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Sirs, We read with the interest the article by Wo et al. studying a ghrelin agonist in gastroparesis.1 Ghrelin has a pervasive influence on feeding and sleep; it triggers slow-wave sleep (SWS) and sleep-deprivation (Sdep) increases ghrelin.2–4

Cirrhotics commonly suffer from sleep disturbances and cognitive impairment, but it is unclear whether they are directly related.5–8 The aim of this study was to determine whether ghrelin secretion under waking, sleeping, or Sdep conditions is altered in cirrhotics with minimal hepatic encephalopathy (MHE) and if Sdep results in cognitive worsening.

Five cirrhotic men (53 ± 2 years, BMI 27, MELD 8 ± 2) with MHE were compared with five age/BMI-matched male controls. At baseline, cognitive testing was performed and a standardised diet was prescribed.9 Subjects were admitted a week later for 24-h with hourly ghrelin sampling; sleep with polysomnographic monitoring was allowed. One week later, subjects returned for a 24-h Sdep study with hourly ghrelin testing, after which cognitive testing was repeated.

We found significant disruptions in sleep architecture. SWS occurred in all controls but not in 80% of cirrhotics (P = 0.04). Median SWS time was lower (0% vs. 15%, P = 0.016) and REM time was higher (19% vs. 7%, P = 0.02) in cirrhotics. During the wake/sleep study (994 vs. 1071 pg/mL, P = 0.024) and Sdep (954 vs. 1154 pg/mL, P = 0.037), 24-h mean cirrhotics’ ghrelin levels were significantly lower than those in the controls. Ghrelin levels in those with SWS were significantly lower than those without (689 vs. 1204 pg/mL, P = 0.02). During Sdep ghrelin rose significantly over baseline in controls (1334 ± 173 vs. 994 ± 423 pg/mL, P = 0.04) but not cirrhotics (1007 ± 182 vs. 901 ± 369 pg/mL, P = 0.50, Figure 1). The physiological postprandial ghrelin decrease was also blunted in cirrhotics compared with controls (−84 ± 55 vs. −159 ± 47.2 pg/mL, P = 0.04). In both groups, Sdep did not affect cognition.

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Figure 1.  Patterns of ghrelin secretion in controls (a) and in cirrhotic patients (b). Normal: visit when subjects were allowed to sleep, SD: visit when subjects were sleep deprived. Meal times during both visits were 07:30 hours, 12:30 hours, 16:30 hours and 20:30 hours and all subjects were allowed to sleep in the last 8 h in the first visit. (a) The graph on the left shows the pattern of ghrelin secretion in the healthy controls with the blue lines indicating the visit when they were allowed to sleep and the red line when they were sleep deprived. There was an increase in ghrelin secretion during sleep and a significant increase over this when controls were sleep deprived. (b) The graph on the right shows ghrelin secretion pattern in patients with cirrhosis; the green line represents the visit in which they were allowed to sleep while the purple line is when they were sleep deprived. There is no significant change in ghrelin secretion while being allowed to sleep or when sleep deprived in patients with cirrhosis.

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We conclude that loss of SWS in cirrhosis and MHE is associated with reduced ghrelin levels. Ghrelin response to Sdep and feeding is blunted in cirrhotics compared with controls. Short term Sdep did not alter cognition. Ghrelin may play an important role in the sleep disturbances seen in cirrhosis.

Acknowledgements

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  2. Acknowledgements
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Declaration of personal interests: None. Declaration of funding interests: This study was funded by the General Clinical Research Center (now Clinical and Translational Research Unit) at the Medical College of Wisconsin and partly by the American College of Gastroenterology Junior Faculty Award (both to JSB). Writing was performed by the authors. Initial data analyses were undertaken by CMS.

References

  1. Top of page
  2. Acknowledgements
  3. References