28-12-2012, 06:18 PM
THE BIOARTIFICIAL LIVER
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INTRODUCTION:
The rationale for artificial liver support is based on the hypothesis that if essential liver functions can be restored during the critical phase of liver failure, it should be possible to improve the survival of patients with severe liver disease. In the case of bridge-to-transplantation, it should provide the patient sufficient metabolic support until a donor liver can be found and transplanted. Since the management of acute liver failure requires the replacement of the liver's myriad metabolic functions, the idea of a hybrid BioArtificial liver (BAL) support system has been proposed. BAL systems incorporate a biological (hepatocytes) and a synthetic housing component (plastic housing shell and semi permeable membrane) coupled in such a way as to facilitate the delivery of essential liver functions. Of the several BAL designs that have been proposed, only the capillary hollow-fiber based systems have been rapidly developed for clinical trials. Capillary hollow-fiber based BAL devices are basically off-the-shelf artificial kidney membranes that have been modified for use as an artificial liver. However, most capillary hollow-fiber based BAL designs have inherent physical limitations of total diffusion surface area and capacity for hepatocyte mass. We have proposed a novel BAL design using microencapsulated hepatocytes to overcome these physical limitations. This new BAL design (UCLA-BAL) involves the direct hemoperfusion of a packed-bed column of microencapsulated porcine hepatocytes within an extracorporeal chamber. In extensive animal studies using a well-characterized animal model fulminant hepatic failure (FHF), we demonstrated that the UCLA-BAL system had superior diffusion surface area and a higher capacity for hepatocytes compared to conventional capillary hollow-fiber based BAL devices. UCLA-BAL treatment significantly (P < 0.001), improved the survival rate of FHF animals and significantly (P < 0.01) prolonged the survival time of similar animals with very severe liver injury. BAL treatment was convenient, easy to operate and well tolerated, and did not adversely affect the animal's hemodynamics during treatment. We therefore suggest that the UCLA-BAL is a significant improvement over conventional, first-generation, capillary hollow-fiber BAL systems.
ABSTRACT:
The relative shortage of donor organs and lack of immediate availability mean that many patients with acute liver failure die before orthotopic liver transplantation can be performed. An effective temporary liver support system could improve the chance of survival with or without a transplant being ultimately carried out. Recent technological advances resulting in improved maintenance of hepatocyte viability and function in culture and bioreactor designs which facilitate adequate perfusion of the cellular component and removal of products of cellular metabolism have led to the development of a number of BioArtificial devices for liver support. Three such devices have undergone preliminary clinical evaluation in the setting of acute liver failure, with a statistically significant reduction in raised intracerebral pressure along with improvements in consciousness level and some biochemical parameters associated with treatment with one of these. Several other devices with different characteristics have shown promise in vitro and/or in animal models but await clinical evaluation. Several new totally artificial systems have also been described, along with the emergence of isolated hepatocyte transplantation, with reports of successful ‘bridging’ to liver transplantation. Controlled trials on a multicentre basis in well-defined patient groups and with standardized outcome measures will be required to properly evaluate the clinical value of each of these approaches to providing liver support in acute liver failure and cirrhosis. A better understanding of mechanisms underlying multiorgan failure and of factors inhibiting liver regeneration, thereby allowing a more targeted approach, will be essential to the further development of effective liver support strategies in these settings.
BIOLOGY OF THE LIVER:
The liver, the largest gland in the body, has both external and internal secretions, which are formed in the hepatic cells. Its external secretion, the bile, is collected after passing through the bile capillaries by the bile ducts, which join like the twigs and branches of a tree to form two large ducts that unite to form the hepatic duct. The bile is either carried to the gall-bladder by the cystic duct or poured directly into the duodenum by the common bile duct where it aids in digestion. The internal secretions are concerned with the metabolism of both nitrogenous and carbohydrate materials absorbed from the intestine and carried to the liver by the portal vein. The carbohydrates are stored in the hepatic cells in the form of glycogen which is secreted in the form of sugar directly into the blood stream. Some of the cells lining the blood capillaries of the liver are concerned in the destruction of red blood corpuscles. It is situated in the upper and right parts of the abdominal cavity, occupying almost the whole of the right hypochondrium, the greater part of the epigastrium, and not uncommonly extending into the left hypochondrium as far as the mammillary line. In the male it weighs from 1.4 to 1.6 kilogm., in the female from 1.2 to 1.4 kilogm. It is relatively much larger in the fetus than in the adult, constituting, in the former, about one-eighteenth, and in the latter about one thirty-sixth of the entire body weight. Its greatest transverse measurement is from 20 to 22.5 cm. Vertically, near its lateral or right surface, it measures about 15 to 17.5 cm., while its greatest antero-posterior diameter is on a level with the upper end of the right kidney, and is from 10 to 12.5 cm. Opposite the vertebral column its measurement from before backward is reduced to about 7.5 cm. Its consistence is that of a soft solid; it is friable, easily lacerated and highly vascular; its color is a dark reddish brown, and its specific gravity is 1.05.
To obtain a correct idea of its shape it must be hardened in situ, and it will then be seen to present the appearance of a wedge, the base of which is directed to the right and the thin edge toward the left. Symington describes its shape as that “of a right-angled triangular prism with the right angle rounded off.”
SURFACES—
The liver possesses three surfaces, viz., superior, inferior and posterior. A sharp, well-defined margin divides the inferior from the superior in front; the other margins are rounded. The superior surface is attached to the diaphragm and anterior abdominal wall by a triangular or falciform fold of peritoneum, the falciform ligament, in the free margin of which is a rounded cord, the ligamentum teres (obliterated umbilical vein). The line of attachment of the falciform ligament divides the liver into two parts, termed the right and left lobes, the right being much the larger. The inferior and posterior surfaces are divided into four lobes by five fossæ, which are arranged in the form of the letter H. The left limb of the H marks on these surfaces the division of the liver into right and left lobes; it is known as the left sagittal fossa,and consists of two parts, viz., the fossa for the umbilical vein in front and the fossa for the ductus venosus behind. The right limb of the H is formed in front by the fossa for the gall-bladder, and behind by the fossa for the inferior vena cava; these two fossæ are separated from one another by a band of liver substance, termed the caudate process. The bar connecting the two limbs of the H is the porta (transverse fissure); in front of it is thequadrate lobe, behind it the caudate lobe.