by Francis Ka-leung Chan. / Thesis (M.D.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (p. 187-210). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Background: Liver transplantation is a curative method for end-stage liver diseases, small unresectable hepatocellular carcinoma and acute liver failure. The discovery of immunosuppressive drugs increases the survival rate of liver transplanted recipients by reducing the incidence of graft rejection. Several complications such as renal dysfunction and increase risk of malignancy result from life-long treatment of transplanted recipients with immunosuppressant. If recipients are over-immunosuppressed, the risk of infection might be increased. On the other hands, if recipients are under-immunosuppressed, the risk of rejection would be increased. It should be useful if a test or a bio-marker that could predict and differentiate infection and rejection in transplanted recipients. Therefore, patients could be treated before adverse conditions. Although therapeutic drug monitoring has been performed as a routine test, it is mainly targeted for minimizing drug toxicity but little help in predicting infection and rejection. A new assay named Cylex? Immuknow? assay is designed to measure global cell mediated immunity of immunosuppressed population, by quantifying the amount of ATP synthesis by CD4+ T cells in response to PHA stimulation. It is undergoing evaluation in assessing the immune status of patients in order to predict the risk of infection and rejection, and also other conditions. (1, 2) Objectives: In this pilot study, we would like to evaluate ImmuKnow for predicting the risk of infection and rejection in liver transplanted recipients in Hong Kong. Methods: Blood samples were collected from liver transplanted recipients at different time intervals. The immune cell response of these patients was measured by Immuknow assay. Patients with low immune response might have a high risk of infection, patients with high immune response might have a high risk of rejection, and patients with moderate immune response should be clinically stable. Results and conclusion: Twenty-six blood samples were collected from eight transplanted recipients. The average Immuknow assay value for the post-transplant samples was 304.6 ng/mL ATP which represented moderate immune cell response according to the interpretation table. (Table 3) This was reasonable as the subjects were all clinically stable by well-controlled immunosuppression. The result was consistent with other studies. (1, 3) However, the association between low immune cell response and infection, and the association between high immune cell response and graft rejection could not be investigated as both of these conditions were not found in this pilot study. A larger study including episodes of infection and rejection should be conducted in order to evaluate the value of Immuknow assay more completely. / published_or_final_version / Pathology / Master / Master of Medical Sciences

published_or_final_version / abstract / toc / Surgery / Doctoral / Doctor of Philosophy

INTRODUÇÃO: O transplante hepático é a terapêutica de escolha para pacientes com hepatopatias avançadas. Melhorias na seleção dos pacientes, avanços cirúrgicos e imunológicos aumentaram a sobrevida. As complicações biliares ocorrem em 15 a 35% dos transplantes e estão associadas a técnicas de redução hepática. A estenose anastomótica ocorre de 5 a 34% e pode ser tratada por cirurgia, acesso endoscópico ou percutâneo. Esse último apresenta bons resultados, mas carece de padronização, critérios de sucesso ou consenso quanto aos fatores que influenciam a resposta terapêutica. Neste trabalho, avaliou-se a relação entre os fatores de risco e a terapêutica, resposta mais adequada, dados de maior relação com a estenose da anastomose bílio-entérica, período de surgimento, tempo de drenagem mais adequado, incidência de complicações, eficácia e segurança terapêutica. MÉTODOS: No período de março de 1993 a maio de 2006, foram avaliadas trinta e cinco pacientes com estenose da anastomose bílio-entérica após o transplante hepático prospectiva e retrospectivamente. Trinta e quatro (97,1%) tinham idade igual ou superior a um ano. Vinte e quatro (68%) tinham mais de 10 kg. Houve compatibilidade ABO em 100%, entre gêneros em 28,6% e na relação de peso entre receptor e doador em 71,4%. A principal indicação foi atresia de vias biliares e 45% dos transplantes foram realizados com doadores vivos. Trinta transplantes (86%) foram eletivos e 18 pacientes (51,4%) foram submetidos previamente à cirurgia de Kasai. A reconstrução biliar foi feita por meio da anastomose bílio-entérica em todos os pacientes. As estenoses foram confirmadas por colangiografia percutânea, dilatadas e drenadas. O calibre dos drenos foi aumentado nas reintervenções, sendo trocado a cada três meses e mantido por pelo menos seis meses. As complicações foram avaliadas e os pacientes foram distribuídos em grupos de resposta terapêutica de G1 a G4. RESULTADOS: Febre, icterícia, exame histopatológico demonstrando padrão obstrutivo biliar e dosagem elevada de gamaglutamiltransferase estiveram mais presentes no grupo com estenose. Os pacientes submetidos à cirurgia de Kasai apresentaram melhor resposta ao tratamento percutâneo (p = 0,05). As outras variáveis não demonstraram correlação estatisticamente significativa com a melhor ou pior resposta ao tratamento. Observou-se tempo médio de drenagem de 10 meses no grupo G1, onde houve menor ocorrência de complicações. CONCLUSÕES: Houve resposta satisfatória nos grupos com uma ou duas sessões (86%) de tratamento percutâneo. A cirurgia de Kasai se associa com melhores respostas ao tratamento; o exame histopatológico demonstrando padrão obstrutivo biliar e a elevação de gamaglutamiltransferase apresentam maior relação com a estenose, que ocorreu mais freqüentemente após o primeiro ano do transplante. Os pacientes drenados por mais de seis meses apresentaram melhores resultados. Entretanto, o prolongamento da drenagem associa-se com mais complicações. O tratamento percutâneo (dilatação e drenagem) é eficaz, seguro, com baixa taxa de complicações. / INTRODUCTION: Hepatic transplant is the chosen therapy for patients with advanced hepathopathy. Improvement on patients selection, surgical and immunologic advances increases the life expectancy. Biliary complications occur between 15 to 35% transplants and are associated to hepatic reduction techniques. The anastimotic stenosis occur between 5 to 14% and can be treated by surgery, endoscopic access or percutaneous. This last one presents fair results. However, it lacks of standard type, success criteria and consensus regarding to therapeutics response. Along this work, we evaluated the relation between risk factors and therapeutic, most adequate response, higher relation data of anastomotic bilioenteric stenosis, appearance period, most adequate time of drainage, incidence of complications, security and effectiveness therapeutic. METHODS: During the period of March 1993 to May 2006, 35 patients with anastomotic bilioenteric stenosis after having hepatic transplant prospective and retrospectively were evaluated. 34 of them (97.1%) were at the age of one year of above. 24 (68%) weighted more than 10kg. There was ABO compatibility in 100%, between genders in 28.6%, and 71.4% in relation to weight between receptor and donator. The main indication was biliary atresia ducts and 45% of transplants were made with living donators. 30 transplants (86%) were elective and 18 patients (51.4%) were previously submitted to Kasai surgery. The biliar reconstruction was made through anastomosis bilioenteric in all patients, The stenosis were confirmed by percutaneous colangiography, expanded and drained. The drain caliber was enlarged during the re-intervention, changed each 3 months and kept for at least 6 months. Complications were evaluated and the patients were allotted in groups according to G1 and G4 therapeutic response . RESULTS: fever, jaundice/icterus, hystopatologic exam with obstructed biliary pattern and high levels of gamaglutamitransferase were all presented in stenosis group. Patients submitted to Kasai surgery presented better response to the percutaneous treatment (p = 0.05). The other varieties did not demonstrate any statistically relevant association including better or worse response to the treatment. For group G1 were occurred less complications, 10 months of drainage was found as medium period. CONCLUSIONS: There was a satisfactory response in the groups with one or two sessions (86%) of percutaneous treatment. Kasai surgery is associated to the best responses to the treatment; hystopatologic exam with obstructed biliary pattern and elevation of gamaglutamitransferase presented better relation to stenosis, which have occurred more often after the first year of the transplant. Patients that have been drained for more than six months presented better results. However, the drainage extension is connected to more complications. The percutaneous treatment (expansion and drainage) is effective, with low complications rate.

INTRODUÇÃO: O transplante hepático é a terapêutica de escolha para pacientes com hepatopatias avançadas. Melhorias na seleção dos pacientes, avanços cirúrgicos e imunológicos aumentaram a sobrevida. As complicações biliares ocorrem em 15 a 35% dos transplantes e estão associadas a técnicas de redução hepática. A estenose anastomótica ocorre de 5 a 34% e pode ser tratada por cirurgia, acesso endoscópico ou percutâneo. Esse último apresenta bons resultados, mas carece de padronização, critérios de sucesso ou consenso quanto aos fatores que influenciam a resposta terapêutica. Neste trabalho, avaliou-se a relação entre os fatores de risco e a terapêutica, resposta mais adequada, dados de maior relação com a estenose da anastomose bílio-entérica, período de surgimento, tempo de drenagem mais adequado, incidência de complicações, eficácia e segurança terapêutica. MÉTODOS: No período de março de 1993 a maio de 2006, foram avaliadas trinta e cinco pacientes com estenose da anastomose bílio-entérica após o transplante hepático prospectiva e retrospectivamente. Trinta e quatro (97,1%) tinham idade igual ou superior a um ano. Vinte e quatro (68%) tinham mais de 10 kg. Houve compatibilidade ABO em 100%, entre gêneros em 28,6% e na relação de peso entre receptor e doador em 71,4%. A principal indicação foi atresia de vias biliares e 45% dos transplantes foram realizados com doadores vivos. Trinta transplantes (86%) foram eletivos e 18 pacientes (51,4%) foram submetidos previamente à cirurgia de Kasai. A reconstrução biliar foi feita por meio da anastomose bílio-entérica em todos os pacientes. As estenoses foram confirmadas por colangiografia percutânea, dilatadas e drenadas. O calibre dos drenos foi aumentado nas reintervenções, sendo trocado a cada três meses e mantido por pelo menos seis meses. As complicações foram avaliadas e os pacientes foram distribuídos em grupos de resposta terapêutica de G1 a G4. RESULTADOS: Febre, icterícia, exame histopatológico demonstrando padrão obstrutivo biliar e dosagem elevada de gamaglutamiltransferase estiveram mais presentes no grupo com estenose. Os pacientes submetidos à cirurgia de Kasai apresentaram melhor resposta ao tratamento percutâneo (p = 0,05). As outras variáveis não demonstraram correlação estatisticamente significativa com a melhor ou pior resposta ao tratamento. Observou-se tempo médio de drenagem de 10 meses no grupo G1, onde houve menor ocorrência de complicações. CONCLUSÕES: Houve resposta satisfatória nos grupos com uma ou duas sessões (86%) de tratamento percutâneo. A cirurgia de Kasai se associa com melhores respostas ao tratamento; o exame histopatológico demonstrando padrão obstrutivo biliar e a elevação de gamaglutamiltransferase apresentam maior relação com a estenose, que ocorreu mais freqüentemente após o primeiro ano do transplante. Os pacientes drenados por mais de seis meses apresentaram melhores resultados. Entretanto, o prolongamento da drenagem associa-se com mais complicações. O tratamento percutâneo (dilatação e drenagem) é eficaz, seguro, com baixa taxa de complicações. / INTRODUCTION: Hepatic transplant is the chosen therapy for patients with advanced hepathopathy. Improvement on patients selection, surgical and immunologic advances increases the life expectancy. Biliary complications occur between 15 to 35% transplants and are associated to hepatic reduction techniques. The anastimotic stenosis occur between 5 to 14% and can be treated by surgery, endoscopic access or percutaneous. This last one presents fair results. However, it lacks of standard type, success criteria and consensus regarding to therapeutics response. Along this work, we evaluated the relation between risk factors and therapeutic, most adequate response, higher relation data of anastomotic bilioenteric stenosis, appearance period, most adequate time of drainage, incidence of complications, security and effectiveness therapeutic. METHODS: During the period of March 1993 to May 2006, 35 patients with anastomotic bilioenteric stenosis after having hepatic transplant prospective and retrospectively were evaluated. 34 of them (97.1%) were at the age of one year of above. 24 (68%) weighted more than 10kg. There was ABO compatibility in 100%, between genders in 28.6%, and 71.4% in relation to weight between receptor and donator. The main indication was biliary atresia ducts and 45% of transplants were made with living donators. 30 transplants (86%) were elective and 18 patients (51.4%) were previously submitted to Kasai surgery. The biliar reconstruction was made through anastomosis bilioenteric in all patients, The stenosis were confirmed by percutaneous colangiography, expanded and drained. The drain caliber was enlarged during the re-intervention, changed each 3 months and kept for at least 6 months. Complications were evaluated and the patients were allotted in groups according to G1 and G4 therapeutic response . RESULTS: fever, jaundice/icterus, hystopatologic exam with obstructed biliary pattern and high levels of gamaglutamitransferase were all presented in stenosis group. Patients submitted to Kasai surgery presented better response to the percutaneous treatment (p = 0.05). The other varieties did not demonstrate any statistically relevant association including better or worse response to the treatment. For group G1 were occurred less complications, 10 months of drainage was found as medium period. CONCLUSIONS: There was a satisfactory response in the groups with one or two sessions (86%) of percutaneous treatment. Kasai surgery is associated to the best responses to the treatment; hystopatologic exam with obstructed biliary pattern and elevation of gamaglutamitransferase presented better relation to stenosis, which have occurred more often after the first year of the transplant. Patients that have been drained for more than six months presented better results. However, the drainage extension is connected to more complications. The percutaneous treatment (expansion and drainage) is effective, with low complications rate.