新型人工肝组合技术双重血浆分子吸附联合血浆置换与单纯血浆置换治疗肝衰竭
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摘要
背景:双重血浆分子吸附不仅能特异性吸附胆红素和胆汁酸,还可以清除体内毒素、炎症递质、细胞因子,在缺乏血浆或血浆不足的情况下,可有效清除有害物质,防止多脏器功能衰竭,为肝脏再生、肝功能的恢复争取时间,适用于各种原因引起的肝衰竭。目的:对比新型双重血浆分子吸附联合血浆置换与单纯血浆置换治疗肝衰竭的有效性和安全性。方法:收集2014年10月至2017年10月在贵州省人民医院收治的肝衰竭患者60例,随机分为2组,每组30例。血浆置换组单纯采用血浆置换治疗,血浆置换量为2 500-3 000 mL;联合组采用双重血浆分子吸附联合血浆置换治疗,血浆置换量为1 000-1 500 mL。均于治疗3次后评估临床效果及肝功能,并观察人工肝治疗过程中出现的不良反应。结果与结论:①治疗后2组血清总胆红素、谷丙转氨酶水平较治疗前显著降低,凝血酶原活动度水平较治疗前显著升高(P <0.05),但治疗前后联合组血清白蛋白水平差异无显著性意义,治疗后联合组血清总胆红素、谷丙转氨酶、血清白蛋白水平显著低于血浆置换组,凝血酶原活动度水平显著高于血浆置换组(P <0.05);②联合组治疗总有效率(83%)显著高于血浆置换组(63%)(P <0.05);③联合组人工肝治疗过程中出现皮疹、寒战、低血压各1例;血浆置换组未出现不良反应;④结果提示,双重血浆分子吸附联合血浆置换与单纯血浆置换均可以显著改善肝衰竭患者肝功能,且不良反应少。但双重血浆分子吸附与血浆置换联合应用的治疗效果更具优势,同时可以减少血浆用量。
BACKGROUND: Double plasma molecular adsorption system cannot only specifically absorb bilirubin and bile acids, but also eliminate toxins, inflammatory transmitters and cytokines in the body. In the absence of plasma or in the case of plasma deficiency, it can effectively remove harmful substances, prevent multiple organ failure and fight for time for the liver regeneration and recovery of liver function, which is suitable for liver failure caused by various reasons. OBJECTIVE: To compare the validity and safety of double plasma molecular adsorption system combined with plasma exchange and simple plasma exchange in the treatment of liver failure. METHODS: Sixty patients with liver failure admitted to the Guizhou Provincial People's Hospital from October 2014 to October 2017 were included and randomized into two groups(n=30/group). Plasmapheresis was used in plasma exchange group, and the volume of plasma exchanged was 2 500-3 000 mL. The combination treatment group was treated by double plasma molecular adsorption system combined with plasma exchange, and the volume of plasma exchanged was 1 000-1 500 mL. In the two groups, the clinical effects and liver function were evaluated after three treatment sessions, and adverse reactions were observed during the artificial liver treatment. RESULTS AND CONCLUSION: After treatment, the levels of serum total bilirubin and alanine aminotransferase were significantly lower than those before treatment, and the prothrombin activity was significantly higher than that before treatment(P < 0.05). However, the serum albumin level showed no significant difference in the combination treatment group before and after treatment. Compared with the plasma exchange group, the post-treatment levels of serum total bilirubin, alanine aminotransferase and serum albumin were significantly lower in the combination treatment group, and the prothrombin activity was significantly higher(P < 0.05).(2) The total effective rate of the combination treatment group(83%) was significantly higher than that of the plasma exchange group(63%)(P < 0.05).(3) During the artificial liver treatment, there was one case of rash, one case of chills and one case of hypotension in the combination group, while no adverse reaction occurred in the plasma exchange group.(4) To conclude, either double plasma molecular adsorption combined with plasma exchange or simple plasma exchange can markedly improve the liver function of patients with liver failure, and produce few adverse reactions. However, the combination of double plasma molecular adsorption and plasma exchange has an advantageous therapeutic effect and can reduce plasma consumption.
BACKGROUND: Double plasma molecular adsorption system cannot only specifically absorb bilirubin and bile acids, but also eliminate toxins, inflammatory transmitters and cytokines in the body. In the absence of plasma or in the case of plasma deficiency, it can effectively remove harmful substances, prevent multiple organ failure and fight for time for the liver regeneration and recovery of liver function, which is suitable for liver failure caused by various reasons. OBJECTIVE: To compare the validity and safety of double plasma molecular adsorption system combined with plasma exchange and simple plasma exchange in the treatment of liver failure. METHODS: Sixty patients with liver failure admitted to the Guizhou Provincial People's Hospital from October 2014 to October 2017 were included and randomized into two groups(n=30/group). Plasmapheresis was used in plasma exchange group, and the volume of plasma exchanged was 2 500-3 000 mL. The combination treatment group was treated by double plasma molecular adsorption system combined with plasma exchange, and the volume of plasma exchanged was 1 000-1 500 mL. In the two groups, the clinical effects and liver function were evaluated after three treatment sessions, and adverse reactions were observed during the artificial liver treatment. RESULTS AND CONCLUSION: After treatment, the levels of serum total bilirubin and alanine aminotransferase were significantly lower than those before treatment, and the prothrombin activity was significantly higher than that before treatment(P < 0.05). However, the serum albumin level showed no significant difference in the combination treatment group before and after treatment. Compared with the plasma exchange group, the post-treatment levels of serum total bilirubin, alanine aminotransferase and serum albumin were significantly lower in the combination treatment group, and the prothrombin activity was significantly higher(P < 0.05).(2) The total effective rate of the combination treatment group(83%) was significantly higher than that of the plasma exchange group(63%)(P < 0.05).(3) During the artificial liver treatment, there was one case of rash, one case of chills and one case of hypotension in the combination group, while no adverse reaction occurred in the plasma exchange group.(4) To conclude, either double plasma molecular adsorption combined with plasma exchange or simple plasma exchange can markedly improve the liver function of patients with liver failure, and produce few adverse reactions. However, the combination of double plasma molecular adsorption and plasma exchange has an advantageous therapeutic effect and can reduce plasma consumption.
引文
[1]Wan YM,Li YH,Xu ZY,et al.Therapeutic plasma exchange versus double plasma molecular absorption system in hepatitis B virus-infected acute-on-chronic liver failure treated by entercavir:A prospective study.J Clin Apher.2017;32(6):453-461.
[2]Gerth HU,Pohlen M,Pavenst?dt H,et al.Extracorporeal liver support of liver failure.Z Gastroenterol.2017;55(4):383-393.
[3]Jain V,Dhawan A.Extracorporeal liver support systems in paediatric liver failure.J Pediatr Gastroenterol Nutr.2017;64(6):855-863.
[4]Zhou YD,Yang L,Han QF,et al.Clinical effect of combined artificial extracorporeal liver support therapy for toxic hepatic failure.Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi.2017;35(1):51-53.
[5]Li M,Sun J,Li J,et al.Clinical observation on the treatment of acute liver failure by combined non-biological artificial liver.Exp Ther Med.2016;12(6):3873-3876.
[6]Hassanein T.Current state of knowledge of hepatic encephalopathy(part IV):Management of Hepatic Encephalopathy by liver support systems.Metab Brain Dis.2017;32(2):303-306.
[7]黄盛玲,黄德绪,闫冰,等.吸附材料在血液灌流技术中的应用研究进展[J].广西医学,2016,38(5):695-697.
[8]刘贻声,张林,洪良通,等.血液灌流器吸附材料研究进展[J].中国医疗器械信息,2014,(8):15-20.
[9]李荣华,傅蕾,黄燕,等.双重血浆分子吸附治疗肝衰竭的临床研究[J].中国现代医学杂志,2018,28(1):78-82.
[10]唐娟,邓薇,唐静,等.双重血浆分子吸附系统对慢加急肝衰竭患者血清炎性因子、肝功能及免疫功能的影响[J].疑难病杂志,2017,16(9):903-906,910.
[11]Karvellas CJ,Subramanian RM.Current evidence for extracorporeal liver support systems in acute liver failure and acute-on-chronic liver failure.Crit Care Clin.2016;32(3):439-451.
[12]Chen JJ,Huang JR,Yang Q,et al.Plasma exchangecentered artificial liver support system in hepatitis Bvirus-related acute-on-chronic liver failure:a nationwide prospective multicenter study in China.Hepatobiliary Pancreat Dis Int.2016;15(3):275-281.
[13]Hoshino T,Takagi H,Suzuki Y,et al.Fatal fulminant hepatitis caused by infection with subgenotype A1 hepatitis B virus with C1766T/T1768A core promoter mutations.Clin J Gastroenterol.2016;9(3):160-167.
[14]Matsuura T,Yoshimaru K,Yanagi Y,et al.Massive pulmonary hemorrhage before living donor liver transplantation in infants.Pediatr Transplant.2016;20(1):89-95.
[15]叶晓玲,程书权,杨景毅,等.不同人工肝方法治疗亚急性重型肝炎的疗效对比研究[J].重庆医学,2015,44(27):3775-3778.
[16]何小凤,罗玲,袁春兰,等.两种人工肝方法治疗重型乙型肝炎的近期疗效对比分析[J].重庆医学,2017,46(18):2475-2477,2480.
[17]周宪伟,房忠卫.血浆凝血酶原活动度和血清甲胎蛋白、前白蛋白联合检测在人工肝血浆置换治疗重型肝炎的临床意义[J].中国医师进修杂志,2017,40(9):773-776.
[18]朱其荣,王川林,刘娇,等.胆红素吸附联合血浆置换对治疗肝衰竭近期疗效影响的相关性研究[J].川北医学院学报,2017,32(4):587-590.
[19]Yamamoto H,Nakae H,Uji Y,et al.Plasma adiponectin levels in acute liver failure patients treated with plasma filtration with dialysis and plasma exchange.Ther Apher Dial.2015;19(4):349-354.
[20]Zhou PQ,Zheng SP,Yu M,et al.Prognosis of acute-on-chronic liver failure patients treated with artificial liver support system.World J Gastroenterol.2015;21(32):9614-9622.
[21]Larsen FS,Schmidt LE,Bernsmeier C,et al.High-volume plasma exchange in patients with acute liver failure:An open randomised controlled trial.J Hepatol.2016;64(1):69-78.
[22]Ide K,Muguruma T,Shinohara M,et al.Continuous veno-venous hemodiafiltration and plasma exchange in infantile acute liver failure.Pediatr Crit Care Med.2015;16(8):e268-274.
[23]Arroyo V,Moreau R,Jalan R,et al.Acute-on-chronic liver failure:A new syndrome that will re-classify cirrhosis.JHepatol.2015;62(1 Suppl):S131-143.
[24]Zhou N,Li J,Zhang Y,et al.Efficacy of coupled low-volume plasma exchange with plasma filtration adsorption in treating pigs with acute liver failure:A randomised study.J Hepatol.2015;63(2):378-387.
[25]Qin G,Shao JG,Wang B,et al.Artificial liver support system improves short-and long-term outcomes of patients with HBV-associated acute-on-chronic liver failure:a single-center experience.Medicine(Baltimore).2014;93(28):e338.
[26]Li MQ,Ti JX,Zhu YH,et al.Combined use of non-biological artificial liver treatments for patients with acute liver failure complicated by multiple organ dysfunction syndrome.World JEmerg Med.2014;5(3):214-217.
[27]Kahraman A,Wand K,Eisele L,et al.Comparison of extracorporeal liver assist devices-albumin dialysis versus plasma exchange-in acute-on-chronic liver failure.Dtsch Med Wochenschr.2014;139(33):1653-1658.
[28]Lodes U,Jacob D,Meyer F.Acute liver failure,acute-on-chronic liver failure,hepatorenal syndrome,hepatopulmonary syndrome and portopulmonary hypertension,artificial liver support on the ICU.Zentralbl Chir.2017;142(3):275-286.
[29]Sakiyama R,Blau BJ,Miki T.Clinical translation of bioartificial liver support systems with human pluripotent stem cell-derived hepatic cells.World J Gastroenterol.2017;23(11):1974-1979.
[30]Gonzalez HC,Jafri SM,Gordon SC.Management of acute hepatotoxicity including medical agents and liver support systems.Clin Liver Dis.2017;21(1):163-180.
[31]Lee KC,Baker LA,Stanzani G,et al.Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liverfailure:Results of a pivotal pre-clinical study.JHepatol.2015;63(3):634-642.
[32]Yin GC,Ya CM,Li Q,et al.Clinical experience of double plasma molecular absorption with a combination of two hemoperfusion machines in treatment of liver failure.Zhonghua Wei Zhong Bing Ji Jiu Yi Xue.2013;25(12):738-42.
[33]段志文,武杨屏,范晶华,等.不同血液净化方式治疗各型肝衰竭的临床疗效比较[J].中国中西医结合急救杂志,2016,23(4):390-392.
[34]周亚东,杨琳,韩秋风,等.组合型人工肝技术治疗中毒性肝功能衰竭的临床研究[J].中华劳动卫生职业病杂志,2017,35(1):51-53.
[35]李守娟,王丽,吴蓓,等.双重血浆吸附联合血浆置换治疗重型乙型肝炎的临床观察[J].临床荟萃,2015,30(7):781-784.
[2]Gerth HU,Pohlen M,Pavenst?dt H,et al.Extracorporeal liver support of liver failure.Z Gastroenterol.2017;55(4):383-393.
[3]Jain V,Dhawan A.Extracorporeal liver support systems in paediatric liver failure.J Pediatr Gastroenterol Nutr.2017;64(6):855-863.
[4]Zhou YD,Yang L,Han QF,et al.Clinical effect of combined artificial extracorporeal liver support therapy for toxic hepatic failure.Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi.2017;35(1):51-53.
[5]Li M,Sun J,Li J,et al.Clinical observation on the treatment of acute liver failure by combined non-biological artificial liver.Exp Ther Med.2016;12(6):3873-3876.
[6]Hassanein T.Current state of knowledge of hepatic encephalopathy(part IV):Management of Hepatic Encephalopathy by liver support systems.Metab Brain Dis.2017;32(2):303-306.
[7]黄盛玲,黄德绪,闫冰,等.吸附材料在血液灌流技术中的应用研究进展[J].广西医学,2016,38(5):695-697.
[8]刘贻声,张林,洪良通,等.血液灌流器吸附材料研究进展[J].中国医疗器械信息,2014,(8):15-20.
[9]李荣华,傅蕾,黄燕,等.双重血浆分子吸附治疗肝衰竭的临床研究[J].中国现代医学杂志,2018,28(1):78-82.
[10]唐娟,邓薇,唐静,等.双重血浆分子吸附系统对慢加急肝衰竭患者血清炎性因子、肝功能及免疫功能的影响[J].疑难病杂志,2017,16(9):903-906,910.
[11]Karvellas CJ,Subramanian RM.Current evidence for extracorporeal liver support systems in acute liver failure and acute-on-chronic liver failure.Crit Care Clin.2016;32(3):439-451.
[12]Chen JJ,Huang JR,Yang Q,et al.Plasma exchangecentered artificial liver support system in hepatitis Bvirus-related acute-on-chronic liver failure:a nationwide prospective multicenter study in China.Hepatobiliary Pancreat Dis Int.2016;15(3):275-281.
[13]Hoshino T,Takagi H,Suzuki Y,et al.Fatal fulminant hepatitis caused by infection with subgenotype A1 hepatitis B virus with C1766T/T1768A core promoter mutations.Clin J Gastroenterol.2016;9(3):160-167.
[14]Matsuura T,Yoshimaru K,Yanagi Y,et al.Massive pulmonary hemorrhage before living donor liver transplantation in infants.Pediatr Transplant.2016;20(1):89-95.
[15]叶晓玲,程书权,杨景毅,等.不同人工肝方法治疗亚急性重型肝炎的疗效对比研究[J].重庆医学,2015,44(27):3775-3778.
[16]何小凤,罗玲,袁春兰,等.两种人工肝方法治疗重型乙型肝炎的近期疗效对比分析[J].重庆医学,2017,46(18):2475-2477,2480.
[17]周宪伟,房忠卫.血浆凝血酶原活动度和血清甲胎蛋白、前白蛋白联合检测在人工肝血浆置换治疗重型肝炎的临床意义[J].中国医师进修杂志,2017,40(9):773-776.
[18]朱其荣,王川林,刘娇,等.胆红素吸附联合血浆置换对治疗肝衰竭近期疗效影响的相关性研究[J].川北医学院学报,2017,32(4):587-590.
[19]Yamamoto H,Nakae H,Uji Y,et al.Plasma adiponectin levels in acute liver failure patients treated with plasma filtration with dialysis and plasma exchange.Ther Apher Dial.2015;19(4):349-354.
[20]Zhou PQ,Zheng SP,Yu M,et al.Prognosis of acute-on-chronic liver failure patients treated with artificial liver support system.World J Gastroenterol.2015;21(32):9614-9622.
[21]Larsen FS,Schmidt LE,Bernsmeier C,et al.High-volume plasma exchange in patients with acute liver failure:An open randomised controlled trial.J Hepatol.2016;64(1):69-78.
[22]Ide K,Muguruma T,Shinohara M,et al.Continuous veno-venous hemodiafiltration and plasma exchange in infantile acute liver failure.Pediatr Crit Care Med.2015;16(8):e268-274.
[23]Arroyo V,Moreau R,Jalan R,et al.Acute-on-chronic liver failure:A new syndrome that will re-classify cirrhosis.JHepatol.2015;62(1 Suppl):S131-143.
[24]Zhou N,Li J,Zhang Y,et al.Efficacy of coupled low-volume plasma exchange with plasma filtration adsorption in treating pigs with acute liver failure:A randomised study.J Hepatol.2015;63(2):378-387.
[25]Qin G,Shao JG,Wang B,et al.Artificial liver support system improves short-and long-term outcomes of patients with HBV-associated acute-on-chronic liver failure:a single-center experience.Medicine(Baltimore).2014;93(28):e338.
[26]Li MQ,Ti JX,Zhu YH,et al.Combined use of non-biological artificial liver treatments for patients with acute liver failure complicated by multiple organ dysfunction syndrome.World JEmerg Med.2014;5(3):214-217.
[27]Kahraman A,Wand K,Eisele L,et al.Comparison of extracorporeal liver assist devices-albumin dialysis versus plasma exchange-in acute-on-chronic liver failure.Dtsch Med Wochenschr.2014;139(33):1653-1658.
[28]Lodes U,Jacob D,Meyer F.Acute liver failure,acute-on-chronic liver failure,hepatorenal syndrome,hepatopulmonary syndrome and portopulmonary hypertension,artificial liver support on the ICU.Zentralbl Chir.2017;142(3):275-286.
[29]Sakiyama R,Blau BJ,Miki T.Clinical translation of bioartificial liver support systems with human pluripotent stem cell-derived hepatic cells.World J Gastroenterol.2017;23(11):1974-1979.
[30]Gonzalez HC,Jafri SM,Gordon SC.Management of acute hepatotoxicity including medical agents and liver support systems.Clin Liver Dis.2017;21(1):163-180.
[31]Lee KC,Baker LA,Stanzani G,et al.Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liverfailure:Results of a pivotal pre-clinical study.JHepatol.2015;63(3):634-642.
[32]Yin GC,Ya CM,Li Q,et al.Clinical experience of double plasma molecular absorption with a combination of two hemoperfusion machines in treatment of liver failure.Zhonghua Wei Zhong Bing Ji Jiu Yi Xue.2013;25(12):738-42.
[33]段志文,武杨屏,范晶华,等.不同血液净化方式治疗各型肝衰竭的临床疗效比较[J].中国中西医结合急救杂志,2016,23(4):390-392.
[34]周亚东,杨琳,韩秋风,等.组合型人工肝技术治疗中毒性肝功能衰竭的临床研究[J].中华劳动卫生职业病杂志,2017,35(1):51-53.
[35]李守娟,王丽,吴蓓,等.双重血浆吸附联合血浆置换治疗重型乙型肝炎的临床观察[J].临床荟萃,2015,30(7):781-784.