Hepatitis C Virus and the Humoral Immune System

Study Overview
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Brief Summary
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The purpose of this study is to measure specific chemokines, antibodies, and antibody-producing B cells in the blood of patients with hepatitis C virus (HCV) infection. Our hypothesis is that changes in chemokine levels affect the development of an effective immune response against HCV.

Detailed Description
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The long-term goal of our research is to understand why immune complexes (ICs) are produced in patients infected with HCV, and whether these complexes affect virus interaction with target cells. We have found that many patients infected with HCV have an increased frequency of circulating B cells, but no evidence that the increased B cells are activated of proliferating. One possible mechanism for such an increase would be a change in levels of chemokines that influence B cell localization and trafficking. Our studies are aimed at testing the following hypotheses: One hypothesis is that HCV infection results in increased levels of specific cytokines and chemokines that may affect the motility and localization of immature and mature B cells. An alternative model is that HCV infection leads to chronic antigenic stimulation of B lymphocytes, and that the abnormalities of B cell function associated with HCV infection reflect this chronic antigenic stimulation. A second hypothesis is that autoantibodies and immune complexes present in HCV patient serum contribute to the persistence and spread of viral infection. To test these hypotheses, we are measuring levels of chemokines, the frequency of circulating B cells (mature resting B cells, mature activated B cells, memory B cells, and immature B cells), and the levels and components of ICs in the blood of HCV-infected patients. Controls include healthy volunteers and patients with chronic liver disease unrelated to HCV infection. No interventions in patient care are planned. When patients elect to undergo standard antiviral therapies under the supervision of their hepatologists, we will study the outcomes of therapy (no virologic response, partial or transient virologic response, sustained virologic response) to determine whether any of the observed alterations in chemokine levels, B cell frequency or activation, or immune complex levels correlate with the patient's response to antiviral therapy.

Official Title
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Hepatitis C Virus and the Humoral Immune System

Conditions
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Hepatitis C Virus

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers, no liver disease Chronic infection with hepatitis C virus Other chronic liver disease unrelated to hepatitis C virus Subjects in all groups must have sufficiently healthy veins to allow blood collection. Exclusion Criteria: Any medical condition that, in the opinion of the investigators, precludes the patient's participation
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HCV infection<br>current HCV infection, including intravenous drug users | |
| cryoglobulinemia<br>cryoglobulinemia and without HCV infection | |
| chronic liver disease<br>chronic liver disease not due to hepatitis C virus infection | |
| Sustained Virologic responders<br>successfully treated for HCV infection | |
| normal<br>normal, healthy volunteers | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define the relationships between HCV infection, B cell phenotype, and B cell function | Define the relationships between HCV infection, B cell phenotype, and B cell function | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis, Hepacivirus, B Lymphocytes, Chemokines, Antibodies