Therapeutic Evaluation Of Chinese Medicine Combined With Ursodeoxycholic Acid For Primary Biliary Cirrhosis

Primary biliary cirrhosis(PBC) is a chronic cholestatic liver disease. By hepatic portal venous inflammatory cell infiltration and immune system mediated hepatic lobule of bile duct injury of PBC occurs in middle-aged women. The main clinical manifestations were fatigue, pruritus, eventually progress to cirrhosis and liver failure.The exact pathogenesis is still unclear. Serum antimitochondrialantibody AMA-M2 subtype positive for the disease diagnosis with very high Sensitivity and specificity, but the PBC and the titer level and prognosis was not related to [1]. For AMA negative patients, they need liver biopsy and pathological examination to confirm the diagnosis[2].Ursodeoxycholic acid is the randomized controlled trials confirmed that the only safe and effective drug in the treatment. UDCA although can improve the biochemical and clinical parameters, but it is not effective for all patients and it doesn’t really improve the long-term survival of patients with rate and the demand for liver transplantation and in patients with poor biochemical response to UDCA, there is still no unified treatment scheme.Traditional Chinese medicine, pay attention to overall concept and differentiation of symptoms and signs on the treatment, combining syndrome differentiation with disease and individualized treatment plan and play its unique advantages. In recent yearson ursodeoxycholic acid combined with traditional Chinese medicine treatment of primary biliary cirrhosis clinical research is increasing, and traditional Chinese medicine combined with ursodeoxycholic acid in the treatment is better than single ursodeoxycholic acid, opinions vary, so we evaluate that if traditional Chinese medicine combined with ursodeoxycholic acid in the treatment of PBC is effective and safe or not by Cochrane systematic retrieval of relevant literature published. We combined use of little found in liver biopsy pathology examination is primary biliary cirrhosis diagnosis and curative effect evaluation of the gold standard, and we in the retrieval process of traditional Chinese medicine combined with ursodeoxycholic acid in the treatment of primary biliary cirrhosis literature mainly confined to clinical symptoms and serological indicators, and the liver tissue pathology observation, whether can improve the liver tissue pathology is worth exploring the key. Therefore, with the aid of tutor’s experience of regulating the liver and spleen can significantly improve the joint ursodeoxycholic acid was observed on primary biliary cirrhosis rat liver tissue pathological changes and analysis of traditional Chinese medicine combined with ursodeoxycholic acid in liver tissue pathology Curative effect. This study mainly from two parts of traditional Chinese medicine combined with ursodeoxycholic acid in the treatment of primary biliary cirrhosis efficacy of exploration, the first part for system evaluation and analysis of traditional Chinese medicine combined with ursodeoxycholic acid in the treatment of primary biliary cirrhosis of the clinical efficacy and safety, the second part is an animal experiment observed Chinese medicine regulating liver and spleen decoction combined with bear of ursodeoxycholic acid on primary biliary cirrhosis of liver tissue in mice pathological effects.Part I: Systematic review Objective: To evaluate the clinical efficacy and safety of traditional Chinese medicine combined with ursodeoxycholic acid in the treatment of primary biliary cirrhosis.Methods: VIP Chinese journal full text database(VIP) was searched by computer system and China knowledge resource database(CNKI), Wanfang medicine, MEDLINE,Pub Med and the Cochrane Library clinical controlled trials database and limit before December 2015 officially published literature. Assessed the quality of the included literature research, meta analysis was performed on data using the software Revman5.3.Results: included in the final 12 research.642 cases(326 cases in the treatment group,316 cases in the control group), the 575 cases of female patients, 67 cases of male patients. Research into the method of quality were lower. The meta analysis results display: compared with the control group, with the combination of traditional Chinese medicine and bear deoxycholic acid group of the total clinical efficacy better[OR=3.61,95%CI(2.26,5.75)].It can significantly improve the symptoms of the patients with integral [OR=4.06,95%CI(0.45,7.67)] in the improved fatigue [OR=4.51,95%CI(1.88,10.79)], itching symptoms [OR=5.58,95%CI(2.27,13.75)], reduce the serum alkaline phosphatase [MD=68.06,95%CI(25.02,56.02)],glutamyl transferase [MD=40.82,95%CI(42.11,94.02)], serum total bilirubin [MD=5.99,95%CI(2.75,9.42)], alanine transfer ammonia lyase [MD=21.66,95%CI(17.52,25.84)] and aspartic acid transaminase[MD=8.61,95%CI(-5.21,22.42)], serum total bile acid [MD=4.02,95%CI(4.26,6.32)],hyaluronic acid [MD=46.20,95%CI(31.36,61.04)], type III collagen [MD=44.42,95%(CI33.78,55.06)], type IV collagen [MD=24.71,95%CI(16.82,32.60)] and layer sticky protein [MD=28.13,95%CI(22.55,33.71)],and the recurrence rate of the [MD=0.32,95%CI(0.11,0.98)].7 literatures observe the traditional Chinese medicine combined with ursodeoxycholic acid in the treatment of primary biliary cirrhosis safety index and adverse reactions, which one study describes the adverse reactions include elevated TBA,skin itching, and diarrhea, ratio is between the two groups had no significant difference; a study medication in treatment group 2 cases of diarrhea, 1 case of nausea, retching,although unwell but tolerance and no special treatment, after spontaneous remission, five studies in the course of treatment were not found adverse reactions, five research did not mention adverse reactions.Validation of a limited number of conclusion: Traditional Chinese medicine combined with the bear deoxycholic acid in the treatment of primary biliary cirrhosis curative effect is better than single use ursine deoxygenate cholic acid treatment can improve the patients symptoms and signs: the total score and improve liver function and hepatic fibrosis index, and reduce the recurrence rate. But because of the included studies and literature quality score is low, there are many limitations, the results should be treated with caution, pending further multi center, large sample, high quality randomized controlled trials. Primary biliary cirrhosis diagnosis relies on liver tissue pathology and retrieval currently found in primary biliary cirrhosis of the liver cirrhosis of Chinese and Western Medicine treatment for clinical research, and the Pathological changes in liver tissue of PBC patients were poorly observed.Part II:Animal experiment Objective: To observe the effect of Chinese medicine regulating liver and spleen decoction combined with bear of ursodeoxycholic acid on primary biliary cirrhosis of liver tissue in mice pathological effects.Method: adaptive feeding a week after, weighed. Using Excel software randomly 100C57 BL / 6J mice were randomly assigned to five groups, with 20 rats in each group,respectively is the normal control group, model control group, Chinese medicine control group(TGLP 5mg·kg-1·d-1) and positive to the contrast group(UDCA 0.1g·kg-1·d-1),positive and traditional Chinese medicine group(TGLP 5mg·kg-1·d-1+UDCA0.1g·kg-1·d-1). Except the normal control group, the other four groups were intraperitoneal injection of poly I-C(poly l:C 5mg/kg) and normal control group were treated with the same volume of saline by intraperitoneal injection, twice a week,continuous 16. 8 weeks, 16 weeks cervical dislocation method mice were killed(before a day of fasting), collection of blood, liver in preparation for the detection, liver tissue with4% paraformaldehyde.AMA-M2 was detected by enzyme linked immunosorbent assay(ELISA). According to the results of AMA-M2, 3 specimens were randomly selected to observe the pathological changes of liver tissues.Results: In the normal control group, 8 weeks, 16 weeks of detection of serum AMA-M2 were negative, while the positive rate was eighth in the model group, positive rate was sixteenth, positive rate was 70%. after 56% weeks, and the positive rate of the model group was the lowest.liver tissue by HE staining PBC model mice, with the extension of the modeling time, structural disorder of hepatic lobules, periportal hepatocyte swelling,spotty and focal necrosis, portal area to expand, the small bile duct injury obviously, with hyperplasia of the small bile duct, bile duct epithelial cell degeneration, irregular shape and size, nuclear enrichment, individual cells disappeared, Hui Guan Qu and injury of bile ducts around lymphocyte infiltration, scattered epithelioid granuloma and eosinophils eosinophil around the bile duct injury, circles could be seen in the piecemeal necrosis.Masson staining showed periportal enlargement, edema, the Department ofGuan Qu and fibrous septum small bile ducts in number Increased significantly, small bile duct lumen enlargement and distortion, visible tube week a lot of blue collagen fibers that surround, connected to each other and abnormal distribution, to the surrounding extension, thicker fibrous septa formation, individual cable strip hyperplasia,but no form of pseudo lobule. Compared with the normal group, model group, bile duct epithelial cell morphology and size of the irregular and arranged in disorder, some cells disappeared. After the treatment, the pathological changes compared with the model group, the improved, reduce the infiltration of inflammatory cells in hepatic tissue,reduce small bile duct proliferation, periportal small amounts of collagen fibers formed,the positive plus traditional Chinese medicine group pathology showed improved significantly, close to in the normal group.Conclusion: regulating the liver and spleen combined with ursodeoxycholic acid capsules in the treatment of can in some extent improve the primary biliary cirrhosis in mice liver tissue inflammation and fibrosis degree and inhibit the proliferation of small bile ducts.