HEPATOCELLULAR TRANSPLANTATION AND TARGETING GENETIC MARKERS TO HEPATIC CELLS 
j to be significant morbidity and mortality associated with this procedure and the paucity 
II of appropriate donor organs as well as the high pecuniary cost of transplantation (>$2- 
I 300,000 for transplantation and $10-20 , 000/year follow-up) make transplantation 
I unavailable to many patients (Whitington and Balistreri, 1991). 
j The severity of the problem of organ availability is evident in the fact that it has 
been estimated that there will be 2000 liver transplants performed in the United States 
' during the 1990s (350 in children). At the same time there are 400-600 new cases of 
! biliary atresia each year for whom OLT is the ultimate therapeutic alternative 
I (Whitington and Balistreri, 1991). The growing acceptance of OLT for other disorders 
: such as hepatitis and metabolic disease will severely test sources of funding, the 
j availability of centers willing to perform these procedures, and systems for organ 
procurement. 
I B. The rationale for hepatocellular transplantation (HOT) . 
I 
' HCT, in which hepatocytes would be isolated from a donor organ and introduced into 
i the diseased organ, could provide an alternative to OLT for many patients. This 
j procedure could greatly increase the number of organs suitable for transplantation, 
I since organs with traumatic damage (which are unsuitable for OLT) and residual segments 
from reduced liver transplants might provide a source of hepatocytes . HCT might also 
entail less extensive surgical manipulations and less severe perturbations of 
metabolism, physiology, and hemostasis because the host liver would not be removed. HCT 
would be particularly suitable for treating hepatitis where there is considerable 
I restorative potential if the acute manifestations of hepatic insufficiency can be 
! managed as well as in the inborn errors of metabolism in which host hepatic function is 
! essentially intact, but specific enzyme activities are deficient. In these diseases 
there is often considerable reluctance to consider OLT with its high cost and acute risk 
of morbidity and mortality. HCT may offer an opportunity to reconstitute essential 
functions without the morbidity and mortality associated with complete hepatectomy and 
OLT. HCT would be inapplicable in cases with biliary atresia, severe cirrhosis, or 
severe portal hypertension where an anatomical correction of the underlying disorder is 
required. 
Another area of research which could lead to alternatives to OLT is work directed 
at developing "artificial livers" or "bioreactors". These systems are based on growing 
hepatocytes (or minimally transformed hepatoma cells) on matrices which could be used 
for hemoperfusion with the expectation that this perfusion would result in elimination 
of toxic metabolites and secretion of liver-specific products by the cells. Several 
variations of this scheme have been tried in animal models, but none have been applied 
I in humans. There is an active interest in hepatic bioreactors at BCM (Kelly, Sussman, 
Iwhisennand, unpublished data). The clinical research protocol by Ferry et al (see 
. below) which will be used to select patients for HCT and establish control data is also 
j constructed to select patients for clinical trials of bioreactors if this technology 
becomes available. It is our sense that this technology may be useful for acute 
maintenance of patients with hepatic insufficiency, though there is no data to suggest 
that long term maintenance of hepatic funct-ions would be feasible. 
Recombinant DNA Research, Volume 14 
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