Obstructive Sleep Apnoea and CPAP Treatment Response in Patients With Non-alcoholic Fatty Liver Disease
Obstructive Sleep Apnoea and CPAP Treatment Response in Patients With Non-alcoholic Fatty Liver Disease
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.
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.
Inclusion Criteria:

 -  symptoms of obstructive sleep apnea with home sleep study showing apnea hypopnea index
 of 5/hour or more, subjects with non-alcoholic fatty liver disease (NAFLD) diagnosed
 by liver biopsy.

 Exclusion Criteria:

 -  (a) unstable cardiovascular diseases (e.g. recent unstable angina, myocardial
 infarction, stroke or transient ischemic attack within the previous 6 months or severe
 left ventricular failure), (b) neuromuscular disease affecting or potentially
 affecting respiratory muscles,(c) moderate to severe respiratory disease (i.e.
 breathlessness affecting activities of daily living) or documented hypoxemia or awake
 oxygen saturation <92% or (d) psychiatric disease that limits the ability to give
 informed consent or complete the study, (e) professional drivers, (f) gross structural
 ear-nose-throat abnormalities (large nasal polyps, gross nasal turbinate hypertrophy
 or septal deviation and enlarged "kissing" tonsils of significant size) who need early
 intervention.