分子吸附再循环系统对肝功能衰竭患者血清单核细胞趋化蛋白-1的影响

目的　评价分子吸附再循环系统 (MARS)治疗对炎性因子单核细胞趋化蛋白 1(MCP 1)血清质量浓度的影响。方法　通过ELISA方法 ,观察 2 0 0 2 - 12～ 2 0 0 3- 12在西安交通大学第一医院经MARS治疗的肝衰竭患者 (2 0例次 )MCP -1血清质量浓度的变化。结果　 (1)MARS治疗后 ,患者临床症状及体征均有不同程度改善 ,患者病死率 4 6 . 6 7%。 (2 )MARS治疗后患者MCP 1明显降低 (P <0. 0 5 ) ,好转组下降较死亡组更为显著。在MARS治疗前亚重肝组MCP -1值较慢重肝组明显升高 ,经过MARS治疗 ,两组MCP -1值显著降低 ,亚重肝组下降更为明显。结论　MARS系统能够清除肝衰竭患者体内MCP -1,MCP- 1减少与患者预后有关 ,患者临床表现的改善与MCP- 1降低存在一致性。     

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。     

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。     

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。     

血浆置换联合血液滤过对乙型肝炎相关慢加急性肝衰竭患者血清IL-17和IL-6的影响

目的探讨血浆置换联合血液滤过对乙型肝炎相关肝衰竭血清白细胞介素(IL)-17、IL-6的影响。方法 30例乙型肝炎慢加急性肝衰竭患者在内科治疗的基础上采用血浆置换联合血液滤过单次治疗。用ELISA检测各组血清IL-17、IL-6浓度,同时记录血清ALT、TBil等值并进行统计分析。结果肝衰竭组患者血清IL-17、IL-6水平分别为(123.5±23.0)pg/ml、(110.0±18.5)pg/ml,高于慢性乙型肝炎患者(48.5±6.3)pg/ml、(27.8±5.9)pg/ml和正常对照组(34.7±3.3)pg/ml、(12.1±5.1)pg/ml,P均<0.001;治疗后血清IL-17、IL-6水平分别为(84.7±21.4)pg/ml、(75.8±16.6)pg/ml,较治疗前下降(t=35.1,P<0.001;t=33.4,P<0.001);与好转组相比,人工肝对恶化组血清IL-17、IL-6清除效率降低(t=3.8,P<0.05;t=3.9,P<0.05);人工肝对血清IL-17、IL-6清除效率均与MELD评分呈负相关(r=-0.53、P=0.003;r=-0.43,P=0.015)。结论血浆置换联合血液滤过能有效降低肝衰竭患者血清IL-17、IL-6水平,其对IL-17、IL-6的清除效率可能与患者预后有关。     

血浆置换对重症肝病患者血清毒素和炎性介质的影响

肝衰竭进展并发生多脏器功能不全综合征（MODS）可能与毒素大量蓄积、内毒素一细胞因子轴损伤等因素有关^[1]。血浆置换（PE）能迅速清除肝衰竭相关毒素和炎症因子，同时补充新鲜冰冻血浆，减轻甚至终止由细胞因子失控性释放引起的系统性炎症反应综合征（SIRS）。我们观察了重症肝病患者PE治疗前后TBil、总胆汁酸（TBA）、     

CAPS人工肝治疗肝衰竭的临床研究

目的应用连续白蛋白净化系统（CAPS）治疗肝衰竭患者,并与分子吸附再循环系统（MARS）进行比较,观察CAPS治疗肝衰竭的疗效及安全性。方法33例肝衰竭患者在一般治疗的基础上,18例行CAPS治疗,15例行MARS治疗,比较两组的疗效。结果CAPS治疗后血清总胆红素由579．6±136．3μmol／L降至473．3±96．3μmol／L（P〈0．05）、肌酐由247．8±154．5μmol／L降至180．8±119．8μmol／L（P〈0．05）;CAPS治疗组与MARS治疗组患者痊愈好转率分别为55．5％和53．3％（P〉0．05）。结论CAPS能清除毒素,改善临床症状和肝功能,其治疗肝衰竭的疗效肯定,CAPS具有较优良的性能价格比,适合于我国的国情,值得进一步探讨、应用。     

血浆置换对肝衰竭患者细胞因子表达的影响

目的观察人工肝血浆置换术治疗对肝衰竭患者血清白细胞介素(IL)6、肿瘤坏死因子(TNF)α及干扰素(IFN)γ的清除效果,进一步探讨人工肝支持系统在肝衰竭治疗中的意义。方法收集2012年2月至2013年2月在蚌埠医学院第一附属医院住院的36例肝衰竭患者,分别在血浆置换术前及多次治疗后的次日清晨采集血标本。用ELISA法测定血浆TNFα、IL-6、IFNγ的含量,计量资料治疗前后组间比较采用t检验,多组间比较采用方差分析,进一步两两比较采用SNK-q检验。结果 36例肝衰竭患者TNFα、IL-6、IFNγ治疗前分别为(381.23±190.57)ng/L、(77.9±83.09)ng/L、(534.65±471.19)ng/L,治疗后分别为(274.12±212.30)ng/L、(54.8±63.32)ng/L、(259.65±312.26)ng/L,治疗前后比较,差异均有统计学意义(P值均0.05)。亚急性肝衰竭和慢加急性(亚急性)肝衰竭患者根据临床表现的严重程度又分为早期、中期和晚期。结果发现,IL-6、TNFα在早、中、晚期组比较差异均有统计学意义(P值均0.05);IFNγ早、中、晚期组差异有统计学意义(P0.05);进一步两两比较IFNγ早期组与晚期组、中期组与晚期组相比,差异均有统计学意义(P值均0.05)。经过人工肝血浆置换治疗,其中有29例肝衰竭患者好转痊愈,余7例恶化,TNFα、IL-6、IFNγ在好转痊愈组降低程度分别为(122.58±57.64)ng/L、(26.93±7.25)ng/L、(284.06±94.31)ng/L,均显著高于恶化组下降水平(P值均0.05)。急性肝衰竭有效率为66.67%,亚急性肝衰竭有效率为85.71%,慢加急性(亚急性)肝衰竭有效率为86.36%,慢性肝衰竭有效率为50.00%。结论连续的人工肝血浆置换术治疗,能有效清除肝衰竭患者血浆促炎性细胞因子水平,改善患者临床症状。     

乌司他丁在自身免疫性肝病合并慢加急性肝衰竭治疗中的作用

目的探讨乌司他丁治疗自身免疫性肝病合并慢加急性肝衰竭的效果。方法选取2011年1月-2012年12月诊断的自身免疫性肝病合并慢加急性肝衰竭患者20例,分为治疗组和对照组,治疗组在常规治疗的基础上加用乌司他丁,其余治疗措施两组相同。结果经过7 d的治疗,治疗组患者的AST水平低于对照组(P=0.03),IL-6下降的水平较对照组明显(P0.05);两组在ALT水平(P=0.61)和MELD评分(P=0.36)方面的差异无统计学意义。结论乌司他丁治疗自身免疫性肝病合并慢加急性肝衰竭具有积极作用,尤其在降低炎性因子方面效果明显。     

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.     

First clinical experience with Molecular Adsorbent Recirculating System (MARS) in six patients with severe acute on chronic liver failure

Despite recent advances in general supportive care, the mortality rate of patients with severe liver insufficiency remains high. Recently a new artificial liver support system MARS has been used for selective removal of albumin-bound toxins. Aim: To assess the safety and efficacy of MARS treatment in patients with acute on chronic liver disease (n = 5) or liver failure after extended hepatic resection (n = 1). Design/Patients: Six patients, aged 34-58 years, with severe liver insufficiency (mean MELD-score 31 (range 24-35)) were treated one to 16 times with the MARS system. At baseline three patients were intubated, three were encephalopathic (HE) and three had multifactorial kidney failure requiring kidney replacement therapy. Results and Conclusion: In all the patients MARS treatment significantly reduced the serum bilirubin levels. In three patients encephalopathy improved. In two patients the extracorporeal treatment precipitated a disseminated intravascular coagulation with clinically significant bleeding. Bridging to liver transplantation was possible in one patient, the other five patients died 30 days (2-74 days) after starting MARS therapy. Our case series shows that MARS treatment in general can be safely performed in patients with severe liver disease. However, in patients with an activated clotting system severe bleeding complication can be triggered and MARS treatment should be used very cautiously in these situations. MARS seems to be a promising new treatment option for patients with acute on chronic liver failure. However, carefully conducted randomized controlled trials are necessary to define its potential place in the treatment of patients with severe liver disease.     

Evaluation of effect of hybrid bioartificial liver using end-stage liver disease model

AIM: To study the role of hybrid bioartificial liver (HBL) in clearing proinflammatory cytokines and endotoxin in patients with acute and sub-acute liver failure and the effects of HBL on systemic inflammatory syndrome (SIRS) and multiple organ dysfunction syndrome (MODS).METHODS: Five cases with severe liver failure (3 acute and 2 subacute) were treated with HBL. The clinical signs and symptoms, total bilirubin (TBIL), serum ammonia,endotoxin TNF-~, 1L-6 and prothrombin activity (PTA),cholinesterase (CHE) were recorded before, during and after treatment. The end-stage liver disease (MELD) was used for the study.RESULTS: Two patients were bridged for spontaneous recovery and 1 patient was bridged for OLT successfully.Another 2 patients died on d 8 and d 21. The spontaneous recovery rate was 30.0%. PTA and CHE in all patients were significantly increased (P&lt;0.01), while the serum TBIL,endotoxin,TNF-α, IL-6 were decreased. MELD score (mean 43.6) predicted 100% deaths within 3 mo before treatment with HBL. After treatment with HBL, four out of 5 patients had decreased MELD scores (mean 36.6). The MELD score predicted 66% mortalities.CONCLUSION: The proinflammatory cytokines (TNFα, IL-6 and endotoxin)can be significantly removed by hybrid bioartificial liver and HBL appears to be effective in blocking SIRS and MODS in patients with acute and sub-acute liver failure. MELD is a reliable measure for predicting short-term mortality risk in patients with end-stage liver disease. The prognostic result also corresponds to clinical outcome.     

Albumin regeneration in liver support-comparison of different methods

Albumin is the most abundant human plasma protein. Among many other functions it is an important transporter of hydrophobic internal and external substances such as intermediate and end products of metabolism and drugs. In liver failure the albumin binding capacity is decreased because of a disproportion between available albumin molecules caused by decreased hepatic synthesis and hydrophobic toxins because of decreased hepatic clearance. The resulting increase in plasma and tissue concentrations of these substances is associated with multiple organ dysfunctions frequently seen in severe liver failure. The scope of the present article is to compare different liver support strategies with regard to their ability to regenerate the patients albumin pool by removing albumin-bound toxins. Most prominent technique in this group is the molecular adsorbent recirculating system (MARS). It will be compared with single pass albumin dialysis (SPAD), fractionated plasma separation and adsorption system (FPSA, Prometheus), and plasma perfusion/bilirubin adsorption with special regard to efficacy and selectivity.     

Acute liver failure and the Molecular Adsorbents Recirculating System: early experience in a tertiary care hospital in Mexico City

Acute liver failure is a clinical condition associated with high mortality despite recent technological advances. Supportive devices such as the Molecular Adsorbents Recirculating System (MARS) provide therapeutic strategies to add time to find an organ for orthotopic liver transplantation or to allow the native liver to recover sufficiently to make transplantation unnecessary. In this series of cases, we discuss our initial experiences with three patients with acute liver failure. One patient had high bilirubin levels caused by Epstein-Barr virus infection and responded well after three MARS sessions. In a second patient, MARS therapy was used to treat acute-on-chronic liver failure caused by chronic hepatitis B virus infection that had not been treated previously; because of severe hemodynamic compromise, only one MARS session was performed. The third patient had an initial diagnosis of acute liver failure and cryptogenic hepatitis, and was treated with five MARS sessions as a supportive measure until the definitive diagnosis (metastatic disease) was performed. In all patients, MARS therapy was well tolerated and induced only mild hypokalemia. In conclusion, although MARS therapy was an effective strategy for these cases of liver failure and greatly improved the biochemical variables, its impact on the mortality rate has not yet been determined.     

MARS treatment in posthepatectomy liver failure

Abstract Posthepatectomy liver failure (PHLF) is a dramatic complication following extensive liver resection or liver resection in a compromised liver, leading to death in 80% of cases. Molecular Adsorbent Recirculating System (MARS) is able to extract water and protein bound toxins out of the blood in liver failure patients. This paper describes the initial experience in the Netherlands using the MARS liver assist device in five patients with PHLF. In all patients, improvement of biochemical parameters was observed during MARS treatment along with clinical improvement in three patients. One patient survived. No clear guidelines for MARS treatment and prognostic factors for outcome after MARS treatment with regard to this patient group are available. In this paper, a MARS treatment regimen for PHLF is suggested based on literature and our own experience.     

Successful treatment of an adult with Amanita phalloides-induced fulminant liver failure with molecular adsorbent recirculating system (MARS)

Despite significant advances in intensive care management of Amanita phalloides-induced fulminant liver failure (FLF), patients with this condition still have a high mortality rate in the absence of orthotopic liver transplantation. Molecular Adsorbent Recirculating System (MARS) is a new, cell-free, extracorporeal liver assistance method utilizing an albumin dialysate for the removal of albumin-bound toxins, and a highly effective depurative therapy in adults with wild mushroom-induced FLF. We report the case of a 39 year old woman with Amanita phalloides-induced FLF, admitted to our intensive care unit (ICU) and treated with MARS. Our patient had severe hepatic dysfunction: hepatic encephalopathy (grade II), ALT = 5022 (2475-10098) IU/L, bilirubin = 7.18 (4.8-10.1) mg/dL, prothrombin time (PT) = 90.4 (29.3-140.4) s. MARS sessions had an immediate impact on liver tests: statistically significant decrease in ammonia, ALT and PT. Hepatic encephalopathy was successfully reduced. The patient survived and the hepatic function completely recovered. MARS appears to be a safe and highly effective depurative therapy in adults with Amanita phalloides-induced FLF.     

分子吸附再循环系统对肝移植术早期成功率的影响

目的 探讨影响肝移植术早期成功率的危险因素,总结在肝移植术前应用分子吸附再循环系统(MARS)治疗对术后患者早期生存率的影响。 方法 回顾性分析50例肝移植患者术前80次MARS治疗的临床资料,对有关临床指标进行排序分析;术后生存30d的28例为生存组,死亡6例为死亡组,对部分术前危险因素进行回归分析。 结果 50例患者中免除移植出院8例,移植前死亡8例,34例过渡到移植,移植后死亡6例。单次6 h MARS治疗较大幅度降低患者血清总胆红素、肌酐、尿酸、血氨、肿瘤坏死因子α(TNF α)和白细胞介素-10(IL-10)水平,同时显著改善系列器官功能衰竭评分(SOFA)(P<0.05);移植术后早期死亡与术前SOFA、肌酐、国际标准化比率(INR)、TNF α和IL-10等存在明显相关性。 结论 术前SOFA、肌酐、INR、TNF α和IL-10水平是移植后早期死亡的主要术前危险因素,术前MARS支持可以显著改善这些危险因素,有效提高移植成功率,甚至避免移植手术。