DISRUPTION OF THE DIURNAL RHYTHM OF PLASMA - MELATONIN IN LIVER-CIRRHOSIS

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 cirr hosis. Design: Prospective cohort study. Patients. A total of 14 subje cts, 7 non-alcoholic cirrhotics and 7 age-, sex-, and educationally-ma tched controls. Exclusion criteria were factors that could affect mela tonin levels (intercontinental travel, shift work, therapy with betabl ockers or corticosteroids), Measurements: Plasma melatonin was measure d every 30 min for 24 hr by radioimmuno assay and sleep recordings by polysomnography. Neuropsychological testing included visual reaction t ime, Trail-making test A and B and the Digit Symbol Test. Sleep diarie s were kept for the week prior to admission. Results: Time of onset of melatonin rise was displaced from 19:50 +/- 26 min in the controls to 21:30 +/- 13 min (p=0.013) in patients with liver cirrhosis. The time of peak melatonin levels was consistently and significantly delayed f rom 00:36 +/- 33 min in controls to 5:36 +/- 29 min (p<0.001) in patie nts. Cirrhotic subjects showed markedly elevated melatonin levels duri ng daytime, when melatonin is normally absent. Polysomnographic tracin gs showed no differences in patients and controls, but sleep diaries i ndicated 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 di sruption may reflect changes in the output of the circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. It i s possible that some of the metabolic disturbances that lead to hepati c encephalopathy may also alter the function of the biological ''clock ''.