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Liver Failure Biography
Liver is a multitasking organ in the body being able to synthesise several plasma proteins, immune factors as well as several metabolising enzymes and factors helping in digestion and excretion within the body. Hence, on liver failure several severe complications are noticed in the body affecting several other organs like kidney, brain, and even causing ultimate death. Although, liver transplantation remains the ultimate solution in case of Acute Liver Failure (ALF) but due to shortage in the availability of donors, other methods to support the liver functions are being devised. Doctors have made progress in the replacement of the different damaged organs within the body with artificial devices when transplantation becomes an issue due to unavailability of the donors or organs. In case of ALF also, Artificial Liver Support Devices (ALSDs) have been developed, which provide a temporary solution between the ALF and liver transplantation or liver regeneration from the donor liver hepatocytes, which have the capacity to regenerate the whole liver and restore its function by continuous proliferation.
ALSDs are based on the idea of removal of toxic substances from the blood. These may be of two types: Non-Biological LSDs and Biological LSDs. The Non-biological LSDs mainly remove the excretory wastes from the body based on the dialysis and filtration principle. It was found that they provide temporary solution and are not much efficient as they are unable to restore other important functions of liver because of which the patients could not survive for long. This led to the idea of development of LSDs, which are biological in nature and could provide long-lasting solution for the survival of the ALF patients. The synthetic, metabolic as well as excretion functions of the liver are being restored largely by the biological LSDs, hence research on bio artificial liver devices is making progress.
The Bio artificial livers are support devices connected to the patients’ plasma circulation outside the body. They are liver cells charged bioreactors, which help in restoring almost all the main functions of the liver. The bioreactors mainly consist of porcine or human hepatocytes, which are parenchymal in nature. However, for the optimum function of the bioreactors, they must contain mixed differentiated cells whereby the liver cells possess 3D configuration. The bioreactors are of four types: hollow fiber types; suspension or encapsulation; monolayer and scaffolds. The bioreactors are mainly used for the improvement in the cell oxygenation as well as mass- exchange. In most of the cases, it is seen that the bioreactors do not consist of the biliary system, which aids in the excretion of conjugated bilirubin. Hence, for proper excretion of this bilirubin, an artificial mode is attached to the bioreactors, which help in the removal of this bilirubin, thereby preventing toxicity.
The bio artificial livers consist mainly of the freshly isolated or cryopreserved porcine hepatocytes as they are easily available. Though, they may provide reliable data regarding the restoration of function of the liver function due to similar biologic properties like human hepatocytes, but there are a number of disadvantages regarding their use. The xenozoonosis i.e xeno transplantation effect due to using cells of different species causes unreliability in the data observed by using porcine hepatocytes in the bioreactors. The transmission of the pathogens like porcine retrovirus also is another added disadvantage in their use. Hence, freshly isolated human hepatocytes must be used as cryopreservation of the same causes the loss of the enzyme function largely. The research carried out using human-origin hepatocytes provides reliable data regarding the advantages in using bioreactors in the treatment of ALF. Immortal hepatocytes developed from hepatoblastoma cell line or other tumor cells have also been developed for the study of bioreactors, though the possible toxicity resulting from using such cells cannot be ignored. Hepatocytes have also been developed from the tissues slices of the discarded donor livers, though their availability at the required time cannot be guaranteed.
The clinical proofs regarding the use of bio artificial livers are not much favourable in the present scenario. The hepatocytes used in the bioreactors may not always be completely differentiated ensuring proper function nor are they always present in 3D conformation. Moreover, the patients used for clinical trials are diverse in nature; hence, the resulting statistical data may not provide concrete positive result. The bioartificial livers may provide bridge in the treatment of the patients until the availability of the liver to be transplanted, but the lasting effect of the use of bioartificial livers on the patients after transplantation has not yet been proved completely. The clinical trials with the human hepatocytes are going on and much research is needed before the bio artificial livers can be successfully used in the treatment of the ALF patients.
Liver Failure Biography
Liver is a multitasking organ in the body being able to synthesise several plasma proteins, immune factors as well as several metabolising enzymes and factors helping in digestion and excretion within the body. Hence, on liver failure several severe complications are noticed in the body affecting several other organs like kidney, brain, and even causing ultimate death. Although, liver transplantation remains the ultimate solution in case of Acute Liver Failure (ALF) but due to shortage in the availability of donors, other methods to support the liver functions are being devised. Doctors have made progress in the replacement of the different damaged organs within the body with artificial devices when transplantation becomes an issue due to unavailability of the donors or organs. In case of ALF also, Artificial Liver Support Devices (ALSDs) have been developed, which provide a temporary solution between the ALF and liver transplantation or liver regeneration from the donor liver hepatocytes, which have the capacity to regenerate the whole liver and restore its function by continuous proliferation.ALSDs are based on the idea of removal of toxic substances from the blood. These may be of two types: Non-Biological LSDs and Biological LSDs. The Non-biological LSDs mainly remove the excretory wastes from the body based on the dialysis and filtration principle. It was found that they provide temporary solution and are not much efficient as they are unable to restore other important functions of liver because of which the patients could not survive for long. This led to the idea of development of LSDs, which are biological in nature and could provide long-lasting solution for the survival of the ALF patients. The synthetic, metabolic as well as excretion functions of the liver are being restored largely by the biological LSDs, hence research on bio artificial liver devices is making progress.
The Bio artificial livers are support devices connected to the patients’ plasma circulation outside the body. They are liver cells charged bioreactors, which help in restoring almost all the main functions of the liver. The bioreactors mainly consist of porcine or human hepatocytes, which are parenchymal in nature. However, for the optimum function of the bioreactors, they must contain mixed differentiated cells whereby the liver cells possess 3D configuration. The bioreactors are of four types: hollow fiber types; suspension or encapsulation; monolayer and scaffolds. The bioreactors are mainly used for the improvement in the cell oxygenation as well as mass- exchange. In most of the cases, it is seen that the bioreactors do not consist of the biliary system, which aids in the excretion of conjugated bilirubin. Hence, for proper excretion of this bilirubin, an artificial mode is attached to the bioreactors, which help in the removal of this bilirubin, thereby preventing toxicity.
The bio artificial livers consist mainly of the freshly isolated or cryopreserved porcine hepatocytes as they are easily available. Though, they may provide reliable data regarding the restoration of function of the liver function due to similar biologic properties like human hepatocytes, but there are a number of disadvantages regarding their use. The xenozoonosis i.e xeno transplantation effect due to using cells of different species causes unreliability in the data observed by using porcine hepatocytes in the bioreactors. The transmission of the pathogens like porcine retrovirus also is another added disadvantage in their use. Hence, freshly isolated human hepatocytes must be used as cryopreservation of the same causes the loss of the enzyme function largely. The research carried out using human-origin hepatocytes provides reliable data regarding the advantages in using bioreactors in the treatment of ALF. Immortal hepatocytes developed from hepatoblastoma cell line or other tumor cells have also been developed for the study of bioreactors, though the possible toxicity resulting from using such cells cannot be ignored. Hepatocytes have also been developed from the tissues slices of the discarded donor livers, though their availability at the required time cannot be guaranteed.
The clinical proofs regarding the use of bio artificial livers are not much favourable in the present scenario. The hepatocytes used in the bioreactors may not always be completely differentiated ensuring proper function nor are they always present in 3D conformation. Moreover, the patients used for clinical trials are diverse in nature; hence, the resulting statistical data may not provide concrete positive result. The bioartificial livers may provide bridge in the treatment of the patients until the availability of the liver to be transplanted, but the lasting effect of the use of bioartificial livers on the patients after transplantation has not yet been proved completely. The clinical trials with the human hepatocytes are going on and much research is needed before the bio artificial livers can be successfully used in the treatment of the ALF patients.
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