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Genetics of Hepatitis C Virus Infection

Primary Purpose

Hepatitis C, Liver Disease

Status
Completed
Phase
Locations
United States
Study Type
Observational
Intervention
Sponsored by
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an observational trial for Hepatitis C focused on measuring Cytokines, Treatment, Genetic Polymorphism, Chronic Hepatitis C, Mononuclear Cells

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
May 6, 2000
Last Updated
June 30, 2017
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT00005657
Brief Title
Genetics of Hepatitis C Virus Infection
Official Title
Immunogenetics of Hepatitis C Virus Infection
Study Type
Observational

2. Study Status

Record Verification Date
April 19, 2011
Overall Recruitment Status
Completed
Study Start Date
May 4, 2000 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
April 19, 2011 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Liver Disease
Keywords
Cytokines, Treatment, Genetic Polymorphism, Chronic Hepatitis C, Mononuclear Cells

7. Study Design

Enrollment
870 (Actual)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
2300741
Citation
Todd JR, West BC, McDonald JC. Human leukocyte antigen and leprosy: study in northern Louisiana and review. Rev Infect Dis. 1990 Jan-Feb;12(1):63-74. doi: 10.1093/clinids/12.1.63.
Results Reference
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PubMed Identifier
1865923
Citation
Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Twumasi P, Rowe PA, Bennett S, Brewster D, McMichael AJ, Greenwood BM. Common west African HLA antigens are associated with protection from severe malaria. Nature. 1991 Aug 15;352(6336):595-600. doi: 10.1038/352595a0.
Results Reference
background
PubMed Identifier
9597143
Citation
Hill AV. The immunogenetics of human infectious diseases. Annu Rev Immunol. 1998;16:593-617. doi: 10.1146/annurev.immunol.16.1.593.
Results Reference
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Genetics of Hepatitis C Virus Infection

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