Mechanism Of Intestinal Mucosal Barrier Dysfunction In Patients With Liver Diseases

Objective The aim of this study is to determine the extent of intestinal mucosal barrier dysfunction in patients with hepatitis,cirrhosis and primary liver cancer,and to investigate the relationship between intestinal mucosal barrier dysfunction and the expression of inflammatory factors.Methods A total of 177 serum samples were collected from patients with hepatitis,liver cirrhosis and primary liver cancer.According to the inclusion and exclusion criteria,54patients with hepatitis,61 patients with liver cirrhosis,52 patients with primary liver cancer and 61 healthy controll patients were included in the final analysis.The level of the indicators of intestinal barrier functions like diamine oxidase(DAO),d-lactic acid(DLA)and endotoxin(ET)were detected by limulus Amebocyte lysate and spectrophotometry.The expression levels of inflammatory factors were measured by enzyme-linked immunosorbent(ELISA),including toll-liked receptor 4(TLR4),nuclear factor-κ-gene binding(NF-κB),tumor necrosis factor-α(TNF-α)interleukin-6(IL-6)and interleukin-10(IL-10).The clinical data and laboratory indexes of all patients were entered into Epi Data database.Using SPSS 22.0 software to analyze the changes of intestinal mucosal barrier function and the expression of inflammatory factors in patients with hepatitis,liver cirrhosis and liver cancer.Results As compared with the healthy controll group,the intestinal mucosal barrier appeared different degrees of damage in the patients with hepatitis,liver cirrhosis and liver cancer,especially in liver cirrhosis.The expression level of d-lactic acid and endotoxin in cirrhosis patients were significantly increased(P=0.003 and P<0.001).According to the child-pugh classification of liver function,cirrhosis patients were divided into three groups:child A,child B and child C.The damage of the intestinal mucosal barrier in child C group was more serious than that in child A and child B groups,especially the level of DAO and endotoxin was significantly increased(P=0.012and P<0.05).According to the etiology,patients with liver cirrhosis were divided into post-viral hepatitis cirrhosis group,autoimmune cirrhosis group and alcoholic cirrhosis group.In the three groups,the damage of the intestinal mucosal barrier in the alcoholic cirrhosis group was the most serious,serum endotoxin level was significantly increased in that group(P<0.05).Compared with the healthy controll group,the expression of TLR4,NF-κB,TNF-αand IL-6 were increased in other three groups,and the expression of TLR4,NF-κB and IL-6 were significantly increased in the liver cirrhosis group(P=0.004,0.017 and 0.001 respectively)and liver cancer group(P=0.001).The inflammatory reaction in child C group was more serious than that in groups A and B,and the expression level of IL6 was statistically significant(P=0.027);according to the etiology classification,patients with alcoholic cirrhosis had a more obvious inflammatory reaction,but this difference was not statistically significant.The inflammatory reaction in child C was more serious than that in groups A and B,and the expression level of IL6 was statistically significant(P=0.027);Patients with alcoholic cirrhosis had a more obvious inflammatory reaction,but the difference was not statistically significant.The TLR4 and NF-κB in patients with hepatitis,liver cirrhosis and liver cancer were used as dependent variables,and diamine oxidase,d-lactic acid and endotoxin were used as independent variables which were included in multiple linear stepwise regression for analysis.The results showed that the expression level of TLR4 was similar to that of d-Lactic acid and endotoxin are positively correlated(R~2=0.630);the expression level of NF-κB is positively correlated with D-lactic acid(R~2=0.559).Conclusion With the progress of the disease and the prolonging course of the disease,the destruction of the intestinal mucosal barrier function and the inflammatory response in patients with hepatitis,cirrhosis and liver cancer were positively correlated.The destruction of the intestinal mucosal barrier function and the inflammatory response increased gradually as the disease progresses.The intestinal mucosal barrier damage could stimulate the expression of TLR4,activates the innate immune response and release inflammatory mediators,which lead to hepato-intestinal circulation disorders and promotes disease progression;improving the intestinal micro ecological environment and maintaining the intestinal mucosal barrier function can reduce the inflammatory response of liver disease,to provide new ideas for the treatment of liver disease.