Clinical trial NCT01350648: Long-Term Study of Liver Disease in People With Hepatitis B and/or Hepatitis C With or Without HIV Infection
Official title: The Natural History of Liver Disease in a Cohort of Participants With Hepatitis B and/or Hepatitis C With or Without HIV Infection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis B
Hepatitis C
HIV-HCV Co-Infection
Keywords: Viral Hepatitis
Acquired Immunodeficiency Syndrome (AIDS)
Hepatocellular Carcinoma
HIV-HCV Co-Infection
Liver Neoplasms
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: Washington D.C. Veterans Affairs Medical Center
First posted: 2011-05-10
Enrollment: 569
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: NIH NIAID Outpatient Clinic 8 Participants, local Washington DC Primary Clinics, and formerly the Washington DC VA Clnic

Brief summary: Background:

- Hepatitis B and hepatitis C can cause liver damage. They can also cause serious illness, including liver cancer, and even death. This study will follow people who have hepatitis B or hepatitis C. The purpose is to understand more about how these viruses affect the immune system over the long term (up to 10 years). The study will also compare how these viruses affect people who do and do not have HIV, the virus that causes AIDS.

Objectives:

* To do a long-term study of hepatitis B and hepatitis C infection.
* To study the effects of hepatitis B and hepatitis C infection in people do and do not have HIV.

Eligibility:

- People at least 18 years of age who have hepatitis B or hepatitis C and have a regular doctor for their medical care.

Design:

* Participants will be screened with a physical exam and medical history. Those who do not have a regular doctor to provide medical care during the study will not be able to take part.
* Participants will have yearly visits with study researchers for up to 10 years. These tests will be done at each visit.
* Medical history and physical exam.
* Questionnaire (optional) on emotions, sexual behaviors, use of alcohol and drugs, and quality of life.
* Blood and urine tests, including HIV testing.
* Tissue sample collections for those who have had a liver or other tissue biopsy.
* Participants may leave the study at any time. They will receive the standard of care from their regular doctor throughout the study.

Detailed description: Chronic viral hepatitis is a major health problem affecting millions globally. The immunosuppressed population, especially those with HIV infection, remains at particular risk and the incidence of hepatocellular carcinoma (HCC) is increasing in the US and worldwide, with high rates in those who are cirrhotic, and is the 10th most common cause of death in the US.

HIV-hepatitis coinfection is problematic in that HIV patients are currently living longer on highly active antiretroviral therapy (HAART). Those who are coinfected with HBV and/or HCV progress more rapidly to cirrhosis and hepatic failure. Further research on the epidemiology, optimal screening and new therapeutic approaches in persons with advanced liver disease, in the setting of effective treatment for viral hepatitis is needed.

The primary objective of the proposed study is to characterize viral liver disease and factors affecting the natural history of viral liver disease in persons with and without HIV with an emphasis on those living in the Washington DC metropolitan area. The cohort will be designed to study research questions with respect to liver disease, disease pathogenesis using genomics, proteomics, and immunologic disease models. Secondary objectives include study of the immunopathogenesis of HBV and HCV disease progression in HIV infected subjects. In addition, this is an invaluable opportunity to determine the prevalence and risk factors associated with the development of hepatocellular carcinoma, the longterm effects of HCV clearance with DAAs, along with biomarker profile(s) for diagnosis and outcome. Moreover, this will serve as a catchment protocol to select appropriate participants for novel HBV and HCV therapeutic trials.

Eligibility criteria: * INCLUSION CRITERIA:

To be eligible for participation on this protocol, a participant must satisfy all of the following conditions:

1. Be greater than or equal to 18 years old
2. HBV-infected and/or HCV-infected, or was HCV-infected and successfully treated
3. Willing to undergo genetic testing
4. Willingness to allow study staff to review your medical records between research visits
5. Willing to have samples stored for future research
6. Must have an identifiable primary care physician
7. Willing to undergo HIV testing
8. Childbearing female must test negative for pregnancy

An HBV infected individual is defined as any individual with documentation of the following:

- Positive Hepatitis B surface antigen within the past 12 months or HBV DNA positive, or prior documentation if the individual is currently on active therapy

An HCV infected individual is defined as any individual with documentation of the following in the past:

- Positive HCV antibody and/or positive HCV RNA test (HCV RNA of 2,000 IU/mL or greater)

An HIV infected individual is defined as any individual with documentation of the following:

- Positive Enzyme Linked Immunosorbent Assay followed by a positive Western Blot or detectable HIV viral load or HIV viral less than 50 copies/mL with documentation this individuals is curently on an active HIV antiretroviral regimen.

EXCLUSION CRITERIA:

A participant will be ineligible to participate on this study if any of the following criteria are met:

1. Unable to comply with research study visits
2. Poor venous access
3. Have any condition that the investigator considers a contraindication to study participation.
4. Childbearing female with positive pregnancy test

Co-enrollment Guidelines: Participants may be enrolled in other protocols as long as the amount of research blood drawn does not exceed the acceptable NIH guidelines.

Primary outcomes:
measure: Progression of liver disease in patients with HCV
timeFrame: Annual visits
measure: Progression of liver disease in patients with HBV
timeFrame: Annual visits
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: VA Medical Center, Washington D.C.
state: District of Columbia
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institutes of Health Clinical Center (CC)
name: Colleen M Hadigan, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009 Sep;50(3):661-2. doi: 10.1002/hep.23190. No abstract available.
citation: Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004 Mar;11(2):97-107. doi: 10.1046/j.1365-2893.2003.00487.x.
citation: Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol. 2006;44(1 Suppl):S6-9. doi: 10.1016/j.jhep.2005.11.004. Epub 2005 Nov 21.
citation: Balmaceda JB, Aepfelbacher J, Belliveau O, Chaudhury CS, Chairez C, McLaughlin M, Silk R, Gross C, Kattakuzhy S, Rosenthal E, Kottilil S, Kleiner DE, Hadigan C. Long-term changes in hepatic fibrosis following hepatitis C viral clearance in patients with and without HIV. Antivir Ther. 2019;24(4):451-457. doi: 10.3851/IMP3327.
citation: Chaudhury CS, Mee T, Chairez C, McLaughlin M, Silk R, Gross C, Kattakuzhy S, Rosenthal E, Kottilil S, Stanley TL, Hadigan C. Testosterone in Men With Chronic Hepatitis C Infection and After Hepatitis C Viral Clearance. Clin Infect Dis. 2019 Aug 1;69(4):571-576. doi: 10.1093/cid/ciy965.