Faculty Bibliography

A causal link has been proposed between presumed consent (PC) and increased donation; we hypothesized that too much heterogeneity exists in transplantation systems to support this inference. We explored variations in PC implementation and other potential factors affecting donation rates. In-depth interviews were performed with senior transplant physicians from 13 European PC countries. Donation was always discussed with family and would not proceed against objections. Country-specific, nonconsent factors were identified that could explain differences in donation rates. Because the process of donation in PC countries does not differ dramatically from the process in non-PC countries, it seems unlikely that PC alone increases donation rates.

Livers from Lewis rats fed with 7% alcohol for 5 weeks were used for transplantation. Reduced sized (50%) livers or whole livers were transplanted into normal DA recipients, which, in this strain combination, survive indefinitely when the donor has not been fed alcohol. However, none of the rats survived a whole fatty liver transplant while six of seven recipients of reduced sized alcoholic liver grafts survived long term. SDF-1 and HGF were significantly increased in reduced size liver grafts compared to whole liver grafts. Lineage-negative Thy-1+CXCR4+CD133+ stem cells were significantly increased in the peripheral blood and in allografts after reduced size fatty liver transplantation. In contrast, there were meager increases in cells reactive with anti Thy-1, CXCR4 and CD133 in peripheral blood and allografts in whole alcoholic liver recipients. The provision of plerixafor, a stem cell mobilizer, salvaged 5 of 10 whole fatty liver grafts. Conversely, blocking SDF-1 activity with neutralizing antibodies diminished stem cell recruitment and four of five reduced sized fatty liver recipients died. Thus chemokine insufficiency was associated with transplant failure of whole grafts, which was overcome by the increased regenerative requirements promoted by the small grafts and mediated by SDF-1 resulting in stem cell influx.

Recurrent hepatitis C virus (HCV) infection is the most common cause of graft loss and patient death after transplantation for HCV cirrhosis. Transplant surgeons have access to uninfected explanted livers before transplantation and an opportunity to deliver RNA interference-based protective gene therapy to uninfected grafts. Conserved HCV sequences were used to design short interfering RNAs and test their ability to knockdown HCV transcript expression in an in vitro model, both by transfection and when delivered via an adeno-associated viral vector. In a rodent model of liver transplantation, portal venous perfusion of explanted grafts with an adeno-associated viral vector before transplantation produced detectable short hairpin RNA transcript expression after transplantation. The ability to deliver anti-HCV short hairpin RNAs to uninfected livers before transplantation and subsequent exposure to HCV offers hope for the possibility of preventing the currently inevitable subsequent infection of liver grafts with HCV.

BACKGROUND: Availability of kidney paired donation (KPD) is increasing in the United States, and a national system through UNOS is forthcoming. However, little is known about attitudes toward KPD among the general public, from which donors (particularly non-directed) are drawn. METHODS: In a national study, we assessed the public's attitudes regarding participation in KPD. RESULTS: Among 845 randomly selected participants, 85.2% of respondents were either "extremely willing" or "very willing" to participate in KPD. Experiences with the medical or organ transplant systems, such as undergoing surgery, having a primary medical provider, a living will, a friend who donated or received an organ, and considering donation after death, were associated with increased willingness. However, increased age, male sex, African American race, Hispanic ethnicity, distrust of the medical system, and not understanding organ allocation were associated with less willingness. CONCLUSIONS: We identify strong support for KPD but some important potential barriers to participation which should be considered as KPD programs are implemented.