Artificial liver

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Artificial liver, also known as artificial liver (Artificial liver), was developed in the middle of the last century and gradually applied i

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Artificial liver, also known as artificial liver (Artificial liver), was developed in the middle of the last century and gradually applied in clinical practice. The original idea of artificial liver is the use of artificial methods, can be used to replace part of the liver function of the device, the application of this device can be expected to change the pathophysiology of patients with liver failure. The original device including the liver, liver tissue, liver perfusion cross, then with the development and progress of all kinds of artificial kidney blood purification device used in artificial liver, in recent years is the emergence of a bioartificial liver based on liver cells (Bioartificial liver), and a variety of blood purification device used in combination to enhance the effect.

Due to the application of artificial liver, clinical treatment strategy of modern liver failure has undergone a great change, many patients due to the application of artificial liver the continuation of life, combined with artificial liver transplantation has become one of the best methods for the treatment of liver failure.

Concept of artificial liver

The concept of artificial liver is put forward by Sorrentino in 1950s, when some scholars studied in vitro and in vivo found in the liver and liver tissue slices can play the metabolism of ketone body, blood ammonia, pentobarbital and protein synthesis function of Sorrentino on the basis of this, combined with the artificial kidney (Artificial kidney) concept, puts forward the concept of "artificial liver".

As the name suggests, artificial liver that is the application of synthetic devices to play the various functions of the liver. The device includes a variety of blood dialysis separation, physical adsorption, chemical synthesis, biological metabolism and some auxiliary equipment support, instead of liver functions of modern artificial liver also covers the liver synthesis, decomposition, metabolism, blood coagulation function.

So far, the development of artificial liver has gone through 4 different stages:

1, the rise of artificial liver research

Sorrentino proposed the concept of artificial liver after 1959, semipermeable membrane device Nose studied liver homogenate, fresh liver tissue and liver tissue frozen dry particles in the gel type, it can maintain the blood glucose concentration, the removal of lactic acid and excessive ammonia in serum; Mikame and Mito also made a similar study and achieved the same the effect of. Over the same period, some scholars also try to apply the method to the treatment of hemodialysis in patients with liver failure, a typical Killy application of hemodialysis in treatment of patients with hepatic encephalopathy, found patients regained consciousness, blood ammonia reduced, but did not extend the survival time of Schechter; the application of ion exchange resin in hemoperfusion in the treatment of hepatic encephalopathy, satisfactory recovery of consciousness.

The people are still in the exploratory stage of artificial liver, then only the semipermeable membrane Sailu film, cuprophane, lack of macroporous film can be used in the whole system, although some ideas similar to the biological artificial liver today, but the method is restricted, the effect is poor.

2, the development of artificial liver - the rise of a variety of technologies

In 1958, the application of Kimoto cross cardiopulmonary bypass in treatment of hepatic encephalopathy, it uses four parallel cross blood through the device and four dog liver circulation is found after treatment of serum bilirubin and blood ammonia decreased, improve the consciousness; Otto proposed the complete in vitro liver perfusion method, Eiseman and Abonna were improved to the clinical effect, that can quickly replace the normal function of the liver. However, it is difficult to solve the problems of complicated equipment, severe bleeding, immune response and so on. In 1964, Yatzidis invented the technology of activated carbon hemoperfusion, and found that it can remove toxic substances with molecular weight of 1500-15000. Ching and Juggi were treated with synthetic resin Dowex50-x8 and Amberlite IR120 perfusion in clinical cases, 54% patients with symptoms improved, consciousness recovery.

With the maturation of renal support technology and the appearance of the polyacrylonitrile membrane, hemodialysis therapy has been paid more attention to. Opolon was used to treat fulminant hepatic failure, and it was found that the consciousness, EEG and neurotransmitters were effectively improved.

3, the climax of non bioartificial liver

During this period, many new blood purification devices were developed and applied to the treatment of liver failure. Ash designed the hemodialysis adsorption device to absorption of toxic substances in the dialysate through the dialysis membrane near the dialysate side suspended tiny adsorbent particles, the more effective Yoshiba hemodialysis; hemodiafiltration device design, combines the advantages of diffusion and convection of the two methods, the better in molecular weight toxicity the effect of material.

Plasma exchange technology has been widely used in this period, it is the first separation of plasma membrane separated from the plasma membrane to be abandoned. By adding a large number of fresh frozen plasma to replace the various functions of the liver. On the basis of the technology in the late 80s, the separated plasma was not given up, but then returned to the body after treatment. A set of data from Japan showed that the survival rate of fulminant hepatic failure was increased by 25%-30%.

4, the rise of biological artificial liver

In fact, the treatment of liver homogenate with biological artificial liver. An in-depth research on the separation technology of liver Seglen in 70s, the development of the two steps in situ perfusion method, the preparation of high yield, high activity of liver cells as possible, has made an important contribution to the development of bio artificial liver.

The core of biological artificial liver is bioreactor. The key technology is to obtain the biological components, namely, the liver cells and the bioreactor. It is almost impossible to use the same kind of liver cells, but because of the serious shortage of donor liver, it is almost impossible for normal human hepatocytes. It is commonly used in modern pig hepatocytes. The obtained hepatocytes must survive in the bioreactor to play a role in liver function. In order to better play the role of biological, three-dimensional cell culture methods have been paid attention to. Sussman was used to treat 11 cases of fulminant hepatic failure with bioartificial liver. After treatment, the mental status of the patients in the treatment group was improved, and the liver transplantation was performed in 4 cases. The recovery of the liver was achieved in all the 8 cases, and in the other group, there were 1 cases recovered and the other died.

According to the structure and the function of supporting the replacement of liver, artificial liver can be divided into three categories: mechanical artificial liver, intermediate artificial liver and bioartificial liver. It should be noted that the three types of artificial liver is not completely isolated, the clinical application can be mixed to form a combination of artificial liver or combination of bioartificial liver.

Mechanical artificial liver: non bioartificial liver. The core part of the reactor device does not contain biological components, but only using the dialysis membrane adsorber device system or by physical and chemical methods for liver function replacement. Liver detoxification function. This kind of artificial liver includes hemodialysis, blood adsorption, hemofiltration, etc.. In the decades of artificial liver concept, the artificial liver obtained great progress, even in twenty-first Century, the technology is still widely used in clinical practice, some technology is even, and the middle bioartificial liver and bioartificial liver devices used in combination, to further increase the efficacy. However, the data suggest that the artificial liver can significantly reduce the number of toxic substances in patients with liver failure, and improve the symptoms of hepatic encephalopathy in patients with liver failure, but can not reduce mortality.

Intermediate type artificial liver: the artificial liver mainly refers to the plasma exchange, it is a method between mechanical artificial liver and bioartificial liver reactor, plasma exchange is a mechanical device used in plasma of patients with isolated, and then directly replace the application of normal blood plasma donation, which not only achieve reduce in patients with various toxins, especially to remove some macromolecular toxins, but also add some important substances, such as protein, opsonin, coagulation factor and other active substances. It is the application of mechanical methods, but it can play a similar biological features of liver function, the academic community will be classified as a separate type of artificial liver.

Bioartificial liver: because the liver biological functions, application of mechanical artificial liver can reduce a variety of toxins in the body, but a variety of other biological functions needed to support the use of alternative to liver cells, make the best possible alternative play the role of the liver. In this application, the artificial liver device which is used to separate the cultured allogeneic or xenogeneic hepatocytes and hollow fiber tubes is called bioartificial liver. The theory of the artificial liver support accords with the physiological function, but because the source of liver cells, the variant virus infection and other factors, the modern biological artificial liver is still in clinical trials, a wide range of promotion is still youdaishiri.

The modern artificial liver device system has made great progress in the early stage of artificial liver development, but it is still composed of two basic parts: Blood extracorporeal circulation system and reactor system. The former includes blood outflow pipeline, blood flow, blood pump and pipeline detection, control, heating device in control with microcomputer, reached the semi automated operation state; the latter is the artificial liver heart, is the most active research in modern medical field of A. Different artificial liver system, the reactor system is part of a huge difference. The reactor system includes a reactor and reactor assisted circulation device, simple system only a single reactor and a single set of auxiliary devices, such as simple hemodialysis, blood adsorption, complex system with multiple reaction device, or even multiple sets of auxiliary devices, such as the combination of bioartificial liver. The function of the artificial liver system is different because of the difference of the reactor system. In the process of clinical application, it should be individualized according to the need.

Table 1: artificial liver classification

Type

Specific technology

Type I (non biological)

Hemodialysis, hemofiltration, hemoperfusion

Type II (intermediate type)

Plasma exchange, blood transfusion, cell transplantation

Type III (biotype)

Liver perfusion and in vitro biological reaction device

Combined bioartificial liver

Second artificial liver device membrane system

The membrane membrane system of artificial kidney development and artificial liver development, has made considerable progress in the middle of the last century, because of the application of high performance synthetic membrane makes artificial purification technology can be widely used in clinic, and the formation of its high efficiency, stability, small side effect characteristics, can be long-term, repeated use the artificial organ replacement therapy can maintain patient life long time.

Artificial liver membrane system can be divided into three categories, namely, natural cellulose membrane, modified cellulose membrane and polymer synthetic membrane (non cellulose).

Table 2: classification of dialysis membrane

classification

Name

Structure or composition

Natural cellulose membrane

Cellulose membrane

Copper imitation film

Dextran chains with free OH groups

The product obtained in the solution of copper oxide in the dissolution or purification of cellulose

Modified cellulose membrane

Cellulose acetate membrane

Two cellulose acetate membrane

TAC film

Hemophan

Excebrane

Part of the OH group is product of cellulose acetate substitution

Part of the OH group is the two product of cellulose acetate substitution

Part of the OH group is the three product of cellulose acetate substitution

Some OH groups are replaced by DEAE

Some of the OH groups covalently bound to some synthetic polymers, the surface of the oil re acylation or vitamin E

Synthetic polymer membrane

Polypropylene film

psf

Polyamide Film

PMMA film

Polycarbonate film

The natural cellulose membrane is composed of regenerated cellulose and its basic structure is a long chain with free OH group. The fact that natural cellulose membrane can be applied in the last century in 40s in the clinical application, the first is the fiber tubular structure Sailu membrane formation, but the structure of the device is not stable, the strength is weak, often need to repair in situ, very inconvenient to use. Until 1960s, there are still many using the membrane system of blood purification device is Sailu membrane or its analogues.

In 1960s, the researchers used in the manufacture of fiber membrane with copper solution in the process of producing a film called imitation copper fiber membrane structure, this structure can make the thickness of the thinner, higher mechanical strength, and device for small molecules with better permeability, a widely used. In fact, copper imitation membrane is not a single structure of the membrane system, but a class of membrane systems, but it all has a copper atom, the manufacturing process using a copper solution.

Until today, the natural cellulose membrane in the world is still widely used, one of the reasons lies in the production and sales of low price, but also because of the existence of a large number of OH groups, hydrophilic cellulose membrane structure is particularly good, in general more uniform aperture, plus today should be a process for production of regenerated cellulose cellulose membrane has been greatly improved. The membrane structure produced not only the strength is improved, and the pore size can also be improved in accordance with the requirements of. In many developing countries, the purification of natural cellulose membrane system is still a better choice.

Modified cellulose membrane modified cellulose membrane structure according to the characteristics of natural cellulose membrane, free OH group long chain structure of dextran on natural cellulose membrane on the substitution of alternative groups including acetate, acetate, acetate two three, DEAE. Application of hydrophilic acetate, two acetate, three acetate instead of the free OH group modified cellulose membrane physical properties was due to the presence of acetate increased, and removal rate increased on water soluble toxin; modified cellulose membrane using DEAE instead of free OH group (e.g. Hemophan) physical structure more uniform. In fact, the structure of modified cellulose film uniformity after morphological detection is superior to the natural cellulose membrane, and because of the substitution groups, modified cellulose membrane biocompatibility is improved, the activation of complement was significantly decreased. Research has shown that although the membrane structure all have certain complement activation, the level of plasma C3a degradation products using process but modified cellulose membrane was decreased in the natural cellulose membrane, including cuprophane, ended after the application of various membrane level degradation products of plasma C3a is quickly approaching the normal level.

A new generation of modified cellulose membrane structure is more complex, for the OH group to covalently combined with some synthetic polymer, surface and oleoyl or vitamin E in order to further improve the compatibility of the membrane structure of organisms, preliminary studies suggest that the combination of platelet and lead to the risk of thrombosis is greatly reduced, and anti oxygen the role of free radicals, blood purification process can reduce the blood oxygen free radical effect.

Study on synthetic polymer film on the cellulose membrane development scholars discussed synthetic polymer materials, the last century after 70s, a variety of excellent performance of polymer materials to be available, and will soon be applied in the field of artificial organs, many synthetic polymers are widely used in modern film still artificial liver structure.

In fact, the initially synthesized membrane structure is mainly used for blood filtration. AN69 is a typical polymer membrane in early stage of synthesis and use, it is double polymer acrylonitrile and Methylallyl sulfonate of. The use of Methallyl sulfonic acid is the main purpose for its characteristics of ionization hydrolysis to produce negative charge, negative charge characteristics look forward to imitate the glomerular basement membrane, but the actual use of the process, although the film structure produced very uniform, but the biocompatibility and poor study showed that may be related to the use of the structure.

Polysulfone and polyamide membrane is early polymer film synthesized, characterized by hydrophobic uneven structure. Although the structure of these two types of film can be made into a very thin and uniform, but its strength is not enough, making fiber tubular structure when needed to support the strong physical structure, which reduces the physical function through adding vinyl pyrrolidone; the production process can improve the strength is not enough. The hydrophobic membrane is characterized by the asymmetry of the molecular structure, and the production of the film is often a foam like structure, the pore structure is not as straight as the cellulose membrane, and the pore size uniformity is poor. Now commercially available polysulfone membrane structure has been improved after further processing, the uniformity of pore size has been improved.

There are many other synthetic materials film, including polymethyl methacrylate film, polycarbonate film, etc.

Due to the complex liver function, the membrane structure of artificial liver is strict, and must be able to pass a certain molecular weight material. By comparing the properties of hydrophilicity, biocompatibility and permeability, the polymer membrane has the advantages of less protein adsorption, good compatibility and ideal permeability. In fact, the membrane materials used in modern artificial liver devices are synthetic polymer membranes.

Clinical application and significance of third artificial liver

Artificial liver development has already appeared in a variety of treatment mode, from simple hemodialysis, blood began perfusion, blood filtration, plasma exchange, to the continuous hemodialysis and continuous hemofiltration technology, non bioartificial liver using a combination of technology, bio artificial liver technology and hybrid bioartificial liver technology. Artificial liver can play a short time the liver better support alternative function in patients with acute liver failure, liver dysfunction, chronic liver failure in patients awaiting liver transplantation can obtain good application effect.

Indications for clinical use of artificial liver include:

1, acute liver failure (acute liver failure): acute liver failure is a clinical basis of short duration without liver disease and jaundice and encephalopathy and some symptoms of the syndrome, which generally consists of four main elements: no history of liver disease, symptoms caused by severe liver damage, is the first symptom of hepatic encephalopathy symptoms and is reversible within 8 weeks. The etiology of acute liver failure is that the acute liver injury leads to the reduction of the effective liver cells, which can not meet the metabolic needs of the body. In the course of treatment, in addition to the first to eliminate the cause of liver damage, it is very important to take effective means to save the dying liver cells. Artificial liver support system can play a very good effect.

The results show that: the application of artificial liver in patients with acute liver failure can not only play a temporary liver function substitution effect, but also can completely break toxic substances cause vicious spiral further necrosis of liver cells, to a certain extent, can also play a role to promote liver regeneration. Statistics show that, due to the application of artificial liver and a variety of modern technology, the mortality rate of acute liver failure has dropped from more than 50 years ago to more than 90%, down to the current 10-30%, the authors reported that even up to 0%.

2, chronic liver failure (Chronic liver failure): acute liver failure and liver function, patients with chronic hepatic failure loss is a process of slow, long-term accumulation, no explosive liver tissue necrosis. Chronic active hepatitis and decompensated cirrhosis can lead to chronic liver failure.

Because the pathophysiology of chronic liver failure lies in the long-term accumulation of liver cell damage, the treatment can not completely reverse the process. The most effective treatment for chronic liver failure is liver transplantation. Artificial liver support for patients with chronic liver failure, so that the general condition of patients improved, while prolonging the lives of patients waiting for liver donors.

3, after liver transplantation of primary liver function: primary liver function is one of the most serious postoperative complications of liver transplantation, yet its etiology is still unknown, may be related to ischemia reperfusion injury, vascular thrombosis, immune rejection and other related factors. The occurrence of primary liver function is not serious, the mortality rate is very high, the only way to save is to transplant. Before the patient is waiting for the donor to be transplanted, the artificial liver can be used to support the patients, and the short time liver replacement can be achieved.

4, surgical limit after hepatectomy liver dysfunction: support in liver surgery during perioperative period, a considerable part because of the limit of liver resection, liver function in patients with short-term can not fully recover, some patients even toxic substances in the body and lead to vicious spiral aggregation of liver cell injury further. In order to prevent the occurrence of this kind of situation, the clinical application of artificial liver can be used to support this kind of patients in a short time.

5 patients with decompensated cirrhosis perioperative support: liver cirrhosis patients, especially in patients with decompensation of risky surgery, generally, decompensated patients not suitable for surgery, but if the surgery really must be carried out in the basis of weighing the pros and cons of the application of artificial liver and liver function in the short term with support, the improvement of liver function, in order to successfully through surgical trauma perioperative blow.

The clinical application of artificial liver, the liver disease diagnosis and treatment today has entered a new stage, it provides a method for clinicians in short time liver function replacement, to reach the correct body liver function discompensation - toxic substance accumulation and further liver damage such a vicious spiral to a certain extent, the protection of endangered the death of liver cells, promote regeneration of the residual liver cells, but also can reduce the body endotoxin and inflammatory cytokines, improve organ function, improve the patients of acute liver failure survival rate, combined with the use of liver transplantation has become the most effective method for the treatment of liver failure.

Table 3: artificial liver detoxification

Artificial liver device

Detoxification

Hemodialysis

Ammonia, mercaptan, GABA

Hemofiltration

Part of the aromatic amino acids, endotoxin, short chain fatty acids, cholic acid, bilirubin, thiols, phenols, nitric oxide, some inflammatory factors

Hemoperfusion

Ammonia, inflammatory factors, cholic acid, bilirubin, thiols, phenols

Plasma exchange

Ammonia, short chain fatty acids, cholic acid, bilirubin, thiols, phenols, nitric oxide, some aromatic amino acids, endotoxin, part of inflammatory factors and drugs

But also need to see, now artificial liver and normal liver also has a considerable distance, has not reached a long time support of liver function, artificial liver liver function has complex shape, but the structure is far from perfect.

The fourth bioartificial liver is the development direction of artificial liver

There are many kinds of modern artificial liver technology, which are commonly used in hemodialysis, hemofiltration, hemoperfusion, plasma exchange and bioartificial liver. But from the development process of the artificial liver, artificial liver is the development direction of artificial liver, this is not only because the bioartificial liver structure is complicated, so that it is completely mimic the liver metabolism, detoxification, synthesis and other functions, so that a variety of alternative functions of the liver can be clinically intact, but how to build a more reasonable and more powerful and less side effects of bioartificial liver, so as to further improve the level of artificial liver therapy, artificial liver at this stage is still an important task in academic circles.

So far, there are still a lot of work to be further explored.

Biomaterials biomaterials are the basis of bioartificial liver, including hepatocytes and bioreactor. At present, the most commonly used biomaterial tube bioreactor for porcine hepatocytes and hollow fiber. Several kinds of bioartificial liver devices have been constructed, such as the United States ELAD, Germany's EMLS and the domestic application of BIOLIV, although they have achieved good curative effect, but compared with the liver, its structure is relatively rough and complicated operation.

The study of biomaterials is mainly focused on 4 aspects. The first is the most common application of porcine hepatocytes, liver cell mass method to obtain mature reaction evaluation research mainly focuses on the establishment of liver cell library and hepatocytes after application of bioartificial liver, after all after large-scale applications require immediate access to liver cells, and the pig liver cell metabolism and has the difference; application of transgenic pigs may it is discussed; the second is immortalized cell lines or liver cell line has been established, the report isolated from the liver fibroblasts in tumor transformed cell lines, such as HepG2, C3A, HuH6, Jhh2, also by transfection obtained after the treatment of human immortalized cell lines such as C8-B, HepZ, OUMS-29, NKNT-3 and so on, have mature liver cells and their function, but also has permanent reproductive characteristics, has been applied in clinical reports of [5, 9], but whether safety has become the focus of; Third directions for cell culture method, biological artificial liver cell requires high activity, form and function are required to maintain good common culture, it is difficult to meet the requirements of liver cell aggregation culture, microcarrier culture, co culture, organization culture can basically meet the needs; fourth directions for the study of biological reactor, in addition to the ordinary hollow fiber bioreactor, composite hollow fiber bioreactor, woven hollow fiber bioreactor, radial flow type or radial flow polyester fabric bioreactor showed good application prospect.

Combined bioartificial liver combined bioartificial liver is an experimental and clinical application of bioartificial liver. It usually consists of three parts, namely, the blood circulation part, the non biological artificial liver part and the bioreactor. The blood circulation includes the pipeline system, the blood pump, and so on. It plays the role of supporting the system, and the part of the non biological artificial liver is initially detoxified. The research mainly focused on the establishment of effective combination system and how to use it to achieve the best support effect. The study shows that the standard of selection of non biological parts, combined with biological reactor, blood circulation, each support for 6 hours, long-term application, can get a satisfactory effect.

Application of bioartificial liver scope theory, can be suitable for all kinds of biological artificial liver support in patients with liver function, but the biological artificial liver support consumes manpower and medical resources, complications may also exist in the use process, it is necessary to determine the scope of application. My experience: on liver regeneration, liver function can be restored with application of bioartificial liver on better curative effect; water and electrolyte disorders serious bleeding tendency, hemodynamic instability, serious taboo.

Physiological and ethical issues in the application of bioartificial liver, from the physiological point of view, the application of bioartificial liver has a certain risk. Because of the lack of the homologous organs, bioartificial liver constructed by human liver is extremely rare. In the clinical application of animal cells in the process of virus disease of animal origin is possible through the ways of infecting humans still makes academia confused; application human immortalized cells or tumor cell lines also will lead to changes in patients treated by confusion. From the perspective of ethics, the problem is more complex, animal rights activists have been opposed to the use of animal organs, that animal should have human like living on earth right; religious circles also have "disease is due to the method of natural selection, survival of the fittest can achieve the purpose of" point of view, application of bioartificial liver whether to save the dying tradition in violation of natural law; transgenic pigs application of bioartificial liver in the study is more controversial, how to determine the attribute and the kinds of animal rights? Pig or pig is bound to be controversial. But in any case, the study of bioartificial liver will eventually break through, the above problems will be solved.

The sixteenth chapter is the combined application of non bioartificial liver

The concept of non bioartificial liver is relative to bioartificial liver, including mechanical artificial liver technology and intermediate artificial liver technology, namely, hemodialysis, hemofiltration, hemoperfusion and plasma exchange. The traditional alternative treatment for liver function failure often used alone single non biological artificial liver technology, but because of limited efficacy of single technology, effective liver support by time and effect, the characteristics of the modern field of artificial liver is to use various single technology, multi technology combined, in order to further increase the treatment and support effect. Objective to better accomplish the liver function support.

Section 1 non bioartificial liver technology

Non bioartificial liver is the basis of modern artificial liver technology, even though the non biological artificial liver is still applied in many cases. Clinicians must be aware of the principles, characteristics and limitations of various artificial liver techniques for better clinical application.

1, hemodialysis

In the early stage of hemodialysis, artificial kidney technology was applied to the treatment of liver failure due to the removal of toxic substances. The basic principle of hemodialysis Gibbs-Donnan film balance principle, namely the concentration gradient material on both sides of the semipermeable membrane, and part of the small molecule solutes will be in accordance with the concentration gradient and osmotic pressure gradient across the membrane, membrane on both sides of the small molecule to reach dynamic equilibrium. In the process of use, synthetic polymer dialysis membrane on both sides of the flow of blood and dialysate dialysis membrane on both sides of the water, electrolyte and small molecule toxins in the concentration gradient, osmotic pressure gradient and pressure gradient under the action of transmembrane movement, and blood cells, proteins and macromolecular substances is still not able to through a semipermeable membrane, through some this small molecule toxins in the blood through a semipermeable membrane diffusion into the dialysis fluid, which can be removed.

According to the principle of hemodialysis, we can find the factors that influence the effect of hemodialysis: 1. Dialysis membrane pore size determines the removal of material types, dialysis membrane thickness determines the rate of dialysis, the production process, the chemical properties of dialysis membrane, especially the effect of hydrophilic or hydrophobic on dialysis efficiency can not be ignored. 2, the effective surface area of dialysis membrane. The greater the surface area of dialysis membrane, the more toxic substances will be obtained under the same conditions. 3, the size of the target dialysis material. The target material dialysis at higher molecular weights through the membrane of the speed will be slower, the effect will be influenced by dialysis. 4, both sides of the concentration gradient dialysis target semipermeable membrane material. The dialysate effective transport substance in semipermeable membrane on both sides of the concentration gradient is dependent on both sides of the membrane, if the concentration gradient is high, obviously effective transfer efficiency is higher, so in the early stages of hemodialysis, which contains no toxic substances in the dialysate target, the dialysis effect is best, but after long time, dialysis efficiency decline, at this time can be replenished by new dialysate to increase therapeutic effect.

According to the above factors, can take measures to improve the curative effect is the first choice of high-performance dialyzer, not only meets the needs of the physical and chemical properties of semipermeable membrane and membrane, relatively thin, the effective surface area large enough; secondly increase dialysate dosage, increase the flow rate. Dialysis fluid and blood infiltration, diffusion function of good varieties, increase the dosage, improve the flow rate so that dialysis effect is more in line with the needs of. Finally, we can increase the blood flow rate of the unit to increase the effect of dialysis time.

The development of hemodialysis technology relies on the development of membrane materials to some extent. The first generation of dialysis equipment using polypropylene film, water soluble small molecular substances such as ammonia, urea nitrogen, creatinine and so on can be cleared, but the elimination of fat soluble substances. Poly methyl methyl diene membrane using three cellulose acetate membrane, the second generation device for removing material efficiency is greatly improved, three cellulose acetate membrane with Yoshiba device in the treatment of 27 cases of patients, 15 cases survived, the remaining symptoms, no significant side effects. In recent years, a lipophilic polysulfone membrane can be applied in the dialyzer, can remove toxic substances lipophilic, compensate for the lack of traditional film.

As a temporary removal of acute liver failure in patients with toxic substances, a method of hemodialysis has the characteristics of simple operation, easy to implement, although patients can improve clinical symptoms, but it is difficult to improve the survival rate. In modern research, it is often used in combination with other types of artificial liver.

2. Hemofiltration

Unlike hemodialysis, hemofiltration using the concentration gradient principle is not using the dialysis membrane on both sides of the pressure gradient, but the use of the dialysis membrane on both sides of the transmembrane movement using the effect of pressure gradient on both sides of the film under the water, and a convection to remove excess moisture in blood, macromolecules material.

It is clear that the blood filtration technology needs to add a certain amount of pressure on the blood side, under the action of transmembrane pressure gradient, the toxin removal efficiency can be effectively improved. In fact, the glomerular filtration function in the human body, due to the high efficiency of filtration, the human body can maintain a certain balance. In the blood filtration technology, in order to be able to mimic the effect of glomerular filtrate volume, always need 20 liters, equivalent to 4-5 times the normal human blood volume, apparently only supplement sufficient replacement fluid can maintain homeostasis. In order to maintain the effectiveness of blood filtration technology, the clinical selection of a short hollow fiber filter to improve the flow of water.

In general, the clearance efficiency of hemofiltration is independent of the molecular weight of the solute, and the clearance rate of different molecular weight substances is basically the same. Due to the removal of different molecular weight substances in hemodialysis was a huge difference, resulting in large hemofiltration on molecular ratio is two times of hemodialysis, and the small molecular weight material removal rate accounted for less than half of hemodialysis. Therefore, the clinical application of the two technologies are combined with hemodiafiltration, in order to achieve the purpose of increasing the effect.

Due to the characteristics of blood filtration technology of isotonic remove toxin causes blood filtration process of hemodynamic effects is very small, plus hemofiltration can be a variety of material was adjusted according to the detection results of blood replacement fluid, to maintain water and electrolyte balance, and a stable internal environment, so the clinical application of this technique in the treatment of liver failure frequency far higher than the pure hemodialysis.

3, hemoperfusion

Hemoperfusion is the application of adsorption of toxic substances in the blood through the extracorporeal circulation device, in order to achieve the purpose of treatment. The commonly used adsorbents are activated carbon and ion exchange resin.

Activated carbon has a large adsorption function, cheap price, a wide range of sources, but the direct application will cause pulmonary embolism, activation of platelets and white blood cells caused by severe bleeding tendency, and now often activated carbon microencapsulation. Ion exchange resin from synthetic material, such as ammonia adsorption of activated carbon is difficult to remove, the combination of fat soluble substances and protein substances have good scavenging effect, the disadvantage is bad histocompatibility, may cause serious bleeding tendency and leukopenia.

The adsorption of activated carbon on the material is non-specific, and has strong adsorption capacity for many organic compounds. In fact, the size of micropore structure of activated carbon adsorption capacity mainly depends on the pore structure of activated carbon, the adsorption capacity of more and more strong, influence factors of activated carbon adsorption and solute molecular size and molecular structure of activated carbon, activated carbon temperature, pH value and the active carbon surface area. The smaller the molecular weight of the solute, the higher the molecular structure, the higher the working temperature, the lower the solute charge and the activated carbon pH, the larger the specific surface area, the stronger the adsorption capacity. Ion exchange resin.

4. Plasma exchange

Plasma exchange is the patient's plasma is separated and discarded, then use normal plasma as a replacement fluid mixed with blood cells to enter the body, through the plasma exchange amount so as to achieve the purpose of removing toxins.

Plasma exchange began to be applied to the clinic is not a liver disease, as early as the beginning of the last century, some scholars have applied it to the immune system disease. Because the amount of plasma replacement, not only can remove some small molecular weight toxins, combination of macromolecules and can be removed and some other methods can not be cleared with protein substances, but also through the input of fresh plasma, supplement the body for disease reasons and not synthesis, absorbing some substances, such as coagulation factor.

The clinical application of plasma exchange methods include centrifugal plasma exchange and membrane filtration plasmapheresis. The principle is the use of different quality of blood components at the same speed centrifugation, with different sedimentation rate, the centrifugal effect of blood visible components and plasma were separated, not only can direct the plasma exchange, can also according to the need for tangible component replacement, but the clinical application is prone to hypotension, low serum calcium, arrhythmia and platelet loss; the latter overcome visible component loss shortcomings, but its ability to separate the plasma by semipermeable membrane sieving coefficient limit, large pipeline need to maintain high blood flow can ensure the effective separation of plasma, and fresh plasma replacement.

Because of the shortage of fresh plasma, the plasma volume and the frequency of plasma exchange were restricted. General plasma exchange volume for each 3000ml is appropriate, blindly increasing the plasma exchange volume sometimes can not effectively improve the curative effect, the reason lies in the distribution of toxins in the body, into the plasma from the extracellular fluid in non plasma also need some time. In order to save the amount of plasma, some scholars will separate the plasma for two times, the purified plasma and then return to the patient's body. These two methods of plasma separation include plasma filtration, adsorption, etc..

Combined application of second artificial liver

Hemodialysis, hemofiltration, hemoperfusion and plasma exchange and other non biological artificial liver in the treatment process have advantages and disadvantages, in patients with liver failure using a single technology and can not be completely replaced in order to improve the liver function, liver support function, can be combined with two kinds, and even a variety of technology, using the principle of technology complementary, in order to enhance the removal effect of toxic substances. Modern more than a variety of non bioartificial liver technology combined with the formation of the device, the clinical use of more convenient, fast.

1, hemodiafiltration

Hemodialysis and hemofiltration technology from the principle of the most close to the concentration gradient using semipermeable membrane on both sides of the dialysis is balanced by natural solute dispersion, high concentrations of toxic substances to remove the blood side of the semipermeable membrane, which is the use of pressure gradient hemofiltration on both sides of the use of semipermeable membrane, the water from the side of the blood high pressure through a semipermeable membrane, in order to achieve the effect of elimination of toxic substances. The clearance effect of hemodialysis on small molecule toxin is high, and the efficiency of blood filtration is high.

The hemodialysis and hemofiltration combined application of dialysate and blood flow in the opposite direction from the same dialysis filtration device, through a semipermeable membrane can achieve the hemodialysis effect; at the same time the blood dialysis filtration device with side pressure, the water flows into the dialysate side through a semipermeable membrane, in order to achieve the effect of hemofiltration; outflow dialysis filtration device the blood flows into the body fluid supplement through replacement. Through such a process, can effectively remove the blood of small molecules, molecules and some macromolecular substances.

Clinical use more continuous hemodiafiltration in the treatment of liver failure, the utility model has the advantages of continuous treatment can better maintain the stability of hemodynamics and acid-base balance, easy control, high efficiency of removing toxic substances, can be very good to remove a variety of substances, can also effectively remove some inflammatory cytokines, etc.. What's more, the technology is simple and can be used in many units. But the disadvantage is that the permeability of the membrane is higher, the ultrafiltration rate is large, and the amount of displacement fluid should be enough.

2, hemodialysis adsorption technology

Because of the possibility of more serious complications, such as adsorption, severe hemorrhage, activation of blood cells or platelets, and so on, it can be used in the treatment of bilirubin. In the process of combining with other technologies, the general use of the principle of adsorption to remove toxins from the plasma or dialysate to enhance the ability of the entire device to remove toxic substances.

Hemodialysis adsorption technology representative in the Biologic-DT device and MARS device in full, but due to the limitation of the dialysis technique to remove small molecules, and the adsorption technology is applied to the dialysate side to increase dialysate removal efficiency, which limits the whole device removal ability of macromolecular toxins. In order to solve the above shortcomings, we can further apply the filtering technology, Biologic-DTPF device is a combination of such devices, the study shows that the latter is more efficient to remove toxic substances.

3. Hemofiltration combined with plasma exchange

The advantages of hemofiltration is can take the initiative to remove toxic substances in the blood of many, plasmapheresis is directly to patients with plasma separation, replacement of fresh plasma, the utility model not only can remove a variety of toxic substances, but also some factors such as the lack of supplementary body.

Combined with the above two technologies, in particular, the application of continuous blood filtration technology and plasma exchange technology can better play the advantages of both. Plasma exchange can be carried out in the first place, and then blood filtration, or plasma exchange in the process of hemofiltration. The disadvantage is that the pipe connection is complex.

There are also blood filtration technology used in plasma exchange after plasma exchange, that is, the first separation of plasma, and then plasma dialysis, filtration and other treatment, and then further back into the body.

4. Plasma exchange combined with plasma exchange

Plasma exchange combined with plasma exchange is actually a two time separation of plasma exchange technology. When the first application on the blood plasma separation, then the plasma branch will not abandon, but the application of activated carbon or ion exchange resin adsorption treatment, removal of various toxic substances in plasma, and then reinfused back.

The advantage of this technique is that it is possible to selectively remove toxic substances, and the destruction rate of blood cells and coagulation factors is low.

5, hemodialysis, adsorption combined plasma exchange technology

The use of a variety of non biological artificial liver technology, in order to use the advantages of various technologies to achieve better removal of toxic substances. Hemodialysis, adsorption combined with plasma exchange can achieve this purpose. Its essence is similar to the two apheresis technology, namely the application of plasma exchange principle isolated plasma, then the separated plasma for a variety of techniques, including dialysis and adsorption, finally will to enter the body, in the process also enter some fresh plasma.

The advantages include saving the amount of plasma, and eliminating the high efficiency, can also add some active substances in lack of plasma processing to avoid the destruction of blood cells, platelets, the disadvantage is more complicated technology, no complete set of equipment.

In fact, in combination with plasma exchange technology has become a distinctive feature of modern non bioartificial liver combined application, its main purpose is to use of active ingredients, safe separation of plasma processing characteristics.

The nineteenth chapter of liver failure in the treatment of artificial liver

Liver failure includes acute liver failure and chronic liver failure two kinds. Acute liver failure is defined as the onset of hepatic encephalopathy and other liver failure in acute 8-24. Its causes include acute food poisoning, acute drug damage, acute viral infection (including hepatitis virus and non hepatitis virus), etc.. Chronic liver failure refers to the development of various liver disease cause severe hepatic decompensation and liver damage due to long days and months multiplying, eventually lead to liver failure. There are a class of patients in the clinical manifestations of liver disease, but in the long term in a compensatory state, the sudden appearance of liver failure, the majority of chronic liver disease is advocated on the basis of acute liver failure.

Methods the treatment of liver failure in addition to traditional place causes, symptomatic support, protect damaged liver cells, not died to save the injured cells, promote the regeneration of liver cells, the more modern can be applied in artificial liver for short-term support, some can be further combined with liver transplantation for treatment. Because of the application of artificial liver and liver transplantation, the mortality rate of modern liver failure, especially acute liver failure has been greatly reduced.

The first section of artificial liver in treatment of liver failure indications and contraindications

In patients with liver failure can be a short time of application of artificial liver support function, because the artificial liver technology and a new type of artificial liver device of the invention, the indications have been greatly expanded compared with the initial treatment of artificial liver, although clinical application has some contraindications, make a careful assessment of the clinical, but overall, various liver failure may consider the use of artificial liver support.

Artificial liver disease

1, the outbreak of acute liver failure

There are many reasons leading to fulminant hepatic failure or acute liver failure, including many kinds of hepatitis virus, liver injury and so on. Our country is the most common cause of acute liver failure caused by a variety of hepatitis virus, especially the number of cases caused by hepatitis B virus. The mechanisms leading to liver failure including the virus itself damage the body of hepatitis virus infection, but more important is the immune response caused by virus antigen, coupled with a variety of inflammatory factors of secondary injury in the body, gathered a large number of toxic substances, the use of artificial liver can remove these inflammatory factors and toxic substances. In order to minimize secondary injury, achieve the therapeutic effect.

Drug induced liver injury, acute fulminant hepatic failure is also common, these drugs include acetaminophen, muscarinic, halothane, three halothane etc.. Drug induced liver damage mechanism mainly includes the direct toxic effects of drugs and drug after metabolism to produce toxic products, sometimes because of allergic reactions, drug induced fatty degeneration can lead to liver failure. In general, drug induced acute liver failure can be divided into predictable and specific fitness class, including all the former leads to drug hepatotoxicity, there is an obvious dose-response relationship of drug to liver damage, taking some drugs such as accidental or Dutch act; idiosyncrasy in contrast, after taking the drug whether the occurrence of liver the damage can be unpredictable, no correlation between the degree of damage and the dosage of the drug, as long as it is drugs as a hapten to elicit hypersensitivity. The application of artificial liver support drugs cause liver failure on one hand can remove part of residual drugs in blood, and also reduce the metabolic wastes and inflammatory factors produced in vivo normal metabolism, reduce secondary liver injury response.

Other causes of acute liver failure include vascular causes, acute fatty liver, acute liver ischemia, etc. The purpose of artificial liver support is similar to that of hepatitis virus

2, various causes of chronic liver disease based on acute exacerbation of liver failure

Chronic liver disease is a long-term liver damage based on liver function gradually lost gradually a series of symptoms, mainly manifested as abnormal liver function, chronic liver damage, liver function normally overall in a compensatory state. The causes of chronic liver disease include viral infection, alcohol damage, autoimmune hepatitis, primary / secondary biliary cirrhosis, some metabolic diseases and some unknown causes. Chronic liver disease in the long-term development process, sometimes because of certain predisposing factors, clinical symptoms of patients with sudden deterioration, known as chronic liver disease of liver failure in acute attack were chronic liver damage on the basis of similar symptoms of acute liver failure.

Similar to the pathogenesis of acute liver failure, acute exacerbation of chronic liver disease can produce a large number of toxic products, including ammonia, thiols, false neurotransmitters, endotoxin, inflammatory factors and so on. Artificial liver as an effective tool to remove these substances can alleviate the symptoms to some extent.

3, liver failure in liver transplantation perioperative support

As an effective treatment for end-stage liver disease, liver transplantation has become the choice of many patients with liver failure. However, patients with liver failure, whether chronic or acute, in the process of waiting for liver transplantation may change the condition, and even life-threatening. As an effective short-term support for liver function, artificial liver can be supported by these patients, so that the process of waiting for the donor liver.

Modern studies have shown that, because of the combination of artificial liver and liver transplantation, the survival rate can reach 100%. On the one hand can be artificial liver liver function in patients with short-term support effectively, so the patient can wait for donor liver, also can effectively improve the patient's general condition, the safety of liver transplantation improved. In China, due to a variety of reasons, patients with liver transplantation, in addition to a number of patients with liver cancer, liver failure in patients with general deterioration of the general situation. Under the condition of condition, it is necessary to support the liver function and improve the general condition in order to improve the success rate of transplantation.

4, the transplanted liver was not functional after liver transplantation

Graft dysfunction is a serious complication after liver transplantation, the incidence rate of about 5-10%, generally occurs in the transplant after a few hours or days, cause of disease and liver ischemia reperfusion injury, mechanical injury and immune rejection reaction, vascular spasm, surgery, often need to again after the occurrence of emergency liver transplantation to save, otherwise serious consequences.

There is no function of liver transplantation in patients with systemic conditions will worsen sharply, bilirubin, ammonia and other toxic substances in the body together, temporarily lack basic liver, liver function replacement requires the application of artificial liver technology, until once again get the donor liver.

5, liver failure after liver surgery after liver resection

After liver resection refers to liver surgery during resection of the liver volume exceeds the body to withstand the maximum amount, usually refers to more than 70%. But the actual situation for patients with different liver function, the maximal completely different concepts. In patients with liver damage, less than 50% of patients with liver resection sometimes have liver dysfunction and even liver failure.

Liver dysfunction during perioperative period is obviously unfavorable for patients. The application of artificial liver for liver function and short-term support for such patients, help patients body detoxification and metabolism function, prevent the body accumulation of toxic substances cause liver injury caused vicious spiral further, promote the regeneration of the remnant liver.

6, other liver injury leading to liver failure

Including radiotherapy, liver injury during chemotherapy, interventional therapy after liver injury, acute fatty liver, the damage can cause liver failure in a certain situation, support the acute application of artificial liver can remove toxic substances, promote the recovery of patients with liver function.

However, the use of artificial liver process there are also some taboos, including application of artificial liver common contraindications:

1, severe hemodynamic disorders. Hemodynamic stability is the basis for the treatment of artificial liver, in the severe hemodynamic instability of any artificial liver treatment may be counterproductive.

2, severe coagulopathy: artificial liver treatment requires a large vein or artery catheterization operation, the treatment process is needed in vitro anticoagulant operation, mild coagulopathy generally does not affect the operation treatment of patients, but for serious obstacle avoidance of coagulation function, artificial liver treatment need to be cautious.

3, systemic severe infection: Patients with liver failure sometimes accompanied by a specific site of infection, infection does not affect the limitations of artificial liver treatment, but if there is systemic infection, it is artificial liver treatment taboo. Attention is needed in the presence of infection under the condition of artificial liver treatment, especially continuous treatment, whether or not to diffusion as the routine evaluation of patients with infection, the patient body temperature is not high, sometimes also normal white blood cell count.

4, the artificial liver membrane device: allergy atopy patients sometimes use of dialysis membrane allergies, if had allergies, apparently can not again artificial liver treatment, for the first time to use artificial liver in the treatment of patients, started to treat tens of minutes observation is very important, once the occurrence of allergic manifestations, need to stop immediate treatment and corresponding treatment.

5, severe cardiopulmonary insufficiency.

6, a large number of ascites, respiratory and circulatory function.

7, severe mental disorders.

In fact, modern artificial liver treatment technology advances rapidly, overall the artificial liver indications can be relaxed to liver failure early and contraindications in severe hemodynamic disorders and systemic infection is absolutely contraindicated, others are relatively taboo, also can consider to use caution under certain circumstances

The second section is reasonable choice of artificial liver technology

Artificial liver technology now has been applied in more than 40 hospitals nationwide, the total data support for patients with incomplete statistics has more than 3000 people, saving many lives, a study of bioartificial liver in clinical hospital, preliminary satisfactory treatment effect. The selection of suitable patients and reasonable artificial liver support technology have become the pursuit of most scholars.

1 indications selection

Artificial liver was originally designed for acute liver failure, using it to temporarily support the liver detoxification function, waiting for the recovery of liver function. The modern artificial liver technology has had the huge change, the long-term support of various functions including liver detoxification, synthesis, secretion and coagulation has become possible, the scope of application of artificial liver from acute liver failure has been extended to a variety of simple hepatic insufficiency. Artificial liver is mainly suitable for liver failure, especially acute and chronic severe liver failure patients, which accounted for over 95% of the total; the second is also suitable for liver transplantation before support; postoperative primary liver function, maximal liver dysfunction.

The specific use of artificial liver is not uniform, there is no uniform international standards. Some scholars will be used strictly for hepatic coma, scholars have also set in the presence of liver dysfunction, this is largely caused by the literature support effect is different, which people have reported no improvement in survival rate, survival rate of 100% others. Obviously, the indications are too strict, in patients with multiple organ failure, the support effect is certainly not good, high mortality rate is reasonable; whereas too loose is a serious waste of resources, and is easy to cause the number of complications.

China is a large developing country with a large number of liver failure, which is associated with the history of hepatitis, which is quite different from foreign countries. We believe that the artificial liver technology has been based on a large scale, to enhance the suitability of China's national conditions of artificial liver disease is imminent. The June 2002 Beijing meeting discussed indications that artificial liver is suitable for severe viral hepatitis, including severe acute and subacute severe and severe chronic liver failure; drug and poison caused by liver transplantation; perioperative treatment and various reasons caused by hyperbilirubinemia. We think that the hepatitis patients with liver failure, treatment indications may be appropriate to relax, early application of artificial liver, especially in the advanced stage of early stage of severe hepatitis, hepatitis and implementation of artificial liver support, can be easily used to correct the disease process, to good effect.

2 rational use of a variety of artificial liver technology

There are many kinds of modern artificial liver technology, which are commonly used in the following categories: hemodialysis, hemofiltration, hemoperfusion, plasma exchange and combined bioartificial liver. How to reasonably apply these techniques to further improve the overall level of artificial liver therapy has become an important task in the field of artificial liver.

The liver function is complex and diverse, the liver failure is different, and the different characteristics of the artificial liver technology are different, so it is impossible to solve all the problems by a single method. In this paper, the author emphasizes the individualized treatment for different patients, and applies the effective technology to solve the main contradiction. For example, the pure hyperbilirubinemia by using blood perfusion with bilirubin adsorption; on hemodynamics in patients with liver failure associated with unstable hemodialysis or filtration; in vivo containing large amounts of protein binding toxin or huge molecular weight toxins, application of plasma exchange to remove. In addition, different artificial liver techniques can be used in combination with the need to increase the therapeutic effect, such as hemodialysis and hemoperfusion.

Preliminary study on combined artificial liver therapy is effective. In theory, it can be applied to all patients, but the selection of non biological parts should adhere to the individual standard, reasonable application.

3 to strengthen the basic and clinical research of bioartificial liver

Non bioartificial liver can achieve detoxification, improve the general condition of the patient, but the liver synthesis, secretion and other functional replacement. Bioartificial liver, which is constructed by the cultivation of hepatocytes and biomaterials, especially the combination bioartificial liver, can completely replace the liver function.

However, there is still much work to be done in the study of bioartificial liver.

3.1 biomaterials biomaterials are the basis of bioartificial liver, including hepatocytes and bioreactor. At present, the most commonly used biomaterial tube bioreactor for porcine hepatocytes and hollow fiber. Several kinds of bioartificial liver devices have been constructed, such as the United States ELAD, Germany's EMLS and the domestic application of BIOLIV, although they have achieved good curative effect, but compared with the liver, its structure is relatively rough and complicated operation.

The study of biomaterials is mainly focused on 4 aspects. The first is the most common application of porcine hepatocytes, liver cell mass method to obtain mature reaction evaluation research mainly focuses on the establishment of liver cell library and hepatocytes after application of bioartificial liver, after all after large-scale applications require immediate access to liver cells, and the pig liver cell metabolism and has the difference; application of transgenic pigs may it is discussed; the second is immortalized cell lines or liver cell line has been established, the report isolated from the liver fibroblasts in tumor transformed cell lines, such as HepG2, C3A, HuH6, Jhh2, also by transfection obtained after the treatment of human immortalized cell lines such as C8-B, HepZ, OUMS-29, NKNT-3 and so on, have mature liver cells and their function, but also has permanent reproductive characteristics, has been applied in clinical reports of [5, 9], but whether safety has become the focus of; Third directions for cell culture method, biological artificial liver cell requires high activity, form and function are required to maintain good common culture, it is difficult to meet the requirements of liver cell aggregation culture, microcarrier culture, co culture, organization culture can basically meet the needs of [10-12]; the fourth direction for the study of biological reactor, in addition to the ordinary hollow fiber bioreactor, composite hollow fiber bioreactor, woven hollow fiber bioreactor, radial flow type or radial flow polyester fabric bioreactor showed good application prospect of [13].

3.2 combined bioartificial liver combined bioartificial liver is the experimental and clinical application of bioartificial liver. It usually consists of three parts, namely, the blood circulation part, the non biological artificial liver part and the bioreactor. The blood circulation includes the pipeline system, the blood pump, and so on. It plays the role of supporting the system, and the part of the non biological artificial liver is initially detoxified. The research mainly focused on the establishment of effective combination system and how to use it to achieve the best support effect. The study shows that the standard of selection of non biological parts, combined with biological reactor, blood circulation, each support for 6 hours, long-term application, can get a satisfactory effect.

3.3 application of bioartificial liver scope theory, can be suitable for all kinds of biological artificial liver support in patients with liver function, but the biological artificial liver support consumes manpower and medical resources, complications may also exist in the use process, it is necessary to determine the scope of application. My experience: on liver regeneration, liver function can be restored with application of bioartificial liver on better curative effect; water and electrolyte disorders serious bleeding tendency, hemodynamic instability, serious taboo..

4 attach importance to transplantation surgery

Liver transplantation is the most effective treatment for liver failure. Just catch up with the international level of domestic liver transplantation. In 2000 China underwent liver transplantation in 231 cases, the most long live up to 7 years. Transplantation is the pursuit of the pursuit of high quality, the improvement of the safety and success rate of surgery, which has become the goal of many scholars.

The liver transplantation, some patients in poor condition, some have entered the hepatic coma, surgical risks; the shortage of donor liver caused by some patients cannot wait until donor liver transplantation surgery is an urgent need to improve the general condition of patients with the application of a technology, make the patients successfully spent waiting period. On the other hand, after liver transplantation, a small number of patients with primary liver function, the need for liver support in the absence of functional period or until another donor liver. Artificial liver technology meets these requirements, but due to the lack of cooperation between departments, some of the transplant surgeons do not know much about artificial liver, resulting in a waste of resources.

The artificial liver community also needs to work with the transplant community to improve long-term outcomes. In China, the number of acute liver failure caused by drugs, poisons and so on is not very large, but the liver failure caused by hepatitis associated with cirrhosis is very large. Liver cirrhosis patients with artificial liver support, although short-term indicators improved significantly, but the liver structure has undergone irreversible changes. Clinical often encountered severe hepatitis with artificial liver support treatment after cured, not long time, patients with liver failure may again, until death. If these patients with liver transplantation, can be completely cured.

Artificial liver and complement each other, mutual exchange of needed products, combined with liver transplantation is bound to make our medical technology level to a higher level. At present, the country has several hospitals, including our hospital to carry out artificial liver in liver transplantation surgery, the effect is very good [14].

 

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