Nonalcoholic Fatty Liver Disease in HIV Database

NCT05023044 | Active Not Recruiting DMC

• 2 other identifiers: IRB00316850R01DK121378
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 8

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 NAFLD in PLWH (HIV-associated NAFLD).

Conditions

Hiv; NAFLD; NASH - Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (2)

• Change in liver stiffness measurement (LSM) measured by VCTE from baseline to one 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).

  Baseline and 1 year

• Change in controlled attenuation parameter (CAP) measured by VCTE from baseline to one 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).

  Baseline and 1 year

Eligibility Criteria

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

Study Population

400 participants who are PLWH at least 18 years of age with a diagnosis of NAFLD, NASH, or NASH-related cirrhosis, supported by either a recent liver biopsy or clinical and imaging criteria

You may qualify if:

• 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 screening (per local pathology report)
• Liver stiffness measurement (LSM) ≥6 kPa from FibroScan exam performed during screening or within 12 months prior to screening and a diagnosis of NAFLD based on clinical and imaging (FibroScan CAP≥263 dB/m, ultrasound, CT or MRI) diagnosis at any time
• LSM ≥8 kPa from FibroScan exam performed during screening or within 12 months prior to screening, in the absence of CAP ≥263 dB/m
• Able to provide written informed consent to part
• Willingness to be in the study for 1 or more years
• Provision of written informed consent

You may not qualify if:

• 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 liver biopsy or before baseline FibroScan VCTE exam
• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (8)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

University of California, San Diego

San Diego, California, 92121, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

University of Texas

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

Location

Related Publications (8)

• Joshi D, O'Grady J, Dieterich D, Gazzard B, Agarwal K. Increasing burden of liver disease in patients with HIV infection. Lancet. 2011 Apr 2;377(9772):1198-209. doi: 10.1016/S0140-6736(10)62001-6.

  PMID: 21459211 BACKGROUND

• Price JC, Thio CL. Liver disease in the HIV-infected individual. Clin Gastroenterol Hepatol. 2010 Dec;8(12):1002-12. doi: 10.1016/j.cgh.2010.08.024. Epub 2010 Sep 17.

  PMID: 20851211 BACKGROUND

• Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, Kowalska JD, de Wit S, Law M, el Sadr W, Kirk O, Friis-Moller N, Monforte Ad, Phillips AN, Sabin CA, Lundgren JD; D:A:D Study Group. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014 Jul 19;384(9939):241-8. doi: 10.1016/S0140-6736(14)60604-8.

  PMID: 25042234 BACKGROUND

• Crum-Cianflone NF. Editorial Commentary: Elevated Aminotransferase Levels Among HIV-Infected Persons: What's Lurking Under the Surface? Clin Infect Dis. 2015 May 15;60(10):1579-81. doi: 10.1093/cid/civ106. Epub 2015 Feb 13. No abstract available.

  PMID: 25681377 BACKGROUND

• Crum-Cianflone N, Dilay A, Collins G, Asher D, Campin R, Medina S, Goodman Z, Parker R, Lifson A, Capozza T, Bavaro M, Hale B, Hames C. Nonalcoholic fatty liver disease among HIV-infected persons. J Acquir Immune Defic Syndr. 2009 Apr 15;50(5):464-73. doi: 10.1097/QAI.0b013e318198a88a.

  PMID: 19225402 BACKGROUND

• Siddiqui MS, Vuppalanchi R, Van Natta ML, Hallinan E, Kowdley KV, Abdelmalek M, Neuschwander-Tetri BA, Loomba R, Dasarathy S, Brandman D, Doo E, Tonascia JA, Kleiner DE, Chalasani N, Sanyal AJ; NASH Clinical Research Network. Vibration-Controlled Transient Elastography to Assess Fibrosis and Steatosis in Patients With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2019 Jan;17(1):156-163.e2. doi: 10.1016/j.cgh.2018.04.043. Epub 2018 Apr 26.

  PMID: 29705261 BACKGROUND

• Sterling RK, Smith PG, Brunt EM. Hepatic steatosis in human immunodeficiency virus: a prospective study in patients without viral hepatitis, diabetes, or alcohol abuse. J Clin Gastroenterol. 2013 Feb;47(2):182-7. doi: 10.1097/MCG.0b013e318264181d.

  PMID: 23059409 BACKGROUND

• Vilar-Gomez E, Chalasani N. Non-invasive assessment of non-alcoholic fatty liver disease: Clinical prediction rules and blood-based biomarkers. J Hepatol. 2018 Feb;68(2):305-315. doi: 10.1016/j.jhep.2017.11.013. Epub 2017 Dec 2.

  PMID: 29154965 BACKGROUND

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.

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Tinsay A Woreta, MD, MPH

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Samer Gawrieh, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 6, 2021
• First Posted: August 26, 2021
• Study Start: May 12, 2022
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): September 30, 2031
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)