The discovery of new immunosuppressive drugs has resulted in an improvement of short-term graft survival. Despite this achievement, long-term cardiac allograft survival has not been correspondingly improved. Cyclosporine A (CsA), an effective immunosuppressive drug, has been shown to increase the risk of hyperlipidemia, hypertension, kidney injuries and chronic rejection despite its extensive use in the clinical setting. Therefore, these side-effects of CsA, may further contribute to graft failure over long-term. Early studies have shown that fish oil may reduce side-effects of CsA. These beneficial effects of fish oil may be related to n-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Flaxseed oil is another major source of an n-3 FA, namely α-linolenic acid (ALA). However, its impact on heart transplantation has not been fully explored. The current study aimed to investigate whether dietary flaxseed oil and fish oil reduce post-transplant complications and prolong graft function in a rat cardiac allograft model. Male Fischer and Lewis rats were used as donors and recipients, respectively, to generate a heterotopic cardiac allograft model. After transplant, animals were randomly assigned into 3 groups and fed a diet supplemented with: a) 5% w/w safflower oil (control n=7), b) 5% w/w flaxseed oil (n=8) or c) 2% w/w fish oil (n=7) and an intraperitoneal injection of cyclosporine A (CsA) (1.5 mg/kg/d) over 12 weeks. Body weight, blood pressure (BP), plasma levels of lipids, CsA, and select cytokines, fatty acid profile of hearts (native and graft) and liver tissues as well as graft function and chronic rejection features were assessed. Body weight and blood CsA levels were similar among the groups. As compared to controls, both diet treated groups demonstrated a significantly lower systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (pressure (DBP) (p<0.001), mean arterial pressure (MAP) (p<0.001), heart rate (p<0.05), abdominal fat (p<0.05) and plasma levels of macrophage chemoattractant protein-1 (MCP-1) (p<0.05). Moreover, the fish oil group had significantly (p<0.05) lower plasma levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), as compared to the control group. High-density lipoprotein cholesterol (HDL) concentrations were significantly higher (P<0.05) in the flaxseed oil-treated group as compared to the other two groups. Data of this study suggest that both flaxseed oil and fish oil may provide similar biochemical, hemodynamic and inflammatory improvements after heart transplantation; however, these apparent beneficial changes were not accompanied with significant reductions in chronic rejection states or apparent histological evidence of cyclosporine-induced nephrotoxicity in this model.

This thesis provides a first description and proof-of-concept of iterative cardiac output measurement (ICO) – a respiratory, carbon-dioxide (CO2) based method of measuring cardiac output (CO). The ICO method continuously tests and refines an estimate of the CO by attempting to maintain the end-tidal CO2 constant. To validate the new method, ICO and bolus thermodilution CO (TDCO) were simultaneously measured in a porcine model of liver transplant. Linear regression analysis revealed the equation ICO = 0.69•TDCO + 0.65 with a Pearson correlation coefficient of 0.89. Analysis by the method of Bland and Altman showed a bias of -0.2 L/min with 95% limits of agreement from -1.1 to 0.7 L/min. The trending ability of ICO was determined using the half-circle polar plot method where the mean radial bias, the standard deviation of the polar angle, and 95% confidence interval of the polar angle were -8º, ±17º, and ±33º, respectively.

This thesis provides a first description and proof-of-concept of iterative cardiac output measurement (ICO) – a respiratory, carbon-dioxide (CO2) based method of measuring cardiac output (CO). The ICO method continuously tests and refines an estimate of the CO by attempting to maintain the end-tidal CO2 constant. To validate the new method, ICO and bolus thermodilution CO (TDCO) were simultaneously measured in a porcine model of liver transplant. Linear regression analysis revealed the equation ICO = 0.69•TDCO + 0.65 with a Pearson correlation coefficient of 0.89. Analysis by the method of Bland and Altman showed a bias of -0.2 L/min with 95% limits of agreement from -1.1 to 0.7 L/min. The trending ability of ICO was determined using the half-circle polar plot method where the mean radial bias, the standard deviation of the polar angle, and 95% confidence interval of the polar angle were -8º, ±17º, and ±33º, respectively.

The discovery of new immunosuppressive drugs has resulted in an improvement of short-term graft survival. Despite this achievement, long-term cardiac allograft survival has not been correspondingly improved. Cyclosporine A (CsA), an effective immunosuppressive drug, has been shown to increase the risk of hyperlipidemia, hypertension, kidney injuries and chronic rejection despite its extensive use in the clinical setting. Therefore, these side-effects of CsA, may further contribute to graft failure over long-term. Early studies have shown that fish oil may reduce side-effects of CsA. These beneficial effects of fish oil may be related to n-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Flaxseed oil is another major source of an n-3 FA, namely α-linolenic acid (ALA). However, its impact on heart transplantation has not been fully explored. The current study aimed to investigate whether dietary flaxseed oil and fish oil reduce post-transplant complications and prolong graft function in a rat cardiac allograft model. Male Fischer and Lewis rats were used as donors and recipients, respectively, to generate a heterotopic cardiac allograft model. After transplant, animals were randomly assigned into 3 groups and fed a diet supplemented with: a) 5% w/w safflower oil (control n=7), b) 5% w/w flaxseed oil (n=8) or c) 2% w/w fish oil (n=7) and an intraperitoneal injection of cyclosporine A (CsA) (1.5 mg/kg/d) over 12 weeks. Body weight, blood pressure (BP), plasma levels of lipids, CsA, and select cytokines, fatty acid profile of hearts (native and graft) and liver tissues as well as graft function and chronic rejection features were assessed. Body weight and blood CsA levels were similar among the groups. As compared to controls, both diet treated groups demonstrated a significantly lower systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (pressure (DBP) (p<0.001), mean arterial pressure (MAP) (p<0.001), heart rate (p<0.05), abdominal fat (p<0.05) and plasma levels of macrophage chemoattractant protein-1 (MCP-1) (p<0.05). Moreover, the fish oil group had significantly (p<0.05) lower plasma levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), as compared to the control group. High-density lipoprotein cholesterol (HDL) concentrations were significantly higher (P<0.05) in the flaxseed oil-treated group as compared to the other two groups. Data of this study suggest that both flaxseed oil and fish oil may provide similar biochemical, hemodynamic and inflammatory improvements after heart transplantation; however, these apparent beneficial changes were not accompanied with significant reductions in chronic rejection states or apparent histological evidence of cyclosporine-induced nephrotoxicity in this model.

Elevated plasma lipids are risk factors for cardiovascular disease (CVD). In certain conditions plasma lipids are normal yet individuals experience increased morbidity. Type 1 diabetes (T1D) is associated with elevated CVD despite normal lipids, while in liver failure low plasma lipids may indicate increasing hepatic damage. Plasma lipids can therefore belie underlying dysregulated lipid metabolism. Islet (ITx) or liver (LTx) transplants represent therapies for T1D and liver failure, respectively, but are associated with altered lipid metabolism attributed to immunosuppressive medications; however, causative mechanisms are unknown. Partial success of dietary therapy in post-transplant patients may be due to interventions limited in scope. Regulation of plasma lipids involve absorption, synthesis, and clearance. These studies examined lipogenesis and cholesterol synthesis using deuterium incorporation. In brittle T1D lipogenesis and cholesterol synthesis were similar to healthy controls; however hepatic lipogenesis and cholesterol synthesis tended to be lower in T1D compared to matched control subjects. Plasma cholesterol was lower and triglyceride similar in liver failure patients compared to controls. Lipogenesis was higher while cholesterol synthesis was lower in liver failure compared to controls. Disturbances in lipid synthesis may be influenced by underlying disease, such as hepatitis C. In ITx and LTx lipogenesis was lower whereas cholesterol synthesis was similar compared to controls. Lipid synthesis is therefore unlikely to contribute to post-transplant hyperlipidemia, inviting investigation of other mechanisms. Dietary intervention emphasizing fish oil, phytosterols, soy, fibers, and almonds lowered plasma lipids in controls but had mixed effects in transplant subjects. Reduction in plasma lipids occurred in transplant patients with higher baseline lipids, suggesting this intervention may be successful in hyperlipidemic patients; however the potential of this diet intervention requires further study in hyperlipidemic patients. Diet intervention lowered lipogenesis but did not significantly change 24h cholesterol synthesis in controls. Diet did not change 24h lipogenesis or cholesterol synthesis in transplant subjects. Plasma lipid response to dietary therapy was related to baseline cholesterol synthesis and to dietary compliance in transplant subjects. Further study is required to determine if cholesterol synthesis is predictive of response to diet. / Nutrition and Metabolism

ABSTRACT Introduction: Renal transplant recipients (RTR) with abnormal glucose tolerance (AGT) are at an increased risk of graft failure and cardiovascular disease (CVD). CVD is the major cause of death in RTR. Whilst there are numerous known risk factors for AGT in RTR, it is unknown whether lifestyle factors are found in the presence or play a role in the development of AGT in RTR. The nutritional status of RTR in an Australian population has also not been extensively investigated. Investigation into these areas could help identify modifiable areas for change in the RTR population. Multidisciplinary lifestyle modification, including diet and physical activity (PA) advice from a dietitian, may help reduce modifiable risk factors for CVD in RTR with AGT. Aims: The principle aims of this thesis are to; 1) assess the incidence of obesity and central obesity in RTR and compare to rates in the general Australian population, 2) investigate and compare modifiable lifestyle factors and adipokine levels in RTR with AGT and normal glucose tolerance (NGT) and 3) investigate the effect of a multidisciplinary lifestyle intervention (including dietetic advice) on modifiable CVD risk factors in RTR with AGT. Methods: Chapter 1 presents a review of the literature describing the main nutritional challenges in RTR, cardiovascular risk factors in RTR including adipokine profiles and the role of body composition, diet and PA in RTR. Chapter 2 details the clinical, biochemical, nutritional, body composition, PA and statistical methodologies used in this thesis. In Chapter 3 a descriptive analysis of the anthropometry and cardiovascular risk profile of RTR in an Australian setting is investigated. Chapter 4 investigates the nutritional status of RTR with NGT and AGT in more detail, assessing diet, PA, adipokines and body composition. In Chapter 5, the current literature on lifestyle intervention management (including nutritional management) for obesity and type 2 diabetes mellitus in the general population is discussed. Building on previous chapters, Chapter 6 investigates the effect of a multi-disciplinary lifestyle intervention (with dietetic input) on modifiable cardiovascular risk factors in RTR with AGT. Results: In Chapter 3 it was found that RTR are significantly more centrally obese than those in the general population, and this was particularly the case in younger RTR. Central obesity was associated with CVD risk factors in RTR. Chapter 4 found that a lower level of PA, obesity and central obesity are associated with AGT in RTR, whereas no difference in adipokines or dietary intake was found. In Chapter 6, multidisciplinary lifestyle intervention with dietetic input was found to improve certain risk factors for CVD in RTR with AGT, such as dietary factors (total fat and saturated fat intake) and lipid levels. Conclusions: Central obesity is a common problem in RTR, particularly in those with AGT. Higher levels of PA are associated with lower risk of AGT in RTR, and may help reduce the incidence of central obesity in RTR. Multidisciplinary lifestyle intervention, with dietetic input, can improve some modifiable CVD risk factors in RTR with AGT, however more intensive intervention is required to significantly reduce the incidence of obesity. Key Words: Renal Transplant; Abnormal Glucose Tolerance, Obesity; Cardiovascular Disease; Physical Activity Australian and New Zealand Standard Research Classifications (ANZSRC) 1111 Nutrition and Dietetics, 1102 Cardiovascular medicine and Haematology, 1199 Other Medicine and Health Sciences

A medição de desempenho é estratégica para as organizações. Este estudo de caso investiga as medidas de desempenho do sistema nacional de transplantes, baseando-se na regional interior de São Paulo, focalizando uma equipe de transplante de fígado. Usa entrevistas abertas e análise de documentos para levantar evidências. Conclui que há carência de um conjunto sistemático de indicadores que auxilie a equipe a melhorar o desempenho logístico. Embora todos os membros reconheçam a importância da logística, faltam indicadores logísticos específicos para monitoramento de processos. A equipe acompanha um conjunto de indicadores de resultado como usual na área da medicina, focados no bem estar dos pacientes. Como alternativa, este trabalho analisa um conjunto de indicadores propostos por auditoria externa, notando que os indicadores propostos ainda são de resultado e não contribuem para a melhoria das funções e processos de transplante. / Performance measurement is strategic for organizations. This case study researches logistics performance measure of brazilian national transplant system, based on countryside regional of São Paulo state, focused in liver transplant team. It uses open interviews and document analysis. It finds out there is no systematic set of indicators that helps the team to improve logistics performance. Although all members recognize logistics importance, there are no specific logistic indicators for monitoring processes. A set of resulting indicators is followed up, as usual in medical area, all of them focused in welfare-state of patients. Alternatively, this work analyses a set of indicators just proposed to the organization by a external audition, realizing that the new indicators don´t contribute to function and processes improvement.

Orientador: Salomon Soriano Ordinola Rojas / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-15T00:59:13Z (GMT). No. of bitstreams: 1 Miguel_GabrielAntonioStanisci_M.pdf: 2975905 bytes, checksum: c45b885c0ebe455da2be8fded7817e46 (MD5) Previous issue date: 2009 / Resumo: Introdução: O transplante (TX) cardíaco é uma alternativa para os indivíduos com doença cardíaca terminal. Na evolução pós-TX, a ocorrência de episódios de rejeição é um evento frequente, sendo responsável pelo aumento da morbimortalidade. Uma alternativa relevante seria o emprego de um exame não invasivo que tivesse uma boa acurácia na detecção das alterações da função sisto-diastólica do coração transplantado, pois a biópsia endomiocárdica (BEM) não é um procedimento isento de complicações. Objetivo: Comparar a função ventricular esquerda entre os pacientes transplantados com rejeição cardíaca e os pacientes transplantados sem rejeição; utilizando como referência o grupo controle e correlaciona-la com rejeição cardíaca imunológica. Métodos: Foram realizados ecocardiogramas transtorácicos no período de janeiro de 2006 a janeiro de 2008, para a avaliação prospectiva de 47 pacientes; sendo 17 pacientes (36,2 %) pertencentes ao grupo controle (grupo GC), 18 (38,3%) pertencentes ao grupo de pacientes transplantados sem rejeição (TX0) e 12 (25,5%) pertencentes ao grupo de pacientes transplantados com rejeição (TX1). Comparou-se a função sisto-diastólica entre os três grupos (GC, TX0, TX1). Para o estudo da homogeneidade entre proporções foi utilizado o teste exato de Fisher. Para a análise da hipótese de igualdade entre os grupos em relação às medianas, utilizou-se o teste não-paramétrico de Kruskal-Wallis seguido do teste de comparações múltiplas. O nível de significância utilizado para os testes foi de 5%. Resultados: Os grupos não diferiram em relação à idade [34,0 (29,5 - 44,0) X 46,0 (33,5 - 51,5) X 39,0 (32,5 - 54,5) p = 0,354], ao peso [70,0 (57,5 - 85,0) X 66,5 (57,5 - 88,0) X 61,0 (57,5 - 73,5) p = 0,661], altura [1,65 (1,59 - 1,73) X 1,66 (1,64 - 1,70) X 1,69 (1,64 - 1,72) p = 0,821] e superfície corpórea [1,84 (1,58 - 1,98) X 1,75 (1,62 - 2,03) X 1,69 (1,63 - 1,88) p = 0,758]. O grupo GC quando comparado com o grupo TX0, apresentou alteração da função sisto-diastólica do ventrículo esquerdo, expressa através do aumento do Índice de Performance Miocádica (IPM), sendo esta mais significativa nos pacientes do grupo TX1 [0,38 (0,29 - 0,44) X 0,47 (0,43 - 0,56) X 0,58 (0,52 - 0,74) p <0,001]. Conclusão: Foi evidenciado que o Índice de Performance Miocárdica encontra-se aumentado nos pacientes transplantados, em relação ao grupo controle e não houve diferença significativa entre os dois grupos de pacientes transplantados; portanto, o ecocardiograma mostrou-se como exame de boa acurácia na detecção das alterações da função sisto-diastólica do coração transplantado e não foi confiável como método substituto da biópsia endomiocárdica para o diagnóstico seguro de rejeição cardíaca. / Abstract: Introduction: The transplant (TX) cardiac is an alternative for the individuals with terminal cardiac illness. In the evolution after TX, the occurrence of rejection episodes is a frequent event, being responsible for the increase of morbi-mortality. An excellent alternative would be the job of a not invasive examination that had a good acurácia in the detention of the alterations of the diastolic function of the transplantated heart, therefore the endomyocardial biopsy (BEM) is not an exempt procedure of complications. Objective: Compare the left ventricular function between patients transplated with rejection and cardiac transplant patients without rejection, using as reference the control group and correlated it with immunological rejection rate. Methods: Transthoracic echocardiograms in the period of January of 2006 had been carried through the January of 2008, for the prospective evaluation of 47 patients; being 17 patients (36,2 %) pertaining to the group it has controlled (group GC), 18 (38,3%) pertaining to the group of patients transplantated without rejection (TX0) and 12 (25,5%) pertaining ones to the group of patients transplantated with rejection (TX1). It was compared sisto-diastolic function between the three groups (GC, TX0, TX1). To study the homogeneity of proportions was used Fisher's exact test. For the analysis the hypothesis of equality between the groups in relation to the medians, we used the nonparametric Kruskal-Wallis test followed by multiple comparisons. The significance level used for the tests was 5%. Results: The groups did not differ in age [34.0 (29.5 to 44.0) X 46.0 (33.5 - 51.5) X 39.0 (32.5 - 54.5) p = 0.354 ], weight [70.0 (57.5 to 85.0) X 66.5 (57.5 to 88.0) X 61.0 (57.5 to 73.5) p = 0.661], height [ 1.65 (1.59 to 1.73) X 1.66 (1.64 - 1.70) X 1.69 (1.64 - 1.72) p = 0.821] and body surface area [1.84 ( 1.58 to 1.98) X 1.75 (1.62 - 2.03) X 1.69 (1.63 to 1.88) p = 0.758]. The GC group compared with the group TX0, had an alteration of the systolic-diastolic function of left ventricle, expressed by increasing the Miocardic Performance Index (IPM), which is more significant for patients in group TX1 [0.38 (0, 29 to 0.44) X 0.47 (0.43 to 0.56) X 0.58 (0.52 to 0.74) p <0.001]. Conclusion: It was shown that the myocardial performance index is increased in transplant patients in the control group and no significant difference between the two groups of transplant patients, so the echocardiogram showed to be taking good accuracy in the detection of systolic-diastolic function of the transplanted heart and was not a reliable method of biopsy substitute for the confident diagnosis of cardiac rejection. / Mestrado / Cirurgia / Mestre em Cirurgia

O osso alógeno fresco-congelado (FFBA, do inglês fresh-frozen bone allograft) é uma alternativa para os procedimentos cirúrgicos de enxerto ósseo, principalmente na preparação do rebordo alveolar para a instalação de implantes osseointegráveis. No entanto, existem alguns paradigmas que envolvem a relação entre resposta do sistema imunológico à aloantígenos presentes no enxerto e o seu comportamento clínico. Procurando entender essa relação, o FFBA foi avaliado como enxerto para preservar o rebordo alveolar pós-extração. Os resultados mostraram que embora tenha ocorrido uma redução estatisticamente significante na altura, espessura e volume do rebordo entre a avaliação inicial e final, essa redução não foi clinicamente significante, permitindo a instalação de implantes osseointegráveis. Em adição, as análises histológicas sugerem um bom comportamento do enxerto, com ausência de reação do tipo corpo estranho e formação de novo osso em todos os sítios analisados. Ao analisar o comportamento da resposta imune, os resultados mostraram que a injeção intradérmica de aloantígenos presentes no FFBA, não induziu uma reação de hipersensibilidade tardia nos pacientes após 4 meses do enxerto. Além disso, os monócitos do sangue periférico (PBMCs) dos pacientes não proliferaram frente aos aloantígenos in vitro. No entanto, os dados também demonstraram que os aloantígenos aumentam a produção de IL-2 e IFN-, mas não alteram a produção de IL-4 e IL-10, por PBMCs dos pacientes. Ao avaliar a relação entre a produção dessas citocinas e o comportamento clínico do enxerto, os dados mostram que existe uma correlação estatisticamente significante entre a produção de IL-2 in vitro e a redução (em %) da altura do rebordo alveolar, embora essa redução não tenha sido clinicamente significante. De fato, a presença de aloantígenos no FFBA não é suficiente para sua contraindicação como material de enxertia. / The fresh-frozen bone allograft (FFBA) is an alternative to surgical procedures of bone grafts, mainly in the preservation of alveolar ridge prior the installation of osseointegrated implants. However there are paradigms that surround the relation between immune response to alloantigens present inside the graft and the clinical response of the graft. An attempt to understand this relationship, the FFBA was evaluated as a graft to preserve the alveolar ridge post-extraction. The results show a statistically significant reduction in height, thickness and volume of the ridge between the initial and final examination, however this reduction was not clinically significant. The ridge preservation allowed implant installation and osseointegration. In addition, histologic analysis suggests a good performance of the graft with no foreign body reaction and formation of new bone at all sites. In analyzing the behavior immune response, the results showed that stimulation with alloantigens present in bone allograft induced no delayed hypersensitivity reaction in vivo. Additionally, periphery blood mononuclear cells (PBMC) from patients no proliferate in response to alloantigens in vitro. However, the data also demonstrated that the alloantigens increase IL-2 and IFN- production, but no IL-4 and IL-10 production, by PBMCs from patients. When evaluate the relation between the cytokines production and clinical parameters, the results demonstrate that there statistically significant correlation between IL-2 production in vitro and ridge height changes (%), although this clinical parameter is not clinically significant. In fact, the alloantigens in FFBA are not sufficient for its contraindications as grafting material.

Orientadores: Ilka de Fatima Santana Ferreira Boin, Raquel Silveira Bello Stucchi / Tese (doutorador) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T02:50:29Z (GMT). No. of bitstreams: 1 Silva_AnaCarolinaGuardiada_D.pdf: 4973684 bytes, checksum: b2c754b94b99a119ae7e84ac207a9555 (MD5) Previous issue date: 2013 / Resumo: Introdução: As infecções oportunistas constituem um dos principais problemas para os transplantados de fígado. O Citomegalovírus (CMV) e o Herpesvirus humano 6 (HHV- 6) são patógenos oportunistas freqüentes nesses pacientes, e o HHV-6 tem sido associado a várias desordens tais como a encefalite. A PCR em tempo real (RT-PCR) é o padrão ouro de diagnóstico para os herpesvirus, pois tem melhor precisão, maior rendimento e menos risco de contaminação em comparação com outros testes convencionais. Objetivo: Este estudo teve como objetivo avaliar a cinética viral do HHV-6 e CMV por RT-PCR nos pacientes submetidos ao transplante hepático correlacionando-a com a presença de encefalite e complicações clínicas ocorridas no período pós-transplante. Método: Foram analisadas prospectivamente pela RT- PCR a carga viral do CMV e HHV-6 de 30 pacientes transplantados de fígado. A monitorização dos pacientes foi realizada prospectivamente desde o pré-transplante (imediatamente antes do ato cirúrgico - dia zero) com amostras do doador e receptor, e no pós-transplante: 2ª, 3ª, 4ª, 6ª, 8ª, 10ª e 12ª semanas, somando 270 amostras de soro. O protocolo foi seguido de acordo com os requerimentos para pesquisas e foi aprovado pelo Comitê de Ética em Pesquisada da Faculdade de Ciências Médicas da Universidade Estadual de Campinas (CEP nº 430/2003). Os achados clínicos foram obtidos através dos prontuários. Para a detecção e quantificação do DNA dos vírus CMV e HHV-6 foram usados os Kits comerciais "CMV Real-TM Quant" e "HHV-6 Real-TM Quant". Os testes de Nested-PCR e antigenemia foram realizados rotineiramente para o vírus CMV, pelos laboratórios do HC-Unicamp, e seu resultados obtidos eletronicamente. A análise estatística comparou as variáveis categóricas usando o teste exato de Fisher. Para identificar os fatores associados ao aumento da carga viral foi utilizado o método das Equações de Estimação Generalizadas e medidas de acurácia. Resultados: Treze (43%) dos 30 pacientes apresentaram infecção pelo HHV-6 e 26 (86%) apresentaram infecção pelo CMV. Nove pacientes apresentaram encefalite após o transplante de fígado sendo que sete deles tiveram infecção pelo HHV-6 (p=0,0012), assim com o aumento da carga viral do HHV-6 se constatou a presença de encefalite após o transplante de fígado (p= 0.0226). O RT- PCR (p= 0,0306) para o CMV mostrou aumento significativo na segunda a quarta semana e décima a décima segunda semanas em relação aos outros testes, mostrando-se também mais sensível. Conclusão: concluímos que o aumento da carga viral do HHV-6 foi associado com a presença de encefalite após o transplante de fígado e a técnica de PCR em tempo real se mostrou como o teste mais sensível para detecção e monitorização do CMV nos pacientes transplantados de fígado / Abstract: Introduction: Opportunistic infections are a major problem for liver transplantation patients. Cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) are opportunistic common pathogens and HHV-6 has been associated with several disorders such as encephalitis. Real-time PCR (RT-PCR) is the gold standard for diagnosis of herpesvirus, as it has better accuracy, higher efficiency and less risk of contamination compared to other conventional tests. Objective: The aim of study was to evaluate the viral kinetics of HHV-6 and CMV by RT-PCR in patients undergoing liver transplantation and correlated with the presence of encephalitis complications occurring in the post-transplant period. Methods: We prospectively analyzed by RT-PCR the viral load of CMV and HHV-6 in 30 liver transplant patients. Monitoring of patients was performed prospectively from pretransplant (immediately before surgery-day zero) with donor and recipient samples and posttransplant: 2nd, 3rd, 4th, 6th, 8th, 10th and 12th weeks with a total of 270 serum samples. The protocol was followed according to the requirements for research and was approved by the Ethics Research Committee of the Faculty of Medical Sciences State University of Campinas (CEP nº 430/2003). The clinical findings were obtained from the medical records. For detection and quantification of DNA of the CMV and HHV-6 virus the commercial kits "Real- CMV Quant TM" and "HHV-6 Real -TM Quant" were used. Nested-PCR and antigenemia tests were performed routinely for CMV virus and their results obtained electronically. Statistical analysis comparing categorical variables was applied using Fisher exact test. To identify associated factors with increased viral load the method of Generalized Estimation Equation (GEE) and the accuracy and precision was used. Results: Thirteen (43 %) of the thirty patients had HHV-6; 26 (86 %) had CMV infection. Nine patients had encephalitis after liver transplantation and seven of them had HHV-6 (p = 0.0012) and with an increasing viral load of HHV-6 the presence of encephalitis after liver transplantation was found (p = 0.0226). RT-PCR (P = 0.0306 ) CMV showed a significant increase at the 2nd to 4th week and 10th to 12th week compared to the other tests, having also more sensibility. Conclusion: We concluded that the increase in viral load of HHV-6 was associated with the presence of encephalitis after liver transplantation and the technique of real-time PCR was shown to be the best sensibility test for the detection and monitoring of CMV in our liver transplant patient / Doutorado / Fisiopatologia Cirúrgica / Doutora em Ciências da Cirurgia