Os enxertos hepáticos com esteatose apresentam risco aumentado para a disfunção e o não funcionamento primário. Entretanto, considerando o permanente desequilíbrio entre a oferta e a demanda de enxertos, justifica-se o uso de fígados esteatóticos com um risco aceitável. O padrão ouro para o diagnóstico do grau da esteatose hepática, na prática clínica, é o exame histológico. Entretanto, no cenário dos transplantes, a estimativa do grau de esteatose do enxerto hepático depende do exame macroscópico. Nesse procedimento a leitura da cor é realizada de forma subjetiva e a força da associação cor-esteatose não é conhecida. Considerando esses aspectos, a presente pesquisa teve como objetivo verificar a associação entre a cor do fígado e a intensidade da esteatose hepática, aferindo a cor do fígado, de forma precisa com um colorímetro e quantificando a esteatose com dois exames considerados de referência. Método: Ratos wistar, machos, foram divididos em quatro grupos de quinze animais. Os animais do grupo controle receberam dieta padrão. Os outros três grupos receberam dieta esteatogênica durante, respectivamente, dois, quatro e seis dias. Os ratos foram submetidos à laparotomia, biópsia hepática (pré e pós-perfusão do fígado) para realizar o exame histológico, colorimetria no padrão RGB (pré e pós-perfusão do fígado), conversão da cor, do padrão RGB, para o padrão CINZA, coleta de sangue para realizar exames laboratoriais e hepatectomia (para determinar o peso relativo do fígado e a extração da gordura). A análise estatística foi realizada com o pacote de software estatístico IBM SPSS Statistics 18, e o valor p < 0.05 foi considerado com significado estatístico. Resultados: Foi observada correlação positiva entre os percentuais de gordura e a intensidade das cores pré perfusão (coeficiente de correlação da cor vermelha 0,874, cor verde 0,747 e cor azul 0,763) e pós-perfusão (coeficiente de correlação da cor vermelha 0,900, cor verde 0,886 e cor azul 0,856). As medias dos valores da colorimetria, pré e pós perfusão, apresentaram diferença estatisticamente significativa (p < 0,001). A acurácia da colorimetria pós perfusão, determinada pela curva ROC, foi de100% na determinação da presença de esteatose, 96,2% para o grau moderado ou intenso e 80,4% para o grau intenso da esteatose. Foi verificada diferença significativa dos valores da colorimetria (p < 0,001) entre as medias dos diversos grupos com exceção entre os grupos concentração de gordura moderada X gordura intensa e entre os grupos graus histológicos da esteatose leve X moderada X intensa. Conclusões: a) A cor do fígado, pré e pós perfusão, apresentou correlação forte com a esteatose, de forma positiva e linear; b) A colorimetria, pré e pós perfusão, apresenta a mesma acurácia na identificação da esteatose c) A colorimetria apresentou acurácia perfeita na identificação da presença da esteatose e tendência para classificar, em um mesmo grupo, a esteatose moderada e intensa. / Hepatic grafts with steatosis are at increased risk for dysfunction and primary non-functioning. However, considering the permanent imbalance between supply and demand of grafts, the use of specially selected livers with steatosis is justified. The gold standard for the diagnosis of hepatic steatosis in clinical practice is histological examination. However, in the transplant scenario, the estimation of the grade of hepatic graft steatosis depends on macroscopic examination. In this procedure the color reading is carried out subjectively and the strength of the association of color-steatosis is not known. Considering these aspects, the present study aimed to verify the association between liver color and liver steatosis intensity, accurately assessing the color of the liver with a colorimeter and quantifying steatosis with two exams considered as reference. Method: Male wistar rats were divided into four groups of fifteen animals. The animals in the control group received a standard diet. The other three groups received a steatogenic diet during, respectively, two, four and six days. Rats were submitted to laparotomy, liver biopsy (pre and post-perfusion of the liver) for conventional histological examination, colorimetry in the RGB pattern (pre and post-perfusion of the liver), color conversion from the RGB standard to the GRAY standard, Blood collection for laboratory tests and hepatectomy (to determine relative liver weight and fat extraction). Statistical analysis was performed with the statistical software package SPSS Statistics 18, and p value <0.05 was considered statistically significant. Results: A positive correlation was observed between fat percentages and preperfusion color intensity (red color correlation coefficient 0.874, green color 0.747 and blue color 0.763) and postperfusion (correlation coefficient of red color 0.900, green color 0.866 and blue color 0.856). The mean values of the colorimetry, pre- and post-perfusion, presented a statistically significant difference (p <0.001). The accuracy of the post-perfusion colorimetry, determined by the ROC curve, was 100% in the determination of the presence of steatosis, 96.2% for the moderate or intense degree and 80.4% for the intense degree of steatosis. There was a significant difference (p <0.001) between the means of the different groups except for the groups of moderate fat X intense fat concentration and between the histological grades groups of mild X intense moderate X steatosis. Conclusions: a) The color of the liver, pre and post perfusion, showed a strong correlation with steatosis, in a positive and linear way; B) Colorimetry, pre- and post-perfusion, shows the same accuracy in the identification of steatosis. C) Colorimetry showed perfect accuracy in the presence of steatosis and a tendency to classify moderate and severe steatosis in the same group.

O transplante de fígado é considerado um dos procedimentos mais complexos da medicina moderna. O ensino do paciente é relevante no contexto da saúde e pode contribuir para o sucesso do tratamento. Dentre as atividades do enfermeiro, ressalta-se o papel de educador. No período pós-operatório de transplante de fígado, este profissional deve implementar intervenções educativas direcionadas para o preparo do paciente no enfrentamento das mudanças no estilo de vida, decorrentes de procedimento cirúrgico complexo. Para tal, o primeiro passo consiste no conhecimento das necessidades de informação indicadas pelos receptores de transplante de fígado. O objetivo geral do estudo foi avaliar as necessidades de informação de receptores de transplante de fígado em atendimento ambulatorial em hospital público. A amostra foi composta por 92 receptores de transplante de fígado atendidos em ambulatório de hospital público do interior do Estado de São Paulo. A coleta de dados ocorreu no período de fevereiro a junho de 2014, por meio da aplicação de instrumento adaptado. Os principais resultados da pesquisa indicaram que a maioria dos receptores de transplante de fígado era do sexo masculino (77,17%) e casada (76,09%). A idade média foi de 54,48 anos, a média de anos de estudo foi de 9,02 anos, sendo 70,65% dos receptores moradores na zona urbana. Dos 92 participantes, 46,74% estavam aposentados e 26,09%, afastados de suas atividades laborais e 36,96%, com renda familiar entre dois e três salários-mínimos. Em relação às características clínicas, observou-se que 47,83% dos receptores eram do grupo sanguíneo tipo O, 72,83% tinham escore MELD entre 20 e 29 pontos, 41,30% estavam com cirrose de etiologia viral (B ou C). Dos 92 pacientes, 45,65% tinham IMC entre 18,50 e 24,99 Kg/m2 (peso normal) e 33,70% estavam acima de 25 Kg/m2 (sobrepeso). A média de dias após o transplante foi de 1.508,85 dias, o tacrolimus era empregado como terapia medicamentosa de imunossupressão principal em 36,96% dos receptores e era associado ao micofenolato sódico em 38,04% dos pacientes. As necessidades de informação que obtiveram as médias maiores foram: sugestão de assunto no 3 (média 5,35) refere- se aos sinais e sintomas de complicações (rejeição, infecção, diabetes, hipertensão arterial, entre outras) agrupada na categoria manejo das potenciais complicações; sugestão no 2 (média 5,29) relativa aos efeitos colaterais e cuidados sobre medicamentos (categoria manejo dos medicamentos) e sugestão no 14, alimentação segura após o transplante (média 4,53), também agrupada na categoria manejo das potenciais complicações. Os resultados evidenciados oferecem subsídios sobre o perfil sociodemográfico e clínico de receptores de transplante de fígado na realidade nacional, bem como das necessidades de informação, as quais podem auxiliar o planejamento de intervenções educativas direcionadas para o processo de transplante de fígado, para principalmente melhorar a qualidade da assistência, a adesão ao tratamento e a prevenção de complicações após o transplante / Liver transplantation is considered one of the most complex procedures in modern medicine. The patient education is relevant in the context of health and may contribute to the success of treatment. Among the activities of nurses, the role of educator is highlighted. In the postoperative period of liver transplantation, this professional must implement educational interventions directed to the preparation of the patient in coping with changes in lifestyle resulting from complex surgical procedure. For this, the first step consists in the identification of information needs indicated by liver transplant recipients. This study aimed to assess the information needs of liver transplant recipients in outpatient treatment at a public hospital. The sample consisted of 92 liver transplant recipients assisted in outpatient clinic at a public hospital in the state of São Paulo. Data collection was performed from February to June 2014, through the application of the adapted instrument. The main results indicated that most liver transplant recipients were male (77.17%) and married (76.09%). The average age was 54.48 years, the average years of schooling was 9.02; and 70.65% of recipients lived in the urban area. Of the 92 participants, 46.74% were retired, 26.09% were on leave from work and 36.96% had incomes between two and three minimum wages. Regarding clinical characteristics, 47.83% of recipients were type O blood group, 72.83% had MELD scores between 20 and 29 score points, and 41.30% had cirrhosis of viral etiology (B or C). Of the 92 patients, 45.65% had a BMI between 18.50 to 24.99 Kg/m2 (normal weight) and 33.70% greater than 25 Kg/m2 (overweight). Average days after the transplantation was 1508.85 days, the tacrolimus was used as the primary immunosuppression drug therapy in 36.96% of the recipients, and associated with mycophenolate sodium in 38.04% of the patients. Information needs with the highest averages were: suggestion of topic no 3 (5.35) which refers to the signs and symptoms of complications (rejection, infection, diabetes, hypertension, etc.), grouped in the category management of potential complications; suggestion no 2 (5.29) related to the side effects and care of medicines (category management of medicines); and suggestion no 14, safe food after transplantation (4.53), also grouped in the category management of potential complications. The results show subsidies on the sociodemographic and clinical profile of liver transplant recipients in the national reality and the information needs which may assist the planning of educational interventions directed to the process of liver transplantation, mainly aiming to improve quality of care, adherence to treatment and prevention of complications after transplantation

O transplante de fígado é considerado um dos procedimentos mais complexos da medicina moderna. O ensino do paciente é relevante no contexto da saúde e pode contribuir para o sucesso do tratamento. Dentre as atividades do enfermeiro, ressalta-se o papel de educador. No período pós-operatório de transplante de fígado, este profissional deve implementar intervenções educativas direcionadas para o preparo do paciente no enfrentamento das mudanças no estilo de vida, decorrentes de procedimento cirúrgico complexo. Para tal, o primeiro passo consiste no conhecimento das necessidades de informação indicadas pelos receptores de transplante de fígado. O objetivo geral do estudo foi avaliar as necessidades de informação de receptores de transplante de fígado em atendimento ambulatorial em hospital público. A amostra foi composta por 92 receptores de transplante de fígado atendidos em ambulatório de hospital público do interior do Estado de São Paulo. A coleta de dados ocorreu no período de fevereiro a junho de 2014, por meio da aplicação de instrumento adaptado. Os principais resultados da pesquisa indicaram que a maioria dos receptores de transplante de fígado era do sexo masculino (77,17%) e casada (76,09%). A idade média foi de 54,48 anos, a média de anos de estudo foi de 9,02 anos, sendo 70,65% dos receptores moradores na zona urbana. Dos 92 participantes, 46,74% estavam aposentados e 26,09%, afastados de suas atividades laborais e 36,96%, com renda familiar entre dois e três salários-mínimos. Em relação às características clínicas, observou-se que 47,83% dos receptores eram do grupo sanguíneo tipo O, 72,83% tinham escore MELD entre 20 e 29 pontos, 41,30% estavam com cirrose de etiologia viral (B ou C). Dos 92 pacientes, 45,65% tinham IMC entre 18,50 e 24,99 Kg/m2 (peso normal) e 33,70% estavam acima de 25 Kg/m2 (sobrepeso). A média de dias após o transplante foi de 1.508,85 dias, o tacrolimus era empregado como terapia medicamentosa de imunossupressão principal em 36,96% dos receptores e era associado ao micofenolato sódico em 38,04% dos pacientes. As necessidades de informação que obtiveram as médias maiores foram: sugestão de assunto no 3 (média 5,35) refere- se aos sinais e sintomas de complicações (rejeição, infecção, diabetes, hipertensão arterial, entre outras) agrupada na categoria manejo das potenciais complicações; sugestão no 2 (média 5,29) relativa aos efeitos colaterais e cuidados sobre medicamentos (categoria manejo dos medicamentos) e sugestão no 14, alimentação segura após o transplante (média 4,53), também agrupada na categoria manejo das potenciais complicações. Os resultados evidenciados oferecem subsídios sobre o perfil sociodemográfico e clínico de receptores de transplante de fígado na realidade nacional, bem como das necessidades de informação, as quais podem auxiliar o planejamento de intervenções educativas direcionadas para o processo de transplante de fígado, para principalmente melhorar a qualidade da assistência, a adesão ao tratamento e a prevenção de complicações após o transplante / Liver transplantation is considered one of the most complex procedures in modern medicine. The patient education is relevant in the context of health and may contribute to the success of treatment. Among the activities of nurses, the role of educator is highlighted. In the postoperative period of liver transplantation, this professional must implement educational interventions directed to the preparation of the patient in coping with changes in lifestyle resulting from complex surgical procedure. For this, the first step consists in the identification of information needs indicated by liver transplant recipients. This study aimed to assess the information needs of liver transplant recipients in outpatient treatment at a public hospital. The sample consisted of 92 liver transplant recipients assisted in outpatient clinic at a public hospital in the state of São Paulo. Data collection was performed from February to June 2014, through the application of the adapted instrument. The main results indicated that most liver transplant recipients were male (77.17%) and married (76.09%). The average age was 54.48 years, the average years of schooling was 9.02; and 70.65% of recipients lived in the urban area. Of the 92 participants, 46.74% were retired, 26.09% were on leave from work and 36.96% had incomes between two and three minimum wages. Regarding clinical characteristics, 47.83% of recipients were type O blood group, 72.83% had MELD scores between 20 and 29 score points, and 41.30% had cirrhosis of viral etiology (B or C). Of the 92 patients, 45.65% had a BMI between 18.50 to 24.99 Kg/m2 (normal weight) and 33.70% greater than 25 Kg/m2 (overweight). Average days after the transplantation was 1508.85 days, the tacrolimus was used as the primary immunosuppression drug therapy in 36.96% of the recipients, and associated with mycophenolate sodium in 38.04% of the patients. Information needs with the highest averages were: suggestion of topic no 3 (5.35) which refers to the signs and symptoms of complications (rejection, infection, diabetes, hypertension, etc.), grouped in the category management of potential complications; suggestion no 2 (5.29) related to the side effects and care of medicines (category management of medicines); and suggestion no 14, safe food after transplantation (4.53), also grouped in the category management of potential complications. The results show subsidies on the sociodemographic and clinical profile of liver transplant recipients in the national reality and the information needs which may assist the planning of educational interventions directed to the process of liver transplantation, mainly aiming to improve quality of care, adherence to treatment and prevention of complications after transplantation

Systemic amyloidoses are a group of lethal diseases where proteins aggregate into fibrillar structures, called amyloid fibrils, that deposits throughout the body. Transthyretin (TTR) causes one type of amyloidosis, in which the aggregates mainly infiltrate nervous and cardiac tissue. Almost a hundred different mutations in the TTR gene are known to trigger the disease, but wild-type (wt) TTR is also incorporated into the fibrils, and may alone form amyloid. Patients with the TTRV30M mutation show, for unknown reasons, two clinical phenotypes. Some have an early onset of disease without cardiomyopathy while others have a late onset and cardiomyopathy. It has previously been described that amyloid fibrils formed from TTRV30M can have two different compositions; either with truncated molecules beside full-length TTR (type A) or only-full-length molecules (type B).  In this thesis, the clinical importance of the two types of amyloid fibrils was investigated. We found that the fibril composition types are correlated to the two clinical phenotypes seen among TTRV30M patients, with type A fibrils present in late onset patients and type B fibrils in early onset patients. The only treatment for hereditary TTR amyloidosis has been liver transplantation, whereby the liver producing the mutant TTR is replaced by an organ only producing wt protein. However, in some patients, cardiac symptoms progress post-transplantationally. We demonstrated that the propensity to incorporate wtTTR differs between fibril types and tissue types in TTRV30M patients, with cardiac amyloid of type A having the highest tendency. This offers an explanation to why particularly cardiac amyloidosis develops after transplantation, and suggests which patients that are at risk for such development. By examining patients with other mutations than TTRV30M, we showed that, in contrast to the general belief, a fibril composition with truncated TTR is very common and might even be the general rule. This may explain why TTRV30M patients often have a better outcome after liver transplantation than patients with other mutations. In conclusion, this thesis has contributed with one piece to the puzzle of understanding the differences in clinical phenotype and treatment response between TTR amyloidosis patients, by demonstrating corresponding differences at a molecular level.

Objetivos: evaluar la eficacia del análisis celular y del control del flujo de secreción lipídica biliar seriado en el control postoperatorio y en el diagnóstico precoz en las complicaciones del injerto en el paciente con trasplante ortotópico de hígado. Material y métodos: se han estudiado 40 pacientes portadores de tubo de Kehr, divididos en dos grupos: grupo control (15 pacientes intervenidos por coledocoliatiasis) y grupo trasplante (25 pacientes con 29 trasplantes hepáticos: 16 con evolución normal, 4 con fallo primario del injerto que requirieron retrasplante, 6 con rechazo y 3 con sepsis), a los que diariamente se les controlaba clínica y analíticamente.

Sjuksköterskan bör ha kunskap om begreppet livskvalitet för att kunna bemöta patienter som genomgått en levertransplantation, då den upplevda livskvalitén är betydelsefull för patienterna. Syftet var att beskriva livskvalitet hos patienter som genomgått en levertransplantation. Studien är genomförd som en litteraturstudie där 12 vetenskapliga artiklar har granskats. Resultatet visar att den upplevda livskvalitén hos levertransplanterade patienter är relativt god men det finns delar av livskvalitén som påverkas negativt efter levertransplantationen. Livskvalitén påverkas av fysiska, psykiska och sociala aspekter. De delar som påverkade livskvalitén positivt var familjen, att kunna återvända till det yrkesverksamma livet och att få en chans till ett nytt liv. Negativa aspekter som framkom i resultatet var bland annat förlorad autonomi, fysisk inaktivitet och en känsla av utanförskap i samhället. Vidare omvårdnadsforskning inom området livskvalitet relaterat till levertransplantation bör utföras. Sjuksköterskor behöver utbildning i ämnet för att i omvårdnadsarbetet kunna främja och bevara patienters livskvalitet. / The nurse should have knowledge of the concept of quality of life to respond to patients who underwent a liver transplant, when the perceived quality of life is important for patients. The aim was to describe the quality of life in patients undergoing a liver transplant. The study was conducted as a literature review of 12 scientific papers that have been reviewed. The results show that the perceived quality of life in liver transplant patients is relatively good but there are elements of quality of life adversely affected by post-liver transplant. Quality of life is affected by physical, psychological and social aspects. The elements affecting the quality of life positively were the family, ability to return to the working life and to get a chance to start a new life. Negative aspects that emerged from the results included the loss of autonomy, physical inactivity and a sense of alienation in society. In addition, nursing research in the field of quality of life related to liver transplantation should be performed. Nurses need education on the topic of the nursing work to promote and preserve patients' quality of life.

Bakgrund: Levercirros är ett sjukdomstillstånd som har hög mortalitet om inte en levertransplantation genomförs. Väntelistan till transplantation är lång samtidigt som organbehovet ökar. Syfte: Syftet med studien är att beskriva patientens upplevelser och livskvalitet i väntan på en levertransplantation. Metod: En litteraturöversikt valdes där 9 vetenskapliga artiklar granskades och analyserades enligt Fribergs modell (2006). Resultat: Beskedet om att bli uppsatt på väntelista präglades av både positiva och negativa känslor; glädje, lättnad, oro samt tveksamhet. Vid väntan uppstod fysiska och psykiska begränsningar. Olika kategorier framkom som var tydliga i de granskade artiklarna; att bli uppsatt på väntelista, att uppleva begränsad frihet, att ha behov av information och supportsamt att uppleva fysiska och psykiska begränsningar. Slutsats: Genomgående sänkt livskvalitet visas hos leversjuka människor som väntar på en levertransplantation vilket stämmer överens med tidigare forskning. Genom vårdpersonalens djupare förståelse för patienten i dennes väntan och dess fysiska och psykiska påverkan kan livskvaliteten samt upplevelsen av väntan förbättras. / Background: Liver cirrhosis is a condition that has a high mortality unless a livertransplantation is carried out. The waiting list for transplantation is long while the need for organs increases. Purpose: The purpose of this study is to describe patient’s experiences and quality of life while awaiting a liver transplant. Method: A literature review was chosen where 9 scientific articles were reviewed andanalyzed according to Friberg's model (2006). Results: The diagnosis and the registration on the waiting list were marked by both positive and negative emotions; joy, relief, worry and doubt. During the waiting period physical and mental limitations were present. Different categories emerged which were evident in the reviewed articles, to be put on waiting list, to experience limited freedom, to have needs for information and support, to experience physical and mental limitations. Conclusion: Consistently lower quality of life having a liver disease and for people waiting for a liver transplant which agree with earlier studies. By health professionals gaining a deeper understanding of the patient's situation while waiting and its physical and psychological impact, the quality of life and the experience of waiting can be improved.

Liver transplantation is the best therapy for patients with end-stage liver diseases and unresectable early hepatocellular carcinoma (HCC). Living donor liver transplantation (LDLT) has been successfully implemented as an alternative to deceased donor liver transplantation (DDLT) and likewise offers comparable excellent survival rate. However, the inferior post-transplant oncological outcomes are found in LDLT recipients with HCC. The liver grafts used in LDLT are usually small-for-size and less effective in coping with shear stress from transient portal hypertension, which results in small-for-size liver graft injury. Acute phase small-for-size liver graft injury may promote late phase tumor recurrence, whereas the underlying mechanism remains unclear. CXCL10, an inflammatory chemokine, initiates liver inflammatory response during hepatic ischemia-reperfusion (IR) injury and may link acute phase small-for-size liver graft injury and late phase tumor recurrence, yet the precise mechanisms remain elusive. Endothelial progenitor cells (EPCs) participate in tissue repair for graft recovery and also provide an angiogenic environment for tumor growth. Myeloid derived suppressor cells (MDSCs) and regulatory T cells (Tregs) can suppress the activation of the immune system and play a critical role in graft rejection and cancer development. We here established the rat orthotopic liver transplantation with whole graft or small-for-size graft model to study the impact of acute phase small-for-size liver graft injury on the mobilization of EPCs, MDSCs and Tregs, and intragraft CXCL10 and its receptor, CXCR3,gene expressions. We further subjected CXCL10-/-mice and CXCR3-/-mice to hepatic IR injury and major hepatectomy to study the role of CXCL10/CXCR3 signaling on the mobilization of EPCs, MDSCs and Tregs. We also investigated the effect of CXCL10 on EPC migration and tube formation in vitroas well as intratumoral microvessel density (MVD) in the rat liver transplantation with tumor growth model and EPCs on tumor growth in nude mice. Key findings: 1. Liver transplantation with small-for-size graft resulted in severe intragraft vascular injury and higher CXCL10 andCXCR3 gene expressions as well as more EPC, MDSC and Treg cell mobilizationin circulation than whole graft. 2. CXCL10-/-mice and CXCR3-/-mice had less circulating EPCs, MDSCs and Tregs than WT mice after hepatic IR injury and major hepatectomy. 3. CXCL10 recruited EPCs in dose-dependent and CXCR3-dependent manners and promoted EPC tube formation in vitro. 4. Higher intratumoral MVD was observed in small-for-size graft than in whole graft in liver transplantation with tumor growth model. 5. Tumor grew more quickly by combining EPC infusionin nude mouse orthotopic liver tumor model. In conclusion, acute phase small-for-size liver graft injury significantly mobilizes EPCs, MDSCs and Tregs after transplantation through CXCL10/CXCR3 signaling. More EPC mobilization and intragraft differentiation after transplantation with small-for-size liver graft may be related to higher intratumoral MVD in small-for-size liver graft after transplantation with tumor development. Therefore, targeting at post-transplant CXCL10/CXCR3 signaling may not only attenuate early phase liver graft injury but also prevent late phase tumor recurrence. / published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Surgery / Master / Master of Surgery

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