published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

The Best MPhil Thesis in the Faculties of Dentistry, Engineering, Medicine and Science (University of Hong Kong), Li Ka Shing Prize,2003-2005 / published_or_final_version / abstract / toc / Surgery / Master / Master of Philosophy

Concerning potential immunological reaction in patients receiving multiple bioartificial liver treatments (with porcine hepatocytes bioreactor), the beneficial effect of sequential plasmapheresis-hemoadsorption-bio-liver treatment protocol was studied. The hypothesis was tested in a trichosanthin-induced anaphylaxis rat model. Fatal anaphylactic response upon antigen challenge was reduced in a previously trichosanthin sensitized rat prior with cross circulation. It was suggested that circulating antibodies responsible for immunological response were removed by the non cell-based treatment. The potential risk of hypersensitivity reaction of subsequent cell-based treatment was reduced. In the design of HBLSS, the sequential plasmapheresis-hemofiltration-bio-liver treatment was suggested to alleviate potential immunological consequences and allow multiple uses in single patient. / In addition to artificial liver research, pharmacological therapies are sought to treat ALF. Recent studies suggested that the local renin-angiotensin system (RAS) in the liver regulate the fibrogenic response. The possible involvement of RAS in acute liver injury was investigated in the present study. In the D-galactosamine induced rat liver failure model, angiotensin II type 1 receptors (AT1R) were detected by immunohistochemical staining in the centrilobular region after induction of acute liver injury which was not evident in normal liver. There were associated elevation of total bilirubin, alanine aminotransferase and tissue inhibitor of metalloproteinase type 1 (TIMP-1). Losartan treatment was able to reduce all these parameters. TIMP-1 protein was reduced by 1.5 fold (p<0.05) on day 1 and 1.56 fold (p<0.05) on day 3 in the losartan treatment group relative to the GalN group. The survival rate of the losartan treatment group was significantly higher than that without treatment (5-day survival, 85% vs 42.5%, p<0.05). This finding suggested the local renin-angiotensin system plays a role in the pathophysiological mechanism of acute liver injury. / In summary, the presence study addressed two approaches in treating liver failure. The HBLSS treatment protocol improved survival of acute-on-chronic liver failure patients. The protective effect of losartan in liver injury suggests AT1R blockade is a potential therapeutic strategy in acute liver injury. / The mainstay treatment of acute liver failure (ALF) is conservative medical therapy. In patients having acute liver insufficiency, the only proven life-saving procedure is liver transplantation. The concept of supportive care in liver failure is to optimize patient's clinical condition by replacing some of the essential functions of liver and allowing liver regeneration in order to compensate the loss of hepatocellular functions. / There was increasing evidence suggesting a role of artificial liver (extracorporeal system) in the treatment of liver failure. A retrospective study was performed in a group of acute-on-chronic liver failure (AoCLF) patients treated with hybrid bioartificial liver support system (HBLSS). From 2001-2004, there were 40 chronic liver disease patients presented with acute deterioration. Patients were treated either with conventional medical therapy (n=21) or integrated with HBLSS treatment (n=19). The 60-day survival rate was 30% and 68.5% respectively (P<0.05 log-rank test). Integration of hybrid bioartificial liver support system (HBLSS) in treating acute-on-chronic liver failure (AoCLF) patients improved the survival outcome. Univariate analysis of admission blood parameters revealed creatinine appeared to predict mortality in AoCLF patients with HBLSS treatment. / Chan Hoi Ming Herman. / "June 2006." / Adviser: Siu-cheung Michael Tam. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1547. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 104-116). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.