【作者】 张炳煌；

【导师】 陆定波；

【作者基本信息】 湖北中医药大学 ， 中西医结合临床， 2010， 硕士

【摘要】 目的原发性胆汁性肝硬化(primary biliary cirrhosis, PBC)是一种病因未明的慢性进行性胆汁淤积性自身免疫性肝脏疾病,多见于中年女性。病理改变主要是由自身免疫介导的,以肝内细小胆管的慢性非化脓性炎症、慢性胆汁淤积、肝纤维化为特征,最终可发展为肝硬化。近年来,随着国内外对该病研究的深入及对其认识的加深,此病的检出率也明显上升。但是目前对于此病的病因尚未完全查明,因此尚无特异的治疗措施,主要是对症和支持治疗。由于熊去氧胆酸(UDCA)可通过免疫调节、增加内源性胆汁酸的分泌和保护肝细胞膜等机制而发挥其改善患者肝功能和延缓疾病进程的作用,对于早期病变有一定的疗效。是目前被公认的具有确实疗效的首选药物。而激素、硫唑嘌呤和甲氨蝶呤等西药疗效不肯定,且有较严重的不良反应,临床上常与UDCA联合使用。中医药在治疗自身免疫性疾病及抗肝纤维化方面已得到了广泛的肯定。为进一步提高治疗本病的疗效,对本病患者采用UDCA联合中医药辨证治疗,并与单纯服用UDCA及单纯服用中药的患者进行对比,从而观察并研究中西医联合治疗对原发性胆汁性肝硬化的临床疗效。方法所有病例均为2007年12月至2010年2月就诊于本院门诊及住院的病人,共有56例,且都符合PBC的临床诊断标准。对这些患者随机分为单用中药治疗组20例(A组)、单用UDCA治疗组15例(B组)和联合中药及UDCA治疗组21例(C组)。对于A组及C组病人,按照中医辨证施治的原则,分为瘀血内停型、湿热中阻型、肝郁脾虚型及肝肾阴虚型四型,分别以膈下逐瘀汤、茵陈蒿汤、柴胡疏肝散及一贯煎为主方,随症加减相应药物；B组病人单用UDCA 250mg/次,口服,日3次；C组则在服用UDCA的同时,配合中医辨证施治,服用相应中药方剂。分别观察治疗4、12、24周后,主要临床症状体征及主要生化、免疫指标的改变。并对治疗后的有效率及按Child-Pugh标准分级的变化等相关指标进行对比。对治疗后各项相关指标的变化使用SPSS13.0软件进行相应的统计学分析。结果(1)症状体征改善方面有瘙痒、乏力及黄疸等症状的患者,三组病人在4、12及24周时症状及体征均有所改善,但在12及24周时,A组和C组病人症状及体征的改善好转较B组病人明显,具有显著性差异(P<0.05)；B组部分病人症状改善不明显；(2)主要生化指标的改变24周时,三组病人的主要生化指标均较前有所改善,尤以C组改善较为明显。且在24周时C组病人主要生化指标的改善较A、B两组病人的改善具有显著性差异(P<0.05)；同时B组大部分病人的主要生化指标较治疗前也有明显改善(P<0.05)。但A组对主要生化指标的改善均不及B组及C组明显。且B组在降低TBIL及GGT方面较A组更为明显(P<0.05)；(3)主要免疫指标的改变单纯服用UDCA的B组病人经治疗后,主要免疫指标IgG、IgM、IgA的改善较单纯服用中药的A组更为明显,但无显著性差异(P>0.05)。C组病人经治疗后,主要免疫指标较治疗前均有明显改善(P<0.05)。与A组相比,也有较明显差异(P<0.05)；(4)按Child-Pugh标准评分分级对比对所有病人按照Child-Pugh标准进行评估分级,并对处于不同等级的病人数及在本组病人总数中所占百分比进行统计和对比,三组病人在治疗前各级病人数及所占比例无显著性差异(P>0.05),在12周及24周时对A级的病例数及所占比例进行比较,C组A级病人数较治疗前有明显增多,但与治疗前相比无显著性差异(P>0.05)。结论(1)单用UDCA在治疗PBC时,对早中期病例效果较为显著,尤其是在改善患者的主要生化及免疫指标方面。但是对于晚期患者,则效果欠佳；(2)中药在改善PBC患者的主要生化及免疫指标方面,虽不及UDCA明显,但中药可有效改善患者的症状及体征。(3) UDCA联合中药辨症治疗PBC可发挥各自的优势,较单用UDCA治疗效果更好,值得临床进一步推广应用。更多还原

【Abstract】 ObjectivePrimary biliary cirrhosis (PBC) is an unexplained and chronic progressive cholestatic autoimmune liver disease, it’s more common in middle-aged women.The main pathological changes are mediated by its own immune ,and its characteristics are chronic non-suppurative inflammation in intrahepatic small bile ducts, chronic cholestasis and liver fibrosis,in the end it can develop cirrhosis. In recent years, international and domestic research on the disease are more deeper and knowledge about the disease are followed to enhance, detection rate about the disease is significantly increased. But now the causes about the disease has not yet fully identified, so there is no specific treatment measures, mainly symptomatic and supportive treatment. As ursodeoxycholic acid (UDCA) can improver liver function of patients and delay disease progression by regulating the immune、increasing secretion of endogenous bile acid、protect the liver cell membrane and other mechanism. It have a certain effect in early lesions of the disease. It is currently recognized as a really effective drug of choice. But efficacy of western medicines such as the hormone, azathioprine and methotrexate etc. is not sure, and there are more severe adverse reactions, it often used with UDCA. Chinese medicine has been widely affirmed in treating autoimmune diseases and hepatic fibrosis. To further enhance the efficacy in treating the disease, let the patients of it take UDCA combined with TCM Differential Treatment, and compare with the patients simply taking UDCA patients and simply taking traditional Chinese medicine, to observe and study clinical efficacy of the treatment of primary biliary cirrhosis through integrative medicine of Western Medicine and TCM.MethodsAll cases are outpatient and hospitalized patients from December 2007 to February 2010 in the hospital, a total of 56 cases, and are consistent with the clinical diagnostic criteria of PBC. These patients were randomly divided into three groups,one group of 20 patients treated with traditional Chinese medicine (A group),one group of 15 cases treated with UDCA (B group),and one group of 21 cases combined with TCM and UDCA (C group). The patients in A group and C group, in accordance with the Chinese medicine’s principles of observing symptom and giving treatment, are divide into blood stasis type, damp heat resistance type, the liver and liver-kidney deficiency type IV, respectively unliquefaction, tarragon soup, fried CHAIHUSUGAN scattered along the main square and, with the disease by adding or reducing appropriate drugs; patients in B group only take UDCA 250mg/time,3 times a day, po.; patients in C group, while taking UDCA, taking the appropriate prescription of Chinese medicine by following the Chinese medicine’s principles of observing symptom and giving treatment. Observe the changes of main clinical symptoms and signs、the major biochemical and immune parameters in 4,12,24 weeks after treatment. And compare the efficient after treatment and the changes of relevant indicators according to Child-Pugh classification standards. And analyses the changes of relevant indicators after treatment by using SPSS13.0 statistical analysis software. Results(1) improvement of symptoms and signs the patients that feeling itching, fatigue ,jaundice and other symptoms, there are effective on improvements symptoms and signs in patients of three groups after 4,12 and 24 weeks ,however, in 12 and 24 weeks, the improvement of symptoms and signs in patients of A group and C group are significant through comparing with patients of B group; there are significant difference (P<0.05); but there are no obvious improvement of symptoms in some patients of B group. (2) The changes of major biochemical targets the main biochemical parameters of three groups patients at 24 weeks were improved by comparing with previous parameters, especially in C group, it’s more significant. And the improvement of main biochemical targets in C group’ patients at 24 weeks are significantly different (P<0.05) in compared with improvement of A, B groups’ patients; The major biochemical indicators of most of patients in Group B are significantly improved (P<0.05) by comparing with it before. But the improvements of major biochemical indexes in patients of A group are not significantly by comparing with patients of group B and C. And in lower TBIL and GGT, the group B is more obvious than the group A (P <0.05);(3) The changes of major immune parameters The improvement of main immune targets IgG, IgM, IgA of B group’s patients simply taking UDCA after treatment is more obvious than the improvement of patients in group A, but no significant difference (P> 0.05). The major immune parameters of patients of group C after treatment were significantly improved compared with them before treatment (P<0.05). Compared with A group, there is a more significant difference (P<0.05);(4) compare grades according to Child-Pugh scores Assess and classify all the patients in accordance with the Child-Pugh classification assessment criteria, and compare the number of patients at different levels and statistic the percentage, patients of three groups before treatment there is no significant difference (P> 0.05) in the number of different levels and percentage, at 12 weeks and 24 weeks compare the number of A-level and percentage of cases,patients of A-level in C Group increased significantly though comparing with the number of them before treatment, but there was no significant difference (P> 0.05) by comparing with them before treatment.Conclusion(1) Only take UDCA in treating PBC, the results were more significant in early and medium-term patients,but the results of advanced cases is ineffective; (2) Compared with single treatment group with TCM, in the improvement of the main biochemical and immunological indices after taking UDCA in some patients were obvious; (3) The effect of treatment by combined traditional Chinese medicine Bianzhenzhiliao with UDCA in treating PBC were better than only take UDCA, and it is worthy of further promotion.更多还原