Liver Fibrosis in HIV-Infected Patients With Elevated Liver Enzymes on Antiretroviral Therapy
|First Received Date ICMJE||May 16, 2006|
|Last Updated Date||April 30, 2016|
|Start Date ICMJE||May 2006|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Presence of hepatic fibrosis on liver biopsy as measured histologically by stage [ Time Frame: At study entry, potential for repeat liver biopsy staging during longitudinal follow-up ] [ Designated as safety issue: No ]|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00326482 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Liver Fibrosis in HIV-Infected Patients With Elevated Liver Enzymes on Antiretroviral Therapy|
|Official Title ICMJE||A Pilot Study of Hepatic Fibrosis in HIV/AIDS Patients With Chronically Elevated Transaminases on Antiretroviral Therapy|
This study will provide a basis for research on the impact of liver injury caused by antiretroviral therapy in HIV-infected patients. Elevated liver enzymes called AST and ALT are common in HIV-infected patients taking antiretroviral medications and can indicate liver damage. Although there are a number of possible causes for these elevations, such as infections with a hepatitis virus, antiretroviral medications alone can lead to the elevations. The study will focus particularly on evidence of liver fibrosis, which is a sign of progressive liver damage.
HIV-infected patients 18 and older who 1) have been taking combination antiretroviral therapy for at least 12 months and have been on a stable regimen for at least 3 months, and 2) have had elevated AST or ALT levels for at least 6 months may be eligible for this study. Patients who have had liver biopsies performed in the past may be eligible for participation.
Participants undergo the following tests and procedures over a 12-month period:
Patients may participate in an additional 4-year follow-up, during which they have visits every 3-12 months and are offered the opportunity to repeat the biopsy no sooner than 1 year after the first biopsy.
|Detailed Description||At present, there are no clear guidelines as to when antiretroviral therapy for human immunodeficiency virus (HIV) infection should be stopped in the setting of elevated liver enzymes. In large part, this is due to a limited understanding of the natural history of antiretroviral-related hepatotoxicity. Although several antiretrovirals have been reported to cause fatal acute hepatitis, more often they cause an asymptomatic elevation in transaminase levels, the optimal management of which is uncertain. This pilot study seeks to create a foundation for research on the impact of antiretroviral-induced liver injury by providing an estimate of the prevalence of hepatic fibrosis in a cohort of sixty HIV-infected patients who have chronically elevated transaminases while on antiretroviral therapy in the absence of chronic hepatitis B (HBV) or C (HCV) coinfection. Liver biopsy specimens will be evaluated for fibrosis by microscopic examination, the current gold standard for assessing the nature and severity of liver disease. The presence of fibrosis, as well as other histopathology, will be described using a validated scoring system. Primarily, this will be a crosssectional study, but subjects will be offered the opportunity to participate in an extended follow-up period and undergo another liver biopsy. Individuals will not be excluded on the basis of alcohol abuse, insulin resistance, or lipodystrophy, but data will be collected on these potentially confounding variables. Noninvasive measures, such as triple-phase computed tomography and transient elastography (an ultrasonic technique), will be assessed for their ability to predict fibrosis. Correlations will also be sought with laboratory markers of fibrosis. The identification of fibrosis (and its precursors) in association with antiretroviral therapy may be very clinically relevant as it may slowly regress with cessation of the causal agent(s). If the causal agent is continued, however, cirrhosis may develop, the reversal of which is thought to be rare.|
|Study Type ICMJE||Observational|
|Study Design ICMJE||Time Perspective: Prospective|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||180|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Age 18 years or older.
Ability to understand and willingness to provide written informed consent.
Willingness to undergo liver biopsy.
Willingness to comply with study requirements and procedures including storage of blood and liver tissue samples for use in future studies of HIV, AIDS, immune function, hepatic diseases, or other related diseases.
Established HIV diagnosis (documentation of HIV-1 infection by licensed ELISA testing and confirmed by Western Blot).
For the antiretroviral cohort on combination antiretroviral therapy for at least 12 months with stable regimen for at least 3 months prior to enrollment.
Chronically elevated transaminases for at least 6 months documented by an elevated AST and/or ALT on the following 3 occasions within the 12 months prior to enrollment:
|Ages||18 Years to 100 Years (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00326482|
|Other Study ID Numbers ICMJE||060153, 06-I-0153|
|Has Data Monitoring Committee||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||National Institute of Allergy and Infectious Diseases (NIAID)|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||April 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP