The use of quality-of-life as an outcome measure provides detailed information about the effectiveness of medical treatments than morbidity or mortality rates alone. The use of quality-of-life data in the clinical setting can inform patients regarding treatment options, treatment benefits and costs. In competing health care markets, outcome measurement is regarded as important as it is concerned with the impact of health care practice and affects health policy decisions. Doessel (1978) conducted the first Australian study on the cost-effectiveness analysis of renal replacement therapies. The study was based on Klarman, Francis & Rosenthal's (1968) the study, where the output was measured in terms of the number of life years gained from kidney transplantation, and a twenty-five percent weight was allocated in an attempt to capture quality-of-life from kidney transplantation. Doessel (1978) used two sources of data: Australian data (Disney 1974) and European data (Gurland et al. 1973; Shiel et al. 1974). The study measured life years gained, and agreed with the Klarman et al. (1974) findings that transplantation is the most effective way to increase life expectancy of persons with chronic renal disease (Butler & Doessel 1989). The outputs of the alternative treatments were not reported in monetary terms; the study focused on life years gained as the output measure. Hence the importance of this current study, which includes a cost-effectiveness analysis for cadaver liver, and living kidney transplantation for end-stage liver and kidney disease patients. Calls to respect patient autonomy and to produce patient-centered outcomes have recently brought the patient’s point of view back into the center of clinical medicine (Sullivan 2003). Survival rates indicate one measure of outcome however they do not reflect patients’ perceptions of health benefit or experiences. Noting that patients’ psychosocial effect on functioning is of more concern to them than their physical Thesis Preamble iii ability, that more accurate knowledge of patients’ conditions be measured prior to transplantation (Tarter et al. 1991). Recently researchers advocated investigating transplant patients' states of health to assess the social benefit of these expensive health care services from their perspective (Joralemon & Fujinaga 1997). The current study's mixed method, bridges the gaps in treatment outcome measurements, as the mixed method applied (Creswell 1994; Sim & Sharp 1998) prospectively measured quality-oflife, determined health utility, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). The study reported the living donors experience of the donation process, described their needs; expressed using a new psychosocial model supporting future living kidney donor's during the donation process.

Introduction : La tyrosinémie de type I est une maladie génétique sévère. Elle se caractérise par des manifestations hépatiques, rénales et neurologiques. Depuis 1994, le NTBC représente la thérapie de première ligne. Ce médicament a conduit à une amélioration radicale de la morbidité et du pronostic de la maladie. Objectif : Évaluer les coûts directs des soins de santé reliés au traitement de cette maladie. Cette évaluation économique a été effectuée en trois groupes dont, un groupe historique de patients non traités; un groupe traitement tardif et un groupe traitement précoce par NTBC. Méthode : L’analyse coûts-conséquences inclut les coûts des hospitalisations, des services médicaux et des thérapies associées. Les données proviennent des banques de la RAMQ, de Med-Echo et des dossiers hospitaliers. Résultats : Le NTBC est associé à une réduction significative des hospitalisations, des séjours aux soins intensifs et des greffes hépatiques. Les coûts hospitaliers sont significativement moindres pour les groupes traités (13 979 $, 6 347 $ et 673 $ par année-patient pour les groupes historique, traitement tardif et traitement précoce,respectivement; valeur p < 0,0001). Les coûts des hospitalisations pour greffes par année-patient sont de 4 676$ pour le groupe historique et de 3 567 $ pour le groupe traitement tardif. Les coûts du NTBC par année-patient sont de 66 965 $ et de 51 493 $ pour les groupes traitement tardif et traitement précoce, respectivement. Conclusion : Les résultats démontrent l’impact majeur du NTBC sur la réduction de l’utilisation des ressources de santé, des greffes hépatiques et des coûts associés. / Introduction : Tyrosinemia type I is a severe genetic disorder. Symptoms include hepatic,renal and neurological manifestations. NTBC became the first-line therapy in 1994. This drug has led to a drastic improvement in the prognosis. Objective : To evaluate direct medical costs of healthcare services related to the treatment for this disease. This economic evaluation was conducted among the 3 following groups: an historical group of untreated patients, a late-treatment group and an early-treatment group with NTBC. Methods : The costs-consequences analysis includes costs incurred by hospitalizations, medical services and related treatments. Data are derived from the RAMQ and Med-Echo administrative databases and patients’ hospital charts. Results : NTBC treatment is associated with a significant reduction in hospitalizations, intensive care unit stays and liver transplantations. The cost of hospitalizations is significantly less for both treated groups (13,979 $, 6,347 $ and 673 $ per year-patient for the historical group, the late-treatment and the early-treatment group, respectively; pvalue< 0,0001). The cost of hospitalizations for liver transplantations per year-patient is 4,676 $ for the historical group and 3,567 $ for the late-treatment group. The cost of NTBC per year-patient is 66,965$ and 51,493$ for the late-treatment and the earlytreatment groups, respectively. Conclusion : These results demonstrate that NTBC treatment results in a major reduction in healthcare resources utilization, liver transplantations and associated costs. / Réalisé dans le cadre d'un mandat de l'Unité d'évaluation des technologies et des modes d'intervention en santé (UETMIS) du CHU Sainte-Justine

Este estudo teve, por finalidade, estabelecer o valor da ressonância magnética em 30 doadores potenciais do lobo direito do fígado, na determinação dos seguintes fatores: esteatose hepática; anatomia biliar; anatomias arterial hepática, venosas portal e hepática, e volume hepático lobar, comparando-os, respectivamente, com os achados anatomopatológicos da biópsia hepática, da colangiografia intraoperatória, da angiografia digital e/ou com os achados cirúrgicos, e com o peso real do enxerto. A RM subestimou a infiltração gordurosa hepática; permitiu identificar a anatomia biliar, com concordância em 83% dos casos; apresentou 100% de concordância na avaliação das anatomias arterial e venosas portal e hepática, e superestimou, em pequeno grau, o volume hepático lobar / The purpose of this study was to establish the value of the magnetic resonance in 30 potential donors for right lobe living liver transplantation. The main goal was to determine the following factors: steatosis; biliar anatomy; hepatic arterial anatomy; portal and hepatic venous anatomy, and lobar liver volume, comparing them to liver biopsy results, to intraoperative colangiography, to digital angiography and/or surgical findings, and to the real graft weight, respectively. The MR has underestimated liver steatosis; it has identified biliar anatomy with 83% of agreement; it has had 100% of agreement in the evaluation of arterial and portal and hepatic venous anatomy, and it has overestimated with small degree the lobar liver volume

As complicações biliares mais comuns pós-transplante hepático são as estenoses da anastomose, as estenoses não-anastomóticas e as fístulas biliares e podem ocorrer de diferentes modos, de forma isolada ou associada. A origem do enxerto (doador cadáver ou doador vivo) tem influência na incidência de estenose biliar, bem como na resposta ao tratamento endoscópico. A terapêutica endoscópica utilizando-se esfincterotomia, dilatação balonada da estenose e inserção de próteses biliares através da CPRE é utilizada como método inicial de tratamento dessas complicações. Objetivos: Comparar as diferentes técnicas de tratamento endoscópico das estenoses biliares pós-transplante hepático. Método: Foi realizada uma revisão sistemática da literatura e metanálise sendo a busca conduzida nas bases MEDLINE, EMBASE, Scielo - LILACS e Biblioteca Cochrane até junho de 2015. A metanálise foi executada utilizando-se os softwares Review Manager, 2012 (RevMan) versão 5.2 e OpenMetaAnalyst e os cálculos dos desfechos foram feitos comparando-se os resultados dos estudos incluídos utilizando-se a diferença de risco absoluto e adotando-se um intervalo de confiança (IC) de 95%. Os estudos foram agrupados comparando-se transplantes hepáticos com doador cadáver versus doador vivo; dilatação biliar endoscópica com balão exclusiva versus dilatação biliar endoscópica com balão associada à inserção de próteses plásticas e próteses biliares plásticas comparadas à prótese biliar metálica por endoscopia. Os desfechos clínicos analisados foram incidência da estenose biliar, falha do tratamento endoscópico, resolução da estenose, recorrência da estenose e complicações. Resultados: Foram recuperados 1.110 artigos, sendo motivo de análise dez ensaios clínicos, com apenas um Ensaio Clínico Randomizado e nove Ensaios Clínicos não randomizados, dos quais sete foram incluídos na metanálise. Comparando-se doador cadáver e doador vivo observou-se redução da incidência de estenose biliar (p=0,0001), bem como da falha técnica do tratamento endoscópico (p=0,0009) e da recorrência da estenose biliar (p=0,03) nos transplantes realizados com enxertos provenientes de doador cadáver. Dois estudos compararam o tratamento da estenose da anastomose biliar pós-transplante hepático utilizando dilatação com balão exclusiva versus dilatação com balão associada à inserção próteses plásticas e não foram observadas diferenças estatisticamente significantes em relação aos desfechos falha de tratamento, recorrência da estenose ou complicações. Somente o desfecho clínico complicações teve resultado estatisticamente significante na comparação entre prótese metálica autoexpansível versus prótese plástica no tratamento da estenose da anastomose biliar pós-transplante hepático (p= 0.03). Conclusões: O tratamento da estenose biliar anastomótica pós-transplante hepático com prótese metálica foi igualmente efetivo quando comparado ao uso de prótese plástica, mas associou-se a um menor risco de complicações. A comparação entre dilatação com balão exclusiva e dilatação com balão associada à prótese plástica apresentou resultados semelhantes em relação à falha do tratamento endoscópico, complicações e recorrência da estenose. A utilização de enxerto proveniente de doador cadáver reduziu o risco de estenose biliar pós-transplante hepático e o tratamento endoscópico nesse grupo de pacientes, foi mais efetivo quando comparado com as estenoses biliares após transplante com doador vivo / The most common biliary complications after liver transplantation are anastomotic strictures, non-anastomotic strictures and biliary fistulas and they can occur in different fashions, isolated or in combination. Graft source (cadaveric liver donor or living liver donor) has an influence on the incidence of biliary strictures as well as on the response to endoscopic treatment. The endoscopic treatment using sphincterotomy, balloon dilation and insertion of biliary stents by ERCP (Endoscopic Retrograde Cholangiopancreatography) is used as an initial endoscopic approach to treat these complications. Objectives: To compare different endoscopic techniques to treat post-liver transplantation biliary strictures. Method: It was performed a systematic review of the literature and meta-analysis and the search was carried out on MEDLINE, EMBASE, Scielo-LILACS and Cochrane Library databases until June, 2015. The meta-analysis was made using Review Manager, 2012 (RevMan) version 5.2 and OpenMetaAnalyst software and the calculations of the outcomes were made comparing the results from the included papers by using the difference in absolute risks, adopting a confidence interval of 95%. The studies were grouped comparing cadaveric liver donor versus living liver donor grafts; exclusive balloon dilation versus balloon dilation associated with plastic stents insertion; and plastic stents versus totally covered selfexpandable metal stents. The clinical outcomes were biliary stricture incidence, endoscopic treatment failure, stricture resolution, stricture recurrence and complications. Results: There were retrieved 1,100 articles. Ten clinical trials were analyzed, with just one Randomized Clinical Trial and nine Non-Randomized Clinical Trials, out of which seven were included in the meta-analysis. When comparing cadaveric liver donor transplantation to living liver donor transplantation, it was observed a decrease in the incidence of biliary strictures (p=0.0001), as well as in the technical failure rate of the endoscopic treatment (p=0.0009) and in the biliary stricture recurrence (p=0.03) in the cadaveric liver donor graft group. Two studies have compared the treatment of anastomotic biliary strictures after liver transplantation using balloon dilation exclusive to balloon dilation associated with the insertion of plastic stents, and no statistically significant differences in relation to endoscopic treatment failure, stricture recurrence or complications rates were observed. Only the clinical outcome complications had statistically significant result in a comparison between self-expandable metal stents versus plastic stents in the treatment of post-liver transplantation anastomotic biliary strictures (p=0.03). Conclusions: The treatment of post-liver transplantation anastomotic biliary strictures was equally effective when compared the use of self-expandable metal stents to plastic stents, but the use metallic stents was associated with a lower complication risk. The comparison between exclusive balloon dilation to balloon dilation associated with plastic stents presented similar results in relation to endoscopic treatment failure, complications and stenosis recurrence. The use of graft from cadaveric donor reduced the risk of biliary stenosis after liver transplantation and endoscopic treatment of biliary strictures in these patients were more effective when compared to biliary strictures after living liver donor transplantation

Atresia de vias biliares (AVB) é uma hepatopatia colestática específica da criança, de etiologia desconhecida, com evolução para fibrose hepática precoce. AVB é a principal causa de cirrose na infância e principal indicação de transplante hepático pediátrico (Tx). Compreender os fatores envolvidos na progressão da fibrose é fundamental para estabelecer tratamentos efetivos nas hepatopatias crônicas. Identificar padrões histopatológicos associados ao prognóstico da AVB permitiria melhor planejamento dos centros de transplante e adequado aconselhamento familiar. OBJETIVO: Estabelecer padrões de marcadores histopatológicos e de imunofluorescência para colágenos em biópsias hepáticas iniciais e finais de pacientes com AVB submetidos a tratamento cirúrgico. Correlacionar esses marcadores com o prognóstico da doença, definido com base no tempo de evolução até realização do Tx. MÉTODO: Avaliação histológica de alterações biliares e fibrose hepática e histomorfometria da fibrose marcada por picrossírius e da deposição dos colágenos tipos I, III, IV e V marcados por imunofluorescência indireta (IF), em biópsias hepáticas iniciais e finais de 36 pacientes com AVB submetidos à hepatoportoenterostomia de Kasai (KPE) e ao Tx nos últimos 20 anos em nossa instituição. RESULTADOS: A mediana das idades de realização da KPE foi de 12,5 semanas (6-20) e do Tx foi de 27 meses (6-120). Reação ductular e malformação de placa ductal foram mais intensas nas biópsias iniciais (p < 0,05), enquanto fibrose hepática e ductopenia apresentaram padrão progressivo (p < 0,001), sem correlações com a idade de realização da KPE nem com o tempo de evolução até Tx. A morfometria da fibrose hepática marcada pelo picrossírius nas biópsias iniciais apresentou correlação positiva com a idade da KPE (p = 0,01), mas não com a idade do Tx (p = 0,24). A deposição perissinusoidal dos colágenos dos tipos III e V foi mais intensa nas biópsias iniciais (p < 0,01), enquanto os colágenos dos tipos I e IV apresentaram padrão de deposição progressiva (p < 0,01). Pacientes com maior deposição perissinusoidal de colágeno tipo I nas biópsias iniciais apresentaram curva de tempo de evolução até Tx sugerindo pior prognóstico (p = 0,04). CONCLUSÃO: Marcadores histopatológicos de alterações biliares, fibrose hepática e deposição de colágenos apresentaram características evolutivas distintas nas fases inicial e final da AVB, sem correlação com o tempo de evolução até Tx. A morfometria da deposição perissinusoidal de colágeno tipo I em biopsias iniciais marcadas por IF pode ser correlacionada ao tempo de evolução até Tx em pacientes com AVB operada / Biliary atresia (BA) is a specific cholestatic liver disease of unknown etiology that affects children and progresses to early hepatic fibrosis. BA is the main indication of pediatric liver transplantation (LTx). Understanding the factors involved in the progress of fibrosis is essential to establish effective treatment to chronic liver disease. Histopathological markers in liver biopsies could be useful to predict progression to end stage disease and to make it possible to improve planning in transplantation centers and parental orientation. OBJECTIVE: To establish histopathological or immunohistochemical markers in initial or final liver biopsies of BA patients and correlate those markers with prognosis, as defined by progression time lapse until LTx. METHOD: Histological analysis of multiple parameters of biliary alterations and morphometrical assessment of liver fibrosis were performed, besides indirect immunofluorescence assays (IF) for type I, III, IV and V collagens in initial and final liver biopsies of 36 patients with BA submitted to Kasai hepatoportoenterostomy (KPE) and LTx in the last 20 years in a single center. RESULTS: The median of the ages at KPE was 12.5 weeks (6-20) and at LTx was 27 months (6-120). Ductular reaction and ductal plate malformation were more severe in the initial biopsies (p < 0.05), while ductopenia and liver fibrosis were more severe in final biopsies (p < 0.001), though without correlation with age at KPE nor with progression time lapse until LTx. Morphometrical assessment of liver fibrosis marked by picrosirius red in initial biopsies demonstrated positive correlation with age at KPE (p = 0.01) but not with age at LTx (p = 0.24). The perisinusoidal deposition of type III and V collagens was more extended in the initial biopsies (p < 0.01), while type I and IV collagens deposition indicated progression (p < 0.01). Patients with large amounts of perisinusoidal type I collagen in the initial biopsies had worse progression time curve until LTx (p = 0.04). CONCLUSION: Biliary alterations, liver fibrosis and collagens deposition demonstrated distinctive progression findings in the initial or final phases of the BA, without prognostic correlation. Morphometrical assessment of perisinusoidal deposition of type I collagen by IF in the initial biopsies can be correlated with progression time until LTx in patients with post-surgical BA