Uncoupling of sympathetic nervous system and hypothalamic-pituitary-adrenal axis in cirrhosis

Abstract

Background and aim: The hypothalamic-autonomic nervous system (HANS) axis and the hypothalamic-pituitary-adrenal (HPA) axis are stimulated in parallel in response to stress factors under healthy conditions. This physiological synergism of the axes aims at optimizing anti-inflammatory actions. Therefore, we investigated whether this synergism is altered in patients with liver cirrhosis.

Methods: As a typical marker of the HANS axis neuropeptide Y (NPY is a neurotransmitter of the sympathetic nerve terminal) and of the HPA axis, cortisol together with adrenocorticotropic hormone (ACTH) and cortisol-binding globulin (CBG), were measured in samples from control subjects and patients with liver cirrhosis.

Results: Plasma NPY was found to be increased in cirrhotic patients compared to control subjects (P < 0.01). This increase was observed to be independent of the severity of liver disease (Child class). Serum cortisol was decreased in cirrhotics, particularly in patients with Child A cirrhosis. Plasma NPY was positively correlated with serum cortisol in control subjects (r = 0.32, P < 0.05) reflecting the parallel activation of both axes under the normal condition. However, serum cortisol was not correlated with plasma NPY in cirrhotic patients. For the subgroup of Child A patients, even a negative correlation between NPY and cortisol was observed (r = -0.43, P < 0.05). No significant change in serum levels of ACTH and its positive correlation with serum cortisol was observed in cirrhotic patients.

Conclusions: The present study demonstrates that the two stress axes seem to act in parallel fashion in control subjects but are uncoupled in liver cirrhosis. We discuss how uncoupling of the two anti-inflammatory axes can occur and may contribute to the increased susceptibility for infections and lethal complications in cirrhotic patients.