Centre for Hepatology, Department of Medicine, Royal Free Campus, University College London Medical School, University College London, London, UK.
Am J Gastroenterol. 2010 Aug;105(8):1773-81. doi: 10.1038/ajg.2010.86. Epub 2010 Mar 23.
Plasma melatonin profile abnormalities have been described in patients with cirrhosis and generally attributed to impaired hepatic melatonin metabolism. The possibility that they might reflect circadian clock dysfunction has not been explored. In addition, the relationship between plasma melatonin profiles and the sleep disturbances observed in these patients remains unclear. The aims of this study were: (i) to evaluate circadian clock function and hepatic melatonin metabolism in cirrhotic patients, and (ii) to study the relationship between plasma melatonin profiles and sleep-wake behavior.
The study population comprised 20 patients with cirrhosis (mean (range) age, 59 (39-77) years) and 9 healthy volunteers (60 (38-84) years). Plasma melatonin/cortisol concentrations were measured hourly, for 24 h, in light/posture-controlled conditions. Urinary 6-sulfatoxymelatonin, the main melatonin metabolite, was measured simultaneously to determine clearance. The ability of light to suppress nocturnal melatonin synthesis was assessed. Habitual sleep quality/timing was evaluated using a questionnaire, actigraphy, and sleep diaries.
There was evidence of central circadian disruption in patients compared with healthy controls: peak plasma melatonin/cortisol times were delayed (04:48+/-02:36 vs. 02:48+/-00:54, P=0.01; 10:18+/-02:54 vs. 08:54+/-01:24, P=0.06) and the plasma melatonin response to light was reduced (12%+/-19% vs. 24%+/-15%, P=0.09). However, the mean 24 h plasma melatonin clearance did not differ significantly between patients and healthy volunteers (0.22+/-0.10 vs. 0.28+/-0.17 l/kg per h, P=0.36). Finally, although patients showed a degree of misalignment between sleep and circadian timings, there was no association between circadian abnormalities and impaired sleep quality.
Plasma melatonin profile abnormalities, predominantly central in origin, are observed in patients with mild to moderately decompensated cirrhosis. However, they are substantially unrelated to the sleep disturbances prevalent in this population.
已经描述了肝硬化患者的血浆褪黑素谱异常，通常归因于肝褪黑素代谢受损。它们是否可能反映昼夜节律钟功能障碍尚未得到探索。此外，这些患者观察到的血浆褪黑素谱与睡眠障碍之间的关系尚不清楚。本研究的目的是：（i）评估肝硬化患者的昼夜节律钟功能和肝褪黑素代谢，以及（ii）研究血浆褪黑素谱与睡眠-觉醒行为之间的关系。
研究人群包括 20 名肝硬化患者（平均（范围）年龄，59（39-77）岁）和 9 名健康志愿者（60（38-84）岁）。在光照/体位控制条件下，每小时测量一次 24 小时的血浆褪黑素/皮质醇浓度。同时测量主要褪黑素代谢物 6-硫酸褪黑素以确定清除率。评估光对抑制夜间褪黑素合成的能力。使用问卷、活动记录仪和睡眠日记评估习惯性睡眠质量/时间。
与健康对照组相比，患者存在中枢昼夜节律紊乱的证据：血浆褪黑素/皮质醇峰值时间延迟（04:48+/-02:36 对 02:48+/-00:54，P=0.01；10:18+/-02:54 对 08:54+/-01:24，P=0.06），对光的血浆褪黑素反应降低（12%+/-19% 对 24%+/-15%，P=0.09）。然而，患者和健康志愿者之间的平均 24 小时血浆褪黑素清除率无显著差异（0.22+/-0.10 对 0.28+/-0.17 l/kg per h，P=0.36）。最后，尽管患者的睡眠和昼夜节律时间存在一定程度的不匹配，但昼夜节律异常与睡眠质量受损之间没有关联。
在轻度至中度代偿失调的肝硬化患者中观察到血浆褪黑素谱异常，主要是中枢性的。然而，它们与该人群中普遍存在的睡眠障碍有很大的关系。
