Part of this work was funded by a grant from the Italian Ministry of Health to S.M. (Giovani Ricercatori 2009). D.J.S. is a Royal Society Wolfson Research Merit Award holder. Stockgrand Ltd. (UK) undertook the melatonin, urinary 6-sulphatoxymelatonin, and cortisol assays. Derungs-Waldmann Illuminotecnica (Italy) provided lighting and light measurement equipment.
Sleep-wake abnormalities in patients with cirrhosis
Article first published online: 23 DEC 2013
© 2013 by the American Association for the Study of Liver Diseases
Volume 59, Issue 2, pages 705–712, February 2014
How to Cite
Montagnese, S., De Pittà, C., De Rui, M., Corrias, M., Turco, M., Merkel, C., Amodio, P., Costa, R., Skene, D. J. and Gatta, A. (2014), Sleep-wake abnormalities in patients with cirrhosis. Hepatology, 59: 705–712. doi: 10.1002/hep.26555
Potential conflict of interest: Dr. Skene consults for Vanda.
- Issue published online: 29 JAN 2014
- Article first published online: 23 DEC 2013
- Accepted manuscript online: 6 JUN 2013 10:23AM EST
- Manuscript Accepted: 22 MAY 2013
- Manuscript Revised: 22 APR 2013
- Manuscript Received: 12 MAR 2013
A considerable proportion of patients with cirrhosis exhibit insomnia, delayed sleep habits, and excessive daytime sleepiness. These have been variously attributed to hepatic encephalopathy and impaired hepatic melatonin metabolism, but the understanding of their pathophysiology remains limited and their treatment problematic. Sleep is regulated by the interaction of a homeostatic and a circadian process. The homeostatic process determines sleep propensity in relation to sleep-wake history, thus the need to sleep increases with the duration of the waking period. The circadian process, which is marked by the 24-hour rhythm of the hormone melatonin, is responsible for the alternation of high/low sleep propensity in relation to dark/light cues. Circadian sleep regulation has been studied in some depth in patients with cirrhosis, who show delays in the 24-hour melatonin rhythm, most likely in relation to reduced sensitivity to light cues. However, while melatonin abnormalities are associated with delayed sleep habits, they do not seem to offer a comprehensive explanation to the insomnia exhibited by these patients. Fewer data are available on homeostatic sleep control: it has been recently hypothesized that patients with cirrhosis and hepatic encephalopathy might be unable, due to excessive daytime sleepiness, to accumulate the need/ability to produce restorative sleep. This review will describe in some detail the features of sleep-wake disturbances in patients with cirrhosis, their mutual relationships, and those, if any, with hepatic failure/hepatic encephalopathy. A separate section will cover the available information on their pathophysiology. Finally, etiological treatment will be briefly discussed. (Hepatology 2014;59:705–712)