MARS人工肝在重型肝炎和肝脏移植中的临床应用和基础研究
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摘要
目的
1.评价MARS人工肝在重型肝炎和肝脏移植中的疗效,为更好地指导MARS人工肝在临床应用提供依据。
2。为临床上肝衰竭患者行MARS人工肝治疗后是否需要肝脏移植提供病情判断指标。
方法
1.对67例肝衰竭病人进行MARS人工肝治疗,检测治疗前后各种有毒物质及凝血因子的改变并进行比较。
2.采用RT—PCR检测好转组和恶化组TNF—αmRNA和TL—6αmRNA表达水平在MARS人工肝治疗前后的变化,并在两者间进行比较。
结果
1.67例肝衰竭病人,经MARS治疗后,临床症状及体征明显改善;血总胆红素、总胆汁酸、肌酐、尿素氮、血氨、内毒素水平明显降低(P＜0.05).
2.血清NO和TNF-α、IL-4、IL-6水平明显降低(P＜0.05).
3.单次的MARS人工肝治疗前后凝血因子Ⅸ(F.Ⅸ)及凝血因子Ⅹ(F.Ⅹ)无显著性改变(P＞0.05),然而在连续的MARS治疗过程中,在连续两次MARS治疗前之间比较,F.Ⅸ以及F.Ⅹ有显著性差异(P＜0.05),即凝血因子呈上升趋势。
4.49例重型乙肝肝衰竭患者存活30例,存活率61.2%;8例肝脏移植术前急性肝衰竭患者均成功接受肝脏移植;8例肝脏移植术后急性肝衰竭患者存活3例,存活率37.5%。
5.好转组的TNF—αmRNA和IL—6mRNA表达水平在MARS治疗后较恶化组明显降低(P＜0.05)。
结论
1.MARS通过全面清除肝衰竭毒素、NO和细胞因子,对肝衰竭有肯定的治疗作用。
2.MARS治疗可改善肝脏合成功能。
3.F.Ⅸ和F.Ⅹ对肝衰竭预后的早期评估有重要意义。
4.MARS对于等待肝脏移植的肝衰竭患者,则发挥过渡性桥梁作用。
5.MARS人工肝治疗后TNF—αmRNA和IL—6mRNA呈弱阳性表达的患者,通过人工肝治疗可以存活;而MARS人工肝治疗后TNF—αmRNA和IL—6mRNA仍呈强阳性表达的患者,可能需进一步施行肝脏移植。
Objective
1.To evaluate the effect of MARS treatment in liver failure of severe hepatitis and liver transplantation.
2.To provide diagnostic parameters for liver failure patients who were treating MARS to or not perform liver transplantation.
Methods
1.67 hepatic failure patients were treated with MARS,changed data in blood were collected before and after every treatment,these laboratory parameters before and after treatment were compared with each other.
2.The levels of TNF-αmRNA and IL-6mRNA expression before and after every MARS trentment,both in improving group and worsening group,were tested with RT-PCR.The expresion levels in improving group and worsening group were compared with each other.
Results
1.MARS therapy achieved a remarkable improvement in clinical symptoms and physic signs;MARS treatment significantly decreased the total bilirubin,total bile acid,creatinine,urea nitrogen,ammonia and endotoxin levels(P < 0.05).
2.as well as the serum NO,TNF -α,IL - 4 and IL - 6 levels(P <0.05).
3.No significant changes of coagulation factorⅨ(F.Ⅸ) and coagulation factorⅩ(F.Ⅹ) levels were found before and after every single MARS treatment (P > 0.05),however during a serial of MARS treatment,the levels of F.Ⅸand F.Ⅹbefore the latter MARS treatment were higher than the levels before the former MARS treatment(P < 0.05).The levels of F.Ⅸand F.Ⅹincreased during MARS treatment.
4.The survival rate in 49 hepatic failure patients of severe hepatitis B was 61.2% (30/49);8 patients with preoperative hepatic failure were successfully performed liver transplantation:the survival rate in 8 postoperative hepatic failure patients undergone liver transplantation was 37.5%(3/8).
5.The levels of TNF-αmRNA and IL-6mRNA expression after every MARS treatment of improving group was significant lower than these of worsening group.
Conclusions
1.We may confirm the positive therapeutic impact of MARS in hepatic failure patients,and the effectiveness of MARS is correlated with overall removing of elevated levels of toxins,NO and cytokines.
2.MARS treatment can improve hepatic synthetic function.
3.F.Ⅸand F.Ⅹhave an important value in early evaluation of the prognosis of hepatic failure patients.
4.MARS acts as a bridge to the hepatic failure patients who are waiting for liver transplantation.
5.The patient can survive by MARS treatment,whose TNF-αmRNA and IL-6mRNA lowly express after MARS treatment.But the patient need liver transplatation whose TNF-αmRNA and IL-6mRNA still highly express after MARS treatment.
1.评价MARS人工肝在重型肝炎和肝脏移植中的疗效,为更好地指导MARS人工肝在临床应用提供依据。
2。为临床上肝衰竭患者行MARS人工肝治疗后是否需要肝脏移植提供病情判断指标。
方法
1.对67例肝衰竭病人进行MARS人工肝治疗,检测治疗前后各种有毒物质及凝血因子的改变并进行比较。
2.采用RT—PCR检测好转组和恶化组TNF—αmRNA和TL—6αmRNA表达水平在MARS人工肝治疗前后的变化,并在两者间进行比较。
结果
1.67例肝衰竭病人,经MARS治疗后,临床症状及体征明显改善;血总胆红素、总胆汁酸、肌酐、尿素氮、血氨、内毒素水平明显降低(P＜0.05).
2.血清NO和TNF-α、IL-4、IL-6水平明显降低(P＜0.05).
3.单次的MARS人工肝治疗前后凝血因子Ⅸ(F.Ⅸ)及凝血因子Ⅹ(F.Ⅹ)无显著性改变(P＞0.05),然而在连续的MARS治疗过程中,在连续两次MARS治疗前之间比较,F.Ⅸ以及F.Ⅹ有显著性差异(P＜0.05),即凝血因子呈上升趋势。
4.49例重型乙肝肝衰竭患者存活30例,存活率61.2%;8例肝脏移植术前急性肝衰竭患者均成功接受肝脏移植;8例肝脏移植术后急性肝衰竭患者存活3例,存活率37.5%。
5.好转组的TNF—αmRNA和IL—6mRNA表达水平在MARS治疗后较恶化组明显降低(P＜0.05)。
结论
1.MARS通过全面清除肝衰竭毒素、NO和细胞因子,对肝衰竭有肯定的治疗作用。
2.MARS治疗可改善肝脏合成功能。
3.F.Ⅸ和F.Ⅹ对肝衰竭预后的早期评估有重要意义。
4.MARS对于等待肝脏移植的肝衰竭患者,则发挥过渡性桥梁作用。
5.MARS人工肝治疗后TNF—αmRNA和IL—6mRNA呈弱阳性表达的患者,通过人工肝治疗可以存活;而MARS人工肝治疗后TNF—αmRNA和IL—6mRNA仍呈强阳性表达的患者,可能需进一步施行肝脏移植。
Objective
1.To evaluate the effect of MARS treatment in liver failure of severe hepatitis and liver transplantation.
2.To provide diagnostic parameters for liver failure patients who were treating MARS to or not perform liver transplantation.
Methods
1.67 hepatic failure patients were treated with MARS,changed data in blood were collected before and after every treatment,these laboratory parameters before and after treatment were compared with each other.
2.The levels of TNF-αmRNA and IL-6mRNA expression before and after every MARS trentment,both in improving group and worsening group,were tested with RT-PCR.The expresion levels in improving group and worsening group were compared with each other.
Results
1.MARS therapy achieved a remarkable improvement in clinical symptoms and physic signs;MARS treatment significantly decreased the total bilirubin,total bile acid,creatinine,urea nitrogen,ammonia and endotoxin levels(P < 0.05).
2.as well as the serum NO,TNF -α,IL - 4 and IL - 6 levels(P <0.05).
3.No significant changes of coagulation factorⅨ(F.Ⅸ) and coagulation factorⅩ(F.Ⅹ) levels were found before and after every single MARS treatment (P > 0.05),however during a serial of MARS treatment,the levels of F.Ⅸand F.Ⅹbefore the latter MARS treatment were higher than the levels before the former MARS treatment(P < 0.05).The levels of F.Ⅸand F.Ⅹincreased during MARS treatment.
4.The survival rate in 49 hepatic failure patients of severe hepatitis B was 61.2% (30/49);8 patients with preoperative hepatic failure were successfully performed liver transplantation:the survival rate in 8 postoperative hepatic failure patients undergone liver transplantation was 37.5%(3/8).
5.The levels of TNF-αmRNA and IL-6mRNA expression after every MARS treatment of improving group was significant lower than these of worsening group.
Conclusions
1.We may confirm the positive therapeutic impact of MARS in hepatic failure patients,and the effectiveness of MARS is correlated with overall removing of elevated levels of toxins,NO and cytokines.
2.MARS treatment can improve hepatic synthetic function.
3.F.Ⅸand F.Ⅹhave an important value in early evaluation of the prognosis of hepatic failure patients.
4.MARS acts as a bridge to the hepatic failure patients who are waiting for liver transplantation.
5.The patient can survive by MARS treatment,whose TNF-αmRNA and IL-6mRNA lowly express after MARS treatment.But the patient need liver transplatation whose TNF-αmRNA and IL-6mRNA still highly express after MARS treatment.
引文
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[3]Kimoto S.Thc artificial liver experiments and clinical application.ASAIO Trans,1959,5:102-125
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[2]Kiley JE,Welch HF,PenderJC,et al.Removal of blood ammonia by hemodialysis.Proc Soc Exp Biol Med,1956,91:489-490
[3]Schechter DC,Nealon TF,Gibbon JH.A simple extracorporeal device for reducing elevated blood ammonia levels.Surgery,1958,44:892-897
[4]Kimoto S.The artificial liver experiments and clinical application.ASAIO Trans,1959,5:102-125
[5]Ching NP,Nealon TF,Gibbon JH.An extracorporeal device for hepatic coma.JAMA,1963,183:350-354
[6]Juggi JS.Extracorporeal cation-exchange circuits in the treatment of hyperammonaemia of hepatic failure.Med J Aust,1963,60:926-930
[7]Yatzidis H.A convenient hemoperfusion microapparatus over charcoal for the treatment of endogenous and exogenous intoxifications:its use as an effective artificial kidney.Proc Eur Dial Transplant Assoc,1964,1:83-87.
[8]Chang TMS.Hemoperfusions over a microencapsulated adsorbent in a patient with hepatic coma.Lancet,1972,ⅱ:1371-1372
[9]Opolon P Rapin JR,Huguet C,et al.Hepatie failure coma treated by polyacrylonitrile membrane hemodialysis.Trans Am Soc Artif Intern Organs,1976,22:701-710
[10]Trey MB,Burns DG,Saunders SJ.Treatment of hepatic coma by exchange blood transfusion.N Engl J Med,1966,274:473-481
[11]Burnell JM,Dawbom JK,Epstein RB,et al.Acute hepatic coma treated by erosscirculation or exchange transfusion.N Engl J Med,1967,276:935-943
[12]Redeker AG,Yamahiro HS.Controlled trial of exchange-transfusion therapy in fulminant hepatitis.Lancet,1973,ⅱ:2-6
[13]Lee C,Tink A.Exchange transfusion in hepatic coma:report of a case.Med J Aust,1958,1:40-42
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[77]Streetz KL,Luedde T,Manns MP,et al.Interleukin-6 and liver regeneration.Int J Gastroenter Hepatol,2000;47:309 -312
[78]Anna MD,Rudra R.Regulation of liver regeneration by pro-inflammatory cytokines.J Gastroenter Hepatol,1996;11(5):466-470
[79]Gallucci RM,Simeonova PP,Toriumi W,et al.TNF-alpha regulates transforming growth factor-alpha expression in regeneration murine liver and isolated hepatocytes.Immunology,2000;164(2):872-878
[80]Peng Y,Du K,Ramirez S.Mitogenic upregulation of the PRL-1 protein-tyrosine phosatatse gene by Egr-1.Egr-1 activation is an event in liver regeneration.J Biol Chem,1999;274:4513-4520
[81]Cressman DE,Greenbaum LE,Deangelis RA.Liver Failure and defective hepatoeyte regeneration in IL-6 deficient mice.Science,1996;274:1379-1383
[82]Denson LA,Held MA,Menon RK,et al.Interleukin-6 inhibits hepatic growth hormone signaling via upregulation of Cis and Socs-3.Am J Physiol Gastrointest Liver Physiol,2003;284:G646-G654
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