Abstract
Up to 50–65% of patients with cirrhosis exhibit interrupted night sleep, delayed sleep habits and excessive daytime sleepiness. These have been variously attributed to disease complications (i.e. ascites, pruritus), hepatic encephalopathy or impaired hepatic melatonin metabolism, but the understanding of their pathophysiology remains limited and their treatment problematic. In addition, use of common hypnotics is contraindicated in these patients because of impaired hepatic disposition and increased cerebral sensitivity to psychoactive medication.
Sleep is regulated by the interaction of a homeostatic and a circadian process. The homeostatic process determines sleep propensity in relation to sleep history, so that the need to sleep increases in parallel with the duration of the wake period. The circadian process, which is marked by the 24-h 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 considerable delays in the 24-h melatonin rhythm, mostly in relation to impaired sensitivity to light cues. However, while circadian abnormalities are associated with delayed sleep habits, they do not offer a comprehensive explanation to the sleep–wake changes exhibited by these patients. Limited data are available on homeostatic sleep control in patients with cirrhosis, which is worthy of further study.
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References
Córdoba J, Cabrera J, Lataif L, Penev P, Zee P, Blei AT. High prevalence of sleep disturbance in cirrhosis. Hepatology. 1998;27:339–45.
Bianchi G, Marchesini G, Nicolino F, et al. Psychological status and depression in patients with liver cirrhosis. Dig Liver Dis. 2005;37:593–600.
Mostacci B, Ferlisi M, Baldi AA, et al. Sleep disturbance and daytime sleepiness in patients with cirrhosis: a case control study. Neurol Sci. 2008;29:237–40.
Montagnese S, Middleton B, Skene DJ, Morgan MY. Night-time sleep disturbance does not correlate with neuropsychiatric impairment in patients with cirrhosis. Liver Int. 2009;29:1372–82.
Spahr L, Coeytaux A, Giostra E, Hadengue A, Annoni JM. Histamine H1 blocker hydroxyzine improves sleep in patients with cirrhosis and minimal hepatic encephalopathy: a randomized controlled pilot trial. Am J Gastroenterol. 2007;102:744–53.
Montagnese S, Middleton B, Mani AR, Skene DJ, Morgan MY. Sleep and circadian abnormalities in patients with cirrhosis: features of delayed sleep phase syndrome? Metab Brain Dis. 2009;24:427–39.
Córdoba J, Dupuis J, Gottstein J, Blei AT. Stenosis of a portacaval anastomosis affects circadian locomotor activity in the rat: a multivariable analysis. Am J Physiol. 1997;273:G1218–25.
Ahabrach H, Piedrafita B, Ayad A, et al. Chronic hyperammonemia alters the circadian rhythms of corticosteroid hormone levels and of motor activity in rats. J Neurosci Res. 2010;88:1605–14.
Kantermann T, Juda M, Merrow M, Roenneberg T. The human circadian clock’s seasonal adjustment is disrupted by daylight saving time. Curr Biol. 2007;17:1996–2000.
Janszky I, Ljung R. Shifts to and from daylight saving time and incidence of myocardial infarction. N Engl J Med. 2008;359:1966–8.
Sherlock S, Summerskill WH, White LP, Phear EA. Portal-systemic encephalopathy; neurological complications of liver disease. Lancet. 1954;267:454–7.
Ross CA. CNS arousal systems: possible role in delirium. Int Psychogeriatr. 1991;3:353–71.
Montagnese S, Jackson C, Morgan MY. Spatio-temporal decomposition of the electroencephalogram in patients with cirrhosis. J Hepatol. 2007;46:447–58.
Marchesini G, Bianchi G, Amodio P, et al. Factors associated with poor health-related quality of life of patients with cirrhosis. Gastroenterology. 2001;120:170–8.
Montagnese S, Middleton B, Skene DJ, Morgan MY. Sleep-wake patterns in patients with cirrhosis: all you need to know on a single sheet. A simple sleep questionnaire for clinical use. J Hepatol. 2009;51:690–5.
Borbely AA. A two process model of sleep regulation. Hum Neurobiol. 1982;1:195–204.
Czeisler CA, Duffy JF, Shanahan TL, et al. Stability, precision, and near-24-hour period of the human circadian pacemaker. Science. 1999;284:2177–81.
Moore RY. Neural control of the pineal gland. Behav Brain Res. 1996;73:125–30.
Arendt J. Light-dark control of melatonin synthesis. Melatonin and the mammalian pineal gland. 1st ed. London: Chapman & Hall; 1995. p. 66–109.
Boutin JA, Audinot V, Ferry G, Delagrange P. Molecular tools to study melatonin pathways and actions. Trends Pharmacol Sci. 2005;26:412–9.
Blake H, Gerard RW. Brain potentials during sleep. Am J Physiol. 1937;119:692–703.
Dement W, Kleitman N. Cyclic variations in EEG during sleep and their relation to eye movements, body motility, and dreaming. Electroencephalogr Clin Neurophysiol. 1957;9:673–90.
Borbely AA, Baumann F, Brandeis D, Strauch I, Lehmann D. Sleep deprivation: effect on sleep stages and EEG power density in man. Electroencephalogr Clin Neurophysiol. 1981;51:483–95.
Werth E, Dijk DJ, Achermann P, Borbely AA. Dynamics of the sleep EEG after an early evening nap: experimental data and simulations. Am J Physiol. 1996;271:R501–10.
Landolt HP. Sleep homeostasis: a role for adenosine in humans? Biochem Pharmacol. 2008;75:2070–9.
Dijk DJ, Czeisler CA. Paradoxical timing of the circadian rhythm of sleep propensity serves to consolidate sleep and wakefulness in humans. Neurosci Lett. 1994;166:63–8.
Steindl PE, Finn B, Bendok B, Rothke S, Zee PC, Blei AT. Disruption of the diurnal rhythm of plasma melatonin in cirrhosis. Ann Intern Med. 1995;123:274–7.
Steindl PE, Ferenci P, Marktl W. Impaired hepatic catabolism of melatonin in cirrhosis. Ann Intern Med. 1997;127:494.
Iguchi H, Kato KI, Ibayashi H. Melatonin serum levels and metabolic clearance rate in patients with liver cirrhosis. J Clin Endocrinol Metab. 1982;54:1025–7.
Montagnese S, Middleton B, Mani AR, Skene DJ, Morgan MY. On the origin and the consequences of circadian abnormalities in patients with cirrhosis. Am J Gastroenterol. 2010;105:1773–81.
Piscaglia F, Hermida RC, Siringo S, Legnani C, Ramadori G, Bolondi L. Cirrhosis does not shift the circadian phase of plasma fibrinolysis. Am J Gastroenterol. 2002;97:1512–7.
Velissaris D, Karamouzos V, Polychronopoulos P, Karanikolas M. Chronotypology and melatonin alterations in minimal hepatic encephalopathy. J Circadian Rhythms. 2009;7:6.
Velissaris D, Karanikolas M, Kalogeropoulos A, et al. Pituitary hormone circadian rhythm alterations in cirrhosis patients with subclinical hepatic encephalopathy. World J Gastroenterol. 2008;14:4190–5.
Thapan K, Arendt J, Skene DJ. An action spectrum for melatonin suppression: evidence for a novel non-rod, non-cone photoreceptor system in humans. J Physiol. 2001;535:261–7.
Montagnese S, Middleton B, Mani AR, Skene DJ, Morgan MY. Changes in the 24-h plasma cortisol rhythm in patients with cirrhosis. J Hepatol. 2011;54(3):588–90.
Bernardi M, De Palma R, Trevisani F, et al. Chronobiological study of factors affecting plasma aldosterone concentration in cirrhosis. Gastroenterology. 1986;91:683–91.
Lockley SW, Skene DJ, Tabandeh H, Bird AC, Defrance R, Arendt J. Relationship between napping and melatonin in the blind. J Biol Rhythms. 1997;12:16–25.
Steindl PE, Finn B, Bendok B, Rothke S, Zee PC, Blei AT. [Changes in the 24-hour rhythm of plasma melatonin in patients with liver cirrhosis—relation to sleep architecture]. Wien Klin Wochenschr. 1997;109:741–6.
Weitzman ED, Czeisler CA, Coleman RM, et al. Delayed sleep phase syndrome. A chronobiological disorder with sleep-onset insomnia. Arch Gen Psychiatry. 1981;38:737–46.
Weyerbrock A, Timmer J, Hohagen F, Berger M, Bauer J. Effects of light and chronotherapy on human circadian rhythms in delayed sleep phase syndrome: cytokines, cortisol, growth hormone, and the sleep-wake cycle. Biol Psychiatry. 1996;40:794–7.
Nagtegaal JE, Kerkhof GA, Smits MG, Swart AC, Van Der Meer YG. Delayed sleep phase syndrome: a placebo-controlled cross-over study on the effects of melatonin administered five hours before the individual dim light melatonin onset. J Sleep Res. 1998;7:135–43.
Blei AT, Zee P. Abnormalities of circadian rhythmicity in liver disease. J Hepatol. 1998;29:832–5.
Cordoba J, Steindl P, Blei AT. Melatonin arrhythmia is corrected after liver transplantation. Am J Gastroenterol. 2009;104:1862–3.
Kurtz D, Zenglein JP, Imler M, et al. [Night sleep in porto-caval encephalopathy]. Electroencephalogr Clin Neurophysiol. 1972;33:167–78.
Boy C, Meyer PT, Kircheis G, et al. Cerebral A1 adenosine receptors (A1AR) in liver cirrhosis. Eur J Nucl Med Mol Imaging. 2008;35:589–97.
Laidlaw J, Read AE, Sherlock S. Morphine tolerance in hepatic cirrhosis. Gastroenterology. 1961;40:389–96.
Assy N, Rosser BG, Grahame GR, Minuk GY. Risk of sedation for upper GI endoscopy exacerbating subclinical hepatic encephalopathy in patients with cirrhosis. Gastrointest Endosc. 1999;49:690–4.
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Montagnese, S. (2012). Sleep Disorders and Hepatic Encephalopathy. In: Mullen, K., Prakash, R. (eds) Hepatic Encephalopathy. Clinical Gastroenterology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-836-8_14
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DOI: https://doi.org/10.1007/978-1-61779-836-8_14
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