Liver Fibrosis in HIV-Infected Patients With Elevated Liver Enzymes on Antiretroviral Therapy
|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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00326482|
Recruitment Status : Recruiting
First Posted : May 17, 2006
Last Update Posted : May 21, 2018
|First Submitted Date||May 16, 2006|
|First Posted Date||May 17, 2006|
|Last Update Posted Date||May 21, 2018|
|Study Start Date||May 15, 2006|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures
||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 ]|
|Original Primary Outcome Measures||Not Provided|
|Change History||Complete list of historical versions of study NCT00326482 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures
|Original Secondary Outcome Measures||Not Provided|
|Current Other Outcome Measures||Not Provided|
|Original Other Outcome Measures||Not Provided|
|Brief Title||Liver Fibrosis in HIV-Infected Patients With Elevated Liver Enzymes on Antiretroviral Therapy|
|Official Title||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 transient elastography (an ultrasonic technique), will be assessed for their ability to predict fibrosis in this population. 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 Design||Observational Model: Cohort
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Study Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
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, Older Adult)|
|Accepts Healthy Volunteers||No|
|Listed Location Countries||United States|
|Removed Location Countries|
|Other Study ID Numbers||060153
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )|
|Study Sponsor||National Institute of Allergy and Infectious Diseases (NIAID)|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||May 17, 2018|