Research progress on artificial liver technology_West China Medical Journal

Authors：

 YANG Rongli , ZHOU Hengjie

Department of Critical Care Medicine, Dalian Central Hospital Affiliated to Dalian Medical University, Dalian, Liaoning 116033, P. R. China;

Corresponding author：

YANG Rongli, Email: yever3000@yeah.net

Keywords：

Hepatic failure; Artificial liver; Bioartificial liver; Non-bioartificial liver

DOI：

10.7507/1002-0179.201806035

Video：

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The main treatment strategies for hepatic failure include drug therapy, artificial liver support system, and liver transplantation. This article introduces the clinically commonly used non biological artificial liver techniques, including plasma exchange, continuous blood purification, plasma bilirubin adsorption, plasma diafiltration, repeatedly pass albumin dialysis, molecular adsorbent recirculating system, Prometheus system, etc; and discusses how to select different artificial liver techniques according to different clinical manifestation. At the same time, the progress of bioartificial liver in recent years is summarized, and the future development of artificial liver is prospected.

Citation： YANG Rongli, ZHOU Hengjie. Research progress on artificial liver technology. West China Medical Journal, 2018, 33(7): 810-815. doi: 10.7507/1002-0179.201806035 Copy

1.	Bañares R, Catalina MV, Vaquero J. Molecular adsorbent recirculating system and bioartificial devices for liver failure. Clin Liver Dis, 2014, 18(4): 945-956.
2.	Chamuleau RA, Poyck PP, van de kerkhove MP. Bioartificial liver: its pros and cons. Ther Apher Dial, 2006, 10(2): 168-174.
3.	程芝灵, 孙桂香, 林辉, 等. 血浆置换治疗肝衰竭临床疗效和安全性的 Meta 分析. 中国循证医学杂志, 2015, 15(6): 664-671.
4.	Yue-Meng W, Yang LH, Yang JH, et al. The effect of plasma exchange on entecavir-treated chronic hepatitis B patients with hepatic de-compensation and acute-on-chronic liver failure. Hepatol Int, 2016, 10(3): 462-469.
5.	Nakae H, Eguchi Y, Saotome T, et al. Multicenter study of plasma diafiltration in patients with acute liver failure. Ther Apher Dial, 2010, 14(5): 444-450.
6.	Tsipotis E, Shuja A, Jaber BL. Albumin dialysis for liver failure: a systematic review. Adv Chronic Kidney Dis, 2015, 22(5): 382-390.
7.	Eguchi Y, Nakae H, Furuya T, et al. Plasma filtration with dialysis (plasma diafiltration) in critically ill patients with acute liver failure. Crit Care, 2014, 18(Suppl 1): 399.
8.	Komura T, Taniguchi T, Sakai Y, et al. Efficacy of continuous plasma diafiltration therapy in critical patients with acute liver failure. J Gastroenterol Hepatol, 2014, 29(4): 782-786.
9.	Sauer IM, Goetz M, Steffen I, et al. In vitro comparison of the molecular adsorbent recirculation system (MARS) and single-pass albumin dialysis (SPAD) Hepatology, 2004, 39(5): 1408-1414.
10.	Maiwall R, Maras JS, Nayak SL, et al. Liver dialysis in acute-on-chronic liver failure: current and future perspectives. Hepatol Int, 2014, 8(Suppl 2): 505-513.
11.	Vaid A, Chweich H, Balk EM, et al. Molecular adsorbent recirculating system as artificial support therapy for liver failure: a meta-analysis. ASAIO J, 2012, 58(1): 51-59.
12.	Kantola T, Koivusalo AM, Höckerstedt K, et al. The effect of molecular adsorbent recirculating system treatment on survival, native liver recovery, and need for liver transplantation in acute liver failure patients. Transpl Int, 2008, 21(9): 857-866.
13.	Bañares 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. Hepatology, 2013, 57(3): 1153-1162.
14.	Saliba F, Camus C, Durand F, et al. Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial. Ann Intern Med, 2013, 159(8): 522-531.
15.	He GL, Feng L, Duan CY, et al. Meta-analysis of survival with the molecular adsorbent recirculating system for liver failure. Int J Clin Exp Med, 2015, 8(10): 17046-17054.
16.	Gerth HU, Pohlen M, Thölking G, et al. Molecular adsorbent recirculating system can reduce short-term mortality among patients with acute-on-chronic liver failure: a retrospective analysis. Crit Care Med, 2017, 45(10): 1616-1624.
17.	Nevens F, Laleman W. Artificial liver support devices as treatment option for liver failure. Best Pract Res Clin Gastroenterol, 2012, 26(1): 17-26.
18.	Sentürk E, Esen F, Ozcan PE, et al. The treatment of acute liver failure with fractionated plasma separation and adsorption system: Experience in 85 applications. J Clin Apher, 2010, 25(4): 195-201.
19.	Rocen M, Kieslichova E, Merta D, et al. The effect of Prometheus device on laboratory markers of inflammation and tissue regeneration in acute liver failure management. Transplant Proc, 2010, 42(9): 3606-3611.
20.	Kribben A, Gerken G, Haag S, et al. Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure. Gastroenterology, 2012, 142(4): 782-789.e3.
21.	Krisper P, Stadlbauer V, Stauber RE. Clearing of toxic substances: are there differences between the available liver support devices? Liver Int, 2011, 31(Suppl 3): 5-8.
22.	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). 中华临床感染病杂志, 2016, 9(2): 97-103.
23.	Wijdicks EF. Hepatic encephalopathy. N Engl J Med, 2016, 375(17): 1660-1670.
24.	Fujiwara K, Oda S, Abe R, et al. On-line hemodiafiltration or high-flow continuous hemodiafiltration is one of the most effective artificial liver support devices for acute liver failure in Japan. J Hepatobiliary Pancreat Sci, 2015, 22(3): 246-247.
25.	刘大为, 杨荣利, 陈秀凯. 重症血液净化. 北京: 人民卫生出版社, 2017: 369-383.
26.	van Wenum M, Chamuleau RA, van Gulik TM, et al. Bioartificial livers in vitro and in vivo: tailoring biocomponents to the expanding variety of applications. Expert Opin Biol Ther, 2014, 14(12): 1745-1760.
27.	Mavri-Damelin D, Damelin LH, Eaton S, et al. Cells for bioartificial liver devices: the human hepatoma-derived cell line C3A produces urea but does not detoxify ammonia. Biotechnol Bioeng, 2008, 99(3): 644-651.
28.	Frühauf JH, Mertsching H, Giri S, et al. Porcine endogenous retrovirus released by a bioartificial liver infects primary human cells. Liver Int, 2009, 29(10): 1553-1561.
29.	Chamuleau RA, Poyck PP, van de Kerkhove MP. Bioartificial liver: its pros and cons. Ther Apher Dial, 2006, 10(2): 168-174.
30.	Pitkin Z, Mullon C. Evidence of absence of porcine endogenous retrovirus (PERV) infection in patients treated with a bioartificial liver support system. Artif Organs, 1999, 23(9): 829-833.
31.	Bhatia SN, Balis UJ, Yarmush ML, et al. Effect of cell-cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells. FASEB J, 1999, 13(14): 1883-1900.
32.	Sakai Y, Nishikawa M, Evenou F, et al. Engineering of implantable liver tissues. Methods Mol Biol, 2012, 826: 189-216.
33.	Iwamuro M, Shiraha H, Nakaji S, et al. A preliminary study for constructing a bioartificial liver device with induced pluripotent stem cell-derived hepatocytes. Biomed Eng Online, 2012, 11: 93.
34.	Jasmund I, Langsch A, Simmoteit R, et al. Cultivation of primary porcine hepatocytes in an OXY-HFB for use as a bioartificial liver device. Biotechnol Prog, 2010, 18(4): 839-846.

1. Bañares R, Catalina MV, Vaquero J. Molecular adsorbent recirculating system and bioartificial devices for liver failure. Clin Liver Dis, 2014, 18(4): 945-956.
2. Chamuleau RA, Poyck PP, van de kerkhove MP. Bioartificial liver: its pros and cons. Ther Apher Dial, 2006, 10(2): 168-174.
3. 程芝灵, 孙桂香, 林辉, 等. 血浆置换治疗肝衰竭临床疗效和安全性的 Meta 分析. 中国循证医学杂志, 2015, 15(6): 664-671.
4. Yue-Meng W, Yang LH, Yang JH, et al. The effect of plasma exchange on entecavir-treated chronic hepatitis B patients with hepatic de-compensation and acute-on-chronic liver failure. Hepatol Int, 2016, 10(3): 462-469.
5. Nakae H, Eguchi Y, Saotome T, et al. Multicenter study of plasma diafiltration in patients with acute liver failure. Ther Apher Dial, 2010, 14(5): 444-450.
6. Tsipotis E, Shuja A, Jaber BL. Albumin dialysis for liver failure: a systematic review. Adv Chronic Kidney Dis, 2015, 22(5): 382-390.
7. Eguchi Y, Nakae H, Furuya T, et al. Plasma filtration with dialysis (plasma diafiltration) in critically ill patients with acute liver failure. Crit Care, 2014, 18(Suppl 1): 399.
8. Komura T, Taniguchi T, Sakai Y, et al. Efficacy of continuous plasma diafiltration therapy in critical patients with acute liver failure. J Gastroenterol Hepatol, 2014, 29(4): 782-786.
9. Sauer IM, Goetz M, Steffen I, et al. In vitro comparison of the molecular adsorbent recirculation system (MARS) and single-pass albumin dialysis (SPAD) Hepatology, 2004, 39(5): 1408-1414.
10. Maiwall R, Maras JS, Nayak SL, et al. Liver dialysis in acute-on-chronic liver failure: current and future perspectives. Hepatol Int, 2014, 8(Suppl 2): 505-513.
11. Vaid A, Chweich H, Balk EM, et al. Molecular adsorbent recirculating system as artificial support therapy for liver failure: a meta-analysis. ASAIO J, 2012, 58(1): 51-59.
12. Kantola T, Koivusalo AM, Höckerstedt K, et al. The effect of molecular adsorbent recirculating system treatment on survival, native liver recovery, and need for liver transplantation in acute liver failure patients. Transpl Int, 2008, 21(9): 857-866.
13. Bañares 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. Hepatology, 2013, 57(3): 1153-1162.
14. Saliba F, Camus C, Durand F, et al. Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial. Ann Intern Med, 2013, 159(8): 522-531.
15. He GL, Feng L, Duan CY, et al. Meta-analysis of survival with the molecular adsorbent recirculating system for liver failure. Int J Clin Exp Med, 2015, 8(10): 17046-17054.
16. Gerth HU, Pohlen M, Thölking G, et al. Molecular adsorbent recirculating system can reduce short-term mortality among patients with acute-on-chronic liver failure: a retrospective analysis. Crit Care Med, 2017, 45(10): 1616-1624.
17. Nevens F, Laleman W. Artificial liver support devices as treatment option for liver failure. Best Pract Res Clin Gastroenterol, 2012, 26(1): 17-26.
18. Sentürk E, Esen F, Ozcan PE, et al. The treatment of acute liver failure with fractionated plasma separation and adsorption system: Experience in 85 applications. J Clin Apher, 2010, 25(4): 195-201.
19. Rocen M, Kieslichova E, Merta D, et al. The effect of Prometheus device on laboratory markers of inflammation and tissue regeneration in acute liver failure management. Transplant Proc, 2010, 42(9): 3606-3611.
20. Kribben A, Gerken G, Haag S, et al. Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure. Gastroenterology, 2012, 142(4): 782-789.e3.
21. Krisper P, Stadlbauer V, Stauber RE. Clearing of toxic substances: are there differences between the available liver support devices? Liver Int, 2011, 31(Suppl 3): 5-8.
22. 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). 中华临床感染病杂志, 2016, 9(2): 97-103.
23. Wijdicks EF. Hepatic encephalopathy. N Engl J Med, 2016, 375(17): 1660-1670.
24. Fujiwara K, Oda S, Abe R, et al. On-line hemodiafiltration or high-flow continuous hemodiafiltration is one of the most effective artificial liver support devices for acute liver failure in Japan. J Hepatobiliary Pancreat Sci, 2015, 22(3): 246-247.
25. 刘大为, 杨荣利, 陈秀凯. 重症血液净化. 北京: 人民卫生出版社, 2017: 369-383.
26. van Wenum M, Chamuleau RA, van Gulik TM, et al. Bioartificial livers in vitro and in vivo: tailoring biocomponents to the expanding variety of applications. Expert Opin Biol Ther, 2014, 14(12): 1745-1760.
27. Mavri-Damelin D, Damelin LH, Eaton S, et al. Cells for bioartificial liver devices: the human hepatoma-derived cell line C3A produces urea but does not detoxify ammonia. Biotechnol Bioeng, 2008, 99(3): 644-651.
28. Frühauf JH, Mertsching H, Giri S, et al. Porcine endogenous retrovirus released by a bioartificial liver infects primary human cells. Liver Int, 2009, 29(10): 1553-1561.
29. Chamuleau RA, Poyck PP, van de Kerkhove MP. Bioartificial liver: its pros and cons. Ther Apher Dial, 2006, 10(2): 168-174.
30. Pitkin Z, Mullon C. Evidence of absence of porcine endogenous retrovirus (PERV) infection in patients treated with a bioartificial liver support system. Artif Organs, 1999, 23(9): 829-833.
31. Bhatia SN, Balis UJ, Yarmush ML, et al. Effect of cell-cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells. FASEB J, 1999, 13(14): 1883-1900.
32. Sakai Y, Nishikawa M, Evenou F, et al. Engineering of implantable liver tissues. Methods Mol Biol, 2012, 826: 189-216.
33. Iwamuro M, Shiraha H, Nakaji S, et al. A preliminary study for constructing a bioartificial liver device with induced pluripotent stem cell-derived hepatocytes. Biomed Eng Online, 2012, 11: 93.
34. Jasmund I, Langsch A, Simmoteit R, et al. Cultivation of primary porcine hepatocytes in an OXY-HFB for use as a bioartificial liver device. Biotechnol Prog, 2010, 18(4): 839-846.

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