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Disruption of the Diurnal Rhythm of Plasma Melatonin in Cirrhosis
Abstract
OBJECTIVES: To assess 24-hour plasma melatonin profile as a marker of output rhythm from the circadian clock and to study sleep diaries as reflections of subjective sleep quality in patients with liver cirrhosis. DESIGN: Prospective cohort study. SETTING: Clinical research center in a university hospital. PATIENTS: Seven patients with cirrhosis but not alcoholism and seven age-, sex-, and education-matched controls. MEASUREMENTS: Neuropsychological testing to confirm subclinical hepatic encephalopathy. Plasma melatonin levels measured every 30 minutes for 24 hours by radioimmunoassay. Sleep diaries kept for 1 week before admission. RESULTS: Patients with cirrhosis had markedly elevated melatonin levels during daytime hours; in addition, the time of onset of melatonin increase and the time at which melatonin levels peaked were consistently and significantly delayed in these patients. Sleep diaries indicated more nocturnal awakenings and more frequent daytime naps in patients with cirrhosis. CONCLUSION: Disruption of the diurnal rhythm of melatonin may reflect alterations of circadian function that could contribute to the disturbances of the sleep-wake cycle frequently seen in patients with cirrhosis.
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“Consequently, the distal-proximal temperature gradient indicative of heat dissipation is blunted, which contributes to the highly prevalent sleep disruptions reported for cirrhotic patients29, among other proposed mechanisms such as displaced melatonin secretion30.”
From Diurnal rhythms of wrist temperature are associated with future disease risk in the UK Biobank (2023) · cites this paper as [30]
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REVIEW: Gastrointestinal Melatonin: Localization, Function, and Clinical Relevance
Bubenik, G. A. (2002) · Digestive Diseases and Sciences · doi:10.1023/a:1020107915919 · Cited by 655
“Furthermore, melatonin levels are higher in the portal vein then in the systemic circulation (37, 47) and the impaired function of liver, which is the major organ of melatonin degradation (68), increased melatonin concentration in peripheral blood of cirrhotic patients (69, 70).”
Physiology and pharmacology of melatonin in relation to biological rhythms
Zawilska, J. B., Skene, D. J., & Arendt, J. (2009) · Pharmacological Reports · doi:10.1016/s1734-1140(09)70081-7 · Cited by 348
Mundigler, G., Delle‐Karth, G., Koreny, M., Zehetgruber, M., Steindl‐Munda, P., Marktl, W., Fertl, L., & Siostrzonek, P. (2002) · Critical Care Medicine · doi:10.1097/00003246-200203000-00007 · Cited by 333
High prevalence of sleep disturbance in cirrhosis
Córdoba, J., Cabrera, J., Lataif, L., Penev, P., Zee, P., & Blei, A. T. (1998) · Hepatology · doi:10.1002/hep.510270204 · Cited by 273
Self-citationPsychological status and depression in patients with liver cirrhosis
Bianchi, G., Marchesini, G., Nicolino, F., Graziani, R., Sgarbi, D., Loguercio, C., Abbiati, R., & Zoli, M. (2005) · Digestive and Liver Disease · doi:10.1016/j.dld.2005.01.020 · Cited by 187
Metadata
- Authors
- Steindl, P. E., Finn, B., Bendok, B., Rothke, S., Zee, P. C., & Blei, A. T.
- Affiliations
- Northwestern Memorial Hospital (US)
- Northwestern University (US)
- From Northwestern Memorial Hospital, Lakeside Veterans Affairs Medical Center, and the Rehabilitation Institute, Chicago, Illinois.
- ORCID
- Zee, Phyllis C.
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 1995-08-15
- Volume
- 123
- Issue
- 4
- Pages
- 274-277
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W2091220140
- Cited by
- 140
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 2 · 2015: 4 · 2014: 9 · 2013: 8 · 2012: 9
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (RR00048)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- liver cirrhosis, plasma melatonin, circadian rhythm, circadian clock, sleep-wake cycle, sleep quality, nocturnal awakenings, daytime napping, hepatic encephalopathy
- MeSH terms
- Adult, Circadian Rhythm, Female, Humans, Liver Cirrhosis, Male, Melatonin, Middle Aged, Prospective Studies, Sleep Wake Disorders, Biomarkers
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