artificial liver


Summary: Devices for simulating the activities of the liver. They often consist of a hybrid between both biological and artificial materials.

Top Publications

  1. Pryor H, Vacanti J. The promise of artificial liver replacement. Front Biosci. 2008;13:2140-59 pubmed
    ..Finally, we identify several improvements critical to the future of the field of bioartificial liver replacement therapy. ..
  2. Stadlbauer V, Davies N, Sen S, Jalan R. Artificial liver support systems in the management of complications of cirrhosis. Semin Liver Dis. 2008;28:96-109 pubmed publisher
    ..The concept of an artificial liver that may impact favorably upon the inflammatory response and provide liver function to prevent complications ..
  3. van de Kerkhove M, Poyck P, Deurholt T, Hoekstra R, Chamuleau R, van Gulik T. Liver support therapy: an overview of the AMC-bioartificial liver research. Dig Surg. 2005;22:254-64 pubmed
    ..The future of the BAL, therefore, resides in the development of a human-derived hepatocyte cell line as biocomponent of BAL systems. ..
  4. Kawazoe Y, Eguchi S, Sugiyama N, Kamohara Y, Fujioka H, Kanematsu T. Comparison between bioartificial and artificial liver for the treatment of acute liver failure in pigs. World J Gastroenterol. 2006;12:7503-7 pubmed
    ..However since PE + CHDF maintain electrolytes and acid-base balance, a combination therapy of BAL plus CPE + CHDF might be more effective for FHF. ..
  5. Qian Y, Lanjuan L, Jianrong H, Jun L, Hongcui C, Suzhen F, et al. Study of severe hepatitis treated with a hybrid artificial liver support system. Int J Artif Organs. 2003;26:507-13 pubmed
    b>Artificial liver support system (ALSS) has been used to treat hepatic failure and has significantly decreased the mortality...
  6. Court F, Wemyss Holden S, Dennison A, Maddern G. Bioartificial liver support devices: historical perspectives. ANZ J Surg. 2003;73:739-48 pubmed
    ..liver transplantation or those with potentially reversible acute hepatitis might be improved with temporary artificial liver support...
  7. Dalgetty D, Medine C, Iredale J, Hay D. Progress and future challenges in stem cell-derived liver technologies. Am J Physiol Gastrointest Liver Physiol. 2009;297:G241-8 pubmed publisher
    ..In this review we will focus on the generation of human hepatic endoderm from different stem/progenitor cell populations with a view to its utility in regenerative medicine. ..
  8. Takahashi K, Umehara Y, Umehara M, Nishimura A, Narumi S, Toyoki Y, et al. Plasma exchange-based plasma recycling dialysis system as an artificial liver support. Ther Apher Dial. 2008;12:264-70 pubmed publisher
    ..Safety of this PE-based PRD system was demonstrated and the removal of toxic substances was significant. This study confirmed the clinical utility of this system as an artificial liver support.
  9. Frühauf J, Mertsching H, Giri S, Frühauf N, Bader A. Porcine endogenous retrovirus released by a bioartificial liver infects primary human cells. Liver Int. 2009;29:1553-61 pubmed publisher
    ..There is no evidence of in vivo productive infection in humans because PERV is inactivated by human serum. However, PERV can infect human cell lines and human primary cells in vitro and inhibit human immune functions...

More Information


  1. Streetz K. Bio-artificial liver devices--tentative, but promising progress. J Hepatol. 2008;48:189-91 pubmed
  2. Poyck P, Mareels G, Hoekstra R, van Wijk A, van der Hoeven T, van Gulik T, et al. Enhanced oxygen availability improves liver-specific functions of the AMC bioartificial liver. Artif Organs. 2008;32:116-26 pubmed
    ..Histological examination demonstrated small differences in cell organization. In conclusion, higher metabolic stability and liver-specific functionality was achieved by enhanced oxygen availability based on a prior modeling concept. ..
  3. McClelland R, MacDonald J, Coger R. Modeling O2 transport within engineered hepatic devices. Biotechnol Bioeng. 2003;82:12-27 pubmed
    ..The importance of this control is evaluated by showing how modifying the O(2) concentration and/or transfer coefficients of the convective flows can affect O(2) transport. ..
  4. van de Kerkhove M, Di Florio E, Scuderi V, Mancini A, Belli A, Bracco A, et al. Phase I clinical trial with the AMC-bioartificial liver. Int J Artif Organs. 2002;25:950-9 pubmed
    Recently a bio-artificial liver (BAL) system has been developed at the Academic Medical Center (AMC) of Amsterdam to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT)...
  5. Kjaergard L, Liu J, Als Nielsen B, Gluud C. Artificial and bioartificial support systems for acute and acute-on-chronic liver failure: a systematic review. JAMA. 2003;289:217-22 pubmed
    ..Artificial and bioartificial support systems did not appear to affect mortality in acute liver failure. ..
  6. Du W, Li L, Huang J, Yang Q, Liu X, Li J, et al. Effects of artificial liver support system on patients with acute or chronic liver failure. Transplant Proc. 2005;37:4359-64 pubmed
    Acute on chronic liver failure (AoCLF) is associated with a high mortality rate. Artificial liver support system (ALSS) is useful to bridge patients with liver failure to liver transplantation or to regenerate their own livers...
  7. Fukuda J, Okamura K, Ishihara K, Mizumoto H, Nakazawa K, Ijima H, et al. Differentiation effects by the combination of spheroid formation and sodium butyrate treatment in human hepatoblastoma cell line (Hep G2): a possible cell source for hybrid artificial liver. Cell Transplant. 2005;14:819-27 pubmed
    ..differentiates by spheroid formation, and treatment with sodium butyrate (SB) as a cell source for hybrid artificial liver (HAL)...
  8. Sakiyama R, Nakazawa K, Ijima H, Mizumoto H, Kajiwara T, Ito M, et al. Recovery of rats with fulminant hepatic failure by using a hybrid artificial liver support system with polyurethane foam/rat hepatocyte spheroids. Int J Artif Organs. 2002;25:1144-52 pubmed
    We studied the recovery of rats with fulminant hepatic failure (FHF) by treating them with our original hybrid artificial liver support system (HALSS). FHF was induced by a two-thirds partial hepatectomy and 10 minutes of hepatic ischemia...
  9. Lee K, Shin S, Kim C, Kim J, Cho Y, Chung B, et al. Microfluidic synthesis of pure chitosan microfibers for bio-artificial liver chip. Lab Chip. 2010;10:1328-34 pubmed publisher
    ..Despite the potential of the chitosan for creating bio-artificial liver chips, its major limitation is the inability to fabricate pure chitosan-based microstructures with controlled ..
  10. Bachli E, Schuepbach R, Maggiorini M, Stocker R, Mullhaupt B, Renner E. Artificial liver support with the molecular adsorbent recirculating system: activation of coagulation and bleeding complications. Liver Int. 2007;27:475-84 pubmed
    Numerous, mostly uncontrolled, observations suggest that artificial liver support with the Molecular Adsorbent Recirculating System (MARS) improves pathophysiologic sequelae and outcome of acute and acute-on-chronic liver failure...
  11. Carpentier B, Ash S. Sorbent-based artificial liver devices: principles of operation, chemical effects and clinical results. Expert Rev Med Devices. 2007;4:839-61 pubmed
    ..Current artificial liver devices use columns or suspensions of sorbents (including adsorbents and absorbents) to selectively remove ..
  12. Carraro A, Hsu W, Kulig K, Cheung W, Miller M, Weinberg E, et al. In vitro analysis of a hepatic device with intrinsic microvascular-based channels. Biomed Microdevices. 2008;10:795-805 pubmed publisher
    ..The design and fabrication processes are scalable, enabling the device concept to serve as both a platform technology for drug discovery and toxicity, and for the continuing development of an improved liver-assist device. ..
  13. Koyama T, Ehashi T, Ohshima N, Miyoshi H. Efficient proliferation and maturation of fetal liver cells in three-dimensional culture by stimulation of oncostatin M, epidermal growth factor, and dimethyl sulfoxide. Tissue Eng Part A. 2009;15:1099-107 pubmed publisher
    ..In conclusion, successive supply of the growth medium containing EGF and OSM and the differentiation medium containing DMSO efficiently induced the growth of the 3-D cultured FLCs and their differentiation into mature hepatocytes. ..
  14. Yu C, Pan X, Li L. Progress in bioreactors of bioartificial livers. Hepatobiliary Pancreat Dis Int. 2009;8:134-40 pubmed
  15. Chamuleau R, Deurholt T, Hoekstra R. Which are the right cells to be used in a bioartificial liver?. Metab Brain Dis. 2005;20:327-35 pubmed
    ..More insight in differentiation-promoting factors and the influence of matrix and co-culture conditions is needed. ..
  16. Imamura T, Cui L, Teng R, Johkura K, Okouchi Y, Asanuma K, et al. Embryonic stem cell-derived embryoid bodies in three-dimensional culture system form hepatocyte-like cells in vitro and in vivo. Tissue Eng. 2004;10:1716-24 pubmed
    ..Therefore, differentiating EBs in the scaffold culture system may be useful in developing bioartificial livers, secondary livers, and as pharmaceutical models. ..
  17. Ichida T. Artificial liver support system for fulminant hepatic failure as bridge-use to living donor liver transplantation. Intern Med. 2003;42:920-1 pubmed
  18. van de Kerkhove M, Hoekstra R, Chamuleau R, van Gulik T. Clinical application of bioartificial liver support systems. Ann Surg. 2004;240:216-30 pubmed
    ..Its clinical value awaits further improvement of BAL devices, replacement of hepatocytes of animal origin by human hepatocytes, and assessment in controlled clinical trials. ..
  19. Li L, Yang Q, Huang J, Xu X, Chen Y, Fu S. Effect of artificial liver support system on patients with severe viral hepatitis: a study of four hundred cases. World J Gastroenterol. 2004;10:2984-8 pubmed
    To assess the effect of artificial liver support system (ALSS) on patients with severe viral hepatitis, who were divided into treatment group and control group...
  20. Sekido H, Matsuo K, Takeda K, Ueda M, Morioka D, Kubota T, et al. Usefulness of artificial liver support for pretransplant patients with fulminant hepatic failure. Transplant Proc. 2004;36:2355-6 pubmed
    This study assessed the usefulness of artificial liver support (ALS) for pretransplant patients with fulminant hepatic failure (FHF)...
  21. Mullin E, Metcalfe M, Maddern G. Artificial liver support: potential to retard regeneration?. Arch Surg. 2004;139:670-7 pubmed
    The concept of an "artificial liver" has been in development for over 40 years...
  22. Chamuleau R. Artificial liver support in the third millennium. Artif Cells Blood Substit Immobil Biotechnol. 2003;31:117-26 pubmed
    ..What is missing is the well differentiated human hepatocyte in sufficient amounts. Successful development of this cell will be the crown on bioartificial liver research in the third millenium. ..
  23. YUAN J, YE Q, Zhao L, MING Y, Sun H, Zhu S, et al. Preoperative risk factor analysis in orthotopic liver transplantation with pretransplant artificial liver support therapy. World J Gastroenterol. 2006;12:5055-9 pubmed
    To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation (OLT)...
  24. Li L, Zhang Y, Liu X, Du W, Huang J, Yang Q, et al. Artificial liver support system in China: a review over the last 30 years. Ther Apher Dial. 2006;10:160-7 pubmed
    ..Following 10 years of development in China, a plasma exchange (PE)-centered artificial liver support system (ALSS), principally dependent on PE technology was developed...
  25. Zeilinger K, Holland G, Sauer I, Efimova E, Kardassis D, Obermayer N, et al. Time course of primary liver cell reorganization in three-dimensional high-density bioreactors for extracorporeal liver support: an immunohistochemical and ultrastructural study. Tissue Eng. 2004;10:1113-24 pubmed
  26. Hessel F, Bramlage P, Wasem J, Mitzner S. Cost-effectiveness of the artificial liver support system MARS in patients with acute-on-chronic liver failure. Eur J Gastroenterol Hepatol. 2010;22:213-20 pubmed publisher
    ..Randomized controlled trials with sufficient sample size are necessary before a final recommendation for MARS can be given. ..
  27. Naruse K. Artificial liver support: future aspects. J Artif Organs. 2005;8:71-6 pubmed
    ..It is possible that this therapy will become the most practical treatment for patients with severe hepatic failure. ..
  28. Kobayashi N. Life support of artificial liver: development of a bioartificial liver to treat liver failure. J Hepatobiliary Pancreat Surg. 2009;16:113-7 pubmed publisher
    ..types of cells and extracellular matrices should be organized and in what type of environments to create an artificial liver, i.e., a life-saving organ...
  29. Onodera K, Sakata H, Yonekawa M, Kawamura A. Artificial liver support at present and in the future. J Artif Organs. 2006;9:17-28 pubmed
    ..In the near future, we hope that both gene therapy and regenerative medicine will contribute to the development of a functional artificial liver.
  30. Lee P, Hung P, Lee L. An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnol Bioeng. 2007;97:1340-6 pubmed
    ..Here, we created a biologically inspired artificial liver sinusoid with a microfluidic endothelial-like barrier having mass transport properties similar to the liver ..
  31. Consolo F, Fiore G, Truscello S, Caronna M, Morbiducci U, Montevecchi F, et al. A computational model for the optimization of transport phenomena in a rotating hollow-fiber bioreactor for artificial liver. Tissue Eng Part C Methods. 2009;15:41-55 pubmed publisher
    A comprehensive computational study modelling the operation of a rotating hollow-fiber bioreactor for artificial liver (BAL) was performed to explore the interactions between the oxygenated culture medium and the cultured hepatocytes...
  32. Chamuleau R, Poyck P, van de Kerkhove M. Bioartificial liver: its pros and cons. Ther Apher Dial. 2006;10:168-74 pubmed
    ..Theoretically, a combination of a cell-free liver support system and a BAL system might be optimal for the treatment of ALF patients in the near future. ..
  33. Jiang J, Kojima N, Guo L, Naruse K, Makuuchi M, Miyajima A, et al. Efficacy of engineered liver tissue based on poly-L-lactic acid scaffolds and fetal mouse liver cells cultured with oncostatin M, nicotinamide, and dimethyl sulfoxide. Tissue Eng. 2004;10:1577-86 pubmed
  34. Moussy Y. Convective flow through a hollow fiber bioartificial liver. Artif Organs. 2003;27:1041-9 pubmed
    ..The results suggest the possible formation of preferential flow channels and hypoperfusion of many cells leading to an inadequately functioning bioreactor. Some simple design changes may improve the performance of the ELAD. ..
  35. Ladurner R, Hochleitner B, Schneeberger S, Barnas U, Krismer A, Kleinsasser A, et al. Extended liver resection and hepatic ischemia in pigs: a new, potentially reversible model to induce acute liver failure and study artificial liver support systems. Eur Surg Res. 2005;37:365-9 pubmed
    ..This technique of extended liver resection after hepatic ischemia in the porcine model may be useful for studies of potentially reversible acute liver failure and experimental bioartificial support. ..
  36. Hanada S, Kojima N, Sakai Y. Soluble factor-dependent in vitro growth and maturation of rat fetal liver cells in a three-dimensional culture system. Tissue Eng Part A. 2008;14:149-60 pubmed publisher
    ..We therefore conclude that the 3D culture system shows promise for the in vitro maturation of fetal liver cells as a means of preconditioning of the cells for engineered liver tissue equivalents in future transplantation studies. ..
  37. Hay P, Veitch A, Gaylor J. Oxygen transfer in a convection-enhanced hollow fiber bioartificial liver. Artif Organs. 2001;25:119-30 pubmed
    ..The results suggest that a substantial proportion of the hepatocytes are exposed to hypoxic conditions under which metabolism may be impaired. ..
  38. Xue Y, Zhao S, Luo Y, Li X, Duan Z, Chen X, et al. TECA hybrid artificial liver support system in treatment of acute liver failure. World J Gastroenterol. 2001;7:826-9 pubmed
    To assess the efficacy and safety of TECA type hybrid artificial liver support system (TECA-HALSS) in providing liver function of detoxification, metabolism and physiology by treating the patients with acute liver failure (ALF)...
  39. Catapano G, Euler M, Gaylor JDS -, Gerlach J. Characterization of the distribution of matter in hybrid liver support devices where cells are cultured in a 3-D membrane network or on flat substrata. Int J Artif Organs. 2001;24:102-9 pubmed
  40. Jalan R, Williams R. Bio-artificial liver support for acute liver failure: should we be using it to treat patients?. Transplantation. 2002;73:165-6 pubmed
  41. Matsuura T, Kawada M, Hasumura S, Nagamori S, Obata T, Yamaguchi M, et al. High density culture of immortalized liver endothelial cells in the radial-flow bioreactor in the development of an artificial liver. Int J Artif Organs. 1998;21:229-34 pubmed
    ..It would therefore be important to include these cells in any hybrid type of artificial liver in addition to hepatocytes. However, it is difficult to culture these cells in vitro...
  42. Gerlach J, Botsch M, Kardassis D, Lemmens P, Schon M, Janke J, et al. Experimental evaluation of a cell module for hybrid liver support. Int J Artif Organs. 2001;24:793-8 pubmed
  43. Werner A, Duvar S, Muthing J, Büntemeyer H, Kahmann U, Lunsdorf H, et al. Cultivation and characterization of a new immortalized human hepatocyte cell line, HepZ, for use in an artificial liver support system. Ann N Y Acad Sci. 1999;875:364-8 pubmed
    ..The new cell line HepZ has proven to retain liver-specific qualities and to be appropriate for mass cell cultivation for bioartificial devices. ..
  44. Sechser A, Osorio J, Freise C, Osorio R. Artificial liver support devices for fulminant liver failure. Clin Liver Dis. 2001;5:415-30 pubmed
    b>Artificial liver-support devices attempt to bridge patients with fulminant hepatic failure until either a suitable liver allograft is obtained for transplantation or the patient's own liver regenerates sufficiently to resume normal ..
  45. Fukuda J, Sakiyama R, Nakazawa K, Ijima H, Yamashita Y, Shimada M, et al. Mass preparation of primary porcine hepatocytes and the design of a hybrid artificial liver module using spheroid culture for a clinical trial. Int J Artif Organs. 2001;24:799-806 pubmed
    ..In conclusion, we succeeded in developing a mass preparation method of porcine hepatocytes and a large hybrid artificial liver module on a clinical trial scale.
  46. Yamashita Y, Shimada M, Tsujita E, Tanaka S, Ijima H, Nakazawa K, et al. Polyurethane foam/spheroid culture system using human hepatoblastoma cell line (Hep G2) as a possible new hybrid artificial liver. Cell Transplant. 2001;10:717-22 pubmed
    The risk of xenozoonosis infections poses the greatest obstacle against the clinical application of hybrid artificial liver support system (HALSS)...
  47. Nitta M, Hirasawa H, Oda S, Shiga H, Nakanishi K, Matsuda K, et al. Long-term survivors with artificial liver support in fulminant hepatic failure. Ther Apher. 2002;6:208-12 pubmed
    Clinical ability of artificial liver support (ALS) has been improved greatly in recent years which has allowed us to encounter long-term survivors with fulminant hepatic failure (FHF) whose liver function has been almost completely lost...
  48. Sen S, Mookerjee R, Davies N, Williams R, Jalan R. Review article: the molecular adsorbents recirculating system (MARS) in liver failure. Aliment Pharmacol Ther. 2002;16 Suppl 5:32-8 pubmed
    In recent years different artificial liver support systems are being developed for use in patients with acute decompensation of chronic liver disease or acute liver failure...
  49. Funatsu K, Ijima H, Nakazawa K, Yamashita Y, Shimada M, Sugimachi K. Hybrid artificial liver using hepatocyte organoid culture. Artif Organs. 2001;25:194-200 pubmed
    We developed 2 types of hybrid artificial liver modules using hepatocyte organoid culture. One was a polyurethane foam (PUF)/hepatocyte spheroid packed-bed module...
  50. Nakazawa K, Ijima H, Fukuda J, Sakiyama R, Yamashita Y, Shimada M, et al. Development of a hybrid artificial liver using polyurethane foam/hepatocyte spheroid culture in a preclinical pig experiment. Int J Artif Organs. 2002;25:51-60 pubmed
    We describe a preclinical study of our original hybrid artificial liver support system (HALSS) for a clinical trial...
  51. Hay P, Veitch A, Smith M, Cousins R, Gaylor J. Oxygen transfer in a diffusion-limited hollow fiber bioartificial liver. Artif Organs. 2000;24:278-88 pubmed
  52. Matsumoto K, Mizumoto H, Nakazawa K, Ijima H, Funatsu K, Kajiwara T. Hepatic differentiation of mouse embryonic stem cells in a bioreactor using polyurethane/spheroid culture. Transplant Proc. 2008;40:614-6 pubmed publisher
    We have previously developed a hybrid artificial liver (HAL) using polyurethane foam (PUF)/hepatocyte spheroid culture. The PUF-HAL has been successfully scaled up to a clinical level...
  53. Yamashita Y, Shimada M, Tsujita E, Shirabe K, Ijima H, Nakazawa K, et al. Efficacy of a larger version of the hybrid artificial liver support system using a polyurethane foam/spheroid packed-bed module in a warm ischemic liver failure pig model for preclinical experiments. Cell Transplant. 2003;12:101-7 pubmed
    ..reported the usefulness of a polyurethane foam packed-bed culture system of hepatocyte spheroids as a hybrid artificial liver support system (PUF-HALSS)...