Trial record 15 of 3237 for:    "Hepatitis, Viral, Human"

Hepatitis C in Clinically Discordant Hemophilic Siblings

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00007371
Recruitment Status : Completed
First Posted : November 28, 2000
Last Update Posted : September 26, 2016
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Brief Summary:
To define the natural history, immunologic, and genetic factors that influence the clinical outcome of hepatitis C in a cohort of hemophilic siblings.

Condition or disease
Blood Disease Hemophilia A Hepatitis, Viral, Human

Detailed Description:


The clinical spectrum of hepatitis C is variable and the factors responsible for these divergent outcomes with chronic hepatitis C infection remain unknown. Dr. Fried and his colleagues are studying a cohort of hemophilic siblings infected with hepatitis C to define the natural history, immunologic, and genetic factors that influence its clinical outcome. Patients with hemophilia have a prevalence rate of hepatitis C as high as 90 percent. The sex-linked pattern of inheritance of hemophilia allows them to identify a cohort of siblings both of who have been infected with hepatitis C. Hemophilic siblings are an attractive population to study because: 1) They are all males; 2) Siblings are relatively close in age; 3) The mode of HCV acquisition is identical; 4) The age at acquisition of hepatitis C is similar 5) The date of acquisition can be confidently estimated upon their factor replacement history; 6) Hemophilic sibs share significant amounts of genetic material.

The study is in response to a Request for Applications entitled "Hepatitis C: Natural History, Pathogenesis, Therapy and Prevention" issued by the National Institute of Diabetes and Digestive and Kidney Diseases


Hemophilic siblings with hepatitis C undergo a detailed clinical evaluation to stage their liver disease and to identify sibling pairs with clinically and/or histologically discordant levels of disease activity. These siblings pairs are further studied to define antigen recognition patterns of lymphocyte cells including peripheral CD8 plus cytotoxic T lymphocytes (CTL) and CD4 plus cells and determine their functional significance. Using peripheral blood mononuclear cells, CD8 plus cells are assayed for CTL activity against three overlapping vaccinia/hepatitis C virus (HCV) constructs covering the entire HCV genome followed by fine cloning to identify HCV-specific CTL epitopes. Peripheral CD4 plus cells are tested for their ability to proliferate to HCV antigens. Using stimulation index, Drs. Fried and colleagues are quantitating the presence and magnitude of this response. They are also trying to identify immunodominant regions targeted by cytotoxic T cells using HLA class I matched hemophilic siblings. Finally, they are identifying specific host genes that are preferentially expressed or repressed in patients with delayed progression of their HCV disease. They are quantitating the expression of mRNAs encoding host antiviral defense and immunoregulatory elements in peripheral blood mononuclear cells (PBMCs) and liver tissue from sibling pairs that have discordant chronic hepatitis C using mRNA libraries that are screened by high density oligonucleotide arrays. The expression levels of these genes (including, but not limited to, interferon alpha, beta, and gamma; IRF-1 and IRF-2; interferon induced protein kinase; the cellular protein activator of PKR (PACT) RNase L; interferon-inducible RNA-specific adenosine deaminase; a ribonuclease specific for inosine- containing RNA; chemokine receptors CCR1, CCR3, CCR5, and their signal transduction elements; 2'-5'-oligoadenylate synthetase; tumor necrosis factor; FAS receptor; signal transduction components of these antiviral pathways, and both type 1 and 2 cytokines) are correlated with delayed progression and diminished pathogenesis in paired hemophilic siblings.

Study Type : Observational
Official Title: Hepatitis C in Clinically Discordant Hemophilic Siblings
Study Start Date : September 1999
Actual Primary Completion Date : August 2004
Actual Study Completion Date : August 2004

Resource links provided by the National Library of Medicine

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   up to 100 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
No eligibility criteria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00007371

Sponsors and Collaborators
University of North Carolina, Chapel Hill
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Michael Fried University of North Carolina


Responsible Party: University of North Carolina, Chapel Hill Identifier: NCT00007371     History of Changes
Other Study ID Numbers: 954
R01HL064817 ( U.S. NIH Grant/Contract )
First Posted: November 28, 2000    Key Record Dates
Last Update Posted: September 26, 2016
Last Verified: January 2005
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Hepatitis, Viral, Human
Hepatitis A
Hepatitis C
Hemophilia A
Hematologic Diseases
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn