發(fā)布時(shí)間：2018-05-19 13:00

  本文選題：李氏人工肝 + 肝衰竭��； 參考：《浙江大學(xué)》2014年博士論文

【摘要】：研究背景：肝衰竭是由大量肝細(xì)胞壞死導(dǎo)致嚴(yán)重肝功能損害,表現(xiàn)以黃疸、凝血功能障礙、肝性腦病等為主要表現(xiàn)的臨床綜合征,可由多種原因所致,在我國(guó)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醫(yī)學(xué)難題,國(guó)內(nèi)外報(bào)道死亡率在60%-80%。雖然肝移植的開展顯著提高了重型乙型肝炎(肝衰竭)的生存率,但供肝來源有限,技術(shù)難度大,費(fèi)用昂貴使臨床應(yīng)用受到很大限制,大部分患者還是以內(nèi)科綜合治療為主。而肝衰竭患者多因并發(fā)癥多,加大了內(nèi)科治療的難度,傳統(tǒng)的內(nèi)科綜合基礎(chǔ)治療病死率仍然很高。自李氏人工肝治療技術(shù)的研究到國(guó)內(nèi)普遍的開展,因?yàn)槠溆行Ы档椭匦鸵腋?慢加急性肝衰竭)的病死率,而逐步成為了肝衰竭的主要治療手段。其原理是通過清除毒素、補(bǔ)充白蛋白凝血因子、穩(wěn)定機(jī)體內(nèi)環(huán)境,暫時(shí)替代肝臟功能,為促進(jìn)肝細(xì)胞的再生和肝功能的恢復(fù)贏得了時(shí)間。在人工肝治療中血漿置換術(shù)是目前應(yīng)用最多的療法,其安全性和療效已經(jīng)被廣泛認(rèn)可,但目前仍缺乏全國(guó)范圍的多中心、大樣本、統(tǒng)一標(biāo)準(zhǔn)的應(yīng)用研究。在十一五重大專項(xiàng)的支持下,課題開展了由全國(guó)10家單位參與的李氏人工肝治療慢性重型乙肝(慢加急性肝衰竭)的應(yīng)用研究,通過對(duì)臨床資料的總結(jié)分析,以明確李氏人工肝的療效,建立人工肝治療的預(yù)后判斷模型,及時(shí)判定肝移植介入的時(shí)機(jī)。通過上述臨床資料的整理和分析,優(yōu)化不同臨床分期下不同李氏人工肝應(yīng)用的研究方案及隨訪策略,以便更好的完成隨機(jī)研究,比較人工肝在重型肝炎肝衰竭救治中的作用。對(duì)人工肝治療肝衰竭的研究涉及多個(gè)中心海量的標(biāo)本收集和檢測(cè),為后續(xù)重型乙型肝炎(慢加急性肝衰竭)的發(fā)病機(jī)制和李氏人工肝的應(yīng)用機(jī)制研究提供樣本,在此需求下建立一個(gè)基于統(tǒng)一隨訪流程的遠(yuǎn)程管理多中心的臨床血液標(biāo)本的管理系統(tǒng),編寫了全國(guó)標(biāo)本運(yùn)輸管理軟件,為后續(xù)的實(shí)驗(yàn)室發(fā)病機(jī)制和診療機(jī)制的研究提供的血液標(biāo)本以科學(xué)客觀的數(shù)字化支持。 方法：我們?cè)O(shè)計(jì)重型乙型肝炎(慢加急性肝衰竭)的住院隨訪流程,收集了2009年12月-2011年12月入住全國(guó)10家三級(jí)甲等醫(yī)院的經(jīng)實(shí)驗(yàn)室檢查確診的250例重型乙型肝炎(慢加急性肝衰竭)的住院數(shù)據(jù),并對(duì)所有患者進(jìn)行跟蹤隨訪觀察1個(gè)月,記錄相關(guān)臨床數(shù)據(jù),比較了不同年齡、性別、不同臨床分期肝衰竭患者的臨床、實(shí)驗(yàn)室以及臨床預(yù)后的差別。以上述患者臨床資料的觀察為基礎(chǔ),設(shè)計(jì)優(yōu)化不同李氏人工肝治療不同分期下慢加急性肝衰竭的大樣本隨機(jī)對(duì)照研究方案和臨床標(biāo)本管理系統(tǒng),并嚴(yán)格按照該方案進(jìn)行臨床研究和樣本管理,為更為準(zhǔn)確的全國(guó)范圍內(nèi)評(píng)價(jià)李氏人工肝的療效和治療機(jī)制提供依據(jù)。結(jié)果：研究共納入250例乙肝所致肝衰竭患者,共接受了661次PE治療,141例患者(56.4%)顯示臨床癥狀及實(shí)驗(yàn)室檢查指標(biāo)的改善。通過單因素分析,結(jié)果提示變量如年齡(P=0)和總膽紅素(P=0),直接膽紅素(P=0),總甘油三酯(P=0),低密度脂蛋白(P=0.022),鈉(P=0.014),氯離子(P=0.038),肌酐(P=0.007),纖維蛋白原(P=0),凝血酶原時(shí)間(P=0),白細(xì)胞(P=0),血小板(P=0.003)與人工肝療效預(yù)后有著顯著的相關(guān)性。通過多因素Logistic回歸分析,結(jié)果顯示,年齡,疾病分期,凝血酶原時(shí)間,血清總膽紅素,肌酐水平是乙肝所致的慢加急性肝衰竭預(yù)后的獨(dú)立危險(xiǎn)因素。疾病分期越晚,患者年齡越大,凝血酶原時(shí)間越長(zhǎng),血清總膽紅素水平越高,肌酐水平越高,則慢加急性肝衰竭患者即使進(jìn)行人工肝治療,預(yù)后仍差。根據(jù)上述研究涉及的病例特點(diǎn),設(shè)計(jì)了優(yōu)化李氏人工肝治療不同分期的慢加急性肝衰竭的臨床觀察方案,并根據(jù)隨訪方案制定了標(biāo)本管理策略,編寫了遠(yuǎn)程標(biāo)本管理軟件,申請(qǐng)了軟件著作權(quán),并應(yīng)用于實(shí)際研究和標(biāo)本管理中。 結(jié)論：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,特別是對(duì)早期肝功能衰竭患者。TBIL、Cr和PT是慢加急性肝衰竭患者進(jìn)行李氏人工肝治療預(yù)后的獨(dú)立因素。此外,當(dāng)將疾病臨床分期概念考慮入預(yù)后判斷中,多元回歸分析提示其成為獨(dú)立的預(yù)后危險(xiǎn)因素,有助于判斷李氏人工肝的療效和患者的預(yù)后。對(duì)晚期患者,應(yīng)盡早行人工肝治療,并列入肝移植受體名單,等待肝移植術(shù)。在此研究基礎(chǔ)上,完成了不同臨床分期下的個(gè)體化李氏人工肝治療方案設(shè)計(jì),制定了隨機(jī)對(duì)照研究的方案策略,形成標(biāo)準(zhǔn)規(guī)范化流程。而標(biāo)本管理軟件也對(duì)人工肝治療隨訪中產(chǎn)生的大量樣本的收集管理和再利用提供軟件數(shù)據(jù)支持,對(duì)得出后續(xù)研究結(jié)論提供科學(xué)可靠的依據(jù),最終有效指導(dǎo)臨床治療。
[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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R575.3

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相關(guān)期刊論文 前4條

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本文編號(hào)：1910197