Relationship of Metabolic Abnormalities to Hepatic Steatosis in HIV

This study is currently recruiting participants.
Verified August 2013 by Virginia Commonwealth University
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT00575757
First received: December 14, 2007
Last updated: August 12, 2013
Last verified: August 2013
  Purpose

Because NASH is now recognized as a significant cause of cirrhosis with associated morbidity and mortality, its recognition as a long term complication of HAART is important to the management of those living with HIV.


Condition
Steatohepatitis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Relationship of Metabolic Abnormalities to Hepatic Steatosis in HIV

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • What is the spectrum of NAFLD in HIV [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • How does the spectrum compare in those that are on a PI compare to those that are not. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • What are the independent predictive factors associated with hepatic steatosis and NASH? [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

sera, liver tissue


Estimated Enrollment: 40
Study Start Date: July 2007
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Primary
HIV infected with abnormal liver enzymes in the absence of HCV or HBV coinfections.

Detailed Description:

Abnormal liver enzymes are frequently seen in those with HIV. Although many of these individuals are co-infected with HBV or HCV, histology in HIV patients with abnormal liver enzymes in the absence of viral hepatitis has not been explored. HAART has significantly improved the survival in those living with HIV. However, components of HAART, particularly protease inhibitors (PIs) and certain nucleoside reverse transcriptase inhibitors (NRTIs), are frequently associated with metabolic abnormalities including insulin resistance (IR), dyslipidemias, fat redistribution and lipodystrophy (LD). Both IR and dyslipidemia are pathogenic mechanisms associated with nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) which often present as asymptomatic liver enzyme elevations. Because NASH is now recognized as a significant cause of cirrhosis with associated morbidity and mortality, its recognition as a long term complication of HAART is important to the management of those living with HIV. In our HIV population without HCV or HBV, there is a higher prevalence of abnormal liver enzymes (AST 21%, ALT 16%, ALP 43%) compared to the general population (ALT 8%) and is independently associated with PI use. The relationship of liver enzyme abnormalities to IR, dyslipidemias, and the development hepatic steatosis/NASH in HIV patients is unknown. We hypothesize that Liver enzyme abnormalities in HIV positive patients without viral hepatitis co-infections on HAART are due to hepatic steatosis related to PI use and that a subset of these individuals has NASH. The Specific Aims focus on HIV positive patients with abnormal liver enzymes in the absence of viral hepatitis co-infections, diabetes, or alcohol abuse to answer the following three questions: (1) What is the spectrum of NAFLD?; (2) How does the spectrum compare in those that are on a PI compare to those that are not; and (3) What are the independent predictive factors associated with hepatic steatosis and NASH? These studies will (1) provide novel data on the histology of HIV infected patients with abnormal liver enzymes in the absence of viral coinfections and their relationship to IR, LD, dyslipidemias, and HAART use and (2) provide the necessary pilot data for a multicenter R0-1 grant to study the long-term impact of HAART on the development of steatohepatitis and subsequent hepatic fibrosis.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

HIV positive with abnormal liver enzymes in the absence of HCV/HBV coinfections.

Criteria

Inclusion Criteria:

  • HIV antibody positive.
  • Age > 18 years
  • Abnormal liver chemistries (AST, ALT, and/or ALP) defined as between 1.25 -5 x ULN.

Exclusion Criteria:

  • Hepatic decompensation: coagulopathy (prothrombin time prolonged > 2 seconds, INR > 1.5), ascites, hepatic encephalopathy, jaundice (serum conjugated bilirubin > 3.0)
  • Thrombocytopenia (platelets < 80,000)
  • Use of vitamin E, thiazolidinediones, metformin
  • Use of medications associated with steatosis: amiodarone, methotrexate, corticosteroids, estrogen, and tamoxifen
  • Renal failure (serum creatinine > 3.0)
  • Diabetes mellitus
  • Advanced HIV disease with life expectancy less than 1 year
  • Alcohol use (> 40 grams/day in men and 20 grams/day in women)
  • Presence of HCV RNA or HBV surface antigen
  • Other liver diseases including alpha-1 antitrypsin (A1AT) deficiency, autoimmune hepatitis, hemochromatosis, Wilson's disease, HIV cholangiopathy, bacillary angiomatosis, lymphoma, and Kaposi's sarcoma
  • Inability to give informed consent.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00575757

Contacts
Contact: Richard K Sterling, MD, MSc 804-828-4060 rksterli@vcu.edu
Contact: Paula Smith, RN, BSN 804-828-4060 pgsmith@vcu.edu

Locations
United States, Virginia
Virgnia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Richard K Sterling, MD MSc    804-828-4060    rksterli@vcu.edu   
Contact: Paula Smith, RN, BSN    804-828-4060    pgsmith@VCU.edu   
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
Principal Investigator: Richard K Sterling, MD MSc VCU
  More Information

No publications provided by Virginia Commonwealth University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT00575757     History of Changes
Other Study ID Numbers: VCUHM10107, 1-R03-DK-075416-01
Study First Received: December 14, 2007
Last Updated: August 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Virginia Commonwealth University:
Steatosis
NASH

Additional relevant MeSH terms:
Congenital Abnormalities
Fatty Liver
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on April 23, 2014