The Role And Mechanism Of Glucocorticoid In Preventing The Occurrence Of Acute Liver Failure

Acute liver failure (ALF) is a serious clinical syndrome, which is characterized with highmortality and great difficulty in treatment. Generally, its treatment measures include nutritionsupport, etiological treatment, prevention and treatment of complication, artificial liversystems, liver transplantation, etc. Except liver transplantation, there is no effective measureat present. However, shortage of liver donated restricts its clinical application. Therefore, it ismore important for active intervention before ALF than passive treatment after ALF.According to Japanese scholars and our early researches, glucocorticoid can effectivelyprevent acute pre-liver failure associated hepatitis B virus (pre-ALF-HBV) from developinginto ALF. However, there is also dispute in the efficacy of glucocorticoid. Its reason isassociated with difference between indefinite realization of glucocorticoid treatmentmechanism and opportunity selection of treatment. Japanese scholars consider the data shouldbe analyzed based on each etiology and the timing of starting glucocorticoid for preciseevaluation of the efficacy of glucocorticoid in ALF, they have realized that the timing forstarting glucocorticoid in ALF is limited to the early stage of illness when aminotransferase ishigh, total bilirubin is low and INR begins to be prolonged. No therapy except livertransplantation is effective in the late stage of liver failure.In this research, glucocorticoid is used for pre-intervention treatment of rats with ALFinduced with D-galactosamine (D-GalN) and lipopolysaccharide (LPS), so as to observe theefficacy of glucocorticoid and its effect on P-glycoprotein expression of rats’ hepatic tissuesand to determine the mechanism of glucocorticoid preventing ALF. At the same time,72patients with severe chronic hepatitis B (CHB) in Infectious Department of SouthwestHospital are collected, observe effects of glucocorticoid on serum cytokines and its clinicalefficacy, and to discuss possible mechanism of glucocorticoid in improving liver functionsand preventing liver failure.The major results as follows:1.12h and24h after rats were subject to intraperitoneal injection with D-GalN/LPS to induce ALF, the P-gp expression level of hepatic tissue was significantly higher than that ofnormal rats (P<0.05).2.2h after rats were subject to intraperitoneal injection with D-GalN/LPS, rats wereprovided with dexamethasone intervention treatment. In the glucocorticoid treatment group,the rat mortality was40%(8/20), significantly lower than that of the control group (75%,15/20), P=0.025.24h after injection with D-GalN/LPS, alanine aminotransferase level in theglucocorticoid treatment group was significantly lower than that of the control group(P<0.05),12h and24h after injection with D-GalN/LPS, aspartate aminotransferase levels inthe glucocorticoid treatment group were significantly lower than those of the control group(P<0.05),12h after injection with D-GalN/LPS, total bilirubin level in the glucocorticoidtreatment group was significantly lower than that of the control group (P<0.05).6h,12h,24hand36h after injection with D-GalN/LPS, the P-gp expression levels of hepatic tissue in theglucocorticoid treatment group were significantly higher than those of the control group(P<0.001).3. The serum IL-1α, IL-10, TNF-α and IFN-γ levels of patients with severe CHB weresignificantly higher than those of chronic asymptomatic HBV carrier (P＜0.05).4. The serum IL-1α level of patients with glucocorticoid at day0was significantly higherthan that of patients at days5and14during treatment (P＜0.05). The differences of the serumIL-1α level in the patients without glucocorticoid at day0, at days5and14during treatmentwere not statistically signifcant (P＞0.05). The serum IL-1α level of patients withglucocorticoid was significantly lower than that of patients without glucocorticoid at days5during treatment (P＜0.05).5. The liver failure incidence of patients with glucocorticoid (8.82%,3/34) wassignificantly lower than that of patients without glucocorticoid (28.95%,11/38), P＜0.05. Themortality of patients with glucocorticoid (8.82%,3/34) was lower than that of patients withoutglucocorticoid (23.68%,9/38), but the difference was not statistically signifcant (P=0.091).6. The serum total bilirubin levels of patients with glucocorticoid at days5and14duringtreatment were significantly lower than those of patients without glucocorticoid, P<0.05, theserum total bilirubin levels of patients with glucocorticoid at days5and14were significantlylower than that of patients with glucocorticoid at day0during treatment.The prothrombinactivity of patients with glucocorticoid at days5during treatment was significantly higher than that of patients without glucocorticoid at days5(P<0.05) and patients withglucocorticoid at day0during treatment (P<0.05).7. The serum IL-1α level of patients during glucocorticoid treatment was significantlypositively correlated with the serum total bilirubin level of patients (rs=0.308, P<0.05), andsignificantly negatively correlated with the prothrombin activity of patients (rs=-0.409,P<0.05).Conclusions:1. Glucocorticoid can effectively prevent the occurrence of ALF, lighten liver damage,improvie liver functions, improve the survival rate and promote the P-gp expression level ofhepatic tissue. Besides, P-gp plays a role in protecting liver cells. As inferred, glucocorticoidcan promote the P-gp expression of hepatic tissue, which is probably one of importantmechanisms of glucocorticoid in preventing the occurrence of ALF.2. Glucocorticoid is effective in improving liver functions and preventing progression ofsevere CHB, its mechanisms may have relationship with significantly reducing the serumIL-1α level of patients with severe CHB.