Prevalence and Predictors of Hepatic Steatosis in Persons Living With HIV

N
Naga Chalasani, MD

Primary Investigator

Enrolling By Invitation
18-80 years
All
Phase N/A
1250 participants needed
3 Locations

Brief description of study

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions associated withumulation that ranges from benign, non-progressive liver fat accumulation to severever injury, cirrhosis, and liver failure. NAFLD is the most common liver disease in USdults and the second leading cause for liver transplantation in the US. The natural historyAFLD in the general population has been well described, with those with non-alcoholicy liver (NAFL, or simple steatosis) destined to have rare incidence of hepatic eventsd to those with non-alcoholic steatohepatitis (NASH), who are at high risk for future development of cirrhosis, liver cancer and liver failure. The NASH Clinical Research Network (NASH CRN) was established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2002, through the mechanism of RFA-DK-01-025, to further the understanding of diagnosis, mechanisms, progression and therapies of NASH. The NASH CRNhas resulted in numerous seminal studies in the field. However, NASH CRN studies haveystematically excluded persons living with HIV (PLWH), as NAFLD in these persons was thoughtbe different from that in the general population due to HIV, ART, concomitant medications,d co-infections. This has resulted in major knowledge gaps regarding NAFLD in the settingHIV. This ancillary study of NAFLD and NASH in Adults with HIV (HIV NASH CRN), HNC 001 goal is to examine the prevalence of hepatic steatosis and NAFLD in a large, multicenter, andultiethnic cohort of PLWH (Steatosis in HIV Study)

Detailed description of study

NAFLD is the most prevalent of all liver disorders and is the most common cause of chronicvations in the United States. NAFLD also represents a major health threat worldwide, with a substantial impact on healthcare expenditures in the US and Europe. Withhe availability of highly effective ART, chronic liver disease has become a leading cause ofAIDS related morbidity and mortality in PLWH. NAFLD is projected to become the leadinguse of liver disease in the aging HIV population. The reported prevalence of NAFLD in PLWH without viral hepatitis co-infection ranges from 15-54% when assessed by imaging modalitiesd vibration-controlled transient elastography (VCTE), and is up to 73% in studies includingver biopsy, exceeding the reported prevalence of NAFLD in the general population. Thesevalence figures vary as different modalities [computed tomography (CT), ultrasound, or Controlled attenuation parameter (CAP)] and criteria to define NAFLD were used. Further,urrent reports of NAFLD prevalence in PLWH are largely limited to single centers with smallumbers of participants, inclusion of patients with concurrent HCV or limiting the studyulation to single sex or military personnel and their dependents. Systematicharacterization of NAFLD in PLWH requires a large, representative, multi-ethnic,ulti-centric cohort, which is currently lacking.
While obesity, insulin resistance and other components of the metabolic syndrome have beend in some studies to increase the risk for NAFLD in PLWH, they are not universallybserved in all PLWH, as studies of men with HIV report lower incidence of hepatic steatosisd lower BMI compared to controls. The impact of HIV and ART on NAFLD risk has also beenuch debated, with some studies supporting a role for the duration of infection and ARTgents used, and others showing no associations. Recent reports suggest a potential decreaseAFLD/NASH frequency and severity with light to moderate alcohol consumption in the general population. While PLWH commonly report alcohol use, the effects of non-heavy alcoholumption on NAFLD and NASH risk and severity have not been studied in this population.y, while coffee consumption has reported benefits on NAFLD in the general population,his effect has not been explored in PLWH. Several genetic variants have been found todulate the risk and severity of NAFLD in the general population (Primary NAFLD), such as PNPLA3, TM6SF2, FADS1, GCKR, MBOAT7, and HSD17B13. To date, only a few studies evaluated genetic variation as a risk for NAFLD and its severity in PLWH. Emerging studies suggest angut microbiome as well as circulating gut derived metabolites indulating the severity of Primary NAFLD but similar studies are lacking in PLWH.
OBJECTIVES
  • To determine the prevalence of hepatic steatosis and NAFLD in a large, multicenter, andultiethnic cohort of PLWH.
  • To enroll at least 1250 PLWH into a cross-sectional study. The presence of hepaticd NAFLD and advanced fibrosis will be defined based on clinical, diagnostic,d VCTE criteria. Core data collection will include clinical, demographic, behavioral,hropometric and laboratory information.
  • To evaluate the prevalence of alcoholic liver disease versus NAFLD and assess thevarying amounts of alcohol and other beverage consumption on the risk andverity of hepatic steatosis.
  • To evaluate the relationship between host (age, sex/gender, race/ethnicity, obesity, genetic variants, gut microbiome, etc.), HIV disease (HIV-1 RNA level, CD4+ T cellunt, HIV duration) and HIV treatment with ART (type and duration), and environmental (alcohol, coffee and other beverages, diet, physical activity, sleep, food insecurity)d the prevalence of hepatic steatosis and NAFLD in PLWH.
  • To establish a robust specimen bank comprised of serum, plasma, genomic DNA as well as PBMC and stool at select sites.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: NAFLD, NAFLD-HIV, Hiv
  • Age: Between 18 Years - 80 Years
  • Gender: All

Inclusion Criteria:
  • 18 years of age or older
  • HIV-1, documented historically by any licensed rapid HIV test or HIV enzyme orhemiluminescence immunoassay (E/CIA) test kit and confirmed by a licensed Westernblot or a second antibody test by a method other than the initial rapid HIV and/or/CIA, or by HIV-1 antigen or plasma HIV-1 RNA.
  • On ART for 6 months prior to screening with HIV RNA <200 copies/mL at entry
Exclusion Criteria:
  • Evidence of current or prior chronic HBV, as marked by the presence of HBsAg in serumy time prior to enrollment (patients with isolated antibody to hepatitis B coregen, anti-HBc total, are not excluded)
  • Evidence of recent or current HCV as marked by the presence of anti-HCV antibody withdetectable HCV RNA in serum within 3 years prior to enrollment. Participants withHCV antibody positivity who have undetectable HCV RNA 3 years prior to enrollment(either due to spontaneous clearance or clearance with treatment) will be eligible toHCV RNA at entry remains undetected.
  • Known other chronic liver disease, including but not limited to alpha-1- antitrypsindeficiency, Wilson's disease, hemochromatosis, polycystic liver disease, autoimmunehepatitis, and primary biliary cholangitis. Note that alcohol-related liver disease isusionary.
  • Disseminated or advanced malignancy
  • Pregnancy
  • Concomitant severe underlying systemic illness that, in the opinion of thevestigator, would interfere with completion of study procedures
  • Inability to complete a FibroScan® VCTE scan:
  • Use of implantable active medical device such as a pacemaker or defibrillator
  • Wound care near the application site of the FibroScan®
  • Pregnancy
  • Ascites (fluid in the abdominal area)
  • Unable or unwilling to complete the FibroScan® without sedation or unable to lie stillufficient duration to complete the exam
  • Any other condition that, in the opinion of the investigator, would impede compliancehinder completion of study procedures
  • Inability to complete the informed consent process or comply with study procedures

Updated on 01 Aug 2024. Study ID: HNC-001
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