Liver Fibrosis in HIV-Infected Patients With Elevated Liver Enzymes on Antiretroviral Therapy

NCT00326482 | Completed

• 2 other identifiers: 06015306-I-0153
• Study Type: observational
• Target: 127
• Locations: 1 country
• Sites: 1

Brief Summary

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:

• Oral glucose tolerance test: The patient drinks a glucose (sugar) drink. Blood samples are then drawn over 2 hours through an intravenous (IV) line in the patient's arm. This test measures how high the patient's blood sugar and insulin levels rise after drinking a standard glucose load.
• Transient elastography: This ultrasound test uses vibration (sound waves) to measure liver stiffness (fibrosis). Vibrations move faster through a fibrotic liver.
• Triple-phase CT scan and single slice CT scan of L4-5: Patients fast for 4 hours before the CT scan. A contrast material is injected through a catheter placed in an arm vein to improve the visibility of the liver in the specialized X-ray images obtained in the CT scanner.
• Liver biopsy: This test removes a small sample of liver tissue for microscopic examination, particularly for evidence of fibrosis. The skin over the biopsy site is numbed and a needle is passed through the skin and rapidly in and out of the liver. Patients may be given a sedative for the procedure.
• Follow-up visits. Patients return for follow-up visits 1 to 4 weeks after the liver biopsy and three more times over the course of the study for a medical history, physical examination and blood tests. 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.

Conditions

Steatohepatitis; Elevated Transaminases; Liver Fibrosis

Keywords

Drug Toxicity; Steatohepatitis; Hepatotoxicity; Liver Biopsy; Liver Disease; Natural History; HIV; Liver Fibrosis

Outcome Measures

Primary Outcomes (1)

• Presence of hepatic fibrosis on liver biopsy as measured histologically by stage

  Liver Biopsy Scoring

  At study entry, potential for repeat liver biopsy staging during longitudinal follow-up

Secondary Outcomes (3)

• Liver biopsy evidence of hepatic steatosis as measured by degree (0 to 4), character and location

  At study entry, potential for repeat liver biopsy staging during longitudinal follow-up

• Liver biopsy evidence of hepatic inflammation by type and severity

  At study entry, potential for repeat liver biopsy staging during longitudinal follow-up

• Correlation between histopathologic findings on liver biopsy and clinical, laboratory and radiologic parameters

  At study entry, longitudinally

Study Arms (3)

Prior Liver Biopsy

HIV+ historical liver biopsy history

Prospective Liver Biopsy with ARV

HIV+ taking c/ARV medications

Prospective Liver Biopsy without ARV

HIV+ not taking c/ARV medications

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV-infected patients with chronically elevated transaminases while on c/ARV medications or not on c /ARV medications that agree to research procedures that investigate the prevalence of hepatic fibrosis in the absence of hepatitis B or C co-infection@@@

You may qualify if:

• 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:
• Screening;
• Less than 6 months (24 weeks) prior to enrollment (distinct from screening);
• More than 6 months prior to enrollment.
• Note: Occasions must be at least 8 weeks apart.
• Specific screening lab criteria:
• AST and/or ALT greater than upper limit of normal;
• Absolute neutrophil count greater than 750/mm(3);
• PT/PTT within normal range;

You may not qualify if:

• Chronic hepatitis B infection (defined as positive HBsAg or hepatitis B viral load greater than 10,000 copies/ml).
• Hepatitis C infection (defined as positive HCV viral load) or history of treatment for chronic hepatitis C.
• Acute Hepatitis A infection (defined as HAV IgM positive).
• Suspected rhabdomyolysis (e.g., markedly elevated AST with elevated CPK).
• Known or suspected autoimmune hepatitis.
• Known or suspected biliary diseases, such as primary biliary cirrhosis or sclerosing cholangitis.
• Known or suspected Wilson's disease, alpha-1-antitrypsin deficiency, celiac disease.
• History of primary hemochromatosis, glycogen storage disease, amyloidosis, or cystic fibrosis.
• Clinical evidence of decompensated liver disease (e.g., jaundice, ascites, esophageal varices, or hepatic encephalopathy).
• Active clinical pancreatitis.
• Chronic renal disease.
• Morbid obesity (BMI greater than or equal to 40), if judged to be a contradiction to percutaneous liver biopsy
• AFP greater than or equal to 100 ng/mL.
• Hepatoma or hepatocellular carcinoma.
• Pregnancy.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA. 2000 Jan 5;283(1):74-80. doi: 10.1001/jama.283.1.74.

  PMID: 10632283 BACKGROUND

• Crum-Cianflone N, Collins G, Medina S, Asher D, Campin R, Bavaro M, Hale B, Hames C. Prevalence and factors associated with liver test abnormalities among human immunodeficiency virus-infected persons. Clin Gastroenterol Hepatol. 2010 Feb;8(2):183-91. doi: 10.1016/j.cgh.2009.09.025. Epub 2009 Oct 2.

  PMID: 19800985 BACKGROUND

• Ingiliz P, Valantin MA, Duvivier C, Medja F, Dominguez S, Charlotte F, Tubiana R, Poynard T, Katlama C, Lombes A, Benhamou Y. Liver damage underlying unexplained transaminase elevation in human immunodeficiency virus-1 mono-infected patients on antiretroviral therapy. Hepatology. 2009 Feb;49(2):436-42. doi: 10.1002/hep.22665.

  PMID: 19085967 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Liver Cirrhosis; Fatty Liver; Drug-Related Side Effects and Adverse Reactions; Liver Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Chemically-Induced Disorders

Study Officials

• Joseph A Kovacs, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2006
• First Posted: May 17, 2006
• Study Start: July 31, 2006
• Last Updated: April 29, 2026

Record last verified: 2026-04-20

Locations

US (1)