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Am J Physiol Gastrointest Liver Physiol 296: G330-G338, 2009. First published November 20, 2008; doi:10.1152/ajpgi.90488.2008
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LIVER AND BILIARY TRACT

Decreased heart rate variability in patients with cirrhosis relates to the presence and degree of hepatic encephalopathy

¹Centre for Hepatology, Royal Free Campus, University College London Medical School, University College London; ²Department of Neurophysiology, Royal Free Hospital, Royal Free Hampstead National Health Service Trust, Hampstead, London; and ³Critical Care Group, Portex Unit, Institute of Child Health, University College London Medical School, University College London, London, United Kingdom

Submitted 10 August 2008 ; accepted in final form 18 November 2008

Heart rate variability (HRV) is reduced in several clinical settings associated with either systemic inflammation or neuropsychiatric impairment. The possibility that the changes in HRV observed in patients with neuropsychiatric impairment might relate to the overproduction of inflammatory cytokines does not seem to have been considered in the studies undertaken to date. HRV is decreased in patients with liver cirrhosis but its relationship to the impairment of neuropsychiatric performance, commonly observed in these patients, is unknown. The aim of this study was to investigate the relationship between HRV, hepatic encephalopathy, and production of inflammatory cytokines in patients with cirrhosis. Eighty patients with cirrhosis [53 men, 27 women; mean (±1SD) age 54 ± 10 yr], classified as neuropsychiatrically unimpaired or as having minimal or overt hepatic encephalopathy, and 11 healthy subjects were studied. HRV was assessed by applying Poincaré plot analysis to the R-R interval series on a 5-min ECG. Inflammatory cytokines (TNF-, IL-6, IL-10, and IL-12) were measured in a subgroup of patients. Long-term R-R variability was significantly decreased in the patients with cirrhosis, in parallel with the degree of neuropsychiatric impairment (P < 0.01) and independently of the degree of hepatic dysfunction (P = 0.011). The relative risk of death increased by 7.7% for every 1-ms drop in this variable. Plasma levels of IL-6 significantly correlated with indexes of both HRV and neuropsychiatric performance. The changes observed in HRV and in neuropsychiatric status in patients with cirrhosis are significantly correlated, most likely reflecting a common pathogenic mechanism mediated by inflammatory cytokines.

inflammatory cytokines; electroencephalogram; linear/nonlinear dynamics; Psychometric tests; systemic inflammatory responses