Obstructive Sleep Apnoea and CPAP Treatment Response in Patients With Non-alcoholic Fatty Liver Disease
Condition: Obstructive Sleep Apnea; Non-alcoholic Fatty Liver Disease
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Interventional

Summary: 
      To study the frequency of obstructive sleep apnea (OSA) and continuous positive airway
      pressure (CPAP) treatment response in patients with non-alcoholic fatty liver disease
      (NAFLD).

      It is hypothesized that CPAP treatment may improve the activities of NAFLD in those with
      concomitant OSA.

      A screening study for OSA followed by a randomized controlled trial of patients with biopsy
      proven NAFLD being followed up at the hepatology clinic.

      Home sleep study, Epworth sleepiness score (ESS), paired proton magnetic resonance
      spectroscopy (MRS), transient elastography by fibroscan, serum cytokeratin-18 fragment, liver
      function tests and liver biopsy (only for those with fibroscan evidence of advanced liver
      fibrosis).

      Patients with confirmed symptomatic OSA will be randomized to receive auto CPAP or
      subtherapeutic CPAP as control over 6 months.

      Primary outcome: changes in intrahepatic triglyceride content (IHTG) measured by proton-MRS
      after 6 months of auto CPAP versus subtherapeutic CPAP.
    

Detailed description: 
      Investigators propose to screen for obstructive sleep apnea (OSA) by performing a home sleep
      study on all the patients with biopsy proven non-alcoholic fatty liver disease (NAFLD) being
      followed up at the Hepatology Clinic, Prince of Wales Hospital, Hong Kong, in phase one of
      this study. The following conditions have already been excluded as the underlying cause of
      liver disease in this specific NAFLD cohort: history of excessive alcoholic consumption (more
      than 30 g/day for men and 20 g/day for women), secondary causes of hepatic steatosis (such as
      chronic use of systemic corticosteroids), positive hepatitis B surface antigen,
      anti-hepatitis C virus antibody, or histological evidence of other concomitant chronic liver
      diseases.

      OSA syndrome is defined by apnoea-hypopnoea index (AHI) of 5 per hours or more of sleep plus
      excessive daytime sleepiness or two of the following symptoms: choking or gasping during
      sleep, recurrent awakenings from sleep, unrefreshed sleep, daytime fatigue, and impaired
      concentration. All patients with suspected OSA will undergo initial assessment at the
      respiratory clinic with the Epworth sleepiness score (ESS) and symptoms evaluation. Patients
      who have ESS score >9 or at least two OSA symptoms as described above will be invited to join
      phase two of the study. They will be invited to undergo a home sleep study.

      Those with biopsy proven NAFLD who have AHI≥ 5/hr will be randomized into either group A )
      auto CPAP with range 4-12 cmH20 or group B) Subtherapeutic CPAP with the auto CPAP fixed at 4
      cmH20 by a balanced block design by a third party not involved in the trial.
    

Intervention name(s): Continuous positive airway pressure (CPAP)
Intervention type(s): Device
Intervention description(s): Continuous positive airway pressure (CPAP) is the gold standard treatment for patients with obstructive sleep apnea (OSA). In a previous trials comparing therapeutic CPAP vs subtherapeutic CPAP, CPAP could reduce 24-hour mean blood pressure in mildly sleepy patients with OSA over 3 months whereas our one-year prospective study has shown that reduction of carotid artery intima-media thickness of OSA patients occurred mostly in the first 6 months and was sustained at 12 months in patients with CPAP compliance about 4.7 hours per night.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment