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.

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Available from: Debra J Skene, Oct 08, 2015
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    • "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). "
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    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
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    • "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. "
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    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
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    • "Mostacci et al. [24] reported that patients with cirrhosis complained of significantly more frequent daytime sleepiness and habitual napping, nighttime sleep problems, and nocturnal awakenings than controls, which were not related to clinical or laboratory parameters. Nighttime sleep disturbance, daytime sleepiness, and preference for evening activities also were noted in a study of the relationship between sleep and QOL in 87 patients with cirrhosis [23•]. In this study, almost 70% of patients were classified as “poor sleepers” using the PSQI, and nighttime sleep disturbance and evening preference were independent predictors of poorer QOL. "
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    ABSTRACT: Chronic infection with the hepatitis C virus (CHC) is associated with physical and mental symptoms including fatigue and depression that adversely affect quality of life. A related complaint, sleep disturbance, has received little attention in the literature, with the exception of sleep changes noted in cirrhosis and end-stage liver disease. We present an overview of studies indicating sleep problems in patients with CHC, with about 60% to 65% of individuals reporting such complaints. Evidence suggests that impairments in sleep quality exist independent of antiviral therapy with interferon-alpha and prior to advanced stages of liver disease. Further investigation of sleep disturbance in CHC patients with a mild stage of liver disease may provide important information on disease course as well as allow additional opportunities for patient support.
    Current Hepatitis Reports 02/2010; 9(1):25-29. DOI:10.1007/s11901-010-0030-x
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