Clinical Study About The Role Of Glucocorticoid In The Course Of Blocking Hepatitis B To Deteriorate

Background: Severe hepatitis which mostly caused by Hepatitis B virus (HBV) in China has a mortality rate of 70% and a complicate pathogenesis. Hadro-immune response induced by HBV was generally accepted as an important factor for severe hepatitis. Regulatory T cells (Treg) which has the function of negative immune regulation can suppress activation of HBV antigen-specific effector T cells, reduce pathological liver cell injury caused by excessive amplification of immune response. Activated CD8~+ cytotoxic T lymphocyte (CTL) express programmed death receptor-1 (PD-1), T lymphocyte- associated antigen-4 (CTLA-4), inhibitory signals can be passed to limit T cell activation. Although it has been considered that glucocorticoid can inhibit excessive cell mediated immune response and stabilize hepatocyte membrane, but it is still controversial about the application of glucocorticoid in the severe hepatitis B. At the same time, the specific mechanism remains unknown. At present, it has been found, in other diseases, that glucocorticoid can motivate immune balance recovery by means of up-regulate Treg expression, promote the release of suppressor cell cytokine, and restore impaired Treg cells, however, there's little research report about the effect of glucocorticoid on Treg and PD-1, CTLA-4 expressed on CTL in severe hepatitis B.Objective: To investigate the change and clinical significance of the effect of glucocorticoid on Tregs and effector T cells, reveal the immune regulation mechanism of glucocorticoid, and provide a theoretical basis about the role of glucocorticoid in the course of blocking hepatitis B to deteriorate.Methods: The subjects were 128 cases of pre-severe hepatitis B patients, and ordered the same period 24 cases of healthy persons as control. Compared the differences of TBIL, ALT and PTA between glucocorticoid group (GC group) and non-glucocorticoid (NG group) before therapy and 2weeks and 4weeks after treatment. Detected by flow cytometry and compared the differences of Treg, CD4~+T cells, CD8~+T cells, CD4~+ /CD8~+, PD-1 and CTLA-4 between two groups before therapy and 2 weeks after treatment. To statistic the incidence rate of severe hepatitis, hospital day, bleeding and infection rate between GC group and NG group.Results: In GC group, TBIL and PTA were 87.52±95.43 (μmol/L), 52.46±27.25 (%), 68.36±106.48 (μmol/L), 62.35±32.36 (%) after 2 weeks and 4 weeks treatment. There were siginificant differerces in TBIL and PTA between two groups. The incidence rate of severe hepatitis in GC group was 13.2% and that in NG group was 35%, there was significant difference between two groups (χ~2=5.2021, P=0.0226). In GC group and NG group, the hospital day were 24.03±6.89 (d) and 32.13±11.86 (d), respectively, there was also significant difference between two groups (P<0.05). There was no statistical difference in bleeding and infection rate between two groups. In GC group, 2 weeks after treatment in peripheral blood the level of Treg was 5.47±1.16 (%) VS 3.99±2.03 (%) before therapy, t=-2.64, P=0.0156. But in NG group before and after treatment there was no significant difference in Treg. There were significant differences compared with the levels of CD8~+T cells, CD4~+/CD8~+ in GC group 2 weeks after treatment and the levels of those before therapy(P<0.05). The levels of PD-1,CTLA-4 expression on CD8~+T cells in GC group 2 weeks were 9.45±2.60(%),12.10±2.48(%), which were higher than those before therapy,respectively, (t=-2.33, P=0.028), (t=-2.42, P=0.019).Conclusion: Glucocorticoid which up-regulate the expression of Treg and inhibitory receptor of PD-1, CTLA-4, can block hepatitis B to deteriorate, decrease the incidence rate of severe hepatitis, improve liver function, shorten hospital day, suppress hadro-immune response of pre-severe hepatitis B, restore the immune balance, had fewer adverse reaction.