The Sleep, Liver Evaluation and Effective Pressure Study
Condition: Non Alcoholic Fatty Liver Disease; Obstructive Sleep Apnea
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Intervention: CPAP (ResMed S9 autoset CPAP)
Intervention description: A ResMed S9 autoset CPAP device will be utilized throughout the study. Throughout the study intervention period, subjects (for AHI> 15) will be instructed to utilize their CPAP and adherence will be monitored using an automatic meter that is built into the CPAP device.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No
Keywords: Non Alcoholic Fatty Liver Disease; NAFLD; Continuous Positive Airway Pressure; CPAP; CPAP Therapy; Apnea Hypopnea Index; Non alcoholic steatohepatitis; NASH; OSA; Obstructive Sleep Apnea; AHI

Summary:

      This research is being done to examine: 1) how common obstructive sleep apnea (OSA) is in
      patients with non-alcoholic fatty liver disease (NAFLD), 2) whether the severity of OSA is
      related to the severity of NAFLD, and 3) whether treatment of OSA with continuous positive
      airway pressure (CPAP) improved NAFLD progression.

      OSA is a condition caused by repetitive collapse of throat tissue during sleep that leads to
      falls in oxygen level and sleep disruption. OSA can be caused by obesity, and especially by
      fat found in the neck and belly.

      NAFLD is a common disease linked to obesity. NAFLD is part of a disease spectrum, which can
      progress from steatosis (fatty liver) to nonalcoholic steatohepatitis (NASH), a progressive
      fibrotic disease, in which cirrhosis and liver-related death can occur. Recent evidence in
      patients with obstructive sleep apnea (OSA) indicates that OSA is associated with NASH. How
      common OSA is in patients with biopsy-confirmed NAFLD and the effect of OSA treatment with
      CPAP on NASH is unknown.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 21

          -  Diagnosis of NAFLD and BMI ≥ 30 or obesity with BMI > 35 and < 400lbs

          -  No other cause of liver disease other than NAFLD (as assessed by patient and physician
             surveys detailed below, blood work and magnetic resonance imaging(MRI))

        Exclusion Criteria:

        Both patients and doctors will be asked to identify potential exclusionary conditions
        including:

          1. Patients with sickle cell anemia, hemoglobinopathies and other hemolytic anemias

          2. Known clinical hypersensitivity or a history of asthma or allergic respiratory
             disorders

          3. Advanced renal failure (currently requiring dialysis or with a Glomerular Filtration
             rate < 30cc/min)

          4. Pregnancy

          5. History of CPAP treatment for OSA

          6. Recent weight loss (6 months) ≥ 10%

          7. Current alcohol use > 20 g/day in women and > 30 g/day in men, or prior use for ≥ 3
             consecutive months during the previous 5 years as assessed with the Lifetime Drinking
             History Questionnaire Viral hepatitis A, B and C

          8. Autoimmune hepatitis

          9. Hemochromatosis

         10. Wilson's disease

         11. Alpha-1-antitrypsin deficiency

         12. Primary sclerosing cholangitis

         13. Cirrhosis of any etiology

         14. History of HIV infection and/or HAART therapy

         15. Evidence of drug-induced liver injury

         16. Use of systemic steroids for > 10 days during prior 6 months

         17. Unstable cardiovascular disease (decompensated chronic heart failure (CHF), myocardial
             infarction or revascularization procedures, unstable arrhythmias)

         18. Uncontrolled hypertension with BP > 190/110

         19. Daytime hypoxemia with oxygen saturation (SaO2)<90%

         20. Supplemental oxygen use

         21. Presence of any contraindication to MR examinations (see MRI Safety Screening Sheet)

         22. History of Metal in the Skull/Eyes

         23. Unable to have an MRI Scan

         24. Severe daytime hypersomnolence as defined by an Epworth Sleepiness Score of greater
             than 10.

         25. Severe sleep apnea as characterized by an apnea-hypopnea index of greater than 80
             episodes/hour or an average low SaO2 during sleep disordered breathing episodes below
             80%.

         26. Work in transportation industry as a driver or pilot.

         27. Patients with a diagnosis of sleep apnea on active treatment.

        Exclusions based on etiology of hepatitis will be assessed by querying both the hepatology
        list and patient about the above mentioned disorders (#7-15) and through testing for viral
        hepatitis A, B, C, ferritin, antinuclear antibody (ANA), antineutrophil cytoplasmic
        antibody (ANCA), anti-mitochondrial antibody, anti-smooth muscle antibody and
        ceruloplasmin.