Effect Of Rifaximin On Gastrointestinal Symptoms、Endotoxin And TLR4 Expression In Patients With SIBO-positive Cirrhosis

BackgroundSIBO often occurs in patients with cirrhosis.Gastrointestinal tract is the most commonly involved extrahepatic organ,often presenting a series of symptoms such as abdominal pain,abdominal distension and diarrhea,which have similar clinical manifestations with digestive tract symptoms caused by SIBO.Currently,many studies^[1-5]have shown that SIBO plays an important role in the occurrence and development of liver cirrhosis complications such as hepatic encephalopathy and endotoxemia,but regarding whether SIBO is involved in the development of gastrointestinal symptoms of cirrhosis.In addition,LPS was one of the ligand of TLR4,which could induce the release of a large number of inflammatory factors and aggravate the condition of cirrhosis.In 2000^[6],the efficacy of rifaximin in the treatment of SIBO was first proved.At present,rifaximin is also widely used in the prevention and treatment of liver cirrhosis related complications,but its mechanism remains to be explored.Therefore,in the second part of this study,while rifaximin was used to partially inhibit SIBO,it was observed whether the LPS-TLR4 target could be regulated to delay the progression of cirrhosis.Objective1.To explore the role of SIBO in gastrointestinal symptoms of patients with hepatitis B cirrhosis;2.To evaluate the improvement of digestive tract symptoms after rifaximin intervention.3.To observe the effect of rifaximin intervention on serum endotoxin and TLR4expression in patients with hepatitis B cirrhosis,and to explore the possible mechanism of the application of rifaximin in patients with SIBO positive cirrhosis.MethodsAll enrolled patients with hepatitis B cirrhosis and healthy subjects were tested for SIBO,and gastrointestinal symptom score was evaluated simultaneously.On the basis of antivirus,liver protection and enzyme reduction and other routine treatment,the disease was relatively stable,Patients with decompensated cirrhosis who were SIBO-positive were treated with rifaximin（Ciphesen,Alfressimann Pharmaceuticals,Italy,200 mg×12 tablets）at 400 mg twice a day for 4 weeks.Gastrointestinal symptom score and SIBO were evaluated on the first day after treatment.At the same time,all patients with decompensated cirrhosis with positive SIBO were measured for endotoxin and TLR4 before rifaximin treatment and after treatment,respectively,to observe the changes in their expression.Results1.The incidence of positive SIBO and gastrointestinal symptom score in the hepatitis B cirrhosis group were significantly higher than those in the healthy division,with statistical difference（χ²=14.46,Z=-3.85,P<0.05）;Compared to the healthy group,the incidence of SIBO and gastrointestinal symptom scores in Child-Pugh grade A cirrhosis patients were not statistically significant（χ²=0.94,Z=-1.59,P>0.05）.The incidence of positive SIBO and gastrointestinal symptom scores in Child-Pugh grade B and grade C cirrhosis patients were significantly higher than those in the healthy group,and showed significant statistic difference（χ²=11.80、28.47,Z=-4.21、-4.13,P<0.05）.There were statistically significant differences in the incidence of positive SIBO and the score of gastrointestinal symptoms between compensatory cirrhosis（group A）and decompensated cirrhosis（group B and C）groups（χ²=12.21,t=-10.55,P<0.05）.See table 1.2.The gastrointestinal symptom score of patients with SIBO positive（8.92±2.02）was higher than that of patients with SIBO negative（7.38±3.04）,the difference between the two was statistically significant（t=2.48,P=0.02）,See table 2.3.Sixteen of the 24 SIBO-positive cirrhosis patients turned negative after treatment with rifaximin,and the score of gastrointestinal symptoms decreased significantly after treatment compared with before treatment（6.46±3.33 VS 8.92±2.02,t=3.62,P=0.001）,which was statistically significant difference,See table 5.The score of gastrointestinal symptoms in patients with negative SIBO after treatment（n=16,3.63±0.96）was significantly lower than that in patients with positive SIBO（n=8,6.13±3.44）,the difference was statistically significant（t=-2.76,P=0.01）,See table 4.4.The endotoxin level of after treatment was obvious lower than before treatment,with statistically difference（0.42±0.05 VS 0.56±0.10,t=6.20,P=0.00）,See table 5.5.GMF of CD14⁺monocytes in peripheral blood after rifamximin treatment were24.41±4.86,which were significantly lower than those before rifamximin treatment 28.21±6.65,with statistical significance（t=2.61,P=0.02）,See table 5.Conclusion1.Patients with decompensated cirrhosis are prone to SIBO and gastrointestinal symptoms.2.After oral administration of rifaximin,SIBO could be partially suppressed,and the symptoms of digestive tract discomfort were improved to varying degrees.It is suggested that SIBO may play a role in gastrointestinal symptoms of decompensated cirrhosis,and provides a new direction for the treatment of gastrointestinal discomfort in patients with cirrhosis.3.Serum endotoxin levels and TLR4 expression were decreased after rifaximin treatment,suggesting that rifaximin may play a role by inhibiting endotoxin and down-regulating TLR4.