Observations on Cryoglobulin Testing: II. The Association of Oligoclonal Mixed Cryoglobulinemia with Cirrhosis in Patients Infected with Hepatitis C Virus: Table 1.

2009 ◽  
Vol 36 (9) ◽  
pp. 1956-1957 ◽  
Author(s):  
FRANCESCO G. DE ROSA ◽  
GYÖRGY ÁBEL ◽  
VINCENT AGNELLO

Objective.To determine whether a mixed cryoglobulin type correlated with cirrhosis in patients infected with hepatitis C virus (HCV).Methods.We investigated the results of mixed cryoglobulin tests performed in the clinical laboratory on patients with and without HCV infection.Results.A higher prevalence of oligoclonal cryoglobulins designated Type IIa was present in HCV-infected patients with cirrhosis than in those without cirrhosis.Conclusion.An association of Type IIa cryoglobulins with cirrhosis in HCV-infected patients has not previously been reported.

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Gianfranco Lauletta ◽  
Sabino Russi ◽  
Vincenza Conteduca ◽  
Loredana Sansonno

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.


Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4296-4301 ◽  
Author(s):  
F Silvestri ◽  
C Pipan ◽  
G Barillari ◽  
F Zaja ◽  
R Fanin ◽  
...  

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.


2021 ◽  
pp. 160-169
Author(s):  
S. P. Lukashyk ◽  
I. A. Karpov ◽  
O. V. Krasko

Objective: to analyze the characteristics of hepatitis C virus chronic infection with concurrent cryogobulinemia, to assess the prevalence of extrahepatic diseases in the population of Belarusian patients under study.Material and methods. An open, non-randomized observational study with the inclusion of patients with hepatitis C virus (HCV) chronic infection and cryoglobulinemia (CG) was conducted.Results. The study has determined the core characteristics of HCV infection in CG patients, incidence rates and a wide array of extrahepatic diseases (EHDs), as well as HCV infection distinctive features compared to those without extrahepatic diseases.Conclusion. The revealed variety of common EHDs in HCV infection indicates that many organs and systems are involved in the pathological process and this variety should be taken into account when considering prognosis and treatment tactics.


Blood ◽  
1995 ◽  
Vol 86 (5) ◽  
pp. 1887-1892 ◽  
Author(s):  
S De Vita ◽  
D Sansonno ◽  
R Dolcetti ◽  
G Ferraccioli ◽  
A Carbone ◽  
...  

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.


Blood ◽  
1996 ◽  
Vol 88 (12) ◽  
pp. 4638-4645 ◽  
Author(s):  
D Sansonno ◽  
S De Vita ◽  
V Cornacchiulo ◽  
A Carbone ◽  
M Boiocchi ◽  
...  

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.


Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3701-3704 ◽  
Author(s):  
C Ferri ◽  
M Monti ◽  
L La Civita ◽  
G Longombardo ◽  
F Greco ◽  
...  

A striking association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia (MC) has been shown; thus, HCV seems to play an important etiopathogenetic role in this lymphoproliferative disorder. Because HCV is both a hepatotropic and lymphotropic virus, this study aimed to investigate the prevalence of HCV infection of peripheral blood mononuclear cells (PBMCs) in a series of 16 patients with type II (IgMk) MC. Antibodies against HCV were detected by commercially available kits (Second Generation Chiron enzyme-linked immunosorbent assay [ELISA] and recombinant-based immunoblot assay [RIBA]), and the presence of HCV RNA was evaluated in both sera and isolated PBMCs using the polymerase chain reaction technique. A previous exposure to HCV was shown by ELISA and confirmed by RIBA in all cases (100%). Moreover, HCV RNA was present in the sera of 8 of 16 patients (50%), whereas its frequency markedly increased (13 of 16 [81%]) when genomic sequences were detected in peripheral lymphocytes. HCV RNA was never detected in the PBMCs of 20 control subjects. These findings showed that HCV infection, alone or in combination with other factors, may be responsible for the clonal B-cell expansion underlying the systemic manifestations of MC, and may explain the appearance of a malignant non- Hodgkin's lymphoma in some subjects.


2016 ◽  
Vol 88 (10) ◽  
pp. 105-113
Author(s):  
M L Zubkin ◽  
V I Chervinko ◽  
Yu V Ovchinnikov ◽  
E V Kryukov ◽  
O N Kotenko

Hepatitis C virus (HCV) infection results in not only chronic hepatitis and subsequent complications as liver cirrhosis and hepatocellular carcinoma, but also in a significant number of other diseases, the so-called extrahepatic manifestations of chronic HCV infection. This is because of viral hepatotropicity and lymphotropicity. The most striking example of the course of chronic HCV infection, in which the infectious and inflammatory processes are concurrent with autoimmune disorders and carcinogenesis, is mixed cryoglobulinemia and B-cell non-Hodgkin’s lymphoma. The pathogenesis of these diseases is based on the clonal expansion of B cells, which occurs under their prolonged stimulation with the virus or viral proteins. Part 1 of this review is devoted to the analysis of a correlation of chronic HCV infection with lymphoproliferative and autoimmune disorders, as well as its association with kidney injury.


Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3701-3704 ◽  
Author(s):  
C Ferri ◽  
M Monti ◽  
L La Civita ◽  
G Longombardo ◽  
F Greco ◽  
...  

Abstract A striking association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia (MC) has been shown; thus, HCV seems to play an important etiopathogenetic role in this lymphoproliferative disorder. Because HCV is both a hepatotropic and lymphotropic virus, this study aimed to investigate the prevalence of HCV infection of peripheral blood mononuclear cells (PBMCs) in a series of 16 patients with type II (IgMk) MC. Antibodies against HCV were detected by commercially available kits (Second Generation Chiron enzyme-linked immunosorbent assay [ELISA] and recombinant-based immunoblot assay [RIBA]), and the presence of HCV RNA was evaluated in both sera and isolated PBMCs using the polymerase chain reaction technique. A previous exposure to HCV was shown by ELISA and confirmed by RIBA in all cases (100%). Moreover, HCV RNA was present in the sera of 8 of 16 patients (50%), whereas its frequency markedly increased (13 of 16 [81%]) when genomic sequences were detected in peripheral lymphocytes. HCV RNA was never detected in the PBMCs of 20 control subjects. These findings showed that HCV infection, alone or in combination with other factors, may be responsible for the clonal B-cell expansion underlying the systemic manifestations of MC, and may explain the appearance of a malignant non- Hodgkin's lymphoma in some subjects.


2017 ◽  
Vol 26 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranţa Iacob ◽  
Roxana Şirli ◽  
Anca Trifan ◽  
...  

Background & Aims: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention has been created. These items were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the first of the two parts of our Society’s recommendations for chronic HCV infection treatment. An agreement was reached regarding the diagnostic tools, the assessment of severity and the up-dated therapy schedules.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to the real-life conditions in this country.Abbreviations: DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESLD: End-stage liver disease; ESRD: End-stage renal disease; eGFR: Estimated glomerular filtration rate; EASL: European Association for the Study of the Liver; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: Fixed-dose combination; GT: Genotype; GRADE: Grading of Recommendations Assessment, Development and Evaluation; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; LLD: Lower limit of detection; MELD score: Mayo-Clinic End-Stage Liver Disease score; ANMDM: National Agency of Medicines and Medical Devices; PPIs: Proton pump inhibitors; PWID: People who inject drugs; RCT: Randomized controlled trial; RDT: Rapid diagnostic test; RAS: Resistance-associated substitution; SRGH: Romanian Society of Gastroenterology and Hepatology; SAE: serious adverse events; SPC: Summary of Product Characteristics; SVR: Sustained virologic response.


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