HEPATOCELLULAR TRANSPLANTATION AND TARGETING GENETIC MARKERS TO HEPATIC CELLS 
samples from laboratory personnel which will be analyzed for antibodies against murine 
retroviruses. Laboratory personnel who were negative for such antibodies at the 
inception of this study, but turn positive after working with recombinant viruses, will 
be admitted to the TCH GCRC and evaluated for evidence of infectious virus, shedding of 
virus particles, or indication of viral induced disease. This protocol is approved by 
the GCRC and a proposal for funding laboratory studies has been submitted to the NIH (in 
"Gene Therapy for Hepatic Deficiencies" S.L.C, Woo, P.I. - review pending). 
L. The balance of risk and benefit. 
We believe this protocol exhibits an extremely beneficial balance between risk and 
benefit. This balance must be considered separately for HCT and for the gene 
transduction portions of this protocol. 
Hepatocellular transplantation. There is considerable benefit to the individuals 
who meet the inclusion criteria and are selected to participate in this protocol. These 
patients will have diseases which are considered inexorably fatal, for which 
conventional therapeutic options have been exhausted, and for whom conventional OLT is 
not available for any reason. We will also select patients whose condition (especially 
with regard to hepatic encephalopathy) is not irreversible and may have a meaningful 
therapeutic response if the transplant procedure is successful. These patients will 
remain eligible for conventional OLT if changes in their condition or status make them 
eligible for this procedure. There is considerable benefit to society in rigorously 
developing methods for HCT as an alternative to OLT. This will increase the organ pool 
and potentially the number of patients who may benefit from OLT. If non- surgical 
(catheterization) methods are successful, the technical difficulty, and morbidity of 
transplantation to restore hepatic functions will be dramatically reduced along with the 
cost. If rejection of hepatocytes is less severe than intact organs, the long-term 
prognosis and course of post- transplant treatment will be significantly improved. 
There is significant risk associated with HCT which represents a completely novel 
surgical procedure in clinical practice. These include common risks associated with 
phlebotomy, urine collection, catheter insertion, surgery, anaesthesia, as well as the 
specific risks of vascular thrombosis, hemorrhage, or rupture of vessels at the site of 
HCT. The patients recruited for this study will be acutely ill and much of the sample 
collection will either be clinically indicated or will be performed coincidentally with 
clinically indicated blood drawing or urine collection. We will monitor blood 
collection and restrict all blood drawing to less than 5% of blood volume/week. Tests 
which are clinically indicated for the benefit of the patient will take priority over 
any tests assessing research issues related to the transplantation or gene transduction. 
Many of the anticipated risks of HCT are similar to those associated with OLT, 
particularly the profound risk associated with the immunosuppressive protocol. These 
are described in detail in a booklet prepared for transplant recipients at TCH which 
will be given to patients (see appendix F) . These issues are also included on a 
"checklist" of information which is reviewed with patients by the attending surgeon and 
the informed consent used for transplantation which will be minimally amended for use 
in this protocol (appendix F) . 
Recombinant DNA Research, Volume 14 
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