Sleep disorder in patients with chronic liver disease: a narrative review

Sleep disturbance is a common feature of chronic liver disease (CLD) with impact on healthrelated quality of life; 60-80% of patients with CLD report subjective poor sleep; frequent presentations of sleep disturbance include insomnia, reduced sleep efficiency, increased sleep latency, reduced time in rapid eye movement (REM) sleep, restless leg syndrome and excessive daytime sleepiness (EDS). Key contributors to sleep disturbance include hepatic encephalopathy (HE) and circadian rhythm imbalance due to altered melatonin metabolism. Specific conditions causing CLD, such as non-alcoholic fatty liver disease (NAFLD), chronic viral hepatitis and primary biliary cholangitis (PBC) result in different types of sleep disturbance, and the treatment of these conditions can often also lead to sleep disturbance. There are currently limited management options for sleep disturbance in CLD. Obstructive sleep apnoea (OSA) is a common condition that causes chronic intermittent hypoxia due to airway collapse during sleep. This chronic intermittent hypoxia appears to contribute to the development of NAFLD. The presence of reactive oxygen species and the overexpression of hypoxia inducible factor 1-alpha secondary to hypoxia may be responsible for the second 'hit' of the 'two-hit' hypothesis of NAFLD. Treatment of the intermittent hypoxia with continuous positive airway pressure therapy has limited efficacy against liver dysfunction. There remain many outstanding areas of investigation in the management of sleep disturbance in CLD, and of liver dysfunction in OSA.