【作者】 郝绍瑞；

【导师】 李兰娟；

【作者基本信息】 浙江大学 ， 内科学（专业学位）， 2013， 博士

【摘要】 乙肝病毒慢性感染过程中可能发生急性发作引起重型肝炎(慢加急性肝衰竭)、肝硬化、肝癌等情况,造成了巨大的社会负担和经济负担。乙肝肝衰竭病情危重,进展迅速,预后极差,目前内科综合治疗仍缺乏特效的治疗药物,病死率高达70%。李氏人工肝系统(Li’s artificial liver system, Li-ALS)治疗重型肝炎肝衰竭获得重大突破,显著降低了患者病死率。早在2005年,李兰娟院士领导的人工肝团队就提出血浆置换联合血液滤过治疗中、晚期慢性乙型重型肝炎的疗效优于血浆置换的观点。本文进行了李氏人工肝系统血浆置换滤过方法治疗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期间采用李氏人工肝系统血浆置换滤过方法治疗的乙肝慢加急性肝衰竭患者为研究对象,通过回顾性研究,分析了李氏人工肝系统治疗前后各种指标的变化,并建立了Cox比例风险回归模型,分析了影响慢加急性肝衰竭预后的因素。李氏人工肝系统血浆置换滤过方法治疗前后血三系都发生了显著的降低,并引起了治疗后血生化及凝血指标的极大改善。治疗后谷氨酸、甲硫氨酸、半胱氨酸、酪氨酸、组氨酸显著降低,其余氨基酸治疗后数值低于治疗前,但差异在统计学上不显著。1月和1年总体生存率分别为51.4%和40.0%。根据肝衰竭不同分期分层,早期1月和1年总体生存率分别为75.0%和50.0%；中期1月和1年总体生存率分别为63.2%和47.4%；晚期1月和1年总体生存率分别为25.0%和25.0%。用Cox比例风险回归模型进行回归分析,得到四个显著的变量：MELD评分(RR=1.379)、白细胞(RR=1.296).HBeAg(RR=0.083).胆碱酯酶/1000(RR=0.552)。血浆置换既可以除去血液中的中小分子物质和与血浆蛋白结合的大分子毒性物质,同时还可补充肝衰竭患者缺乏的凝血因子、白蛋白等。但其对水电解质平衡以及酸碱失衡等内环境紊乱的调节作用较小,对中小分子物质的清除能力不如血液滤过和透析,对水负荷过重的情况无改善作用,而血液滤过正好弥补了这些不足。晚期患者体内蓄积的毒素高于早、中期,李氏人工肝系统血浆置换滤过方法经过持续性的血液滤过,更大程度上清除了血液中的毒素从而进一步提高了晚期患者生存率。更多还原

【Abstract】 In the progress of chronic HBV infection, severe hepatitis (acute on chronic liver failure, ACLF), cirrhosis, hepatic carcinoma can occure and cause substantial social and economical burden. Hepatitis B liver failure is a critical condition with rapid progress and poor prognosis, currently there is still a lack of the effective medical treatment, mortality rate is as high as70%. Li’s artificial liver system, short for Li-ALS, achieved a major breakthrough in treatment of severe hepatits liver failure, and significantly reduced the mortality of patients. As early as2005, Academician Li Lanjuan and her team pointed out that combination of plasma exchange and continuous veno-venous hemofiltration is superior in treatment of mid-stage and late-stage chronic HBV-induced severe hepatits. This thesis is a case analysis of35hepatitis B ACLF patients treated with Li-ALS plasma exchange hemofiltration method.The study object is hepatitis B ACLF patients who was admitted in the first affiliated hospital, Zhejiang Univ. and treated with Li-ALS in the artificial liver center during2011.6.1and2012.1.30. By retrospective study, different index pre-and post Li-ALS treatment were analyzed, besides, a Cox proportional hazards regression model was established to analyze the impacting factors of prognosis.After the treatment of Li-ALS plasma exchange hemofiltration method, blood cells declined significantly, while biochemical index and coagulation fuction were vastly improved. Glutamic acid, methionine, cysteine, tyrosine, histidine decreased after Li-ALS treatment. The survival rate of1month and1year was51.4%and40.0%, respectively. When stratified according to different stage of liver failure, the survival rate of1month and1year was75.0%and50.0%for early stage,63.2%and47.4%for mid-stage,25.0%and25.0%for late stage. Four factors, MELD score (RR=1.379), white blood cell (RR=1.296), HBeAg (RR=0.083) and cholinesterase/1000(RR=0.552), were significant in the Cox proportional hazards regression model.Plasma Exchange could exclude middle and small molecular weight substance and more importatly large molecular weight toxins binding to plasma proteins, at the same time, coagulation factors and albumin were suplymented. While hemofiltration could maintain the balance of water, electrolytes and PH, and have better clear rate of middle molecular weight substances, which perfectly maked up the deficiencies of plasma exchange. So Li-ALS using plasma exchange hemofiltration method could remove blood toxins in a greater extent and thus further improve the survival rate of late stage patients compared to using Li-ALS plasma exchange method only.更多还原