Tuesday, July 25, 2017

Most Individuals With Advanced Cirrhosis Have Sleep Disturbances, Which Are Associated With Poor Quality of Life

Clinical Gastroenterology and Hepatology
August 2017 Volume 15, Issue 8, Pages 1271–1278.e6

Most Individuals With Advanced Cirrhosis Have Sleep Disturbances, Which Are Associated With Poor Quality of Life
Marwan Ghabril , Mollie Jackson, Raghavender Gotur, Regina Weber, Eric Orman, Raj Vuppalanchi, Naga Chalasani
In summary, we describe a high prevalence of disturbed sleep in patients with cirrhosis at a large transplant center. Disturbed sleep was predicted by muscle cramps, which is an important although poorly understood complication of end-stage liver disease. Disturbed sleep in this population appears to be multifactorial in etiology and may be associated with neurocognitive dysfunction. Disturbed sleep is strongly associated with decreased quality of life, and its severity may be meaningfully categorized on the basis of PSQI. Further studies to elucidate the pathogenesis and therapies for disturbed sleep in patients with cirrhosis are needed in the face of this significant and unmet need.
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Abstract
Background & Aims
Sleep disturbances are common in patients with cirrhosis, but their determinants and effects on health-related quality of life are not well-understood. We investigated the prevalence of disturbed sleep in these patients, factors associated with sleep disruption, and effects on quality of life.

Methods
We performed a prospective, cross-sectional study of 193 stable ambulatory patients with cirrhosis (154 with decompensated cirrhosis). Participants completed the Pittsburgh Sleep Quality Index (to assess sleep quality), the Chronic Liver Disease Questionnaire (CLDQ), and muscle cramp questionnaires and underwent neurocognitive testing. Actigraphy was performed in a subset of patients with normal and disturbed sleep. We collected serum samples from subjects with normal and disturbed sleep and performed non-targeted metabolomic analyses.

Results
Of the study subjects, 157 (81%) had disturbed sleep, with Pittsburgh Sleep Quality Index scores >5. Disturbed sleep was associated with muscle cramps, daytime somnolence, and decreased quality of life on the basis of CLDQ scores. Factors independently associated with disturbed sleep in logistic regression analysis included hypoalbuminemia, opiate therapy, and muscle cramps. Disturbed sleep was independently associated with CLDQ score (correlation parameter, –36.6; 95% confidence interval, –24 to –49; P < .001) on linear regression. Disturbed sleep was associated with neurocognitive impairment and with significantly delayed bedtime and decreased total sleep time, measured by actigraphy. Disturbed sleep was associated with metabolome signatures of alterations to the intestinal microbiome and lipid, arginine, and urea cycle metabolism.

Conclusions
Most patients with advanced cirrhosis (81%) have disturbed sleep. This has negative effects on quality of life and is associated with disruptions of several metabolic pathways, including metabolism by the intestinal microbiota.

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