人工肝在肝衰竭中的应用进展
|
摘要
肝衰竭是各种肝病发展的严重阶段,病情发展快且危重,病死率高。人工肝不仅可以清除患者体内的有害物质,补充必需物质,为肝细胞再生及肝功能恢复创造机会,而且能延长患者等待肝移植的时间,是肝移植前的桥接。但如今人工肝治疗的广泛开展面临重重困难,如血源紧张、细胞来源困难、疗效不够理想、价格昂贵等,迫切需要创新及改进人工肝治疗方法。近年来发展的新型非生物型人工肝模式,如双重血浆分子吸附系统、分子吸附再循环系统、连续白蛋白净化系统、血浆滤过透析等多种模式的联合应用,在保证疗效的同时节省了血浆用量,减少了副作用。生物型及混合型人工肝具有肝特异性解毒、生物合成及转化功能,有巨大的应用潜能,但细胞来源、细胞培养及生物反应器是其临床应用主要的局限因素。阐述了人工肝在肝衰竭治疗中的现状及应用进展,并为人工肝的发展指出了研究方向。
Liver failure is a serious stage in the development of various liver diseases,with rapid progression,critical conditions,and a high mortality rate. Artificial liver can eliminate toxic substances in the body,supplement essential substances,and create opportunities for hepatocyte regeneration and liver function recovery,and in addition,it can also prolong the waiting time for liver transplantation and thus acts as a bridge to liver transplantation. However,the wide application of artificial liver is facing many difficulties nowadays,such as shortage of blood sources,difficulties in cell sources,a lack of satisfactory effects,and high costs,and therefore,artificial liver treatment needs innovation and improvement. New non-bioartificial liver systems developed in recent years,such as double plasma molecular absorption system,molecular absorbent recirculating system,continuous albumin purification system,and plasma diafiltration,can help to achieve a good clinical outcome and meanwhile reduce the amount of plasma used and minimize side effects. Biological artificial liver and hybrid artificial liver systems have the functions of specific detoxification,biosynthesis,and transformation and thus have great potential in clinical application,which is limited by cell source,cell culture,and bioreactor. This article elaborates on the current status and advances in the application of artificial liver in the treatment of liver failure and provides research directions for the development of artificial liver.
Liver failure is a serious stage in the development of various liver diseases,with rapid progression,critical conditions,and a high mortality rate. Artificial liver can eliminate toxic substances in the body,supplement essential substances,and create opportunities for hepatocyte regeneration and liver function recovery,and in addition,it can also prolong the waiting time for liver transplantation and thus acts as a bridge to liver transplantation. However,the wide application of artificial liver is facing many difficulties nowadays,such as shortage of blood sources,difficulties in cell sources,a lack of satisfactory effects,and high costs,and therefore,artificial liver treatment needs innovation and improvement. New non-bioartificial liver systems developed in recent years,such as double plasma molecular absorption system,molecular absorbent recirculating system,continuous albumin purification system,and plasma diafiltration,can help to achieve a good clinical outcome and meanwhile reduce the amount of plasma used and minimize side effects. Biological artificial liver and hybrid artificial liver systems have the functions of specific detoxification,biosynthesis,and transformation and thus have great potential in clinical application,which is limited by cell source,cell culture,and bioreactor. This article elaborates on the current status and advances in the application of artificial liver in the treatment of liver failure and provides research directions for the development of artificial liver.
引文
[1]Liver Failure and Artificial Liver Group,Chinese Severe Liver Disease and Artificial Liver Group,Chinese of Hepatology,CMA.Guideline for diagnosis and treatment of liver failure[J].Chin JClin Infect Dis,2012,5(6):321-327.(in Chinese)中华医学会感染病学分会肝衰竭与人工肝学组.中华医学会肝病学分会重型肝病与人工肝学组.肝衰竭诊治指南(2012年版)[J].中华临床感染病杂志,2012,5(6):321-327.
[2]Liver Failure and Artificial Liver Group,Chinese of Hepatology,CMA.Guideline for non-bioartificial liver support systems in treatment of liver failure:2016 update[J].Chin J Clin Infect Dis,2016,9(2):97-103.(in Chinese)中华医学会感染病学分会肝衰竭与人工肝学组.非生物型人工肝治疗肝衰竭指南(2016年版)[J].中华临床感染病杂志,2016,9(2):97-103.
[3]WANG YY,HUANG JR.Research advances in artificial liver support therapy for liver failure[J].J Clin Intern Med,2014,31(8):509-512.(in Chinese)王银银,黄建荣.人工肝治疗肝衰竭研究进展[J].临床内科杂志,2014,31(8):509-512.
[4]MOREAU R,ARROYO V.Acute-on-chronic liver failure:a new clinical entity[J].Clin Gastroenterol Hepatol,2015,13(5):836-841.
[5]XU X,LIU X,LING Q,et al.Artificial liver support system combined with liver transplantation in the treatment of patients with acute-on-chronic liver failure[J].PLo S One,2013,8(3):e58738.
[6]LIU YY,HUANG JR.Changes and perspectives of non-biological artificial liver treatment[J].Chin J Hepatol,2017,25(9):646-650.(in Chinese)刘月英,黄建荣.非生物型人工肝治疗的变迁与展望[J].中华肝脏病杂志,2017,25(9):646-650.
[7]LI RH,FU L,HUANG Y,et al.Clinical research of double plasma molecular absorption system in treatment of liver failure[J].China J Modern Med,2018,28(1):78-82.(in Chinese)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.
[8]ZHANG BW,YANG XF,LUO XJ,et al.Comparison of clinical effects of double plasma molecular adsorption system,plasma bilirubin adsorption and plasma exchange in liver failure[J].China JModern Med,2016,26(12):103-106.(in Chinese)张宝文,阳学风,罗湘俊,等.双重血浆吸附、胆红素吸附及血浆置换治疗肝衰竭的疗效比较[J].中国现代医学杂志,2016,26(12):103-106.
[9]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].J Clin Apher,2017,32(6):453-461.
[10]OLIN P,HAUSKEN J,FOSS A,et al.Continuous molecular adsorbent recirculating system treatment in 69 patients listed for liver transplantation[J].Scand J Gastroenterol,2015,50(9):1127-1134.
[11]HANISH SI,STEIN DM,SCALEA JR,et al.Molecular adsorbent recirculating system effectively replaces hepatic function in severe acute liver failure[J].Ann Surg,2017,266(4):677-684.
[12]SPONHOLZ C,MATTHES K,RUPP D,et al.Molecular adsorbent recirculating system and single-pass albumin dialysis in liver failure-a prospective,randomised crossover study[J].Crit Care,2016,20:2.
[13]GERTH HU,POHLEN M,THLKING G,et al.Molecular adsorbent recirculating system can reduce short-term mortality among patients with acute-on-chronic liver failure-a retrospective analysis[J].Crit Care Med,2017,45(10):1616-1624.
[14]BANARES R,NEVENS F,LARSEN FS,et al.Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure:The RELIEF trial[J].Hepatology,2013,57(3):1153-1162.
[15]DONG QH,GUO LM,WANG Y,et al.Clinical study of continuous albumin purification system in the treatment of patients with liver failure[J].J Pract Hepatol,2009,12(5):352-354.(in Chinese)董庆华,郭利民,王宇,等.CAPS人工肝治疗肝衰竭的临床研究[J].实用肝脏病杂志,2009,12(5):352-354.
[16]KOMARDINA E,YAROUSTOVSKY M,ABRAMYAN M,et al.Prometheus therapy for the treatment of acute liver failure in patients after cardiac surgery[J].Kardiochir Torakochirurgial Pol,2017,14(4):230-235.
[17]LIU XH,GUO HQ.Progress in technology and clinical application of non-bioartificial liver support system[J].J Clin Hepatol,2013,29(9):661-665.(in Chinese)刘晓慧,郭海清.非生物型人工肝技术及其临床应用新进展[J].临床肝胆病杂志,2013,29(9):661-665.
[18]XING HQ,LIU JW,WANG KL,et al.Analysis of clinical effect of continuous plasma diafiltration for the therapy of liver failure[J].BME Clin Med,2013,17(2):152-155.(in Chinese)邢汉前,刘俊微,王开利,等.持续缓慢血浆透析滤过治疗肝功能衰竭的临床疗效分析[J].生物医学工程与临床,2013,17(2):152-155.
[19]KOMURA T,TANIGUCHI T,SAKAI Y,et al.Efficacy of continuous plasma diafiltration therapy in critical patients with acute liver failure[J].J Gastroenterol Hepatol,2014,29(4):782-786.
[20]YANG XS,ZHOU L,LI L,et al.Influence of duration of plasma diafiltration on therapeutic outcome of liver failure[J].J Clin Hepatol,2018,34(5):1052-1054.(in Chinese)杨仙珊,周莉,李璐,等.血浆透析滤过治疗时间对肝衰竭治疗效果的影响[J].临床肝胆病杂志,2018,34(5):1052-1054.
[21]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].J Hepatol,2015,63(2):378-387.
[22]LI S,CHEN Y.Coping with shortage of plasma-the new therapeutic pattern of non-bioartificial liver[J].J Clin Hepatol,2017,33(9):1687-1692.(in Chinese)李爽,陈煜.血浆紧缺情况下非生物型人工肝治疗新模式的探讨[J].临床肝胆病杂志,2017,33(9):1687-1692.
[23]ZHOU YD,YANG L,HAN QF,et al.Clinical effect of combined artificial extra corporeal liver support therapy for toxic hepatic failure[J].Chin J Ind Hyg Occup Dis,2017,35(1):51-53.(in Chinese)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.
[24]ZHOU J,WAN H,YANG ZM,et al.Clinical effect of plasma perfusion combined with plasma exchange in treatment of patients with acute-on chronic liver failure[J].J Clin Hepatol,2017,33(4):715-718.(in Chinese)周渐,万红,杨正茂,等.血浆灌流联合血浆置换治疗慢加急性肝衰竭的效果观察[J].临床肝胆病杂志,2017,33(4):715-718.
[25]FAN JH,CHEN HY,WANG HT,et al.Plasma exchange combined with plasma perfusion in treatment of patients with liver failure[J].J Pract Hepatol,2016,19(2):184-187.(in Chinese)范晶华,陈红英,王宏图,等.血浆置换联合血浆灌流治疗肝衰竭患者临床疗效分析[J].实用肝脏病杂志,2016,19(2):184-187.
[26]WANG GH,LIU KH,ZHANG XY,et al.The clinical efficacy analysis of plasma exchange combined with plasma perfusion in treatment of acute liver failure[J].Chin J Gastroenterol Hepatol,2017,26(11):1294-1297.(in Chinese)王盖昊,刘凯辉,张潇艺,等.血浆置换联合血浆灌流治疗急性肝衰竭的临床疗效分析[J].胃肠病学和肝病学杂志,2017,26(11):1294-1297.
[27]LI LJ.Liver failure and the progress of Li’s artificial liver system[J].Chin J Clin Infect Dis,2017,10(2):91-94.(in Chinese)李兰娟.肝衰竭与李氏人工肝进展[J].中华临床感染病杂志,2017,10(2):91-94.
[28]SHI XL,GAO Y,YAN Y,et al.Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes[J].Cell Res,2016,26(2):206-216.
[29]TAO KS,LI X,DOU KF.The history and development of xenogeneic liver transplantation[J].Ogran Transplant,2017,8(2):85-88.(in Chinese)陶开山,李霄,窦科峰.异种肝移植的历史与发展[J].器官移植,2017,8(2):85-88.
[30]LIU H,YOU S,RONG Y,et al.The newly established human liver cell line:A potential cell source for the bioartificial liver in the future[J].Hum cell,2013,26(4):155-161.
[31]YAN Q,DENG L,ZHAO X,et al.Establishment and characterization of an immortalized human hepatocyte line for the development of bioartificial liver system[J].Cytotechnology,2018,70(2):665-674.
[32]SHI XL,GAO Y,YAN Y,et al.Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes[J].Cell Res,2016,26(2):206-216.
[33]HUANG P,ZHANG L,GAO Y,et al.Direct reprogramming of human fibroblasts to functional and expandable hepatocytes[J].Cell Stem Cell,2014,14(3):370-384.
[34]DING YT.Bioartificial liver and liver transplantation:New modalities for the treatment of liver failure[J].J Clin Hepatol,2017,33(9):1693-1698.(in Chinese)丁义涛.生物人工肝和肝移植:肝衰竭治疗新模式[J].临床肝胆病杂志,2017,33(9):1693-1698.
[35]HOU P,LI Y,ZHANG X,et al.Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds[J].Science,2013,341(6146):651-654.
[36]LI GL,WANG SM.The development and status of bioartificial liver[J].Chin J Surg,2017,55(12):957-959.(in Chinese)李刚磊,王世明.生物型人工肝的发展及现状[J].中华外科杂志,2017,55(12):957-959.
[37]ZHANG S,CHEN L,LIU T,et al.Integration of single-layer skin hollow fibers and scaffolds develops a three-dimensional hybrid bioreactor for bioartificial livers[J].J Mater Sci Mater Med,2014,25(1):207-216.
[38]ZHANG S,ZHANG B,CHEN X,et al.Three dimensional culture in a microgravity bioreactor improves the engraftment efficiency of hepatic tissue constructs in mice[J].J Mater Sci Mater Med,2014,25(12):2699-2709.
[39]VERMA SK,MODI A,BELLARE J.Three-dimensional multiscale fiber matrices:Development and characterization for increased Hep G2 functional maintenance for bio-artificial liver application[J].Biomater Sci,2018,6(2):280-291.
[40]SHI XL,HAN B,ZHENG YS,et al.Primary clinical study of a novel multi-layer flat-plate bioartificial liver for patients with liver failure[J].Chin J Organ Transplant,2012,33(4):212-216.(in Chinese)施晓雷,韩冰,郑以山,等.新型多层平板型生物人工肝体外支持系统治疗肝功能衰竭的临床研究[J].中华器官移植杂志,2012,33(4):212-216.
[41]PODOLL AS,DEGOLOVINE A,FINKEL KW.Liver support systems-a review[J].ASAIO J,2012,58(5):443-449.
[42]GU JY,SHI XL,REN HZ,et al.Systematic evaluation of extracorporeal bioartificial liver support system for the treatment of liver failure[J].Chin J Tissue Engineer Res,2013,17(18):149-155.(in Chinese)顾劲扬,施晓雷,任昊帧,等.体外生物人工肝支持系统治疗肝功能衰竭的系统评价[J].中国组织工程研究,2013,17(18):149-155.
[43]YOU SL,LIU HL,RONG YH,et al.Preliminary investigation of hybrid bioartificial liver support system in treatment of HBV-related acute-on-chronic liver failure[J].J Clin Hepatol,2013,29(9):685-688.(in Chinese)游绍莉,刘鸿凌,荣义辉,等.混合型生物型人工肝治疗HBV相关慢加急性肝衰竭患者的初步探讨[J].临床肝胆病杂志,2013,29(9):685-688.
[44]HUANG JR.Current status and perspectives of artificial liver for treatment of acute-on-chronic liver failure[J].Chin J Hepatol,2016,24(12):935-939.(in Chinese)黄建荣.人工肝在慢加急性肝衰竭中的应用现状及展望[J].中华肝脏病杂志,2016,24(12):935-939.
[45]YU XP,PAN XP,LI LJ.Research advances in stem cell-derived hepatocytes and their application in bioartificial liver[J].Chin J Infect Dis,2014,32(10):632-634.(in Chinese)虞晓鹏,潘小平,李兰娟.干细胞来源的肝细胞及其在生物型人工肝中的应用研究进展[J].中华传染病杂志,2014,32(10):632-634.
[2]Liver Failure and Artificial Liver Group,Chinese of Hepatology,CMA.Guideline for non-bioartificial liver support systems in treatment of liver failure:2016 update[J].Chin J Clin Infect Dis,2016,9(2):97-103.(in Chinese)中华医学会感染病学分会肝衰竭与人工肝学组.非生物型人工肝治疗肝衰竭指南(2016年版)[J].中华临床感染病杂志,2016,9(2):97-103.
[3]WANG YY,HUANG JR.Research advances in artificial liver support therapy for liver failure[J].J Clin Intern Med,2014,31(8):509-512.(in Chinese)王银银,黄建荣.人工肝治疗肝衰竭研究进展[J].临床内科杂志,2014,31(8):509-512.
[4]MOREAU R,ARROYO V.Acute-on-chronic liver failure:a new clinical entity[J].Clin Gastroenterol Hepatol,2015,13(5):836-841.
[5]XU X,LIU X,LING Q,et al.Artificial liver support system combined with liver transplantation in the treatment of patients with acute-on-chronic liver failure[J].PLo S One,2013,8(3):e58738.
[6]LIU YY,HUANG JR.Changes and perspectives of non-biological artificial liver treatment[J].Chin J Hepatol,2017,25(9):646-650.(in Chinese)刘月英,黄建荣.非生物型人工肝治疗的变迁与展望[J].中华肝脏病杂志,2017,25(9):646-650.
[7]LI RH,FU L,HUANG Y,et al.Clinical research of double plasma molecular absorption system in treatment of liver failure[J].China J Modern Med,2018,28(1):78-82.(in Chinese)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.
[8]ZHANG BW,YANG XF,LUO XJ,et al.Comparison of clinical effects of double plasma molecular adsorption system,plasma bilirubin adsorption and plasma exchange in liver failure[J].China JModern Med,2016,26(12):103-106.(in Chinese)张宝文,阳学风,罗湘俊,等.双重血浆吸附、胆红素吸附及血浆置换治疗肝衰竭的疗效比较[J].中国现代医学杂志,2016,26(12):103-106.
[9]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].J Clin Apher,2017,32(6):453-461.
[10]OLIN P,HAUSKEN J,FOSS A,et al.Continuous molecular adsorbent recirculating system treatment in 69 patients listed for liver transplantation[J].Scand J Gastroenterol,2015,50(9):1127-1134.
[11]HANISH SI,STEIN DM,SCALEA JR,et al.Molecular adsorbent recirculating system effectively replaces hepatic function in severe acute liver failure[J].Ann Surg,2017,266(4):677-684.
[12]SPONHOLZ C,MATTHES K,RUPP D,et al.Molecular adsorbent recirculating system and single-pass albumin dialysis in liver failure-a prospective,randomised crossover study[J].Crit Care,2016,20:2.
[13]GERTH HU,POHLEN M,THLKING G,et al.Molecular adsorbent recirculating system can reduce short-term mortality among patients with acute-on-chronic liver failure-a retrospective analysis[J].Crit Care Med,2017,45(10):1616-1624.
[14]BANARES R,NEVENS F,LARSEN FS,et al.Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure:The RELIEF trial[J].Hepatology,2013,57(3):1153-1162.
[15]DONG QH,GUO LM,WANG Y,et al.Clinical study of continuous albumin purification system in the treatment of patients with liver failure[J].J Pract Hepatol,2009,12(5):352-354.(in Chinese)董庆华,郭利民,王宇,等.CAPS人工肝治疗肝衰竭的临床研究[J].实用肝脏病杂志,2009,12(5):352-354.
[16]KOMARDINA E,YAROUSTOVSKY M,ABRAMYAN M,et al.Prometheus therapy for the treatment of acute liver failure in patients after cardiac surgery[J].Kardiochir Torakochirurgial Pol,2017,14(4):230-235.
[17]LIU XH,GUO HQ.Progress in technology and clinical application of non-bioartificial liver support system[J].J Clin Hepatol,2013,29(9):661-665.(in Chinese)刘晓慧,郭海清.非生物型人工肝技术及其临床应用新进展[J].临床肝胆病杂志,2013,29(9):661-665.
[18]XING HQ,LIU JW,WANG KL,et al.Analysis of clinical effect of continuous plasma diafiltration for the therapy of liver failure[J].BME Clin Med,2013,17(2):152-155.(in Chinese)邢汉前,刘俊微,王开利,等.持续缓慢血浆透析滤过治疗肝功能衰竭的临床疗效分析[J].生物医学工程与临床,2013,17(2):152-155.
[19]KOMURA T,TANIGUCHI T,SAKAI Y,et al.Efficacy of continuous plasma diafiltration therapy in critical patients with acute liver failure[J].J Gastroenterol Hepatol,2014,29(4):782-786.
[20]YANG XS,ZHOU L,LI L,et al.Influence of duration of plasma diafiltration on therapeutic outcome of liver failure[J].J Clin Hepatol,2018,34(5):1052-1054.(in Chinese)杨仙珊,周莉,李璐,等.血浆透析滤过治疗时间对肝衰竭治疗效果的影响[J].临床肝胆病杂志,2018,34(5):1052-1054.
[21]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].J Hepatol,2015,63(2):378-387.
[22]LI S,CHEN Y.Coping with shortage of plasma-the new therapeutic pattern of non-bioartificial liver[J].J Clin Hepatol,2017,33(9):1687-1692.(in Chinese)李爽,陈煜.血浆紧缺情况下非生物型人工肝治疗新模式的探讨[J].临床肝胆病杂志,2017,33(9):1687-1692.
[23]ZHOU YD,YANG L,HAN QF,et al.Clinical effect of combined artificial extra corporeal liver support therapy for toxic hepatic failure[J].Chin J Ind Hyg Occup Dis,2017,35(1):51-53.(in Chinese)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.
[24]ZHOU J,WAN H,YANG ZM,et al.Clinical effect of plasma perfusion combined with plasma exchange in treatment of patients with acute-on chronic liver failure[J].J Clin Hepatol,2017,33(4):715-718.(in Chinese)周渐,万红,杨正茂,等.血浆灌流联合血浆置换治疗慢加急性肝衰竭的效果观察[J].临床肝胆病杂志,2017,33(4):715-718.
[25]FAN JH,CHEN HY,WANG HT,et al.Plasma exchange combined with plasma perfusion in treatment of patients with liver failure[J].J Pract Hepatol,2016,19(2):184-187.(in Chinese)范晶华,陈红英,王宏图,等.血浆置换联合血浆灌流治疗肝衰竭患者临床疗效分析[J].实用肝脏病杂志,2016,19(2):184-187.
[26]WANG GH,LIU KH,ZHANG XY,et al.The clinical efficacy analysis of plasma exchange combined with plasma perfusion in treatment of acute liver failure[J].Chin J Gastroenterol Hepatol,2017,26(11):1294-1297.(in Chinese)王盖昊,刘凯辉,张潇艺,等.血浆置换联合血浆灌流治疗急性肝衰竭的临床疗效分析[J].胃肠病学和肝病学杂志,2017,26(11):1294-1297.
[27]LI LJ.Liver failure and the progress of Li’s artificial liver system[J].Chin J Clin Infect Dis,2017,10(2):91-94.(in Chinese)李兰娟.肝衰竭与李氏人工肝进展[J].中华临床感染病杂志,2017,10(2):91-94.
[28]SHI XL,GAO Y,YAN Y,et al.Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes[J].Cell Res,2016,26(2):206-216.
[29]TAO KS,LI X,DOU KF.The history and development of xenogeneic liver transplantation[J].Ogran Transplant,2017,8(2):85-88.(in Chinese)陶开山,李霄,窦科峰.异种肝移植的历史与发展[J].器官移植,2017,8(2):85-88.
[30]LIU H,YOU S,RONG Y,et al.The newly established human liver cell line:A potential cell source for the bioartificial liver in the future[J].Hum cell,2013,26(4):155-161.
[31]YAN Q,DENG L,ZHAO X,et al.Establishment and characterization of an immortalized human hepatocyte line for the development of bioartificial liver system[J].Cytotechnology,2018,70(2):665-674.
[32]SHI XL,GAO Y,YAN Y,et al.Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes[J].Cell Res,2016,26(2):206-216.
[33]HUANG P,ZHANG L,GAO Y,et al.Direct reprogramming of human fibroblasts to functional and expandable hepatocytes[J].Cell Stem Cell,2014,14(3):370-384.
[34]DING YT.Bioartificial liver and liver transplantation:New modalities for the treatment of liver failure[J].J Clin Hepatol,2017,33(9):1693-1698.(in Chinese)丁义涛.生物人工肝和肝移植:肝衰竭治疗新模式[J].临床肝胆病杂志,2017,33(9):1693-1698.
[35]HOU P,LI Y,ZHANG X,et al.Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds[J].Science,2013,341(6146):651-654.
[36]LI GL,WANG SM.The development and status of bioartificial liver[J].Chin J Surg,2017,55(12):957-959.(in Chinese)李刚磊,王世明.生物型人工肝的发展及现状[J].中华外科杂志,2017,55(12):957-959.
[37]ZHANG S,CHEN L,LIU T,et al.Integration of single-layer skin hollow fibers and scaffolds develops a three-dimensional hybrid bioreactor for bioartificial livers[J].J Mater Sci Mater Med,2014,25(1):207-216.
[38]ZHANG S,ZHANG B,CHEN X,et al.Three dimensional culture in a microgravity bioreactor improves the engraftment efficiency of hepatic tissue constructs in mice[J].J Mater Sci Mater Med,2014,25(12):2699-2709.
[39]VERMA SK,MODI A,BELLARE J.Three-dimensional multiscale fiber matrices:Development and characterization for increased Hep G2 functional maintenance for bio-artificial liver application[J].Biomater Sci,2018,6(2):280-291.
[40]SHI XL,HAN B,ZHENG YS,et al.Primary clinical study of a novel multi-layer flat-plate bioartificial liver for patients with liver failure[J].Chin J Organ Transplant,2012,33(4):212-216.(in Chinese)施晓雷,韩冰,郑以山,等.新型多层平板型生物人工肝体外支持系统治疗肝功能衰竭的临床研究[J].中华器官移植杂志,2012,33(4):212-216.
[41]PODOLL AS,DEGOLOVINE A,FINKEL KW.Liver support systems-a review[J].ASAIO J,2012,58(5):443-449.
[42]GU JY,SHI XL,REN HZ,et al.Systematic evaluation of extracorporeal bioartificial liver support system for the treatment of liver failure[J].Chin J Tissue Engineer Res,2013,17(18):149-155.(in Chinese)顾劲扬,施晓雷,任昊帧,等.体外生物人工肝支持系统治疗肝功能衰竭的系统评价[J].中国组织工程研究,2013,17(18):149-155.
[43]YOU SL,LIU HL,RONG YH,et al.Preliminary investigation of hybrid bioartificial liver support system in treatment of HBV-related acute-on-chronic liver failure[J].J Clin Hepatol,2013,29(9):685-688.(in Chinese)游绍莉,刘鸿凌,荣义辉,等.混合型生物型人工肝治疗HBV相关慢加急性肝衰竭患者的初步探讨[J].临床肝胆病杂志,2013,29(9):685-688.
[44]HUANG JR.Current status and perspectives of artificial liver for treatment of acute-on-chronic liver failure[J].Chin J Hepatol,2016,24(12):935-939.(in Chinese)黄建荣.人工肝在慢加急性肝衰竭中的应用现状及展望[J].中华肝脏病杂志,2016,24(12):935-939.
[45]YU XP,PAN XP,LI LJ.Research advances in stem cell-derived hepatocytes and their application in bioartificial liver[J].Chin J Infect Dis,2014,32(10):632-634.(in Chinese)虞晓鹏,潘小平,李兰娟.干细胞来源的肝细胞及其在生物型人工肝中的应用研究进展[J].中华传染病杂志,2014,32(10):632-634.