HEPATOCELLULAR TRANSPLANTATION AND TARGETING GENETIC MARKERS TO HEPATIC CELLS 
5 . Patient management, public, and psychosocial aspects of gene transfer in human 
subjects (Some of these issues are addressed in ancillary protocols.) 
a. How should patients in gene transfer protocols be managed in the hospital? 
Following discharge? 
b. What are the perceptions of gene transfer or gene therapy among prospective 
patients and their families? How does this affect patient participation and 
informed consent? 
c. What are the psychosocial consequences of genetic manipulation to patients and 
their families? 
d. How can long-term follow-up be maintained to ensure ':ne provision of optimal 
medical care, surveillance for potential complications, appropriate diagnostic 
and therapeutic interventions required by gene transfer, and psychosocial 
support? 
e. How can the privacy and confidentiality of patients be maintained during the 
course of the gene transfer protocol and through long-term follow-up. 
f. What are the public consequences of gene transfer protocols in a private 
hospital? Can the public be adequately informed and educated? 
III. 
SCIENTIFIC AND TECHNICAL BACKGROUND 
A. The state of the art in hepatic transplantation. 
Liver transplantation has become the treatment of choice for many causes of hepatic 
failure including congenital malformations of the liver and biliary tract, genetic 
disorders of intermediary metabolism, and acquired diseases such as infectious or drug 
induced toxicity (Starzl et al, 1989a; 1989b; 1989c; Bismuth et al, 1987; Whitington and 
Balistreri, 1991). The efficacy and availability of hepatic transplantation has 
improved in the last decade for several reasons. First, the advent of cyclosporin 
(Iwatsuki et al, 1988) and FK506 (Todo et al, 1988a) has improved the control of 
rejection. Second, methods for preserving and transporting organs in Collins (EC) 
solution (Benichou et al, 1977), and more recently University of Wisconsin (UW, 
Belzer's, Southard et al, 1990) solution (Jamieson et al, 1988a; Todo et al, 1989; 
Sumimoto et al, 1989) have increased the pool of organs available for transplant and 
their viability (Olthoff et al, 1990). Third, methods have been developed for segmental 
or reduced size liver transplants (Bismuth and Houssin, 1983; Broelsch et al, 1984; 
1988a; 1988b; de Hemptinne et al, 1988; Pichlmayr et al, 1988a; Otte et al, 1988; 1990; 
Broelsch et al, 1990) and heterotopic transplantation (Terpstra et al, 1988). One 
exciting development is the recent transplantation of a liver lobe from a living donor 
to a familial recipient (Broelsch et al, 1990; Strong, et al, 1990; Editorial, 1990). 
There have been significant advances in pediatric liver transplantation (Andrews et 
al, 1989; Kalayoglu et al, 1989; Otte et al, 1988. Published data describes a 80% one 
year survival and 70% long-term survival (>5 yrs) in children <15 years of age, but only 
50% long-term survival in children less than one year of age (Sokal et al , 1990; 
Whitington and Balistreri, 1991). Despite these encouraging statistics, there continues 
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Recombinant DNA Research, Volume 14 
