Hepatitis Delta Infections in Hemophiliacs

Hemophilia A Clinical Trial

Official title:

Prevalence and Consequences of Hepatitis Delta Virus Infection in Hemophiliacs

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005305
• Other study ID #: 3006
• Secondary ID: R01HL037974
• Status: Completed
• Phase: N/A
• First received: May 25, 2000
• Last updated: June 13, 2016
• Start date: September 1987
• Est. completion date: September 1991

Study information

• Verified date: June 2016
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

To elucidate the role of hepatitis delta virus (HDV) in the development of chronic liver disease in patients with hemophilia.

Description:

BACKGROUND:

Patients with classical hemophilia (hemophilia A) and Christmas disease (hemophilia B) were exposed to many hepatotropic viruses during the course of their therapy. Severe chronic hepatitis among these patients was most likely related to persistent infection with non-A, non-B hepatitis virus, hepatitis B virus, or delta hepatitis virus, a defective RNA virus which is dependent upon coinfection with HBV for essential helper functions. Carriers of HBV could contract an acute delta hepatitis infection that was invariably more severe than the illness caused by HBV alone. The morbidity and mortality of delta hepatitis infection was remarkably high. Transmission of the delta hepatitis agent appeared to follow the same routes of transmission as HBV. Direct parenteral inoculation was the classic mode of transmission of HBV which suggested a similar mode of transmission for delta hepatitis.

In 1986, hemophiliacs treated with commercial concentrates of coagulation factors prepared from pools of plasma were at great risk to contract delta hepatitis infection. About 50 percent of these patients had delta hepatitis virus antibodies. Also, studies of small cohorts indicated that hepatitis delta infection was a major cause of chronic liver disease and cirrhosis. Therefore, there was a critical need to evaluate the frequency and effect of hepatitis delta infection in hemophiliacs, comparing those with presumed chronic non-A, non-B hepatitis, chronic hepatitis B alone, and combined chronic delta and HBV infections.

The project was awarded in response to a Request for Applications issued in 1986 on The Prevalence and Consequences of Hepatitis Delta Infection in Hemophiliacs. The concept for the initiative originated in the Blood Resources Working Group of the Blood Diseases and Resources Advisory Committee and was approved by The National Heart, Lung, and Blood, Advisory Council in February 1985.

DESIGN NARRATIVE:

The study was conducted collaboratively within the seven hemophilia treatment centers which comprised the Southeastern Hemophilia Group. Upon entry into the study, patient data were collected on transfusion and factor concentrate therapy, age, race, type of hemophilia, sex, homosexuality, drug abuse and HTLV-III antibody status. Liver function was assessed noninvasively. Since available tests for HDV infection had limited sensitively and were not necessarily specific for HDV persistence, HDV RNA was detected in serum by molecular hybridization using cloned HDV cDNA and single-stranded RNA probes. Western blot analysis was used to assess antibody responses to HDV. A multifactorial analysis of clinical and virological data was conducted at the end of the first year of the study. Patients were reevaluated clinically and virologically at six month intervals to ascertain risk factors for acquisition of HBV and HDV infections, and to assess the prevalence and rate of progression of liver disease in each group. Follow-up of patients who had not been previously transfused, allowed an assessment of the efficacy of current control measures such as HBV immunization and use of heat-treated factor concentrates for prevention of viral infections in hemophiliacs.

Plans for extended follow-up of HDV-infected vs non-infected subjects were confounded by the unexpected emergence of human immunodeficiency virus infection in the hemophilic subjects who comprised the study population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: September 1991
• Est. primary completion date: September 1991
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 100 Years
• Eligibility: No eligibility criteria

Study Design

N/A

Related Conditions & MeSH terms

• Blood Disease
• Hematologic Diseases
• Hemophilia A
• Hepatitis
• Hepatitis A
• Hepatitis D
• Hepatitis, Viral, Human
• Liver Diseases

Intervention

Other:
• No interventions - observational study

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Heart, Lung, and Blood Institute (NHLBI)

References & Publications (5)

Andes AA, Smiley ML, White II, et al: Hepatitis Delta in Hemophiliacs: Preliminary Observation in Hepatitis B Antigen Positive and Negative Patients. In: Hepadna Viruses, Alan R. Liss, Inc., pp 619-627. 1987

Lemon SM, Becherer PR, Wang JG, White GC, Lesesne H, Janco RL, Hanna WT, Davis C, Johnson CA, Poon MC, et al. Hepatitis delta infection among multiply-transfused hemophiliacs. Prog Clin Biol Res. 1991;364:351-60. — View Citation

Rozzelle JE Jr, Wang JG, Wagner DS, Erickson BW, Lemon SM. Self-association of a synthetic peptide from the N terminus of the hepatitis delta virus protein into an immunoreactive alpha-helical multimer. Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):382-6. — View Citation

Wang JG, Jansen RW, Brown EA, Lemon SM. Immunogenic domains of hepatitis delta virus antigen: peptide mapping of epitopes recognized by human and woodchuck antibodies. J Virol. 1990 Mar;64(3):1108-16. — View Citation

Wang JG, Lemon SM. Hepatitis delta virus antigen forms dimers and multimeric complexes in vivo. J Virol. 1993 Jan;67(1):446-54. — View Citation