HEPATOCELLULAR TRANSPLANTATION AND TARGETING GENETIC MARKERS TO HEPATIC CELLS 
artery) , though engraftment has not been demonstrated via this approach in animal 
studies. It is also important that the procedures used in this protocol do not 
interfere the opportunity to perform OLT if this therapeutic alternative should become 
available after HCT is performed. We have avoided procedures which require laparotomy 
in order to maximize the benefit/risk ratio of the procedure and minimize the 
possibility that this experimental procedure would complicate subsequent OLT. 
Three different surgical approaches will be considered in each patient. The 
decision concerning which method to employ will be made on a clinical basis by the 
surgical investigators in an attempt to minimize the risk of the procedure, extent and 
invasiveness of surgery, and maximize the potential benefits to the individual patient. 
1) Direct intrasplenic injection. Direct intrasplenic injection has been the 
most efficacious procedure in animal experiments. The presence of uncorrectable 
coagulapathy or portal hypertension would make this approach surgically contraindicated. 
We will employ the intrasplenic technique in patients who have no significant 
coagulapathy (or in whom coagulopathy can be corrected with fresh frozen plasma or 
plasmapheresis) and no evidence of portal hypertension by doppler analysis. 
Transplantation to this site could be performed through the laparoscope in the operating 
room, and laparotomy will be performed only if indicated for complications such as 
bleeding. 
2) Direct catheterization of portal vein. Patients who are thought to present 
inappropriate risks for direct splenic injection will be transplanted via 
catheterization of the portal, splenic, or superior mesenteric vein. A clinical 
decision will be made by the surgical investigators whether to do this via a trans- 
hepatic route, under laparoscopic visualization, or by laparotomy. 
3) Transjugular catheterization of portal vein. Transjugular catheterization of 
the portal vein is performed by introducing a catheter into the jugular vein via the 
vena cava to the hepatic vein (Goldman et al, 1978; Rosch et al, 1975). A wire is then 
advanced through the hepatic parenchyma into the portal venous system. The location of 
the catheter and the distribution of blood flowing via the catheterized vessel can be 
documented via infusion of dye and fluoroscopy. Because this technique is entirely 
intravascular, the risk of intra- abdominal bleeding is minimal. This method can be 
performed in patients with coagulopathies or portal hypertension, though it has not been 
performed in small children. This method may prove to be an attractive approach to 
HCT in the future and may be used on patients who are large enough for the procedure to 
be performed safely in the judgment of the surgical investigators. 
Other issues in clinical management: i) In order to minimize the risk to the 
recipient, all blood product transfusions (Red Blood Cells, Fresh Frozen Plasma, 
platelets, etc.) should be from seronegative donors. This policy is commonly enforced 
from the time patients are referred for potential transplantation and will be maintained 
throughout this protocol. ii) "Universal" precautions will be enforced on patients 
undergoing gene transfer. These precautions are used will all hospitalized patients and 
are effective at controlling spread of known pathogens including HIV and HBV. 
Recombinant DNA Research, Volume 14 
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