非生物人工肝支持系统治疗肝功能衰竭的血清氨基酸谱变化

目的 分析肝功能衰竭患者接受非生物人工肝支持系统(ALSS)治疗引起的血清氨基酸谱变化,阐述非生物ALSS治疗肝功能衰竭的有效性.方法 对2009年6月至2010年8月间146例肝功能衰竭患者行非生物ALSS治疗,观察治疗前后患者血清氨基酸谱的变化情况,并对不同预后、不同肝功能衰竭类型以及处于不同肝功能衰竭时期患者的血清氨基酸水平的变化进行研究.计量资料采用配对样本的t检验.结果 非生物ALSS治疗后,血清谷氨酸和赖氨酸下降明显[(395.62±200.24)μumol/L比(260.05±169.56)μmol/L,(436.73±326.18)μmol/L比(407.12±292.01)μmol/L;t＝8.611,t＝2.659;均P＜0.01],苏氨酸、支链氨基酸/芳香族氨基酸显著上升[(1302.90±1288.70)μmol/L比(1406.70±1272.34)μmol/L,1.23±0.53比1.36±0.57;t＝2.895,t＝1.061;均P＜0.01].在预后不同的患者间、不同肝功能衰竭类型以及处于不同时期的肝功能衰竭患者间,谷氨酸、酪氨酸、精氨酸以及蛋氨酸等治疗前后差异有统计学意义.结论 非生物ALSS治疗可以改善肝功能衰竭患者血清氨基酸紊乱状况.不同肝功能衰竭分类、分期以及不同预后患者的血清氨基酸谱在非生物ALSS治疗后有显著不同的变化.

Abstract：

Objective To analyze the patterns of amino acid changes in liver failure patients treated with non-bioartificial liver support system (ALSS), and to explore the efficacy of ALSS in liver failure treatment. Methods A total of 146 liver failure patients treated with ALSS from June 2009 to August 2010 were recruited in this study. Paired blood samples were collected from every patient and serum amino acids and ammonia were tested by automatic amino acid analyzer. The changes of amino acids in patients with different prognoses, different types/phases of liver failure were evaluated.Measurement data were compared by paired t test. Results After ALSS treatment, liver failure patients experienced a significant decrease in serum glutamic acid and lysine [(395.62±200.24)μmol/Lvs (260. 05±169.56) μmol/L and (436. 73±326. 18)μmol/L vs (407. 12±292.01) μmol/L,respectively; t= 8. 611 and 2. 659, respectively; both P＜0.01)], while experienced greatly increases in threonine and branched-chain amino acids/aromatic amino acid ratio [( 1302. 90 ±1288.70) μmol/L vs (1406.70 ±1272. 34) μmol/L and 1. 23 ± 0. 53 vs 1. 36 ± 0.57, respectively; t = 2. 895 and 1. 061,respectively; both P＜0. 01)]. The changes of glutamic acid, tyrosine, arginine and methionine before and after ALSS treatment in patients with different prognoses, different types/phases of liver failure were all significantly different. Conclusions ALSS treatment could improve the serum amino acid disorder in liver failure patients. The amino acids in patients with different types/phases or different prognoses of liver failure change significantly after ALSS treatment.     

非生物人工肝支持系统治疗肝功能衰竭的血清氨基酸谱变化

Objective To analyze the patterns of amino acid changes in liver failure patients treated with non-bioartificial liver support system (ALSS), and to explore the efficacy of ALSS in liver failure treatment. Methods A total of 146 liver failure patients treated with ALSS from June 2009 to August 2010 were recruited in this study. Paired blood samples were collected from every patient and serum amino acids and ammonia were tested by automatic amino acid analyzer. The changes of amino acids in patients with different prognoses, different types/phases of liver failure were evaluated.Measurement data were compared by paired t test. Results After ALSS treatment, liver failure patients experienced a significant decrease in serum glutamic acid and lysine [(395.62±200.24)μmol/Lvs (260. 05±169.56) μmol/L and (436. 73±326. 18)μmol/L vs (407. 12±292.01) μmol/L,respectively; t= 8. 611 and 2. 659, respectively; both P＜0.01)], while experienced greatly increases in threonine and branched-chain amino acids/aromatic amino acid ratio [( 1302. 90 ±1288.70) μmol/L vs (1406.70 ±1272. 34) μmol/L and 1. 23 ± 0. 53 vs 1. 36 ± 0.57, respectively; t = 2. 895 and 1. 061,respectively; both P＜0. 01)]. The changes of glutamic acid, tyrosine, arginine and methionine before and after ALSS treatment in patients with different prognoses, different types/phases of liver failure were all significantly different. Conclusions ALSS treatment could improve the serum amino acid disorder in liver failure patients. The amino acids in patients with different types/phases or different prognoses of liver failure change significantly after ALSS treatment.     

人工肝支持系统治疗急慢性肝功能衰竭的临床研究

背景：目前肝功能衰竭尚缺乏有效的治疗方法，除非及时接受肝移植，否则患者要经受长时间的住院治疗．死亡率高。应用肝脏辅助支持系统治疗急、慢性肝功能衰竭在临床上已广泛开展。目的：对各种病因所致的肝功能衰竭患者应用血浆置换（PE）和分子吸附再循环系统（MARS）进行治疗，探讨两种非生物人工肝在急、慢性肝功能衰竭中的作用。方法：148例肝功能衰竭患者在常规内科治疗的基础上分为两个治疗组，PE组60例．MARS组88例。观察患者治疗前后肝肾功能、血氨、凝血机制、电解质、血常规等指标的变化，同时评价两个治疗组的临床转归和存活率。结果：经1—3个月的随访，PE和MARS组的存活率分别为55．0％和64．8％，MARS组存活率略优于PE组，但差异无统计学意义。PE和MARS治疗后肝功能指标明显改善．血氨显著降低，总蛋白、肾功能、电解质、血常规和血气分析指标无显著变化。治疗结束72h后复查凝血指标的变化，发现凝血酶原活动度显著升高，凝血酶原时间显著降低。PE组寒颤、胸闷气短、恶心呕吐等不良反应发生率较高，MARS组不良反应主要是恶心呕吐，发生率较低。结论：PE和MARS是治疗肝功能衰竭患者安全、有效的辅助方法，尤其对非病毒性终末期患者疗效更加显著。     

人工肝支持系统治疗肝功能衰竭简介

人工肝的研究是基于肝细胞具有强大再生能力，通过一个体外的机械或理化装置，担负起暂时辅助或代替严重病变的肝脏的功能，清除各种有害物质，从而使肝细胞得以再生，直至自体肝脏恢复或等待机会进行肝移植。目前的人工肝多数只能取代肝脏的部分功能，因此又被称为人工肝支持系统(artificial live support system，ALSS)，简称人工肝。     

组合型人工肝支持系统在肝功能衰竭治疗中的临床应用

人工肝支持系统 (artificialliversupportsystem ,ALSS)的研究已有 40余年 ,作为具有里程碑意义的一种临床治疗方法 ,ALSS在肝衰的治疗中将发挥越来越重要的作用。本文主要就其中的组合型人工肝在肝衰竭中的临床应用现状进行简述。一、人工肝支持系统(ALSS)的历史回顾和分型1 .历史回顾鉴于人工肾治疗肾衰取得革命性突破的启发 ,人们试图研制一种人工肝脏应用于肝衰的治疗 ,从而为治疗肝衰开辟一条新路。真正对人工肝的研究始于本世纪 50年代。 1 958年 ,Kiley首次报道用血液透析治疗肝衰[1 ] 。随后人们陆续应用血液透析、血液滤过、…     

MARS人工肝治疗急慢性肝功能衰竭的临床研究

目的　评价应用分子吸附再循环系统治疗各类原因所致肝功能衰竭的治疗效果。方法　回顾并随访分析5 0例次MARS人工肝治疗的疗效。结果　单次 6～ 8小时MARS人工肝治疗显著降低患者血清总胆红素 ( 5 19.3 7±15 2 .70 μmol/L降至 3 61.0 6± 177.98μmol/L ,p <0 .0 5 )和血氨 ( 167.44± 80 .73 μmol/L降至 86.82± 15 .5 2 μmol/L ,P <0 .0 5 )水平 ;升高凝血酶原活动度 ( 3 6.5 5 %± 15 .2 9%到 74.13 %± 2 5 .40 %,P <0 .0 5 )。而电解质、血常规和血气分析等指标无显著变化 (P >0 .0 5 )。 2 5例患者中治愈和好转 15例 ,10例死亡 ,存活率 60 %。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     

人工肝支持系统治疗慢性重型肝炎的氨基酸谱变化

慢性重型肝炎伴发肝性脑病者的特征性血清氨基酸谱表现为ＢＣＡＡ/ＡＡＡ比值下降 ,测定血清氨基酸对于肝性脑病具有肯定的价值[1,2 ] 。我们应用氨基酸自动分析仪检测了 2 5例慢性重型肝炎患者在人工肝支持系统 (Ａｒｔｉｆｉｃｉａｌｌｉｖｅｒｓｕｐｐｏｒｔｓｙｓｔｅｍ ,ＡＬＳＳ)治疗前后的血清氨基酸含量 ,分析其血清氨基酸谱的特点 ,并进一步阐明ＡＬＳＳ治疗慢性重型肝炎的作用机制。病例和方法一、病例选择2 5例均为 1995～ 1999年浙江大学医学院附属第一医院传染科住院的慢性重型肝炎患者 ,按 1995年 (北京 )全国传染病与寄生虫…     

非生物型人工肝技术的优化与生物型人工肝研究进展

肝衰竭是临床常见综合征,进展快速,预后不良。目前其内科治疗方法仍有限,人工肝治疗是一种有效的治疗方法。非生物型人工肝技术在临床上广泛应用,其具体的启动时机、模式的选择、参数的设置需要临床医生根据疾病的病理生理机制及动态演变过程,结合患者具体情况决定。与非生物型人工肝相比,生物型人工肝能更好地模拟肝细胞的生物学功能,目前其核心技术已取得实质性的进展,相关临床研究也在积极进行,在未来有广阔的发展前景。本文就非生物型人工肝技术的优化及生物型人工肝相关进展进行总结与探讨,以期为人工肝技术的临床应用与研究提供参考。     

急性肝功能衰竭肝支持系统的评价

急性肝功能衰竭 (ALF)病死率高 ,而肝脏支持系统的应用能够维持患者生命 ,帮助其渡过难关 ,以争取时间寻找供肝进行肝移植 ,或是经药物治疗后肝功能得以自身恢复 ,从而起到桥梁作用。许多研究发现 ,生物人工肝技术具有改善患者的意识 ,比较安全 ,并能有效去除与蛋白质结合的毒素。一些未经对照的研究证明它能改善存活率。生物人工肝技术的心脏部位是生物反应器。它由许多条中空纤维毛细管构成 ,患者的血浆经此流过被保温、氧合和分离 ,在毛细管外有许多肝细胞 ,或是单独存在或是与胶原的微载体小粒结合在一起 ,这一支持系统可模拟肝脏的解…     

人工肝治疗对重型肝病患者生存期的影响

目的通过前瞻性、多中心、大样本的对照研究,探讨人工肝治疗对重型肝病患者生存期的影响。方法前瞻性地选择首都医科大学附属北京佑安医院等5家医院的重型肝炎和慢性肝炎重度(且凝血酶原活动度<50％)患者518例,将患者分为人工肝治疗组和常规内科治疗对照组,记录其诊断、分期等原始资料并进行随访,采用Kaplain-Maier方法进行生存情况分析。结果急性重型肝炎患者人工肝治疗组的中位生存期为(8．0±0．4)d,内科治疗对照组为(4．0±0．2)d,P=0．004。人工肝治疗2次以上疗效更加明显,它可使慢眭重型肝炎患者生存期由(27．0±1．6)d延长至(39．0±4．0)d,重型肝炎中期患者生存期由(38．0±17．5)d延长至(66．0±18．6)d;晚期患者生存期由(18．0±4．0)d延长至(26．0±2．5)d,差异均有统计学意义。结论人工肝治疗能够延长急性重型肝炎患者、慢性及亚急性重型肝炎中晚期患者的生存时间,多次治疗效果显著优于单次治疗和内科治疗。     

人工肝支持系统对肝移植围手术期肝衰竭患者Gc球蛋白的影响

目的 研究人工肝支持系统(血浆置换联合连续性静脉-静脉血液透析滤过)对肝衰竭患者血清Gc球蛋白的影响,探讨血清Gc球蛋白在肝衰竭患者病情预后评估中的意义.方法 将81例肝衰竭患者按治疗方案不同分为人工肝治疗组(43例),常规治疗组(38例);然后再分为人工肝治疗有效组(A组)、人工肝治疗无效组(B组)、常规治疗有效组(C组)和常规治疗无效组(D组),比较各组间治疗前后及治疗过程中Gc球蛋白的变化,分析Gc球蛋白分别和白细胞介素(IL)-18、IL-10、IL-4、肿瘤坏死因子α、内毒素、一氧化氮合酶、可溶性血管细胞黏附分子1、可溶性细胞间黏附分子1之间的关系.根据资料不同分别采用t检验、单因素方差分析(one-way ANOVA)、Pearson相关分析或x2检验.结果 (1)人工肝治疗组好转率为67.44%(29/43),常规治疗组治疗好转率为34.21%(13/38,P＜0.01).(2)人工肝治疗组治疗后Gc球蛋白显著升高,治疗前后比较,差异有统计学意义(P＜0.01);治疗后与常规治疗组治疗后比较,差异有统计学意义(P＜0.01),其中A组和C组治疗后明显升高,但A组治疗后较C组治疗后升高明显,两组间差异有统计学意义(P＜0.01);与B组和D组治疗后比较,差异有统计学意义(P＜0.01);各组肝衰竭患者血清Gc球蛋白水平的动态观察结果显示:A组和C组患者血清Gc球蛋白水平呈现由低到高的变化趋势;B组和D组患者的血清GC球蛋白水平波动,但无显著升高(P＞0.05).(3)Gc球蛋白和IL-4、IL-18和肿瘤坏死因子α、一氧化氮合酶、可溶性血管细胞黏附分子1、可溶性细胞间黏附分子1成负相关关系,而与IL-10之间无相关性.结论 人工肝支持系统能提高肝衰竭患者血清Gc球蛋白的水平,并最终可提高肝衰竭抢救成功率,改善预后.Gc球蛋白水平可作为临床转归的预测指标.

Abstract：

Objective To investigate the effects of artificial liver support system(plasma exchange combined with continuous veno - venous hemodiafiltration, PE + CVVHDF) on Gc globulin in patients with liver failure. Methods 81 patients with liver failure were divided into 4 groups according to the treatment protocols and indicators such as liver function and clinical symptoms. Totally 29 effective cases and 14 ineffective cases in the ALSS group versus 15 effective cases and 23 ineffective cases in the medical group were included. Finally the changes of Gc globulin were observed in four subgroups before and after treatment.The correlation between Gc globulin and IL-10, IL-4, IL-18, TNF c, endotoxin, NO, sVCAM-land sICAM-1 were analyzed by Pearson correlation analysis. Results The effectiveness rate was 67.44% in ALSS group and 34.21% in the medical treatment (P ＜ 0.01). Gc globulin, one of liver cell protection proteins was notably increased following the artificial liver treatment as compared with the increase in the medical treatment (P ＜0.01). The time-response curve of Gc globulin level had a significant upward trend in the effective group as compared to no significant rise in the ineffective group. Moreover, the Gc globulin was negatively correlated with IL-4, IL-18, TNFα, SVCAM-1, SICAM-1 and NO. In contrat, no correlation existed between Gc globulin and IL-10. Conclusion The treatment with artificial liver can improve the outcome of the patients with liver failure. The level of Gc globulin was correlated with the curative effect and thus may be used as a potential indicator for curative effect forcast in the patients with liver failure.     

人工肝治疗对肝衰竭患者肝脏储备功能的影响

肝衰竭患者病情危重,病死率高,人工肝治疗是积极有效的治疗手段.以吲哚氰绿(ICG)排泄试验为代表的肝脏储备功能检测是评价肝脏功能的重要方法之一.脉冲式色素浓度分析仪分析法(PDDG)进行ICG排泄试验,具有微创、简便、实时、快速和兼容等优点,但目前尚多用于肝脏手术术前肝脏储备功能的评价和肝硬化患者肝脏储备功能的评估.本研究通过ICG排泄试验为指标来预测肝衰竭患者预后,评价人工肝治疗对改善肝衰竭患者肝脏储备功能的临床意义.     

人工肝血浆置换治疗124例肝衰竭的临床观察

目的观察血浆置换(PE)术治疗肝衰竭的临床疗效、安全性及转归。方法对124例肝衰竭患者应用PE治疗223例次,通过比较治疗前后患者临床症状、血生化指标、凝血酶原时间等指标判断临床疗效,观察治疗相关的不良反应及转归情况。结果血浆置换术后自觉症状改善者达58.3%,血清胆红素显著下降(P<0.01),凝血酶原时间显著缩短(P<0.01)。治疗过程中出现血压一过性下降、皮疹、心慌、烦躁等不良反应,经对症处理后好转,未发生严重并发症。早期及中晚期肝衰竭的患者好转率分别为89.5%及12.5%(P<0.005),存在显著差异。结论PE可显著改善肝功能衰竭患者的临床症状及血生化指标,且安全可行。     

乙型肝炎慢加急性肝功能衰竭患者人工肝治疗的生存分析及其影响因素

目的 探讨人工肝治疗对乙型肝炎慢加急性肝功能衰竭患者生存率的影响及其影响因素.方法 前瞻性选择2009年1月至2010年6月在福州市传染病医院住院的乙型肝炎慢加急性肝功能衰竭患者157例,根据患者意愿分成两组:治疗组93例,对照组64例.两组均给予内科综合治疗,治疗组加用人工肝治疗.记录两组基线时的临床基本资料,并进行...     

血浆置换治疗肝功能衰竭的疗效评价

目的 总结血浆置换型人工肝治疗11例肝功能衰竭的临床疗效。方法 11例肝功能衰竭病人采用血浆置换治疗(治疗组),9例为常规药物治疗(对照组),观察血浆置换对肝功能恢复的影响,并分析其疗效。结果 血浆置换后患者血清总胆红素(TBIL)明显下降(210±86μmol/L VS 342±96μmol/L,P<0.05);凝血酶原时间缩短(26±12s VS 38±11s,P<0.05),但治疗前后血清谷丙转氨酶(ALT)变化不显著(852±221U/L VS 795±195U/L,P>0.05)。血浆置换组存活7例,存活率为63.6％(7/11);高于对照组的37.5％(3/9,P<0.05)。结论 血浆置换治疗肝功能衰竭可明显降低血清TBIL、缩短凝血酶时间,并可提高患者生存率,是目前治疗肝功能衰竭的重要手段之一。     

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.     

人工肝支持系统治疗慢加急性肝衰竭效果的网状Meta分析

目的采用网状Meta分析系统评价不同人工肝支持系统治疗慢加急性肝衰竭（ACLF）的疗效。方法计算机检索PubMed、EMBASE、Cochrane library、Clinical Trial、CNKI、SinoMed和万方数据库中关于不同形式人工肝治疗ACLF患者的随机对照试验。根据纳入排除标准进行文献筛选、资料提取及方法学质量评价,采用Stata15.1及R4.1.0软件进行网状Meta分析。结果共纳入14篇文献,共计1141例患者。网状Meta分析结果显示:不同干预方式交叉对比降低病死率差异均无统计学意义（P值均>0.05）,排序概率图显示降低30 d病死率血浆置换（PE）最优,其他依次为体外细胞疗法（ELAD）、分级血浆分离吸附（Prometheus）、分子吸附再循环系统（MARS）、Biologic-DT肝脏透析设备、PE+MARS。降低90 d病死率PE最优,其他依次为Prometheus、ELAD、MARS。改善肝性脑病方面,Biologic-DT最优,其他依次为MARS、PE+MARS、ELAD。出血风险最低者为ELAD,与标准医学治疗（SMT）相比Biologi...