Sleep and circadian abnormalities in patients with cirrhosis: Features of delayed sleep phase syndrome?

Centre for Hepatology, Department of Medicine, Royal Free Campus, University College London Medical School, Rowland Hill Street, London NW3 2PF, UK.
Metabolic Brain Disease (Impact Factor: 2.64). 09/2009; 24(3):427-39. DOI: 10.1007/s11011-009-9146-5
Source: PubMed


Sleep disturbances are common in patients with cirrhosis but their origins are unknown. The aim of this study was to investigate possible involvement of the circadian system. Sleep was monitored for two weeks, in the home environment, using sleep diaries and actigraphy, in 35 patients with cirrhosis (21 men; mean age [+/- 1SD] 58 +/- 10 yr) and 12 matched healthy controls (eight men; mean age 56 +/- 15 yr); urinary 6-sulphatoxymelatonin (aMT6s), the major metabolite of melatonin, was measured over 56 h, to assess circadian rhythmicity. The patients woke up and got up significantly later than the healthy volunteers and their sleep was significantly more fragmented. Mean 24-hour urinary aMT6s outputs were comparable in the patients and controls (15.5 +/- 13.1 vs. 20.3 +/- 13.8 microg/24 h) but were significantly lower in the decompensated patients (9.8 +/- 11.3 vs. 17.0 +/- 13.3 microg/24 h; p = 0.03). Significant 24-hour urinary aMT6s rhythms were observed in 26 (79%) of the 33 patients with complete urine collections; 20 patients had a normally timed (midnight-06:00) urinary aMT6s peak, while it was delayed (> or = 06:00) in the remainder. Significant correlations were observed between abnormalities in the urinary aMT6s profile (delays and/or lack of a 24-hour rhythm) and indices of sleep timing; parallel delays were observed in sleep habits and urinary aMT6s peaks. The association between delayed circadian rhythms and delayed sleep habits observed in approximately one-third of the patients with cirrhosis is reminiscent of 'delayed sleep phase syndrome'; this condition is managed by attempting to resynchronise the circadian clock by exposure to bright light shortly after morning awakening.

Download full-text


Available from: Debra J Skene,
  • Source
    • "Sleep-wake disturbances, as assessed by a simple, structured interview were found to be common in patients with cirrhosis. This is in line with previous studies based on similar structured interviews (Cordoba et al. 1998; Bianchi et al. 2005), validated questionnaires (Mostacci et al. 2008; Montagnese et al. 2009b) and semi-quantitative assessment tools, such as actigraphy (Cordoba et al. 1998; Montagnese et al. 2009a). Of interest, while no association was observed between difficulties falling asleep/frequent night awakenings and HE, excessive daytime sleepiness was associated with quantitative HE indices (EEG slowing), a history of HE and its development over time. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The relationship between hepatic encephalopathy (HE) and the sleep-wake disturbances exhibited by patients with cirrhosis remains debated. The aim of this study was to examine the usefulness of sleep-wake interview within the context of HE assessment. One-hundred-and-six cirrhotic patients were asked three yes/no questions investigating the presence of difficulty falling asleep, night awakenings and daytime sleepiness. All underwent formal HE assessment, quantitative electroencephalography and standardised psychometry. Fifty-eight were monitored for 8 ± 6 months in relation to the occurrence of HE. Patients complaining of daytime sleepiness (n = 75, 71 %) had slower EEGs than those who did not report it (relative alpha power: 37 ± 19 vs. 48 ± 17 %, p < 0.05). In addition, daytime sleepiness was associated with the presence of portal-systemic shunt (79 vs. 57 %, p < 0.05) and HE history (72 vs. 45 %, p < 0.05). Finally, the absence of excessive daytime sleepiness had a Negative Predictive Value of 92 % (64-100) in relation to the development of HE during the follow-up period. These data support the appropriateness of adding a yes/no question on the presence of excessive daytime sleepiness to routine assessment of patients with cirrhosis, to help identify those who do not need further, formal HE screening.
    Metabolic Brain Disease 11/2012; 28(2). DOI:10.1007/s11011-012-9360-4 · 2.64 Impact Factor
  • Source
    • "Other results similar to the present study were reported by Mostacci et al. [17] who described 178 Patients with cirrhosis (23.5% Child A, 48.2% Child B, 28.3% Child C) and showed that the cirrhotic patients complained of more daytime sleepiness (P < 0.005), bad sleep at least three times a week (P < 0.005), difficulties in falling asleep (P < 0.01) and frequent nocturnal awakening (P < 0.005) than controls. Also, Montagnese et al. [18] studied 87 patients with liver cirrhosis [59 patients Child A (68%), 16 patients Child B (18%) and 12 patients Child C (14%)] and concluded that patients with cirrhosis slept significantly less well (i.e. decreased sleep efficiency) than the healthy volunteers (P < 0.01) and these patients also reported more pronounced daytime sleepiness according to ESS (P < 0.05). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Liver cirrhosis is considered as a major cause of mortality worldwide and is the most common non-neoplastic cause of death among hepatobiliary and digestive diseases. One of the least studied complications of liver cirrhosis is the disturbed sleep pattern, which is being increasingly recognized as a major health problem affecting the quality of life.Methods This study included two groups; the first group consisted of 30 patients diagnosed as liver cirrhosis based on abdominal ultrasound and liver biopsy and the second group consisted of 10 healthy subjects served as controls. ESS was calculated for every patient and all patients were subjected to complete overnight polysomnography to detect sleep disturbances among all participants.ResultsOur results showed that cirrhotic patients had ESS, AHI and OSA significantly higher than the control group [16.4 ± 2.6 vs 11.1 ± 1.8, P = 0.0001; 10.9 ± 8.5 vs 2.4 ± 1.6, P = 0.005 and 3.1 ± 3.1 vs 1.1 ± 0.9, P = 0.03, respectively]. The percentage of sleep efficiency was significantly lower in cirrhotic patients than the control group [61.9 ± 12.9 vs 73.1 ± 7.6 (P = 0.02)]. Also, the percentages of S1, S3–S4 and REM sleep in relation to the total sleep time were significantly higher in the cirrhotic patients than the control group (P = 0.01, 0.02 and 0.06, respectively) while the percentage of S2 was significantly lower (P = 0.02). Cirrhotic patients of Child class C had ESS, AHI and OSA significantly higher and sleep efficiency significantly lower than cirrhotic patients of classes A and B (P = 0.001 for all). Cirrhotic patients with tense ascites had ESS, AHI and OSA significantly higher and sleep efficiency lower than patients with mild, moderate, or no ascites.Conclusion This study revealed that cirrhotic patients had disturbed sleep pattern, correlating with the degree of cirrhosis.
    10/2012; 61(4):447–451. DOI:10.1016/j.ejcdt.2012.09.012
  • Source
    • "As the final common pathway of most chronic liver diseases [11], liver fibrosis which leads eventually to cirrhosis and hepatocellular carcinoma is the major causes of morbidity and mortality worldwide [12] [13]. It is reported that a variety of circadian parameters , including fibribolysis [14], variceal bleeding [15], heptatic catabolism of melatonin and plasma melatonin [16] [17], arterial blood pressure and heart rate [18] [19], gastric acidity [20] and even sleep [21] [22] are disrupted in cirrhosis patients or mice. In view of the reality that altered circadian rhythms of physiological parameters are observed in cirrhosis patients, it is of interest to explore the relationship between liver fibrogenesis and hepatic circadian clock genes expression. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Disruption in circadian rhythms either by mutation in mice or by shiftwork in people, is associated with an increased risk for the development of multiple organ diseases. In turn, organ disease may influence the function of clock genes and peripheral circadian systems. Here we showed that hepatic fibrosis induced by carbon tetrachloride in mice leads to alterations in the circadian rhythms of hepatic clock genes. Especially, we found an impaired daily Cry2 rhythm in the fibrotic livers, with markedly decreased levels during the day time while compared with control livers. Associatively, the expressions of two important clock-regulated genes peroxisome proliferator-activated receptor alpha and cytochrome P450 oxidoreductase lost circadian rhythm with significantly decreased levels during the light-dark (12/12h) cycle in fibrotic livers.
    FEBS letters 03/2010; 584(8):1597-601. DOI:10.1016/j.febslet.2010.03.019 · 3.17 Impact Factor
Show more