Expanding Horizons in Liver Transplantation

Keywords:liver transplantation, live donor, tolerance, hepatitis B virus,hepatocellular carcinoma The Program Project Grant (EX90-8702SP) awarded by the National Health Research Institutes in 1997 aimed at advancing a fledgling small-scale living donor liver transplantation (LDLT) program from an experimental status to a practical therapeutic modality. This goal was successfully achieved by obtaining survival outcomes that are above par on an international scale. A major milestone was the initiation of right lobe LDLT which has led to a remarkable increase in patient accrual. Today LDLT is the major feature of this comprehensive liver transplant program that caters to both pediatric and adult candidates of a wide variety of indications, currently performing elective LDLT on a weekly basis. This renewal proposal seeks support for another five years for the explicit purpose of further strengthening the infrastructure of the Liver Transplantation Program at the Chang Gung Memorial Hospital/ Chang Gung University. The objective is to advance this unit into a world-class center with the finest clinical and scientific program serving not only Taiwan but also the neighboring Asian countries, and in the process contribute to the advancement of transplantation science. The guiding principle will be based on providing improvements in the lives of patients with advanced liver disease. This will be achieved by putting emphasis on both basic science and clinically applied research, while fostering an atmosphere of multidisciplinary interaction and developing domestic and international collaboration in transplantation. The already active clinical program will be continued with vigor. Through further refinement of surgical techniques and advancement of imaging studies, the LDLT will be applied to a greater number of adult recipients including those with liver failure with a fulminant course who need urgent liver replacement. The use of the cadaveric liver grafts will be optimized by systematically splitting those with suitable characteristics in order to provide for two patients. Support will be used to continue to pursue the subject of tolerance, to better understand its mechanisms and determinants. If successfully carried out, the potential impact of further consolidating a program of this scope can be directly related to both the welfare and prestige of the country. The proposed renewal grant shall consist of four subprojects. While excellent survival outcomes have been achieved in our LDLT recipients, there is yet no reliable marker to determine when immunosuppressive drugs can be terminated in long-term survivors. Subproject 1 aims to further explore the potential key tolerance proteins and genes identified in our previous research, elucidate the mechanism(s) of drug-free tolerance and develop tolerance assay(s). The other three projects are clinically oriented and focus on the application of non-invasive imaging techniques in emergency LDLT (Subproject 2), the prevention of hepatitis B infection, whether as de novo or recurrent disease (Subproject 3), and the improvement of survival outcomes after LDLT for hepatocellular carcinoma (Subprojects 4). These three subprojects address a national health problem that remains to be a major cause of morbidity and mortality not only in Taiwan but in most of Asia, namely hepatitis B viral infection and its related complications.

Project ID:PG9204-0407
External Project ID:NHRI-EX92-9228SP