Liver support systems today

Abstract

Liver failure carries a high mortality, both the acute type with no pre-existing liver disease (acute liver failure) and the acute decompensation superimposed on a chronic liver disorder (acute on chronic liver failure). Today, liver transplantation still represents the only curative treatment for liver failure due to end-stage liver diseases. Donor organ shortage is still the major limitation and many patients die while awaiting transplantation. Due to the scarcity of donor organs, liver support technologies are being developed to support patients with severe liver failure until either an organ becomes available for transplantation or their livers recover from injury. Early devices including hemodialysis, hemoperfusion, exchange transfusion, cross-hemodialysis, cross-circulation and plasmapheresis appeared inefficient. In the present day, liver support systems' designs fall into two main categories: cell-based, so-called bioartificial and non-cell-based, also known as artificial systems. Bioartificial liver support systems use either porcine hepatocytes or human hepatoma cell lines housed within a hollow-fiber bioreactor. The system perfuses the patient's whole blood or separated plasma through the luminal space in the bioreactor. Theoretically, these methods should optimally resemble normal hepatic tissue structure and function. However, the existing bioartificial systems are far from ideal solution in terms of immunological, infectological, oncological and financial problems and must still be thought of as experimental. The artificial systems are already available for the clinicians in limited quantities. These non-cell-based devices are intended to remove protein-bound and water-soluble toxins without providing synthetic function, which can be partially replaced with substitution of the failing substances (plasma proteins, coagulation factors). These systems include the hemodiabsorption (Liver Dialysis Unit) which is commercially available in the United States, the albumin dialysis which is available in Europe and the newly developed fractionated plasma separation and adsorption (FPSA) system. The simple method of albumin dialysis is "single pass albumin dialysis" (SPAD), which evolved into the so-called "molecular adsorbent recirculating system"(MARS). Prometheus system combines the FPSA method with high-flux hemodialysis. Although the results of many experimental and clinical trials prove the efficacy of the above mentioned methods, large randomized controlled trials are mandatory to establish the impact on survival benefit of artificial and bioartificial support systems versus standard therapy.

[Retracted] Effects of High‐Flux Dialysis Combined with Hemoperfusion on Serum GRP78 and miR‐495‐3p in Renal Failure Patients

“…At present, the morbidity of RF is increasing all over the world, and it puts an increasingly serious threat to patients [ 17 , 18 ]. The treatment of RF patients is the top priority in clinical research, and the effect of HF-HD combined with systemic HP on RF has been preliminarily determined [ 19 , 20 ]. In order to further apply this treatment scheme clinically, this study evaluated the changes of GRP78 and miR-495-3p during HF-HD combined with systemic HP, which can provide more accurate reference for future clinical practice.…”

Monitoring oxidative stress in acute‐on‐chronic liver failure by advanced oxidation protein products

“…Damaged proteins may be highly sensitive protein‐based biomarkers of oxidative processes in mammalian systems. Albumin, an important transport vehicle, was found to be severely oxidized in ACLF patients; these patients can thus benefit from artificial liver support systems via the removal of albumin‐bound toxins 29 . The report from China showed that plasma exchange, one of the artificial liver support systems, was found to significantly improve survival 30,31 .…”

Acute-on-chronic liver failure: extracorporeal liver assist devices

“…Challenges include selecting the sources of hepatocytes for the bioreactor; the stabilization of these primary hepatocytes in the bioreactor to maintain morphology, differentiation and function; and the design of the bioreactor, which requires adequate bidirectional mass transport, and cell viability to perform liver functions. Issues of safety with regard to infection and oncogenesis, as well as high cost are major concerns of these systems, which are considered as yet to be experimental [22].…”