hcv Infection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cross Sectional

Background:The lack of a vaccine for Hepatitis C virus (HCV) places children at a high risk of contracting the infection. It becomes necessary to accurately diagnose this infection for proper treatment as well as identifying potential risk factors for effective management.Aim:This study was conceived to assess the test performance of the commonly used Immunochromatographic test (ICT) strip and identify the associated clinical manifestations and risk factors of HCV in children in Enugu Metropolis.Method:A cross-sectional study involving randomly selected 270 children below six years of age was conducted in Enugu Nigeria. The subjects were screened for anti-HCV by ICT and Enzyme-Linked Immunosorbent Assay (ELISA) and the demographic, signs and symptoms and risk factors were collected.Results:A total of 50 out of 270 children were positive for anti-HCV with a seropositivity of 18.5%. ICT strip had a very low sensitivity of 38.00% with an accuracy of 88.52% in detecting anti-HCV. The presence of dark urine was associated (p= 0.01) with HCV infection.Conclusion:A seroprevalence of 18.5% of Anti-HCV was found in children below six years old in Enugu metropolis and the performance of ICT in diagnosing HCV infection was poor compared to ELISA.

B-cell frequency in hepatitis C virus-related mixed cryoglobulinemia

Hepatology ◽  
2013 ◽  
Vol 58 (1) ◽  
pp. 448-448 ◽  
Author(s):  
Domenico Sansonno ◽  
Sabino Russi ◽  
Vincenza Conteduca ◽  
Loredana Sansonno
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Mixed Cryoglobulinemia ◽  
Cell Frequency

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.

Clinical Features and Outcome of 147 Patients with Diffuse Large B-Cell Lymphoma and Hepatitis C Virus Infection.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1921-1921
Author(s):  
Carlo Visco ◽  
Luca Arcaini ◽  
Michele Merli ◽  
Annalisa Andreoli ◽  
Sara Burcheri ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Hcv Infection ◽  
Low Grade ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Hepatitis C virus (HCV) has been implicated in the pathogenesis of a subset of low-grade non-Hodgkin lymphomas. Furthermore, diffuse large B-cell lymphoma (DLBCL) has been correlated to HCV infection in several series from our geographical area (north-east of Italy), but little is known about the characteristics of such high-grade tumors. We analyzed presentation features of 147 previously untreated HCV-positive patients with DLBCL who presented to the three participating centers between 1993 and 2004. All patients were provided with complete clinical information, were HIV negative, and had been tested at tumor onset for HCV antibodies by ELISA and RIBA. Median age at presentation was 64 years old (range 29–88), 47% were males, ECOG performance status was >1 in 20%, Ann Arbor stage was I in 20%, II in 27%, III in 26%, IV in 27%, and B-symptoms were present in 37% of patients. The International Prognostic Index (IPI) value at diagnosis was low in 18%, int/low in 23%, int/high in 32%, and high in 27% of patients. Surprisingly, DLBCL transformed from a low-grade histology represented only 7% of the whole population, while primary mediastinal DLBCL were extremely rare (1/147, <1%). Patients frequently presented as primary extranodal DLBCL (65/147, 44%). Most involved extranodal sites were skin, liver, stomach, and spleen, with the latter being the most represented syte (33% of patients). Remarkably, spleen was the only extranodal involved organ in 20% of patients. Treatment was delivered with cure-intent, and consisted of CHOP-like regimens +/− Rituximab for the large majority of patients, except for 16 (11%) patients with cirrhosis or severe hepatic dysfunction, who received mono-chemotherapy or radiotherapy. Only three (2%) HCV-positive patients had to discontinue chemotherapy due to liver function impairment. The addition of Rituximab to chemotherapy did not seem to affect patients’ tolerance to treatment. With a median follow-up of 48 months for survivors, 5-year overall survival (OS) was 75%, while 5-year failure-free survival (FFS) was 51%. In particular, the 65 patients with primary extranodal DLBCL shared a better 5-year OS (83% vs 71%, p=0.01) and FFS (75% vs 39%, p=0.009) than their nodal counterpart. Nodal origin of the tumor resulted the strongest independent adverse factor both in terms of OS and FFS in multivariate analysis. The peculiar clinical behavior shared by HCV-positive DLBCL may disclose relevant biological features of these tumors, and may be relevant for future studies aiming to clarify the link between HCV infection and aggressive lymphoproliferative disorders.

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.

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.

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