Liver support strategies: cutting-edge technologies

Key Points

  • Despite almost three decades of research on artificial and bioartificial liver support, appropriate, randomized, controlled, and adequately powered studies are rare

  • Compared with the effect of a suitable orthotopic liver graft on a patient's clinical course, the clinical effects of extracorporeal liver support systems seem to be very limited

  • The main issues for all liver support therapy concepts are the need for tissue vascularization and integration into the host circulation, and a lack of reliable sources of safe and metabolically active cells

  • Strategies to overcome the conceptual limitations of (bio)artificial liver support devices include hepatocyte transplantation and various tissue engineering approaches (for example repopulation of decellularized organs, organ printing and induced organogenesis)

  • Hepatocyte transplantation seems to be at least a temporary alternative treatment strategy in certain metabolic liver disorders, and might have a role in the treatment of acute liver failure and chronic liver disease

  • Translation of regenerative medicine into the clinical routine, especially transplantation of recellularized liver grafts, seems possible but further intense research is needed

Abstract

The treatment of end-stage liver disease and acute liver failure remains a clinically relevant issue. Although orthotopic liver transplantation is a well-established procedure, whole-organ transplantation is invasive and increasingly limited by the unavailability of suitable donor organs. Artificial and bioartificial liver support systems have been developed to provide an alternative to whole organ transplantation, but despite three decades of scientific efforts, the results are still not convincing with respect to clinical outcome. In this Review, conceptual limitations of clinically available liver support therapy systems are discussed. Furthermore, alternative concepts, such as hepatocyte transplantation, and cutting-edge developments in the field of liver support strategies, including the repopulation of decellularized organs and the biofabrication of entirely new organs by printing techniques or induced organogenesis are analysed with respect to clinical relevance. Whereas hepatocyte transplantation shows promising clinical results, at least for the temporary treatment of inborn metabolic diseases, so far data regarding implantation of engineered hepatic tissue have only emerged from preclinical experiments. However, the evolving techniques presented here raise hope for bioengineered liver support therapies in the future.

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Figure 1: Artificial liver support systems.
Figure 2: Bioartifical liver support devices aim to combine detoxification with the synthetic and regulatory functions of hepatocytes.
Figure 3: Concept of recellularization of decellularized livers and consecutive implantation or extracorporeal application.
Figure 4: 3D organ printing.

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Correspondence to Igor M. Sauer.

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Struecker, B., Raschzok, N. & Sauer, I. Liver support strategies: cutting-edge technologies. Nat Rev Gastroenterol Hepatol 11, 166–176 (2014). https://doi.org/10.1038/nrgastro.2013.204

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