本文選題：李氏人工肝　切入點：血漿置換濾過方法　出處：《浙江大學(xué)》2013年博士論文

【摘要】：乙肝病毒慢性感染過程中可能發(fā)生急性發(fā)作引起重型肝炎(慢加急性肝衰竭)、肝硬化、肝癌等情況,造成了巨大的社會負擔(dān)和經(jīng)濟負擔(dān)。乙肝肝衰竭病情危重,進展迅速,預(yù)后極差,目前內(nèi)科綜合治療仍缺乏特效的治療藥物,病死率高達70%。李氏人工肝系統(tǒng)(Li's artificial liver system, Li-ALS)治療重型肝炎肝衰竭獲得重大突破,顯著降低了患者病死率。早在2005年,李蘭娟院士領(lǐng)導(dǎo)的人工肝團隊就提出血漿置換聯(lián)合血液濾過治療中、晚期慢性乙型重型肝炎的療效優(yōu)于血漿置換的觀點。本文進行了李氏人工肝系統(tǒng)血漿置換濾過方法治療乙肝慢加急性肝衰竭35例的病例分析。 本文以浙大一院人工肝中心2011.6.1到2012.1.30期間采用李氏人工肝系統(tǒng)血漿置換濾過方法治療的乙肝慢加急性肝衰竭患者為研究對象,通過回顧性研究,分析了李氏人工肝系統(tǒng)治療前后各種指標(biāo)的變化,并建立了Cox比例風(fēng)險回歸模型,分析了影響慢加急性肝衰竭預(yù)后的因素。 李氏人工肝系統(tǒng)血漿置換濾過方法治療前后血三系都發(fā)生了顯著的降低,并引起了治療后血生化及凝血指標(biāo)的極大改善。治療后谷氨酸、甲硫氨酸、半胱氨酸、酪氨酸、組氨酸顯著降低,其余氨基酸治療后數(shù)值低于治療前,但差異在統(tǒng)計學(xué)上不顯著。1月和1年總體生存率分別為51.4%和40.0%。根據(jù)肝衰竭不同分期分層,早期1月和1年總體生存率分別為75.0%和50.0%；中期1月和1年總體生存率分別為63.2%和47.4%；晚期1月和1年總體生存率分別為25.0%和25.0%。用Cox比例風(fēng)險回歸模型進行回歸分析,得到四個顯著的變量：MELD評分(RR=1.379)、白細胞(RR=1.296).HBeAg(RR=0.083).膽堿酯酶/1000(RR=0.552)。 血漿置換既可以除去血液中的中小分子物質(zhì)和與血漿蛋白結(jié)合的大分子毒性物質(zhì),同時還可補充肝衰竭患者缺乏的凝血因子、白蛋白等。但其對水電解質(zhì)平衡以及酸堿失衡等內(nèi)環(huán)境紊亂的調(diào)節(jié)作用較小,對中小分子物質(zhì)的清除能力不如血液濾過和透析,對水負荷過重的情況無改善作用,而血液濾過正好彌補了這些不足。晚期患者體內(nèi)蓄積的毒素高于早、中期,李氏人工肝系統(tǒng)血漿置換濾過方法經(jīng)過持續(xù)性的血液濾過,更大程度上清除了血液中的毒素從而進一步提高了晚期患者生存率。
[Abstract]:Severe hepatitis may occur in the process of chronic hepatitis B virus infection (chronic and acute liver failure, liver cirrhosis, liver cancer, and so on), resulting in a huge social and economic burden.Hepatitis B liver failure is in critical condition, rapid progress and poor prognosis. At present, comprehensive medical treatment is still lack of special treatment drugs, the mortality is as high as 70.Li-ALS artificial liver system (Li-ALS) has made a great breakthrough in the treatment of severe hepatitis liver failure, and has significantly reduced the mortality of patients.As early as 2005, the artificial liver team led by Academician Li Lanjuan proposed that the efficacy of plasma exchange combined with hemofiltration in the treatment of advanced chronic severe hepatitis B was better than that of plasma exchange.In this paper, 35 cases of chronic hepatitis B and acute hepatic failure were analyzed.The patients with chronic hepatitis B and acute liver failure treated by plasma exchange filtration in Li's artificial liver system between January 2011 and January 30, 2012 were selected as the study subjects, and a retrospective study was carried out on the patients with chronic hepatitis B and acute liver failure, who were treated with plasma exchange filtration method in Li's artificial liver system from January 1, 2011 to January 30, 2011.The changes of various indexes before and after the treatment of Li's artificial liver system were analyzed. The proportional risk regression model of Cox was established and the factors influencing the prognosis of chronic and acute liver failure were analyzed.The three blood lines of Li's artificial liver system were significantly decreased before and after treatment with plasma exchange filtration method, and the blood biochemical and coagulation indexes were greatly improved after treatment.After treatment, glutamate, methionine, cysteine, tyrosine, histidine were significantly decreased, the other amino acid values were lower than before treatment, but the difference was not statistically significant. The overall survival rates of 1 month and 1 year were 51.4% and 40.0%, respectively.According to different stages of liver failure, the overall survival rates of early 1 month and 1 year were 75.0% and 50.0%, those of middle stage and 1 year were 63.2% and 47.4%, and that of late January and 1 year were 25.0% and 25.0%, respectively.By using the Cox proportional risk regression model, four significant variables were obtained: rmeld 1.379, WBC RV 1.296, HBeAg-RN 0.083.Cholinesterase / RRN 0.552%.Plasma exchange can not only remove the small and medium molecular substances in blood and macromolecular toxic substances combined with plasma protein, but also supplement the coagulation factors, albumin and so on in the patients with liver failure.However, it has little effect on the balance of water and electrolyte and the disturbance of internal environment, such as acid and base imbalance. It has less ability to remove small and medium molecular substances than hemofiltration and dialysis, and has no effect on the situation of water overload.And hemofiltration makes up for these deficiencies.The accumulation of toxins in patients with advanced stage is higher than that in early and middle stage. Plasma exchange filtration method of Lee's artificial liver system through continuous hemofiltration to a greater extent clears the toxins in the blood and further improves the survival rate of patients with advanced stage.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2013
【分類號】：R512.62;R575.3

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