Introduction:
The liver is one of the principal organs of the human body. It is responsible for various functions such as the secretion of bile, maintenance of metabolism, secretion of clotting factors, and detoxification of toxic substances. But due to different medical conditions, the standard functionality needs to be recovered. The artificial liver system can be a fruitful way to restore the liver's normal function.
What Is the Need for an Artificial Liver Support System?
The liver is one of the most important organs of the human body. The liver helps in various functioning like the synthesis of plasma proteins and clotting factors, metabolism and digestion of glucose and fats, and elimination of toxic substances. The liver transforms potentially harmful substances like s metabolites, toxins, and excess hormones into water-soluble, harmless substances. But the deterioration of liver functions leads to the accumulation of substances like bilirubin, bile acids, ammonia, lactate, glutamine, mediators of oxidative stress, free fatty acids, endogenous benzodiazepines, and proinflammatory cytokines. The conditions that lead to these situations are acute live failure, acute or chronic liver failure, hepatic encephalopathy, and Budd-Chiari syndrome.
What Are the Different Types of Artificial Liver Systems?
Artificial liver support systems can be of three types. These are:
1. Artificial Liver Support (ALS):
These cell-free systems act on the principle of filtration and absorption. This system is based on the normal dialysis-based system that eliminates albumin-bound and water-soluble substances. Most patients suffering from liver failure also suffer from renal failure, which is why such procedures help control both situations. Detoxification of this system is based on various factors like materials, pore size, placement of filters, the active surface of the absorbers, plasma flow rate, and albumin concentration. Charcoal haemoperfusion is one of the main techniques in this procedure. In this procedure, the patient's plasma is separated through activated charcoal filters. These filters are potent enough to remove water-soluble toxins. Loss of thrombocytes and clotting problems are associated with this. Another technique that is used in this process is plasma exchange/plasmapheresis. Here, cellular components are separated from plasma by plasma filters. After this, plasma is replaced by fresh frozen plasma, albumin solution, or plasma substitutes. Types of systems developed based on conventional extracorporeal procedures are:
- Hemodialysis and Hemofiltration: This is exactly based on a conventional dialysis system. Small water-soluble contents (molecular weight less than 5000) like urea and ammonia are eliminated through this procedure. But, the elimination of the protein components is difficult.
- Plasmapheresis and High-Volume Plasmapheresis/Plasma Exchange With or Without Hemodiafiltration: This procedure is helpful enough in removing proteins and large, molecular-weight inflammatory mediators. One of the main drawbacks of this procedure is the removal of a large volume of plasma. This causes severe hypovolemia. Substances like albumin and fresh frozen plasma replace this plasma. Another drawback of this system is the elimination of essential substances like clotting factors.
- Hemoperfusion and Plasma Perfusion: In this procedure, toxins are removed by the plasma absorbent systems. Absorbent systems are resins and activated charcoal changing ions. This system removes lipophilic substances along with water-soluble substances. This system can be used in patients suffering from hepatic coma. Potential side effects are thrombocytopenia, hypotension, and pulmonary embolisms.
- Hemodiabsorbtion and the Liver Dialysis Unit: In this procedure, blood is passed through a flat dialyzer with a cellulose membrane. The dialysis fluid is continuously renewed with cation-charging resins and charcoal suspension. A large surface area is helpful in removing toxins with molecular weights up to 5000.
Other than conventional systems, two other systems are also being developed. These are:
2. Artificial Liver Support Using Albumin Dialysis:
In this procedure, albumin is used as a carrier for removing protein-bound toxins. Liver toxins bound to albumin can be removed with the help of regular dialysis procedures. Additionally, water-soluble toxins, creatinine, amino acids, and inflammatory substances. Techniques used in this procedure are:
- Single-Pass Albumin Dialysis: The principle of hemodialysis or hemodiafiltration is used in this technique. The blood is passed through a standard high-flux albumin-impermeable dialyzer, and an albumin-containing dialysis solution is used. The albumin concentration of this solution is 2 to 5 percent. As the albumin solution is renewed and can not be used repeatedly, that is it is called the single-pass technique. Toxins that can be passed through membraneous molecules can be trapped by this technique. This technique has similarities with continuous venovenous hemodialysis (CVVHD) or continuous venovenous haemodiafiltration (CVVHDF).
- Molecular Adsorbent Recirculating System (MARS): This system was developed by Stange and Mitzner in 1993. This technique is based on three circuits one with a high-flux dialyzer impermeable to albumin, another with albumin solution, and an open-loop single-pass circuit. Detoxification of the process is based on the principle of dialysis, filtration, and adsorption. In this procedure, a pump removes the patient's blood from the body at the rate of 150 to 200 millimeters per minute. This blood is passed through the albumin-impermeable membrane with a pore size of less than 60 kDa. In the secondary circuit, a 20 percent albumin solution is present that act as a dialysis solution. This solution rotates in the counterclockwise direction and collects the toxins. The toxins have a higher affinity towards resins present on the membrane. Thus toxins attached to the albumin are separated. The usual duration of one MARS season usually lasts for four to six hours. This procedure can be used in various diseases like hepatic encephalopathy, cerebral edema, kidney dysfunction, hepatorenal syndrome, drug-related liver damage, and pruritus.
- Biological Extracorporeal Liver Perfusion: In this procedure, an extracorporal liver from an animal or human is utilized in establishing liver functions. It was first used by Sen et al. in the year 1964. In general porcine livers are used for this purpose. In general, genetically modified pig liver is used. Complexities of the xenotransplant, immunological issues, and complex procedures are major drawbacks for this purpose.
3. Bioartificial Liver Support:
In this procedure, human or animal cells are used for the purification process. Obtaining human cells and their isolation is a difficult procedure, so genetically modified pig cells are utilized in this process. This device is divided into two components like, the bioreactor and the cellular compartment. The bioreactor provides an ideal environment for cellular growth, proliferation, and development. These cells are arranged within the bioreactor in various configurations like hollow-fiber cartridges, encapsulation systems, packed beds, and flat plate systems. In the cellular component, cells from different animals are used. Apart from human cells, hepatic cells from pigs, rabbits, and rodents are used. Through genetic modification, harmful genes are removed from the body of those animals. In recent cases, different cell lines for the different human liver cells have been developed for rapid proliferation. Stem-cell technology is also being used for developing new cell lines.
Conclusion:
The liver is an essential organ. Several medical conditions lead to a decrease in liver functions. This causes accumulation of toxins in the body. The function of the artificial liver system is to remove these toxins. The latest artificial liver is made up of living cells. These cells help in the removal of toxins from the body.
