3 In patients with cirrhosis, overt HE is common after a gastrointestinal bleed, which can be simulated by the oral administration of a mixture of amino acids mimicking the composition of hemoglobin.4 Ribociclib Such a test, termed amino

acid challenge (AAC), has been used to assess the risk of developing HE.5 Sleep-wake disturbances are common in patients with cirrhosis and have been traditionally associated with HE.1 More recent data seem to indicate that daytime sleepiness is part of the HE spectrum, whereas night sleep disturbances may have a different pathophysiology.6, 7 Abnormalities in the circadian rhythm of melatonin of both central (reduced cerebral sensitivity to dark/light cues) and peripheral origin (reduced melatonin clearance) have been described in this patient population but they do not offer a comprehensive explanation for the observed sleep-wake abnormalities.8, 9 Limited information is available on the sleep electroencephalogram (EEG) features

of patients with cirrhosis.10, 11 The largest studies date back to the BMS-354825 clinical trial 1970s and were conducted in decompensated patients with severe, overt HE.10 Correlations were observed between the clinical severity of encephalopathy and the degree of disruption of sleep architecture.10 The transition between wake and sleep, as well as the transitions between non-rapid eye movement (non-REM) and REM sleep, are characterized by well-defined EEG characteristics. Non-REM sleep is divided into stages 1 to 4, with stages 3 and 4 representing deep sleep. Non-REM stage 1 is considered a transitional state between waking and sleep. Non-REM stage 2 is characterized by K-complexes and sleep spindles, whereas stages 3 and 4 (or slow wave sleep) are dominated by high-amplitude,

low frequency (delta) Non-specific serine/threonine protein kinase waves.12 Delta activity (power in the 0.75-4.5 Hz range of the EEG spectrum) in non-REM sleep is a reliable indicator of sleep homeostasis, which reflects the effect of sleep/wake history on sleep propensity: delta activity increases as a function of the duration of prior wakefulness and dissipates with progression of sleep.13 Brief sleep EEG recordings of 90-120 minutes, or “nap” studies, are easier to perform than all-night polysomnography, especially in a clinical setting. Naps have been shown to accurately reflect the current level of homeostatic sleep pressure, which accumulates during the wake period.14 Furthermore, naps taken later in the day are characterized by a higher level of sleep pressure, and thus a higher amount of slow wave sleep.15 Protocols with repeated naps require patients to maintain regular sleep-wake schedules prior to/during the study, thus only medically stable subjects can be included.