Literature Analysis And Clinical Study Of Traditional Chinese Medicine In The Regulation Of Intestinal Microecology With Chronic Liver Disease

Objective:This dissertation main contains two relevant parts: the first part is literature analysis of traditional Chinese Medicine in the regulation of intestinal microecology with chronic liver disease;the second part is cinical study on the influence of entero-hepatic immune and intestinal flora at chronic hepatitis B treated by DWYGJWF combined with Entecavir.There are lots of modern literature on TCM in the treatment of chronic liver disease, but there is little literature of TCM within the regulation of intestinal microecology at chronic liver disease,and also lack of systematic concluded and summary. The first part reviewed the literature on TCM clinical and animal studies in recent15 years,we analyzed, concluded and summarized the law of TCM in the regulation of intestinal microecological with chronic liver disease, which could provide a theoretical basis for clinical treatment and scientific research.The second part compared the clinical efficacy of "Fuzheng Quxie" DWYGJWF combined with Entecavir that treated in patients withchronic hepatitis B, we also compared the varity of TCM symptoms,entero-hepatic immune, plasma endotoxin level and intestinal flora with the patients. By observing the incidence of adverse events,we evaluated the safety of this study.Method and Results:1 Literature analysis of TCM in the regulation of intestinal microecology with chronic liver disease1.1 Method:We searched the related literature from CNKI and Wanfang Med Online that from January 1999 to September 2015. By reading the literature title and summary, we rejected literature review,nursing, theoretical study and repeated literature reports after screening.We use Excel 2010 to statistics and analysis of the using of TCM in the literature, counting the frequency of TCM use, the probability of TCM classification, four properties, five tastes and channel tropism.1.2 Results:1.2.1 A total of 64 literatures were selected, including 7 kinds of diseases, 50 TCM compound, 13 TCM patent prescription and 126 kinds of medicinal herbs.1.2.2 All TCM herbs appears 502 times, the largest medicine frequency is 36 times, the minimum is 1 times. The top ten are: rheum officinale, radix paeoniae rubra, radix salviae miltiorrhizae,fructus aurantii immaturus, magnolia officinalis, herba artemisiae scopariae, rhizoma atractylodis macrocephalae, poria, radix, astr-agali seuhedysari, glycyrrhiza uralensis. 126 kinds of TCM herbal were recorded by "Chinese Materia Medica", and cover 17 categories and 34 small classifications. The top five of categories were: tonicdrug, heat clearing drugs, eliminating dampness, blood activating and stasis eliminating drugs, regulating qi flow drugs.1.2.3 In 126 kinds of TCM herbal, the most of four properties was cold, the most of five tastes was bitter, and the most of channel tropism was liver meridian.1.2.4 In seven kinds of diseases, the severe hepatitis was the first,the liver cirrhosis was second and fatty liver disease was third.2 Cinical study on the influence of entero-hepatic immune and intestinal flora at chronic hepatitis B treated by DWYGJWF combined with Entecavir2.1 Method:2.1.1 According to successively sequence, the chronic hepatitis B patients who met the inclusion criteria were randomly assigned to the treatment group and the control group with 1:1.2.1.2 There were 90 cases of chronic hepatitis B patients who met the inclusion criteria, 45 cases were control group(oral Entecavir)and 45 cases were treatment group(DWYGJWF combined with Entecavir).The course of treatment was 24 weeks.2.1.3 All patients filled in the TCM syndrome score table and chronic liver disease quantity table at first visit, 12 weeks and24 weeks.2.1.4 By observing and anasising the HBV-DNA, liver function,immune index, plasma endotoxin, intestinal flora and adverse events after treatment, we evaluated the integrity and effectiveness of TCM combined treatment.2.1.5 We use SPSS for windows 20.0 to statistics. All statistical tests were two sided test, P<0.05 showed significant differences;P>0.05 showed no significant differences.2.2 Results:2.2.1 Comprehensive clinical efficacy compared after 24 weeks of treatment, treatment group had zero markedly effective cases, 36 effective cases, 8 ineffective cases, and the total efficiency was81.8%; control group had zero markedly effective cases, 34 effective cases, 10 ineffective cases, and the total efficiency was77.3%. The two groups comparing, P=0.661,P>0.05,the difference was not statistically significant.2.2.2 TCM syndrome score compared, treatment group after 12 W, 24 W treatment, P<0.001, there was a significant difference. Control group treated for 12 W, P=0.058,P>0.05,there was no significant difference; after 24 W treatment, P<0.001,there was a significant difference. Between the two groups comparison, P<0.05, there was a significant difference.2.2.3 Curative effect of TCM syndrome compared, after 24 W treatment,treatment group had 7 cured cases, 14 markedly effective cases, 19 effective cases, 4 ineffective cases, and the total efficiency was90.9%; control group had 5 cured cases, 7 markedly effective cases,21 effective cases, 11 ineffective cases, and the total efficiency was 75.0%. Two groups comparing, P=0.021,P<0.05,there was a significant difference.2.2.4 Chronic liver disease quality of life compared, before and after treatment, treatment group in terms of AS,FA, SS, AC, EF,WO was significant difference(P<0.01), while control group in terms of AS, FA, SS had improved(P < 0.05),in terms of EF had no improvement(P>0.05), but in terms of WO was invalid.2.2.5 Serum HBV-DNA levels compared, two groups after 12 W, 24 W trea-tment compared with before, P<0.001, it was showed significant differences. Compared between the two groups at 12 W treatment, P>0.05, it was showed no significant difference; at 24 W treatment,P<0.05, there was a significant difference.2.2.6 Serum HBV-DNA negative rate compared, it was 61.3% and 81.8%at treatment of 12 W and 24 W in treatment group; 56.8% and 72.7% in control group. The two groups were compared, serum HBV-DNA negative rate at 12 W, 24 W, P>0.05, there was no significant difference.2.2.7 Serum levels of ALT compared, two groups treated after 12 W and 24 W were significantly decreased compared with before. Two groups treated 12 W compared with before, P<0.001, there was a significant difference; but compared with 24 W, P>0.05.Comparing of the two groups in treatment of 12 W and 24 W respectively, P>0.05, it was showed no significant difference.2.2.8 Serum ALT recovery rate compared, the two groups after 12 W treatment compared, P=0.538,P>0.05, there was no significant difference; after 24 W treatment compared, P=3.153,P>0.05,there was no significant difference.2.2.9 CD4+、CD8+、CD4+/CD8+compared, after treated for 24 weeks,each group of CD4+、CD8+、CD4+/CD8+compared with treatment before respectively, P < 0.05, there was a significant difference;compared CD4+、CD8+、CD4+/CD8+among two groups, P<0.05, there was a significant difference.2.2.10 IL-10、TGF-βcompared, after treated for 24 weeks, each group of IL-10、TGF-βcompared with treatment before respectively,P<0.05,there was a significant difference;compared IL-10、TGF-βamong two groups, P<0.05,there was a significant difference.2.2.11 IL-6、TNF-αcompared, after treated for 24 weeks, each groupof IL-6、TNF-αcompared with treatment before respectively, P<0.05,there was a significant difference; compared IL-6、TNF-αamong two groups, P<0.05, there was a significant difference.2.2.12 Plasma endotoxin level compared, after treated for 24 weeks,each group of plasma endotoxin level compared with treatment before respectively, P<0.05, there was a significant difference compared plasma endotoxin level among two groups, P<0.05, there was a significant difference.2.2.13 After 24 weeks treatment, a total of 43 stool samples were collected, including 23 cases in treatment group and 20 cases in control group. Each group was randomly selected 7 cases for detecting which used Illumina Mi Seq high throughput sequencing platform. We received 811157 effective sequences, 657799 highly quality sequences from the 14 cases of stool samples(7 cases in treatment group, 7 cases in control group).High-quality sequences accounted for more than 75% of the effective sequence.Through comparison of OTU number, ACE, Chao, Simpson, Shannon value,Abundance Rank curve and PCA analysis with the two groups, the results showed that there was no significant difference in the diversity of intestinal flora in the treatment group and the control group, but there were differences in the intestinal flora abundance,and the abundance in treatment group was rich. Phylum level of the two groups compared, Firmicutes in treatment group was higher than that in control group and had statistical difference(66% VS35%,one-way ANOVA test,P<0.05); Bacteroidetes were significant differences,too(18% VS 46%,P<0.05). Genus level of the two groups compared, Prevotella in two groups had significant difference;Bifidobacterium in treatment group had significant differencecompared with the control group(7% VS 2%,P<0.05); Lactobacillus in both groups were less than 1%, the difference is not obvious(P>0.05).Conclusions:1 The most of categories of TCM in the regulation of intestinal microecology with chronic liver disease is tonic drug. “Fuzheng Quxie” may be the general principle through out the treatment process.2 DWYGJWF combined with Entecavir treated in patients with chronic hepatitis B showed significant clinical effect. It can signify-cantly improve the clinical symptoms of TCM, and enhance the quality of life of chronic hepatitis B patients.It can obviously reduce the level of HBV-DNA and ALT. It can regulate the body-intestinal immune system and reduce inflammatory damage by improving the marks of CD4+、CD8+、CD4+/CD8+、IL-10、TGF-β、IL-6、TNF-α.It also can remission the intestinal endotoxemia by reducing the level of plasma endotoxi.4 The effect of DWYGJWF in the regulation of the diversity of intestinal flora is not obvious, but in the intestinal flora richness and dominant bacteria abundance has a certain regulatory function.5 The treatment plan of this study is highly safety, less side effect and worthy of promoting.