Glucocorticoid Receptor Expression In Acute-On-Chronic Liver Failure

Objectives The present study was aimed to evaluate the glucocorticoid receptor(GR) expression profiles in patients with acute-on-chronic liver failure(ACLF), and to explore the role and significance of GR expression in the pathogenesis of ACLF.Methods Twenty-four patients with ACLF from out-patients of Shanghai Public Health Clinical Center were enrolled in this present study, and the diagnoses conformed to the Diagnostic and treatment guidelines for liver failure made by Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association and Severe Liver Diseases and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association in 2006. Twenty patients with chronic hepatitis B from out-patients of Department of Hepatology, Qilu Hospital of Shandong University were also enrolled. The diagnosis of CHB was made according to the criteria established on the Viral Hepatitis Conference held in Xi'an in 2000.Sixteen healthy volunteers come from Health Examination Center, Qilu Hospital of Shandong University.Flow cytometry was used to analyze the protein expression of GR in CD3+T lymphocytes in both early and late stages of ACLF and CHB. GRa and GRβmRNA expression in PBMCs were determined by RT-PCR. Serum cortisol concentrations were determined by radioimmunoassay.Continuous normally distributed variables were represented graphically as mean±standard error (SEM). To compare the means between groups, one-way analysis of variance (ANOVA) or t-test was performed. The post hoc comparisons were performed using Duncan's multiple test. The degree of association between variables was assessed using pearson correlation. All statistical analyses were performed using SPSS for windows, version 14.0 (SPSS Inc. Chicago, IL, USA). Ap-value of less than 0.05 was considered to be statistically significant.Results1. Compared with healthy controls (HC), the protein levels of CD3/GR in patients with ACLF and CHB were decreased, especially in late-stage ACLF (P<0.01).2.The concentrations of cortisol in early-stage ACLF were significantly lower compared with HC, but higher in late-stage ACLF (P<0.05; P<0.01).The expression of GR in CD3+T cells in patients with ACLF was significantly negatively correlated with serum cortisol concentrations (P<0.05).3.Compared with HC, the positive rates of GRβmRNA expression in PBMCs in patients with CHB and ACLF were gradually increased, especially in ACLF group (P <0.05).Conclusions Glucocorticoid receptors are down-regulated in CD3+T lymphocytes in association with increased adrenal secretion of cortisol in ACLF. It is possible that glucocorticoid receptor down-regulation indicates disorders of stress response and also may be associated with altered immune status of patients with ACLF of different stages. Furthermore, we found that increasing GRβmRNA in PBMCs may participate in the mechanism of ACLF.