Genetics of Hepatitis C Virus Infection
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.
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.