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Nonalcoholic Fatty Liver Disease in HIV Database

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. Identifier: NCT05023044
Recruitment Status : Not yet recruiting
First Posted : August 26, 2021
Last Update Posted : October 21, 2021
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions associated with fat accumulation that ranges from benign, non-progressive liver fat accumulation to severe liver injury, cirrhosis, and liver failure. The spectrum of NAFLD encompasses simple nonalcoholic steatosis (nonalcoholic fatty liver [NAFL]) and nonalcoholic steatohepatitis (NASH) in which there is evidence of hepatocellular injury and/or fibrosis. NAFLD is the most common liver disease in adults and the second leading cause for liver transplantation in the U.S. The natural history of NAFLD in the general population has been well described. The NASH Clinical Research Network (NASH CRN) was established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2002 to further the understanding of the diagnosis, mechanisms, progression and therapies of NASH. This effort has resulted in numerous seminal studies in the field. However, NASH CRN studies have systematically excluded persons living with HIV (PLWH) , as NAFLD in PLWH was thought to be different from that in the general population due to HIV infection, antiretroviral therapy (ART), concomitant medications and co-infections. This resulted in major knowledge gaps regarding NAFLD in the setting of HIV infection. Thus, the natural history of NAFLD in PLWH is largely unknown. The goal of this ancillary study of NAFLD and NASH in Adults with HIV (HIV NASH CRN), is to conduct a prospective, observational, multicenter study of biopsy-proven NAFLD in PLWH (HIV-associated NAFLD).

Condition or disease
NAFLD NASH - Nonalcoholic Steatohepatitis Hiv

Detailed Description:
NAFLD is the most prevalent of all liver disorders and is the most common cause of chronic aminotransferase elevations in the U.S. With the availability of highly effective ART, chronic liver disease has become a leading cause of non-AIDS related morbidity and mortality in PLWH. NAFLD is projected to become the leading cause of liver disease in the aging HIV population. While there is evidence that both Hepatitis B and Hepatitis C infection follow an accelerated course in PLWH, it is unknown if NAFLD is also accelerated in PLWH. Unlike NAFLD in the general population, there is a significant lack of characterization of the natural history of NAFLD in PLWH. This prospective observational study of PLWH with histologically-characterized NAFLD will examine the natural history of HIV-associated NAFLD. It will also test the accuracy of non-invasive assessments of advanced fibrosis in detecting histologically confirmed advanced fibrosis in PLWH, and establish a robust biospecimen bank (plasma, serum, genomic DNA, and urine; peripheral blood mononuclear cells (PBMCs) and stool at select sites).

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Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Nonalcoholic Fatty Liver Disease In Persons Living With HIV Database Study
Estimated Study Start Date : November 2021
Estimated Primary Completion Date : August 2025
Estimated Study Completion Date : August 2025

Primary Outcome Measures :
  1. Change in liver stiffness measurement (LSM) measured by VCTE from baseline to one year [ Time Frame: Baseline and 1 year ]
    Vibration-controlled transient elastography (VCTE) measures the speed of a mechanically generated shear wave across the liver to derive a liver stiffness measurement (LSM), which corresponds to the liver fibrosis stage. LSM is measured in kilopascals (kPa).

  2. Change in controlled attenuation parameter (CAP) measured by VCTE from baseline to one year [ Time Frame: Baseline and 1 year ]
    Controlled attenuation parameter (CAP) measures the increased attenuation of ultrasound waves when traveling through fat in the liver and is a non-invasive method to assess hepatic steatosis. CAP is measured in decibels per meter (dB/m).

Biospecimen Retention:   Samples With DNA
Fasting serum and plasma, DNA (in participants consenting to genetic research), PBMCs, stool, and snap frozen liver tissue will be banked in the NAFLD in HIV Database. Blood will be drawn for serum and plasma banking during screening and yearly visits on all participants enrolled in the study. If a standard of care liver biopsy is obtained at any time for any reason after the participant has signed the informed consent form, a portion of the liver sample will be collected for banking. The samples will be shipped on dry ice to the Indiana University Biorepository.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
400 participants who are PLWH at least 18 years of age with biopsy-confirmed NAFLD, NASH, or NASH-related cirrhosis; biopsy within 6 months of enrollment

Inclusion Criteria:

  • Documented HIV infection
  • ≥18 of age at time of initial screening
  • HIV suppression with HIV RNA <200 copies/ml on stable ART for ≥ 6 months and no change in ART class for ≥ 3 months, prior to enrollment
  • Histologically confirmed NAFLD (defined as NAFL [>5% steatosis, with or without lobular or portal inflammation], borderline NASH or definitive NASH) within 6 months prior to start of screening
  • Willingness to be in the study for 1 or more years
  • Provision of written informed consent

Exclusion Criteria:

  • Positive hepatitis B surface antigen
  • Evidence of recent or current hepatitis C virus (HCV) as marked by the presence of anti-HCV antibody with detectable HCV RNA in serum within 3 years prior to enrollment. Participants with anti-HCV antibody positivity who have undetectable HCV RNA 3 years prior to enrollment (either due to spontaneous clearance or clearance with treatment) will be eligible to participate if HCV RNA at entry remains undetected
  • Significant alcohol consumption (≥ 3 drinks daily on average in men and ≥ 2 drinks daily on average in women)
  • Evidence of other causes of chronic liver disease
  • History of prolonged (> 1 month) total parenteral nutrition within a 6 month period before baseline liver biopsy
  • Short bowel syndrome
  • History of biliopancreatic diversion
  • History of bariatric surgery within 2 years of enrollment (participants expecting to undergo bariatric surgery can be enrolled prior to the procedure)
  • Solid organ transplant recipients
  • Other condition that is likely to interfere with study follow-up

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05023044

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Contact: Tinsay A Woreta, MD, MPH 4106143369
Contact: Quintara Williams 4109559944

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United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35233
United States, California
University of California, San Diego
San Diego, California, United States, 92121
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Texas
University of Texas
Houston, Texas, United States, 77030
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23284
Sponsors and Collaborators
Johns Hopkins University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Tinsay A Woreta, MD, MPH Johns Hopkins University
Principal Investigator: Samer Gawrieh, MD Indiana University
Principal Investigator: Edgar T Overton, MD University of Alabama at Birmingham

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Responsible Party: Johns Hopkins University Identifier: NCT05023044    
Other Study ID Numbers: HNC-002
R01DK121378 ( U.S. NIH Grant/Contract )
First Posted: August 26, 2021    Key Record Dates
Last Update Posted: October 21, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases