Genetics of Hepatitis C Virus Infection

The diverse clinical syndromes associated with hepatitis C underscore the multifactorial and
polygenic nature of HCV infection. Both viral and host factors likely contribute to
variations in infection outcome, disease susceptibility and progression, and treatment
response. This protocol will focus on the immunogenetics of HCV infection. Various candidate
genes, most of them related to host immune response in microbial infection, have defined
genetic polymorphisms that have been associated with variable manifestations of infections
including malaria, tuberculosis, leprosy, AIDS and hepatitis B. In this proposal, we plan to
collect peripheral blood mononuclear cells as a source of DNA from approximately 1500
patients with HCV infection, analyze genetic polymorphisms of various candidate genes in
association with viral clearance, disease progression or treatment response, and
characterize the functional consequences of these polymorphisms in patients with
well-defined clinical sequelae of HCV infection. We will also collect blood from patients
with other forms of liver diseases (approximately 300) or normal volunteers (approximately
200) as controls. By identifying relevant host factors genetically and investigating their
molecular interactions with HCV, we may gain additional insights into HCV pathogenesis and
uncover new potential targets for vaccine development and treatment intervention.

- INCLUSION CRITERIA:

Patients who have recovered from past HCV exposure (positive anti-HCV but negative HCV
viremia and absent liver disease).

Patients with asymptomatic HCV infection (positive anti-HCV and HCV viremia, but
persistently normal or minimally elevated ALT and normal or mild disease on liver biopsy).

Patients with active liver disease (positive anti-HCV and HCV viremia, persistently
elevated ALT and/or moderate disease on liver biopsy).

Patients with active extrahepatic manifestations of HCV infection (cryoglobulinemia,
glomerulonephritis, vasculitis, etc.).

Patients with rapidly progressive, severe liver disease and/or hepatocellular carcinoma.

Patients who have undergone or are undergoing treatment.

Patients from a single-source outbreak of HCV infections (in which the viral factors
should be identical and the patients are often from a homogeneous population with less
genetic variability).

HCV infected family members and twins.

Patients with other forms of liver disease including HBV infection, primary biliary
cirrhosis, autoimmune hepatitis, nonalcoholic steatohepatitis, hemochromatosis, and
Wilson's Disease, as well as normal volunteers.

EXCLUSION CRITERIA:

Adult subjects with a Hct of less than 30 or pediatric subjects less than 25 will be
excluded.

Children with HCV infection younger than 2 years of age will be excluded.

Unaffected healthy volunteers who are minors are not eligible for this study.