李氏人工肝治疗慢加急性肝衰竭的临床观察研究

发布时间：2018-05-19 13:00

本文选题：李氏人工肝 + 肝衰竭　；参考：《浙江大学》2014年博士论文

【摘要】：研究背景：肝衰竭是由大量肝细胞坏死导致严重肝功能损害,表现以黄疸、凝血功能障碍、肝性脑病等为主要表现的临床综合征,可由多种原因所致,在我国由乙型肝炎病毒(HBV)所致的肝衰竭高居首位,占80%左右。乙肝所致的慢加急性肝衰竭的救治仍是医学难题,国内外报道死亡率在60%-80%。虽然肝移植的开展显著提高了重型乙型肝炎(肝衰竭)的生存率,但供肝来源有限,技术难度大,费用昂贵使临床应用受到很大限制,大部分患者还是以内科综合治疗为主。而肝衰竭患者多因并发症多,加大了内科治疗的难度,传统的内科综合基础治疗病死率仍然很高。自李氏人工肝治疗技术的研究到国内普遍的开展,因为其有效降低重型乙肝(慢加急性肝衰竭)的病死率,而逐步成为了肝衰竭的主要治疗手段。其原理是通过清除毒素、补充白蛋白凝血因子、稳定机体内环境,暂时替代肝脏功能,为促进肝细胞的再生和肝功能的恢复赢得了时间。在人工肝治疗中血浆置换术是目前应用最多的疗法,其安全性和疗效已经被广泛认可,但目前仍缺乏全国范围的多中心、大样本、统一标准的应用研究。在十一五重大专项的支持下,课题开展了由全国10家单位参与的李氏人工肝治疗慢性重型乙肝(慢加急性肝衰竭)的应用研究,通过对临床资料的总结分析,以明确李氏人工肝的疗效,建立人工肝治疗的预后判断模型,及时判定肝移植介入的时机。通过上述临床资料的整理和分析,优化不同临床分期下不同李氏人工肝应用的研究方案及随访策略,以便更好的完成随机研究,比较人工肝在重型肝炎肝衰竭救治中的作用。对人工肝治疗肝衰竭的研究涉及多个中心海量的标本收集和检测,为后续重型乙型肝炎(慢加急性肝衰竭)的发病机制和李氏人工肝的应用机制研究提供样本,在此需求下建立一个基于统一随访流程的远程管理多中心的临床血液标本的管理系统,编写了全国标本运输管理软件,为后续的实验室发病机制和诊疗机制的研究提供的血液标本以科学客观的数字化支持。方法：我们设计重型乙型肝炎(慢加急性肝衰竭)的住院随访流程,收集了2009年12月-2011年12月入住全国10家三级甲等医院的经实验室检查确诊的250例重型乙型肝炎(慢加急性肝衰竭)的住院数据,并对所有患者进行跟踪随访观察1个月,记录相关临床数据,比较了不同年龄、性别、不同临床分期肝衰竭患者的临床、实验室以及临床预后的差别。以上述患者临床资料的观察为基础,设计优化不同李氏人工肝治疗不同分期下慢加急性肝衰竭的大样本随机对照研究方案和临床标本管理系统,并严格按照该方案进行临床研究和样本管理,为更为准确的全国范围内评价李氏人工肝的疗效和治疗机制提供依据。结果：研究共纳入250例乙肝所致肝衰竭患者,共接受了661次PE治疗,141例患者(56.4%)显示临床症状及实验室检查指标的改善。通过单因素分析,结果提示变量如年龄(P=0)和总胆红素(P=0),直接胆红素(P=0),总甘油三酯(P=0),低密度脂蛋白(P=0.022),钠(P=0.014),氯离子(P=0.038),肌酐(P=0.007),纤维蛋白原(P=0),凝血酶原时间(P=0),白细胞(P=0),血小板(P=0.003)与人工肝疗效预后有着显著的相关性。通过多因素Logistic回归分析,结果显示,年龄,疾病分期,凝血酶原时间,血清总胆红素,肌酐水平是乙肝所致的慢加急性肝衰竭预后的独立危险因素。疾病分期越晚,患者年龄越大,凝血酶原时间越长,血清总胆红素水平越高,肌酐水平越高,则慢加急性肝衰竭患者即使进行人工肝治疗,预后仍差。根据上述研究涉及的病例特点,设计了优化李氏人工肝治疗不同分期的慢加急性肝衰竭的临床观察方案,并根据随访方案制定了标本管理策略,编写了远程标本管理软件,申请了软件著作权,并应用于实际研究和标本管理中。结论：李氏人工肝有助于降低乙肝所致的慢加急性肝衰竭的病死率,特别是对早期肝功能衰竭患者。TBIL、Cr和PT是慢加急性肝衰竭患者进行李氏人工肝治疗预后的独立因素。此外,当将疾病临床分期概念考虑入预后判断中,多元回归分析提示其成为独立的预后危险因素,有助于判断李氏人工肝的疗效和患者的预后。对晚期患者,应尽早行人工肝治疗,并列入肝移植受体名单,等待肝移植术。在此研究基础上,完成了不同临床分期下的个体化李氏人工肝治疗方案设计,制定了随机对照研究的方案策略,形成标准规范化流程。而标本管理软件也对人工肝治疗随访中产生的大量样本的收集管理和再利用提供软件数据支持,对得出后续研究结论提供科学可靠的依据,最终有效指导临床治疗。
[Abstract]:Background: liver failure is a clinical syndrome mainly manifested by jaundice, coagulation dysfunction and hepatic encephalopathy, which is mainly manifested by jaundice, coagulation dysfunction and hepatic encephalopathy. It can be caused by a variety of causes, and the liver failure caused by hepatitis B virus (HBV) is the highest in China, accounting for about 80%. The treatment of exhaustion is still a medical problem. The death rate at home and abroad has been reported at home and abroad in 60%-80%., although the development of liver transplantation has significantly improved the survival rate of severe hepatitis B (liver failure), but the source of the donor liver is limited, the technical difficulty is great, the cost is very expensive and the clinical application is very limited. The major part of the patient is mainly integrated with the internal medicine. Because of many complications, the difficulty of internal medicine treatment is increased. The mortality rate of traditional internal medicine comprehensive basic treatment is still high. The research from Li's artificial liver treatment technology has been widely carried out in China, because it effectively reduces the mortality of severe hepatitis B (slow and acute liver failure), and has gradually become the main treatment method of liver failure. By removing toxins, supplementing albumin and coagulation factors, stabilizing the body environment and temporarily replacing the liver function, it has won time to promote the regeneration of liver cells and the recovery of liver function. In the treatment of artificial liver, plasma exchange is the most widely used therapy at present, its safety and efficacy have been widely recognized, but there is still a lack of national model. Under the support of the major special project of 11th Five-Year, the application of Li's artificial liver in the treatment of chronic severe hepatitis B (slow and acute liver failure) was carried out by 10 units of the country in 11th Five-Year. Through the summary and analysis of clinical data, the effect of Li's artificial liver was clearly defined and artificial liver was established. In order to better complete the randomized study and compare the role of artificial liver in the treatment of liver failure of severe hepatitis. The study of the treatment of liver failure involves the collection and detection of multiple central mass specimens, providing samples for the pathogenesis of subsequent severe hepatitis B (slow plus acute liver failure) and the study of the application mechanism of Li's artificial liver. Under this requirement, establish a management department of the clinical blood specimens based on a unified follow-up process based on a long range management and multi center. The national specimen transportation management software has been compiled to provide scientific and objective digital support for the blood specimens provided for the follow-up laboratory pathogenesis and diagnosis and treatment mechanism.
Methods: we designed the hospitalization process of severe hepatitis B (slow and acute liver failure) and collected data of 250 cases of severe hepatitis B (slow and acute liver failure) diagnosed in 10 three class first class hospitals of the country in December -2011 December 2009, and followed up for 1 months. The clinical, laboratory, and clinical outcomes of patients with different age, sex, and clinical stage of liver failure were compared. Based on the observation of the clinical data of these patients, a large sample randomized controlled study and clinical study of different Li's artificial liver treatments for slow and acute liver failure under different stages were designed and optimized. The sample management system, and strictly according to the program to carry out clinical research and sample management, provides a more accurate national range of evaluation of the curative effect and treatment mechanism of Li's artificial liver. Results: a total of 250 cases of hepatitis B induced liver failure were included in the study, 661 PE treatments were accepted, and 141 patients (56.4%) showed clinical symptoms and experiments. By single factor analysis, the results suggest variables such as age (P=0) and total bilirubin (P=0), direct bilirubin (P=0), total triglyceride (P=0), low density lipoprotein (P=0.022), sodium (P=0.014), chlorine ion (P=0.038), creatinine (P= 0.007), fibrinogen (P=0), Prothrombin time (P=0), leukocyte (P=0), platelet (P=0.003) and platelets (P=0.003)) The outcome of the artificial liver has a significant correlation. Through multiple factor Logistic regression analysis, the results show that age, disease staging, prothrombin time, serum total bilirubin, creatinine level are independent risk factors for the prognosis of chronic liver failure induced by hepatitis B. The later the period of the disease is, the older the patient is, the longer the prothrombin time is, the longer the blood is, the longer the blood is, the longer the blood is, the longer the blood is, the longer the blood is, the longer the blood is, the more the blood is, the longer the prothrombin time, the longer the blood The higher the level of total bilirubin and the higher the level of creatinine, the prognosis of the patients with acute liver failure is still poor even with the treatment of artificial liver. According to the characteristics of these cases, we designed the clinical observation plan of optimizing Li's artificial liver for different stages of slow and acute liver failure, and set up the management strategy according to the follow-up plan. A software for remote specimen management has been compiled, which has applied for software copyright and applied to actual research and specimen management.
Conclusion: Li's artificial liver helps to reduce the mortality of chronic liver failure induced by hepatitis B, especially for patients with early liver failure,.TBIL, Cr and PT are independent factors for the prognosis of Li's artificial liver treatment in patients with slow and acute liver failure. It is suggested that it is an independent prognostic risk factor, which is helpful to judge the curative effect of Li's artificial liver and the prognosis of the patients. For the late patients, the early manual liver treatment should be done, and the liver transplantation recipients list and wait for the liver transplantation. On the basis of this study, the individualized Li's artificial liver treatment scheme under different clinical stages is designed and formulated. The program strategy of randomized controlled study is made to form a standard standardization process, and the specimen management software provides software data support for the collection management and reuse of a large number of samples produced during the follow-up of artificial liver treatment, providing a scientific and reliable basis for the conclusion of the follow-up study and the final effective guidance of clinical treatment.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R575.3

【参考文献】