Emerging Role of Extracorporeal Support in Acute and Acute-on-Chronic Liver Failure: Recent Developments

Abstract

Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are life-threatening illnesses requiring intensive care admission and potentially liver transplantation. Artificial extracorporeal liver support (ECLS) systems remove water-soluble and albumin-bound toxins to maintain normal serum chemistry, prevent further hepatic/organ system damage, and create an environment for potential hepatic regeneration/recovery (ALF) or bridge to liver transplantation (ALF and ACLF). Use of artificial ECLS has been studied in both ALF and ACLF. Artificial ECLS systems have been found to be safe and have demonstrated the following benefits: improvement of biochemistries, hemodynamic status, and hepatic encephalopathy. Despite this, only one prospective randomized controlled trial examining the use of high-volume plasma exchange has demonstrated improvement in transplant-free survival. Bioartificial (cell-based) ECLS systems build on the technology of artificial systems, incorporating living hepatocytes in a bioactive platform to further mimic endogenous hepatic detoxification and synthetic functions. Currently, no bioartificial system has been found to confer a mortality benefit; however, these platforms offer the greatest potential for future development.

The Use of High Volume Plasmapheresis in Acute Liver Failure

“…Presently, liver transplantation remains the only definitive management strategy for ALF patients for whom spontaneous liver recovery does not occur. However, many patients do not survive to liver transplant or they may not be candidates either for medical or psychosocial reasons, similar to this case [8]. As a result, this case demonstrates that there may be potential benefits of conducting HVP in centers without access to MARS or transplantation.…”

“…This combination of proinflammatory cascade and hepatic dysfunction results in the build-up of toxins that cause systemic disturbances associated with ALF [7]. HVP technically falls under the umbrella term of artificial ECLS in which it replaces the patients' plasma with fresh-frozen plasma with the objective of detoxification and regulation of serum chemistry function [2,8]. By removing plasma cytokines, adhesion molecules and toxins while replacing plasma factors, HVP aims for the potential of modulating the immune system [1].…”

“…There has only been one study that demonstrated any statistical significance and efficacy for the use of any of the ECLS systems in ALF and that was with HVP [1,8]. In this prospective multicenter randomized control trial done by Larson et al in 2016, 182 ALF patients were randomized to receive standard medical therapy (SMT) or SMT plus HVP for three days [1].…”

Artificial liver treatment improves survival in patients with hepatitis B virus‐related acute‐on‐chronic liver failure: A case‐control matched analysis

“…However, a critical shortage of donor organs for transplantation results in the deaths of many patients waiting for LT 4,5 . The artificial liver support system (ALSS) has been recognized as a promising alternative to LT in patients with ACLF by replacement of the dysfunctional liver 6–9 . Albumin (ALB) dialysis with the molecular adsorbent recirculation system and fractionated plasma separation and adsorption, the most commonly used ALSS models for the treatment of alcoholic liver disease‐related ACLF (ALD‐ACLF) in Europe, have shown beneficial effects for improving hepatic and renal functions 10–13 .…”

Pharmacotherapy of Hepatic Encephalopathy

“…Other interventions may improve overall liver function, e.g., balloon-occluded retrograde transvenous obliteration, taking into consideration the applicability of each procedure on case-by-case manner [16]. Nevertheless, artificial liver support system was reported to have positive impact on overall liver cirrhosis complications, including HE [17,18].…”