The artificial liver, referred to as the artificial liver, has a short history of existence as a separate artificial organ from other artificial organs. Research on artificial livers began in the 1950s, when Sorrentino first introduced the concept of the “artificial liver” in 1956 by demonstrating that fresh liver tissue homogenates could metabolize ketone bodies, barbiturates and ammonia. The artificial liver is an extracorporeal mechanical, chemical, or biological device that temporarily or partially replaces liver function, thereby assisting in the treatment of liver insufficiency or related diseases. The main difference between artificial liver and general medical drug treatment is that the former is mainly through “functional replacement” and the latter is mainly through “functional enhancement”. Therefore, in the clinical application of this new technology, special attention should be paid to the identification of indications, each therapy has its own advantages and disadvantages, and should be selected according to the individual and the disease. In the 1950s, most researchers believed that the main cause of liver coma was the abnormal accumulation of toxic substances in the body, and that most of these toxins were small dialyzable molecules (less than 500 daltons), so early artificial liver devices were designed to provide small molecules of toxic substances. The early artificial liver devices were designed to provide blood purification of small molecules of toxins. If the artificial liver is further coarsely divided, it can be understood as mechanical or physical and biological. The main mechanism of mechanical is to remove harmful substances from the patient’s body by physical means using the unique biofilm and adsorption of chemicals, and to replenish the body with the required substances, while the biological artificial liver is a bioreactor in vitro that uses human-derived or animal-derived hepatocytes to replace the body that cannot perform the In this regard, biological artificial liver is more symbolic of the name “artificial liver”. However, because biological artificial liver has many problems and is far from being clinically necessary, the treatment of artificial liver is still mainly physical. Blood/plasma perfusion The exact meaning of blood perfusion is blood adsorption, where substances dissolved in blood are adsorbed onto a solid substance with abundant surface area to remove toxic substances from the blood. Hemoperfusion equipment consists of a hemoperfusion machine, accessories (arterial and venous lines, etc.) and a hemoperfusion device. There are two types of perfusers in common use: one is activated carbon and the other is synthetic resin. Activated carbon is mainly made from coconut shells as raw material, others are petroleum, wood, polyvinyl alcohol, bone, sugar, etc. In 1970, Canadian scholar Mingrui Zhang applied microcapsules made of activated charcoal wrapped in albumin sponge gel semi-permeable membrane for blood perfusion, which not only improved the blood compatibility of activated charcoal, but also effectively prevented charcoal particles from falling off. Activated carbon can effectively adsorb small and medium-sized water-soluble substances with a molecular weight of 5000 Daltons or less, such as thiols, r-aminobutyric acid and free fatty acids, but it cannot effectively adsorb blood ammonia and has poor adsorption capacity for toxins bound to albumin. Adsorbent resins are macromolecular polymers with a reticulated structure, including neutral and anion-cation exchange resins. Clinically, adsorbent resins are more commonly used, and their adsorption capacity is slightly inferior to that of activated carbon, but they have a greater adsorption rate for various lipophilic and hydrophobic groups such as bile acids, bilirubin, free fatty acids and amides. The adsorption resin has a better effect on the removal of endotoxin and cytokines, and its selective endotoxin binding effect can lead to a significant improvement in the patient’s toxic symptoms. Currently hemoperfusion as one of the methods of artificial liver is mainly used for heavy hepatitis hepatic coma, heavy hepatitis with sepsis, bile stasis and pruritus. The disadvantage of blood perfusion technique is that it does not effectively adsorb small molecules of toxins and activated charcoal has poor adsorption capacity for toxins bound to albumin. Since non-specific adsorbents are used, some hepatocyte growth factors and hormones are also removed in addition to toxic substances being removed. If the adsorbent is poorly biocompatible, it may also activate the complement system and cause a systemic inflammatory response. Plasma replacement Plasma replacement is a commonly used technique for artificial liver. Classically, the patient’s blood is drawn out, the plasma and cellular components are separated, the plasma is discarded, and the cellular components, as well as the supplemented albumin, plasma, and balancing fluid, are returned to the body for the therapeutic purpose of removing the disease-causing mediators. Modern technology can not only separate whole plasma, but also a certain type or a certain plasma component so that it can selectively or specifically remove the disease-causing mediators, further improving the efficacy and reducing complications. In the early days, the commonly used method of plasma separation was the closed centrifugal plasma separator, but in the late 1970s, a membrane plasma separation device emerged, in which whole blood is filtered out directly through a membrane, making plasma replacement technically more simplified and practical. Currently, most treatments are performed with membrane separators, which are hollow fiber-type or plate-type filters made of polymers, with a hole that permits plasma filtration but blocks all cellular components. The disadvantages of plasma replacement are potential infections (pathogenic agents, HIV, etc. that are not detected by current tests), allergies, citrate toxicity, etc. After plasma exchange treatment, the concentration of the reduced pathogenic mediator in the blood can rise again for two reasons: first, because the cause of the disease has not been removed, the body will continue to produce the mediator and may also stimulate accelerated production due to its low concentration; second, the pathogenic mediator may be redistributed in body fluids. Plasma replacement is currently the more established liver replacement therapy, and despite the rapid development of various biologic and nonbiologic artificial liver technologies, plasma replacement remains the primary and basic artificial liver therapy for patients with liver failure today. For most diseases, this therapy does not affect the underlying pathological process and is still not etiologic, therefore, treatment for the etiology cannot be neglected while performing the treatment. Continuous hemodialysis technique With the continuous research on the pathophysiology and pathogenesis of acute renal failure and the gradual innovation of hemodialysis technique, researchers found that the traditional intermittent hemodialysis technique has its inevitable defects. In 1977, Kramer et al. pioneered the concept of continuous arteriovenous hemodiafiltration, which largely overcame the shortcomings of intermittent hemodialysis and marked the birth of a new hemodialysis technique, continuous renal replacement therapy. –The birth of continuous renal replacement therapy. In recent years, this technology has been vigorously developed at home and abroad, and its clinical application has been expanded from the initial improvement of the efficacy of critical acute renal failure to the emergency treatment of various common clinical critical cases, such as acute liver failure, hepatorenal syndrome, systemic inflammatory response syndrome, multi-organ dysfunction syndrome, etc. There are reports of successful application. This treatment is usually preferred in the clinical treatment of critically ill patients, especially those who are hemodynamically unstable and severely hypercatabolic. It can control water-electrolyte and acid-base balance, maintain endostasis, and ensure the need for large amounts of fluid input for adequate protein and caloric intake. However, as the application of this technology expands, questions have been raised about its “blood purification” ability: firstly, further research is needed on the effect of TNF clearance, because active TNF exists mostly in the form of trimers, while monomers are mostly bound to soluble receptors with molecular weights of 27-33 KD, which are larger than the membrane retention capacity, limiting the clearance of TNF. which limits the clearance of TNF. Secondly, due to the interactions between cytokines, the effects of charge, membrane hydrophilic and hydrophobic sites, and the properties of binding to proteins and cellular receptors, especially the highly variable convective and adsorptive transport processes of cytokines through the membrane, the clearance of cytokines by high permeability filters is affected, and it is difficult to achieve clinically satisfactory clearance efficacy. Molecular adsorption recirculation system Recently, the molecular adsorption recirculation system (MARS), which consists of albumin recirculation system, activated carbon, resin and dialysis, can remove lipid-soluble, water-soluble and large, medium and small molecular weight toxins bound to albumin, and also has a good effect on the regulation of water-electrolyte and acid-base imbalance. The advantages of MARS are that the intermediate proteins and plasma do not come into contact with activated carbon and anionic resin, no adsorption and destruction of clotting factors and proteins, no loss of hepatocyte growth factors and other nutrients, hemodynamic stability, continuous removal of small and medium molecule toxins and correction of electrolyte disturbances. MARS artificial liver is mainly used to improve cerebral function, hemodynamics and synthetic function of the liver in hepatic encephalopathy with severe hepatitis, and has a better therapeutic effect on hepatorenal syndrome. This is an artificial liver support system that combines organs, tissues and cells from homologous or heterologous animals with special materials and devices. Biological artificial livers include the previous isolated liver perfusion, human-mammalian cross-perfusion, and initial in vitro bioreactors (containing liver tissue homogenate, fresh liver sections, liver enzymes, or artificially cultured liver cells). In the late 1980s, biologic artificial liver devices were gradually abandoned because of their uncertain efficacy, side effects, and complexity of operation, etc. In the late 1980s, biologic artificial liver generally refers exclusively to in vitro bioreactor systems with artificially cultured hepatocytes as the basic building blocks. It not only has the specific detoxification function of liver, but also has higher efficacy, such as participating in energy metabolism, having biosynthetic transformation function, and secreting active substances for hepatocyte growth. Because toxic substances in the plasma of liver failure patients are damaging to hepatocytes in vitro, the current bioartificial liver generally removes some of the toxic substances from the patient’s plasma first by activated carbon adsorption or plasma replacement, and then exchanges the substances with the hepatocytes in the reactor. Such devices that combine abiotic and biotic artificial livers are known as combined bioartificial livers. Animal and preliminary clinical studies suggest that this type of artificial liver device has some efficacy in fulminant liver failure. Currently, a biologic artificial liver support device has been approved by the State Drug Administration for clinical use in China. The instrument consists of a biological culture device and a mixed plasma pool, forming a hybrid artificial liver support system with the functions of plasma separation, plasma adsorption and plasma replacement, which has the characteristics of high automation, simple operation, safety and reliability. The clinical results of its treatment of heavy hepatitis show that the apparent efficiency is 36.7%, the effective rate is 46.7%, and the total effective rate is 83.3%. Foreign biological artificial liver therapeutics, except for individual composed of human C3A cells (human liver fibroblast carcinoma, etc.), the rest mostly use pig liver cells as the biological part. These bioartificial livers are currently undergoing phase II/III clinical trials and have not yet been approved by the FDA. The disadvantages of bioartificial liver are, first, the possible allogeneic rejection caused by the use of in vitro cultured allogeneic/heterologous liver cells as well as tumor cells, and the potential risk of zoonotic diseases and carcinogenesis. Second, the limited ability of in vitro cultured cells to replace natural liver and the limitations of hepatocyte culture technology, biomaterials for mass production, preservation and transportation make the clinical dissemination of bioartificial liver somewhat limited.