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Cortisol as Biomarkers in Cirrhosis

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Biomarkers in Liver Disease

Abstract

Cortisol is the main glucocorticoid in humans. It is released in a dynamic and circadian manner from the adrenal cortex. Its secretion is regulated by the Hypothalamus-pituitary-adrenal axis. Glucocorticoids function to maintain homeostasis both in response to normal diurnal changes in metabolism and in the face of stressful perturbations. The physiological actions of glucocorticoids are mediated by the glucocorticoid receptor that is expressed in nearly every cell of the body. Increasing evidences support the role of cortisol as biomarker of liver disease. An impairment of adrenal function is a newly defined complication of liver cirrhosis. The term hepato-adrenal syndrome was introduced to define the presence of adrenal insufficiency in patients with advanced liver disease with or without sepsis. The prevalence of adrenal insufficiency is strictly related to disease severity in term of Child Pugh and model for end-stage liver disease scores. The diagnosis of adrenal insufficiency in cirrhosis constitutes a crucial point. Published studies have used a variety of biochemical criteria to define abnormalities in adrenal function during liver cirrhosis. Common methods used in the general population to assess adrenal insufficiency could be invalid in cirrhotic patients because there are a number of confounding factors that make interpretation difficult. The common methods for assessing adrenal function, based on total cortisol, may lead to overestimation of adrenal insufficiency in patients with cirrhosis. The optimal method could be the direct evaluation of free cortisol, but its measurement is difficult in daily clinical practice. The determination of serum free cortisol provides not only the best estimation of adrenal function but has also a prognostic value. Salivary cortisol is a good surrogate marker of free cortisol, but its assay need to be standardized. Cortisol response in cirrhotic patients is an independent prognostic factor. In septic patients, in variceal bleeding, and also in noncritically cirrhotic patients, adrenal insufficiency is related with worse prognosis. Cortisol is a surrogate marker of inflammatory stress, reflecting systemic inflammatory response to intestinal bacterial translocation and occult infections. Adrenal dysfunction may contribute to cardiovascular derangement and represents a marker of circulatory dysfunction. In long-standing decompensated cirrhosis, adrenal glands respond poorly to hypotensive stress, preventing a rise in cortisolemia and reducing the vascular effects of vasoconstrictors. Finally, reduced release of corticosterone from adrenal glands contribute to the impairment of circadian rhythms of motor activity in hyperammonemia and hepatic encephalopathy.

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Abbreviations

11β-HSD-1:

11β-hydroxysteroid dehydrogenase-1

11β-HSD-2:

11β-hydroxysteroid dehydrogenase-2

ACTH:

Adrenocorticotropic hormone

AI:

Adrenal insufficiency

AP-1:

Activator protein-1

CBG:

Corticosteroid binding globulin

CNS:

Central nervous system

CRH:

Corticotropin- releasing hormone

CRP:

C-reactive protein

DBD:

Central-DNA binding domain

EEG:

Electroencephalograms

FCI:

Free cortisol index

GCs:

Glucocorticoids

GEVB:

Gastroesophageal variceal bleeding

GI:

Gastrointestinal

GR:

Glucocorticoid receptor

HDL:

High-density lipoprotein

HE:

Hepatic encephalopathy

HPA:

Hypothalamus-pituitary-adrenal

HRS:

Hepatorenal syndrome

Hsp:

Heat shock protein

LBD:

C-terminal ligand-binding domain

LD-SST:

Low dose short synacthen test

MELD:

Model for end-stage liver disease

NAF:

Normal adrenal function

NAFLD:

Nonalcoholic fatty liver disease

NF-kB:

Nuclear factor- kB

NTD:

N-terminal transactivation domain

RAI:

Relative adrenal insufficiency

REM:

Rapid eye movement

SD-SST:

Standard dose short synacthen test

SFC:

Serum free cortisol

Smad:

Sma and Mad- related proteins

STAT:

Signal transduction and activator of transcription

SWS:

Slow wave sleep

T2D:

Type-2 diabetes

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Correspondence to Luisa Spadaro , Graziella Privitera , Giuseppe Fede , Giovanni Meli or Francesco Purrello .

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Spadaro, L., Privitera, G., Fede, G., Meli, G., Purrello, F. (2016). Cortisol as Biomarkers in Cirrhosis. In: Preedy, V. (eds) Biomarkers in Liver Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7742-2_39-1

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  • DOI: https://doi.org/10.1007/978-94-007-7742-2_39-1

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