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

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Abstract

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 μg/24 h) but were significantly lower in the decompensated patients (9.8 ± 11.3 vs. 17.0 ± 13.3 μg/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 (≥ 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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Abbreviations

AFMK:

N1-acetyl-N2-formyl-5-methoxy-kynurenine

AMK:

N1-acetyl-5-methoxy-kynurenine

aMT6s:

6-sulphatoxymelatonin

DSPS:

delayed sleep phase syndrome

SCN:

suprachiasmatic nuclei

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Acknowledgement

The authors are grateful to Stockgrand Ltd. (Guildford, Surrey, UK) for undertaking the urinary 6-sulphatoxymelatonin assays and to Dr D. S. Minors (University of Manchester, UK) for the software to undertake the cosinor analysis of the urinary aMT6s.

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Author notes

  1. Sara Montagnese

    Present address: Department of Clinical and Experimental Medicine, University of Padova, Largo Meneghetti 2, 35131, Padova, Italy

Authors and Affiliations

  1. The Centre for Hepatology, Department of Medicine, Royal Free Campus, University College London Medical School, University College London, Rowland Hill Street, London, NW3 2PF, UK

    Sara Montagnese, Ali R. Mani & Marsha Y. Morgan

  2. Centre for Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK

    Benita Middleton & Debra J. Skene

Authors
  1. Sara Montagnese
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  2. Benita Middleton
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  3. Ali R. Mani
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  4. Debra J. Skene
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  5. Marsha Y. Morgan
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Corresponding author

Correspondence to Marsha Y. Morgan.

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Grant Support

SM was the recipient of an EASL Sheila Sherlock Fellowship

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Montagnese, S., Middleton, B., Mani, A.R. et al. Sleep and circadian abnormalities in patients with cirrhosis: features of delayed sleep phase syndrome?. Metab Brain Dis 24, 427–439 (2009). https://doi.org/10.1007/s11011-009-9146-5

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  • DOI: https://doi.org/10.1007/s11011-009-9146-5

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