Autonomic Dysfunction in Non-Alcoholic Fatty Liver Disease
Condition: Non-alcoholic Fatty Liver Disease; NAFLD; Fatty Liver, Nonalcoholic; Nonalcoholic Fatty Liver Disease
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Autonomic Nervous System Diseases; Primary Dysautonomias
Study type: Observational

Summary: 
      There is a significant association between autonomic dysfunction and symptoms experienced by
      NAFLD patients mediated by increased systemic inflammation and insulin resistance, resulting
      in deteriorating quality of life of affected patients; fatigue and other symptoms drive
      worsening autonomic dysfunction in these patients. We aim to describe the severity of
      autonomic dysfunction (AD) in non-alcoholic fatty liver disease (NAFLD) and the relationship
      of AD to symptoms experienced by NAFLD patients (such as fatigue, chronic pain, depression,
      sleep disturbance, and cognitive dysfunction), and to the quality of life of NAFLD patients.
      We also hope to examine the impact of systemic inflammation and insulin resistance as
      mediators of manifestations of AD and symptoms experienced by NAFLD patients.
    

Detailed description: 
      Aim 1. Describe the severity of AD in NAFLD and the relationship of AD to symptoms
      experienced by NAFLD patients (fatigue, chronic pain, depression, sleep disturbance, and
      cognitive dysfunction) (Aim 1a) and to the quality of life of NAFLD patients (Aim 1b).
      Primary screening for inclusion/exclusion criteria will be done at the VCUHS clinic. Subjects
      meeting inclusion criteria will be approached about study participation during their routine
      NAFLD clinic visit. Those who agree to participate in the study will return for a study visit
      at the CCTR Clinical Research Services. All subjects will be asked to fast and avoid caffeine
      for 12 hours prior to study visit. Demographic and clinical data will be collected by study
      coordinators. After a focused exam, conducted by a hepatologist to determine health status of
      the participants, the PI and a research nurse will interview participants to assess their
      symptoms and AD (Aim 1). Blood (20 ml) samples will be collected via venipuncture for serum
      and plasma inflammatory markers and IR (Aim 2).

      Aim 2. Examine the impact of systemic inflammation (SI) and insulin resistance (IR) as
      mediators of manifestations of AD and symptoms experienced by NAFLD patients. Increased
      presence of adipocytes may produce high, chronic levels of cytokines such as IL-6 and TNF-α
      resulting in higher levels of APRPs which contribute to overall inflammation as well as
      cognitive decline and fatigue. Secondly, elevated levels of IL-6 and TNF-α lower levels of
      CTRPs which exacerbate IR, AD, and muscle and cardiac problems reported in NAFLD. Through the
      use of plasma analysis, levels of cytokines such as IL-6, TNF-α, and APRPs can be performed
      in a high throughput BioPlex® assay (Bio-Rad Laboratories, Inc.: Hercules, CA). We have
      extensive experience with these types of assays and have generated data using human samples
      in numerous studies conducted through the Center of Excellence for Biobehavioral Approaches
      to Symptom Management (CEBASM) at the School of Nursing. CTRP family members are also
      expressed in the plasma and at detectible levels. We will perform ELISA analysis to compare
      circulating levels of the various CTRPs using commercially available CTRP ELISA
      kits/reagents. Insulin resistance (IR) will be assessed by HOMO-IR utilizing fasting glucose
      and insulin.
    

Observational model: Other
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Adults with NAFLD who are patients at the NAFLD Clinic at VCU Health Systems in Richmond,
        VA.