Whoop there it is: decoding sleep, cirrhosis, and HE.

Abstract

Sleep abnormalities in cirrhosis and HE have long been an area of interest.1 Sleep disturbances are highly prevalent in patients with cirrhosis, and HE is often characterized as a reversal of the sleep-wake cycle.2 As assessed by validated questionnaires, such as the Pittsburgh Sleep Quality Index, studies have reported over 80% of patients with cirrhosis suffer from poor sleep and associated low quality of life scores.3 Patients with cirrhosis have impaired hepatic clearance of melatonin, a major regulator of the sleep-wake cycle. Higher daytime serum melatonin and peak levels later in the day contribute to daytime sleepiness, and nighttime arousal observed in many patients with HE.4 Not only do patients with cirrhosis suffer from disrupted sleep timing, but conventional methods of monitoring sleep, that is, polysomnography (PSG), have also demonstrated disrupted sleep architecture resulting in less restorative sleep.5,6 Patients with cirrhosis have been found to have decreased sleep efficiency, decreased rapid eye movement (REM) sleep, and increased sleep latency compared with healthy controls.7 These disturbances appear to increase in severity along with more advanced cirrhosis.7 Abnormal sleep architecture, including decreased REM and slow wave sleep on PSG, has also been observed in patients with covert HE (CHE) compared with controls.8 In this issue of Hepatology Communications, Buckholz and colleagues remotely monitored sleep in 25 patients with cirrhosis for almost 3000 nights of data, using the Whoop fitness tracker. They found that patients with CHE were more likely to experience decreased restorative sleep, especially lowered REM sleep. The team provided insight into sleep characteristics and cycle changes over almost 6 months. Furthermore, the authors discovered that these disturbances, such as the percent of time spent in REM sleep, vary from night to night. These are clear advantages of using this technique over traditional PSG, and this unique study furthers the trend of extending the patient-clinician relationship beyond the clinic into their homes.9 Although the study excluded patients with current treatment of overt HE, there remains a major overlap in patients with obstructive sleep apnea (OSA), HE, and those with disordered sleep due to altered melatonin metabolism secondary to cirrhosis (Fig. 1).10 As obesity rates rise, NAFLD represents an increasing proportion of the population with cirrhosis, and OSA as an etiology of sleep disturbances is likely concordantly increasing in prevalence.7 Symptoms such as daytime sleepiness, fatigue, and nighttime arousal are nonspecific, making diagnosis challenging based on the interview alone.10 Adding to the challenge of making the appropriate diagnosis, sleep architecture is disrupted in both OSA and cirrhosis. When using PSG to compare patients with OSA alone to patients with both OSA and cirrhosis, patients had similar sleep architecture with no significant differences in time spent in restorative sleep, such as REM sleep or slow wave sleep.8 In addition, patients with OSA without cirrhosis may have abnormal results on common tests for CHE, including inhibitory control, number connection, and digit symbol tests.11FIGURE 1: Sleep apnea and disordered sleep secondary to melatonin dysregulation share greater symptom overlap than with covert HE (CHE). Not all daytime sleepiness, fatigue, nighttime arousal, and disrupted sleep architecture in patients with cirrhosis can be attributed to CHE alone.Although appropriate identification of the cause of daytime sleepiness in patients with cirrhosis is challenging, it is critical in determining the next steps in management. Patients with OSA and cirrhosis treated with continuous positive airway pressure have demonstrated improvement in PSQI and improvement in executive function on inhibitory control testing.11 In patients with overt and CHE, there is mixed evidence that traditional HE therapies affect sleep parameters or architecture.5,12 Given the relative overlap in symptoms among OSA, disordered sleep secondary to melatonin dysregulation, and CHE, as well as the lack of specificity of current tests for CHE, clinicians should consider testing at-risk patients for sleep apnea and employing multiple modalities for appropriate CHE diagnosis. Although more work is needed, encouraging monitoring of sleep architecture remotely to gauge response to therapy, as outlined in by Buckholz and colleagues, may be an important first step.