Anti-hepatic Failure Compound Treatment Of Severe Hepatitis Clinical Observation And Experimental Study, The Protective Effect Of Acute Liver Failure In Rats

Objective:To observe clinical effect of KangGanShuaiFuFang (KGSFF) decoction in patients who were suffering from fulminant hepatitis and to investigate the effect of KGSFF decoction in protection of acute liver failure, explore its possible mechanism, we established the model of acute liver failure in Wistar rats.Methods:Clinical study: One hundred and twenty cases of fulminant hepatitis were selected at random and divided into tow groups,60 cases in control group were treated with western medicine ,60 cases in treatment group were treated combined with western medicine and KGSFF(orally taken and/or enema),which was taken 100ml each time ,1 time a day and 14 days as a treating course. The patients were treated 3 treating courses. Their clinical manifestation, clinical signs and result of liver function test were observed and compared. The total effective rate was counted.Experimental research: 110 Wistar male rats, weighed 180-220g,were randomly divided into 6 group: normal group(8 rats),ALF group(20 rats),PHGF group(20 rats),YinChenHaoTang group(20 rats),KGSFF group of small dose(20 rats),KGSFF group of large dose(20 rats).All rats except the normal group were injected with D-GalN 800mg/kg and LPS 0.1mg/kg to induce the model of acute liver failure in rats and the normal group injected with the 0.9% salt solution intraperitoneally. After tow hours of the administration with D-GalN/LPS, the rats were treated with corresponding drug including sodium chloride, PHGF, YinChenHaoTang and KGSFF large and small dosages, respectively 1.5ml/100g twice a day. 72 hours later, the mortality of the rats was counted. The serum levels of ALT, AST, TBil and TNF-αwere determined respectively. The pathological alterations of the livers were examined with hematoxylin and eosin stain under optics microscopy. The expression of TNF-αwas detected by immunohistochemistry. Results:The results of clinical study: The marked improvement rate was 48.3% and total effective rate was 71.7% in treatment group, compared to 20.0% and 51.7% in control group. The difference was significant (P < 0.05 or P < 0.01). After 3 treating courses, the clinical manifestation, clinical signs were ameliorated. The improvement of AST, TBil in treatment group was greater than those of in control group. The difference was significant (P < 0.05 or P < 0.01).The results of experimental research: 1. The mortality of the rats: After the administration with D-GalN/LPS,the mortality of the rats were increased, there were significant different between the normal group and the model group (P < 0.01). There were also significant difference among KGSFF group of large dose, the PHGF group and the model group (P < 0.05).2. The serum level of liver function: After the administration with D-GalN/LPS, the serum level of liver function (ALT, AST, TBil) increased obviously. There were significant different between the normal group and the model group (P < 0.01).These indexes were improved in other groups, there were also significant difference between KGSFF group of large dose and the model group (P < 0.01, P < 0.05).But there were insignificant differences among YinChenHaoTang group, KGSFF group of large dose and small dose (P > 0.05).3. The serum level of TNF-α: After the administration with D-GalN/LPS, the serum level of TNF-αincreased distinctly. There were significant different between the normal group and the model group (P < 0.01). As compared with the model group, KGSFF group of large dose and PHGF group were decrease evidently (P < 0.01).4. The pathological alterations of the livers: Hepatic cells were distributed radiatively around central vein in normal group. Diffuse necrosis of hepatic cell and inflammatory cell infiltration were observed. The ultrastructures of livers were ameliorated in the PHGF group, YinChenHaoTang group, KGSFF group of large dose and small dose. KGSFF group of large dose is better than others.5.The expression of TNF-αin the liver: In the normal group, the expression of TNF-αin hepatic tissue is the lowest than other groups. There were significant different between the normal group and the model group (P < 0.01). As compared with the model group, KGSFF group of large dose and PHGF group were decrease obviously (P < 0.01).Conclusion:KGSFF decoction was helpful to improve total effective rate, ameliorated the clinical manifestation and clinical signs, reduce the serum level of AST and TBil.It shows that this treatment is one of the effective measures to improve overall treatment of fulminant hepatitis.KGSFF decoction can decrease the mortality of the rats of ALF and the indexes of liver function (ALT, AST, TBil), reduce the serum level of TNF-α, ameliorate the damage of liver, inhibit the expression of TNF-αin hepatic tissue. These results fully demonstrated that KGSFF decoction had positively preventive effects on acute liver failure. Its possible mechanism can be explored. We think it relate to promoting the choleresis and the evacuation of bilirubin,declining aminotransferase decreasing the lever of TNF-α, alleviating the degree of liver injury, protecting the hepatocyte, resuming the lever of the liver. And it can be have the action of detoxicate and purgation which can promote the excretion of poisonous material, reduce source and absorption of endotoxin, intercept the occurrence of intestinal endotoxemia, control and reduce various complications.