Disruption of the diurnal rhythm of plasma melatonin in liver cirrhosis

http://www.lef.org/protocols/abstracts/4

Steindl P.E.; Finn B.; Bendok B.; Rothke S.; Zee P.C.; Blei A.T.
Dr. P.E. Steindl, Universitatsklinik Innere Med IV, Abteilung Gastroenterologie/Hepatol., Wahringer Gurtel 18-20, A-1090 Wien Austria
Wiener Klinische Wochenschrift (Austria), 1997, 109/18 (741-746)

Objective: To assess the 24 hr plasma melatonin profile as a marker of the output rhythm from the circadian clock and to study sleep diaries as reflection of subjective sleep quality in patients with liver cirrhosis .

Design: Prospective cohort study. Patients: A total of 14 subjects, 7 non-alcoholic cirrhotics and 7 age-, sex-, and educationally-matched controls. Exclusion criteria were factors that could affect melatonin levels (intercontinental travel, shift work, therapy with betablockers or corticosteroids).

Measurements: Plasma melatonin was measured every 30 min for 24 hr by radioimmuno assay and sleep recordings by polysomnography. Neuropsychological testing included visual reaction time, Trail-making test A and B and the Digit Symbol Test. Sleep diaries were kept for the week prior to admission.

Results: Time of onset of melatonin rise was displaced from 19:50 plus or minus 26 min in the controls to 21:30 plus or minus 13 min (p=0.013) in patients with liver cirrhosis . The time of peak melatonin levels was consistently and significantly delayed from 00:36 plus or minus 33 min in controls to 5:36 plus or minus 29 min (p < 0.001) in patients. Cirrhotic subjects showed markedly elevated melatonin levels during daytime, when melatonin is normally absent. Polysomnographic tracings showed no differences in patients and controls, but sleep diaries indicated more frequent nocturnal awakenings (p = 0.05) and daytime naps.

Conclusions: A marked alteration of plasma melatonin rhythm is found in cirrhotic patients with subclinical hepatic encephalopathy. This disruption may reflect changes in the output of the circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. It is possible that some of the metabolic disturbances that lead to hepatic encephalopathy may also alter the function of the biological 'clock'.