Hepatitis C Virus and the Humoral Immune System

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:

1. 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.

2. 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.

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