Continuous Positive Airway Pressure Does Not Improve Nonalcoholic Fatty Liver Disease in Patients with Obstructive Sleep Apnea. A Randomized Clinical Trial

Rationale: Obstructive sleep apnea (OSA) is associated with development of nonalcoholic fatty liver disease (NAFLD). The effects of continuous positive airway pressure (CPAP) on NAFLD in patients with concomitant OSA are unknown.Objectives: To investigate the effects of autoadjusting CPAP versus subtherapeutic CPAP treatment over 6 months on NAFLD activities.Methods: Patients with NAFLD and OSA, as defined by respiratory event index ≥5/h diagnosed by a validated level 3 Embletta device, were randomized into group A) autoadjusting CPAP (4-20 cm H₂O) or group B) subtherapeutic CPAP (pressure fixed at 4 cm H₂O). The primary endpoint was the difference in changes in intrahepatic triglyceride as measured by proton magnetic resonance spectroscopy after 6 months of therapy. Key secondary endpoints included changes in controlled attenuation parameter (CAP) and liver stiffness measurement measured with transient elastography, and serum cytokeratin-18 fragment.Measurements and Main Results: A total of 120 patients were randomized equally into two groups. There were significant correlations between CAP and respiratory event index (r = 0.203, P = 0.026), percentage of total recording time with Sa_O2 < 90% (r = 0.265, P = 0.003), and oxygen desaturation index (r = 0.214, P = 0.019). After 6 months of treatment, there were no significant differences of changes in primary and secondary endpoints between the two treatment groups. Regression analysis showed that weight change over 6 months correlated with changes in both intrahepatic triglyceride and CAP (P < 0.001).Conclusions: Despite significant correlations between hepatic steatosis and markers of severity of OSA, CPAP alone did not improve hepatic steatosis and fibrosis. However, the additional role of weight reduction through lifestyle modification deserves further investigation.