应用分子吸附再循环系统治疗肝衰竭的初步临床研究

肝衰竭是病毒性肝炎的危重表现 ,病死率高 ,是肝移植的指征 ,但由于供肝来源有限 ,或者病情发展迅速 ,常常失去肝移植机会。分子吸附再循环系统 (ｍｏｌｅｃｕｌａｒａｄｓｏｒｂｅｎｔｒｅｃｉｒｃｕｌａｔｉｎｇｓｙｓｔｅｍ ,ＭＡＲＳ)是近年来发展的一种新型人工肝支持系统。该系统在分子水平上模拟肝细胞的解毒功能 ,选择性地有效清除肝衰竭时与白蛋白结合的毒性代谢产物和水溶性毒素 ,保留体内有用的物质 ,调整水电解质酸碱平衡 ,改善肾功能 ,并减轻胆汁酸内毒素对肝细胞的进一步损害作用 ,为肝细胞再生功能恢复及等待肝移植提供有效…     

分子吸附再循环系统治疗肝衰竭合并肝性脑病临床分析

目的探讨分子吸附再循环系统(MARS)治疗肝功能衰竭合并肝性脑病(HE)的临床价值。方法回顾性对比中南大学湘雅医院2004年12月至2005年12月收治的肝功能衰竭合并肝性脑病普通治疗组(对照组)78例和MARS治疗组(MARS组)60例的治疗效果。结果治疗3d后,MARS组血总胆红素、血氨均明显低于对照组(P<0.05,P<0.01),Glasgow昏迷评分均明显高于对照组(P<0.01);MARS组的肝性脑病清醒率90.0%,显著高于对照组(19.4%),MARS组30d病死率(10.0%)显著低于对照组(42.3%)(P均<0.01)。结论MARS可安全有效地治疗肝衰竭合并肝性脑病。     

分子吸附循环系统治疗肝衰竭52例

目的 评价分子吸附循环系统(MARS)治疗重型乙型肝炎肝衰竭的疗效,并探讨其机理。 方法 应用MARS对重型乙型肝炎肝衰竭的患者在常规治疗的基础上进行每次6～8h的MARS治疗,治疗前后检测各种有毒物质的改变,并与血浆置换组、常规治疗组进行比较。 结果 52例重型乙型肝炎肝衰竭患者。经MARS治疗后,临床症状及体征明显改善,血胆红素、血氨、尿素氮、芳香氨基酸、内毒素、白细胞介素-6、肿瘤坏死因子水平明显降低,治疗前后分别为(521.5±122.5)μmol/L和(360.1±81.2)μmol/L、(227.1±66.7)μg/ml和(105.0±42.0)μg/ml、(12.3±5.4)mmol/L和(6.4±2.4)mmol/L、(37.0±24.0)×10-3g/L和(23.0±16.0)×103g/L、(1.4±0.9)Eu/ml和(0.2±0.2)Eu/ml、(10.1±1.3)pg/ml和(5.7±1.0)pg/ml、(28.5±11.6)μg/ml和(1 7.9±7.8)μg/ml,t值为2.303～4.702,P<0.05或0.01。MARS与血浆置换在治疗后清除胆红素差异无显著性,而治疗后72 h血胆红素反跳,血浆置换组明显高于MARS组。总体存活率:MARS治疗组50％(26/52),血浆置换组45％(9/20),而常规治疗组存活率40.5％(17/42),MARS治疗组与常规治疗组相比较差异有显著性,u=3.024,P<0.01。 结论 MARS人工肝治疗肝衰竭,可明显提高其存活率,无明显不良反映。     

分子吸附再循环治疗慢加急性肝衰竭疗效观察

目的观察分子吸附再循环系统(MARS)在慢加急性肝衰竭中的治疗作用。方法比较15例慢加急性肝衰竭患者MARS治疗前后肝、肾功能,血氨、凝血酶原活动度及Glasgow评分等指标。结果 MARS人工肝治疗后,患者体内的血清总胆红素水平较治疗前明显下降,差异有统计学意义(P0.05)。但血清转氨酶、尿素氮、肌酐、凝血酶原活动度无显著变化(P0.05),治疗前后Glasgow评分差异无统计学意义(P0.05)。结论 MARS人工肝是一项安全的治疗措施,其对清除胆红素为代表的蛋白结合毒素效果明显,但并不能改善慢加急性肝衰竭患者肝性脑病的程度及总体预后,其意义在于为肝移植患者赢得时间。     

人工肝治疗肝衰竭研究进展

肝衰竭是由多种因素引起的肝细胞大块、亚大块坏死或严重损害,导致其合成、解毒、排泄和生物转化等功能发生严重障碍或失代偿,出现黄疸、凝血功能障碍、肝性脑病和腹水等为主要表现的一组临床症候群[1].肝衰竭有着极高的死亡率[2-3],肝移植作为最有效的一种治疗方法受到器官短缺的限制[4-5],人工肝是治疗肝衰竭的有效方法之一,其治疗机制是基于肝细胞强大的再生能力,通过一个体外的机械、理化和生物装置,清除各种有害物质,补充必需物质,改善内环境,暂时替代衰竭肝脏的部分功能,为肝细胞再生及肝功能恢复创造条件或等待机会进行肝移植.     

分子吸附再循环系统治疗急慢性肝功能衰竭的临床研究

目的 总结用分子吸附再循环系统(moleclular adsorbent recirculating system, MARS)治疗各类原因所致肝功能衰竭患者的经验。方法 回顾并随访分析25例次MARS人工肝治疗的疗效。结果 单次6h MARS治疗显著降低患者血清总胆红素[(618.51±200.68)mmol/L到(390.81±146.02)mmol/L, t=2.729,P＜O.01]、间接胆红素[(490.03±163.39)mmol/L到(303.28±113.06)mmol/L,t=2.516,P＜0.01]和血氨[(152.44±82.62)mmol/L到(84.84±13.30)mmol/L,t=2.174, P＜0.05] 水平;升高凝血酶原活动度(70.55±32.39到93.63±14.20,t=1.728,P＜0.05)。肝功能酶谱、血清蛋白质、肾功能、电解质、血常规和血气分析指标无显著变化。17例患者,治愈和好转13例,死亡4例,存活率76.5%。结论MARS人工肝是治疗肝功能衰竭患者安全、有效的辅助方法。     

非生物型人工肝治疗肝衰竭的现状

肝衰竭（重型肝炎）的主要治疗目标是通过支持治疗使肝脏再生以达到有效的重建肝脏基本功能,或者等到肝移植。肝移植作为改善肝衰竭患者的生存率最有效治疗手段存在着供肝来源困难的问题。而人工肝支持技术能明显改善肝衰竭患者的临床症状和生化学指标,并为肝移植起到了良好的桥梁作用。人工肝可分为非生物型人工肝和生物型人工肝。非生物型人工肝以去除体内蛋白结合毒素及水溶性毒素、补充一些体内缺乏的但必需的有益物质为目的,通过为肝脏的自我修复创造时间和机会来达到治疗肝衰竭的目的。生物型人工肝可以较好的替代肝脏解毒、生物合成和分泌代谢等功能,是国内外研究的热点。     

分子吸附再循环系统治疗甲状腺功能亢进合并严重肝损害的临床研究

甲状腺功能亢进（甲亢）合并严重肝功能损害是临床上治疗颇为棘手的一类疾病。为探讨解决此临床治疗难题的方法，我们采用分子吸附再循环系统（MARS）并结合同位素^131Ⅰ治疗，对甲亢合并严重肝损害的临床治疗方法进行探讨。[第一段]     

肝性脑病分子吸附再循环系统人工肝治疗中的Glasgow评分

我科自2001年5月引进分子吸附再循环系统(MARS)人工肝治疗重型肝炎取得了较好的效果；在肝性昏迷病人治疗时，采用Glsgow昏迷评定标准来判断患者意识障碍改善的程度。     

混合型人工肝支持系统治疗慢性重型肝炎

目的 评价混合型人工肝支持系统治疗慢性重型肝炎患者的临床疗效。方法 应用内含5×10~9以上猪肝细胞的生物反应器结合血浆置换装置,构建混合型人工肝支持系统(HALSS),并用于治疗15例慢性重型病毒性肝炎患者。结果 每次治疗后患者临床症状不同程度减轻,乏力、腹胀明显改善,腹水减少。总胆红素在混合型人工肝支持系统治疗后由(493.5±139.8)μmol/L降至(250.9±91.3)μmol/L,凝血酶原活动度由(24.5±8.4)％升至(30.6±6.3)％。15例患者中11例经混合型人工肝支持系统治疗肝细胞迅速坏死得到控制,最终好转出院,4例患者病情无好转死亡。15例患者治疗中未发生严重不良反应。结论 混合型人工肝支持系统对于慢性重型肝炎是一种有效的辅助支持和治疗手段。     

中间型和混合型人工肝对肝衰竭支持效果对比研究

目的　比较中间型 (血浆置换 )和混合型 (血浆置换加血液灌流吸附 )人工肝支持方法对肝衰竭患者肝功能的支持效果及安全性。方法　 1999- 0 1～ 2 0 0 2 - 0 2第三军医大学西南医院住院的 5 1例重型病毒性肝炎肝衰竭患者分别进行血浆置换 (17例 )和血浆置换加血液灌流吸附 (34例 )治疗 ,观察治疗前后患者临床症状变化 ,比较治疗前、后肝肾功能、血常规、凝血酶原时间变化。结果　血浆置换和血浆置换加血液灌流吸附治疗后 ,患者的临床症状均有不同程度改善。两种方法治疗后转氨酶、总胆红素、直接胆红素、凝血酶原时间、总蛋白、凝血酶原活动度的改善程度均差异有显著性 (P <0 0 5 ) ,但两种治疗方法间比较各项指标变化程度均差异无显著性。两种方法治疗的不良反应均较轻。结论　中间型、混合型人工肝对重型肝炎肝衰竭患者的肝功能均有肯定的支持效果。     

Application of Molecular Adsorbents Recirculating System to remove NO and cytokines in severe liver failure patients with multiple organ dysfunction syndrome

Background: Molecular Adsorbents Recirculating System (MARS) is a new promising artificial liver support therapy, the aim of this study was to assess the effectiveness of MARS to remove nitrous oxide (NO) and cytokines in severe liver failure patients with multiple organ dysfunction syndrome (MODS). Methods: Sixty single MARS treatments were performed with length of 6–24 h on 24 severe liver failure patients (18 males/6 females) with MODS. Results: The MARS therapy was associated with a significant removal of NO and certain cytokines such as TNF‐α, IL‐6, IL‐8, and INF‐γ, together with marked reduction of other non‐water‐soluble albumin bound toxins and water‐soluble toxins, these were associated with a improvement of the patients' clinical conditions including hepatic encephalopathy, deranged hemodynamic situation and as well as renal and respiratory function, thus resulted into marked decrease of Sequential Organ Failure Assessment (SOFA) score and improved outcome: nine patients were able to be discharged from the hospital or bridged to successful liver transplantation, the overall survival of 24 patients was 37.5%. Conclusion: We can confirm the positive therapeutic impact and safety to use MARS on liver failure patients with MODS associated with elevated levels of NO and cytokines.     

An Australian experience with the molecular adsorbents recirculating system (Mars)

The molecular adsorbents recirculating system (MARS) is a form of artificial extracorporeal liver support which has the potential to remove substantial quantities of albumin-bound toxins postulated to contribute to the pathogenesis of liver cell damage, hemodynamic instability and multi-organ failure in patients with acute liver failure and acute-on-chronic liver failure (AoCLF). We assessed the efficacy of MARS therapy in a cohort of patients with severe liver damage unresponsive to intensive medical therapy. MARS therapy was instituted late in the clinical course of six patients with severely impaired liver function refractory to intensive medical therapy, including four with AoCLF precipitated by sepsis and two with liver dysfunction due to sepsis in the absence of pre-existing chronic liver disease. Outcome measures included markers of hemodynamic stability, renal function, serum bilirubin and bile acid levels, arterial ammonia levels, the arterial ketone body (acetoacetate/beta-hydroxybutyrate) ratio, hepatic encephalopathy grade and the plasma disappearance rate of indocyanine green. The rates of discharge from the intensive care unit and in-hospital mortality were determined. Our findings suggest that MARS treatment might be associated with some clinical efficacy even in patients with advanced multi-organ dysfunction occurring in the setting of severe liver damage and in whom treatment is instituted late in the clinical course. However, the overall survival rate (1/6; 17%) was poor. More data obtained from larger cohorts of patients enrolled in randomized controlled studies will be required in order to identify categories of liver failure patients who might benefit most from MARS treatment and to ascertain the most appropriate timing of intervention.     

分子吸附再循环应用于重度黄疸患者的疗效评估

评估分子吸附再循环系统(molecular-adsorbent recirculating system,MARS)治疗对降低肝功能衰竭患者血清总胆红素(TBil)的疗效。应用德国TERAKLN公司生产的MARS对17例肝衰竭患者进行每次6h的治疗,检测治疗前中后不同时段TBil。13例肝衰竭患者经治疗后TBil降低28％(P<0．05),治疗过程前3h及后3h分别降低 22．2%和5．8％;4例TBil>800μmoL／L患者在治疗5h时TBil降低29．6%,更换负离子交换树脂吸附柱继续3小时治疗TBil仅降低5．1％。4例TBil<350μmol／L并发肝性脑病患者,MARS治疗3小时及6小时TBil均无明显降低,肝性脑病随治疗时间的延长逐步得到明显改善。MARS治疗肝衰竭,TBil降低主要住前3小时,治疗清除TBil的幅度和初始基础TBil水平正相关,与负离子交换树脂吸附柱的大小无相关性。MARS治疗效果主要以其患者整体病情的改善进行综合分析评价。     

Hybrid artificial liver support system for treatment of severe liver failure

AIM: To construct a novel hybrid artificial liver support system (HALSS) and to evaluate its efficacy in patients with severe liver failure. METHODS: Hepatocytes were isolated from suckling pig by the modified Seglen's method. Isolated hepatocytes were cultured in a spinner flask for 24 h to form spheroids before use and the functions of spheroids were detected. HALSS consisted of a plasma separator, a hemo-adsorba and a bioreactor with hepatocytes spheroids in its extra-fiber space. HALSS was applied to 10 patients with severe liver failure. The general condition and the biochemical indexes of the patients were studied just before and after the treatment. RESULTS: The number of cells per liver was about 2-4×1010 (mean, 3.1±1.5×1010). The cell viabilities were more than 95%. After 24 h of spheroid culture, most hepatocytes formed spheroids. The levels of albumin and urea in the medium of spheroid culture were higher than those in supernatant of petri dish culture (P= 0.0015 and 0.0001, respectively). The capacity of albumin production and urea synthesis remained stable for more than one wk and declined rapidly after two weeks in vitro. In HALSS group, the duration of HALSS treatment was 6-10 h each time. All patients tolerated the treatment well without any fatal adverse reaction. After HALSS treatment, the general condition, psychic state, encephalopathy and hepatic function of the patients were improved. The survival rate of the HALSS group, Plasmapheresis group and control group was 30% (3/10), 20% (2/10) and 0% (0/10), respectively (P = 0.024). Two weeks after treatment, Tbil and ALT decreased and the PTA level elevated in HALSS group and pasmapheresis group (Pvalue: 0.015 vs0.020, 0.009 vs 0.012 and 0.032 vs 0.041, respectively). But there was no significant change of blood albumin concentration before and after treatment in HALSS group and Plasmapheresis group. CONCLUSION: The HALSS established by us is effective in supporting liver function of patients with severe liver failure.     

分子吸附循环系统治疗慢性重型肝炎患者预后的改善

研究分子吸附循环系统(MARS)治疗对多脏器功能衰竭的治疗效果以及引入终末期肝病计分标准对在广州市第八人民医院肝病科行人工肝治疗的10例慢性重型肝炎患者的3个月临床转归进行分析评价,并对其临床实用价值进行初步探讨。