Liver Support Devices - An Overview

Introduction

The liver carries out various functions encompassing immunological, metabolic, synthetic, and excretory processes, all vital for maintaining organ function and overall body homeostasis. Despite the organ's remarkable capacity for regeneration, a severe, serious injury can disrupt the critical mass of hepatocytes (principal tissue cells are responsible for several biological tasks such as glucose, lipid, and protein metabolism, detoxification, and immune cell activation to maintain liver health) required to maintain homeostasis (the ability of an organism or system to maintain a stable internal environment despite external changes or disturbances) in cases of acute liver failure (ALF) or an acute hepatic injury in people who already have chronic liver disease (acute-on-chronic liver failure).

What Is a Liver Support Device?

Liver failure is distinguished by the presence of hepatic encephalopathy (hepatic encephalopathy is a brain disorder induced by liver disease; it has an impact on the central nervous system, as well as the thoughts, feelings, and actions), jaundice, cerebral edema (swelling of the brain), and coagulopathy (abnormal blood clotting disorder). The fatality rate linked to liver failure, including both acute liver failure (ALF) and acute-on-chronic liver failure (AoCLF), remains elevated. While some individuals experiencing acute liver failure may undergo hepatic regeneration and subsequently recover, a significant number of patients may die as a result of cerebral edema, infections, or multi-organ failure.

Although liver transplantation has brought about significant advancements in the treatment of these individuals, a considerable number of patients continue to experience mortality while awaiting transplantation. Extracorporeal liver support systems have been developed to stabilize patients and serve as either a bridge to liver transplantation or a means for the liver to recuperate after injury.

An optimal liver support device would obviate the necessity for transplantation and perhaps provide a long-term substitution for end-stage liver illness, similar to renal dialysis.

What Are the Types of Liver Support Devices?

Various categories of liver support devices have been developed to provide therapeutic assistance to patients with liver dysfunction.

In patients experiencing liver failure, it is anticipated that efficient artificial liver support systems would fulfill three primary roles: detoxification, production of clinically significant proteins, and promotion of the regeneration of native hepatocytes.

The categorization of liver support devices can be broadly classified into two main groups:

• Artificial Liver Support Devices- Artificial liver support devices are mechanical devices or non-cell-based liver support devices. These devices solely offer detoxification capabilities.

• Bio-Artificial Liver Support Devices- Bio-artificial liver support devices support the liver and contain a biological component, such as primary hepatocytes or hepatic cell lines. These devices incorporate cellular components to effectively substitute crucial liver processes such as oxidative detoxification, biotransformation, excretion, and synthesis.

Toxic substances present in human blood can be categorized into two primary groups based on their solubility: those soluble in water and those predominantly bound to albumin.

• Traditional Dialysis Method- Traditional dialysis methods, such as hemodialysis (a medical procedure used to remove waste products and excess fluid from the blood when the kidneys are unable to do so) and hemofiltration, have limited effectiveness in eliminating water-soluble toxins.

• Alternate Methodology- Since most liver toxins exhibit an affinity for albumin, supplementary methodologies are necessary to eliminate these toxic substances effectively. One potential strategy involves the incorporation of albumin into the dialysate to eliminate toxins linked to albumin. An alternate methodology involves the utilization of large pore filters, which can retain biological components and effectively separate plasma proteins, including albumin. This strategy has been employed in several medical technologies, such as Prometheus and selective plasma filtration technology (SEPET). The filtrate has the potential to undergo reabsorption to remove the toxin-attached albumin. This process may be observed in medical treatments, where the albumin is recycled.

Which Are the Different Artificial Supporting Devices?

Non-cell-based liver support devices, also known as artificial liver support devices, are medical technologies designed to support patients with liver failure temporarily. These devices aim to mimic the functions of a healthy liver, such as detoxification, metabolism, and synthesis of essential molecules. By utilizing advanced technology, these devices offer a potential solution for patients awaiting liver transplantation or those who are unable to undergo this procedure.

Several non-biological systems have been assessed for the treatment of liver failure. These systems include the molecular adsorbent recirculating system (MARS), Prometheus, single pass albumin dialysis (SPAD), and selective plasma filtration system therapy (SEPET).

1. Molecular Adsorbents Recirculating Systems (MARS): The molecular adsorbent recirculating system (MARS) is a therapeutic approach that combines conventional dialysis with hemodialysis using an albumin dialysate solution over an impenetrable barrier that restricts the passage of albumin.

• The MARS system consists of two distinct circuits: the blood circuit and the secondary circuit. The blood circuit transports the patient's blood through a high-flow dialyzer containing an albumin impermeable membrane. The albumin in the secondary circuit undergoes a rejuvenation process by being passed through columns containing anion-exchange resin and activated charcoal.

• The mortality rates of individuals without transplantation who have had MARS treatment have been seen to range from 78 percent to 100 percent.

• Therefore, utilizing MARS as an intervention may serve as an effective means to stabilize patients before transplantation. However, its implementation alone may only improve survival outcomes with transplantation.

• Although MARS therapy has demonstrated improvements in indicators such as bilirubin levels and encephalopathy, it is important to consider potential adverse effects. These may include exacerbation of coagulopathy, induction of hypoglycemia, and alteration of medication pharmacokinetics.

• It may be advisable to consider refraining from administering albumin infusion before MARS to enhance its efficacy.

2. Prometheus System

• The fractional plasma separation and adsorption system utilizes a filtration process employing a filter with a pore size of 250 kDa to generate a filtrate.

• In contrast to MARS, where the membrane is impermeable to albumin, Prometheus allows the diffusion of albumin-bound toxins over its albumin-permeable membrane. Subsequently, the filtrate is sent through a pair of columns containing neutral resin and anion-exchange material before reintroducing into the patient's system.

• Therefore, the patient's albumin is effectively purified from the linked poisons without the need for any external albumin.

• In general, Prometheus offers increased clearance for most liver toxins, particularly those with a strong binding affinity to albumin.

3. Single Pass Albumin Dialysis (SPAD)

• It is a medical procedure used for the treatment of acute liver failure.

• The method described employs a low concentration of albumin (five percent) instead of MARS. The albumin solution is eliminated with a single countercurrent pass against the patient's blood in a hemofilter.

• The efficacy of SPAD can be considered comparable to that of MARS in terms of its influence on clinical and standard laboratory markers.

• The therapeutic approach, selective plasma filtration treatment (SEPET), involves using hollow fiber membranes with certain hole sizes. These membranes selectively enable the passage of molecules with a molecular weight below 100 kDa while retaining important components such as immunoglobulins, complement proteins, clotting factors, and hepatocyte growth factors.

• The extracted fluid is substituted with albumin, fresh frozen plasma, and electrolytes.

Which Is the Bio Artificial Liver Support System?

• The failure of artificial liver support systems to increase survivability emphasizes the significance of BAL development.

• BALs are intended to perform both synthetic and detoxifying activities.

• Even though human hepatocytes seem to be the most suitable cells for BAL, their limited availability and difficulty in regenerating in vitro hinder their widespread usage, and cultured human hepatocytes perform less well.

• Hepatassist, extracorporeal liver assist device (ELAD), Modular Extracorporeal Liver Support (MELS), BLSS, and AMC-BAL are the BAL systems undergoing clinical study.

  • HepatAssist: The HepatAssist uses a hollow fiber extracorporeal bioreactor filled with cryopreserved swine hepatocytes. Only some patients with hepatic failure demonstrated a survival benefit, with a small mortality decrease in favor of the BAL group.

  • Extracorporeal Liver Assist Device: Hollow fiber cartridges loaded with C3A human hepatoblastoma cell lines are used in the extracorporeal liver assist device (ELAD). Despite improvements in ammonia, bilirubin, and hepatic encephalopathy, a definite survival advantage has not been demonstrated.

  • Modular Extracorporeal Liver Support (MELS): The system is based on hollow fibers containing live porcine hepatocytes, as the device is safe to use when bridging to transplant. The device may not be widely used because it is expensive and relatively sophisticated.

  • Bioartificial Liver Support System (BLSS): The bioartificial liver support system (BLSS), which contains porcine hepatocytes in a single hollow fiber cartridge, is undergoing research.

  • Bioartificial Liver (AMC-BAL): Porcine hepatocytes are attached to a spiral-shaped polyester fabric with an embedded hollow fiber in the Amsterdam Medical Centre Bioartificial Liver (AMC-BAL). Although early research seems promising, larger trials are necessary.

Conclusion

The care of patients with liver failure may benefit from the use of artificial and bioartificial liver devices. Even though artificial liver devices have improved in biochemical parameters, the benefit in terms of survival has not been convincingly shown. Detoxification is the only function of artificial liver devices. On the other hand, BAL tries to replace additional liver functions and might have greater promise in the future. However, there is still much to be done to create BAL devices and conduct clinical trials to prove both their usefulness and safety.