O impacto do transplante hepático nos níveis de testosterona e sua correlação com o MELD

Orientador: Prof. Dr. Júlio Cezar Uili CoelhoDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Clínica Cirúrgica. Defesa: Curitiba, 28/08/2015Inclui referências : f. 33-36Área de concentração : Avaliação anátomo-funcional dos transplantesResumo: O hipogonadismo é uma situação clínica comum em pacientes do sexo masculino com cirrose hepática e é caracterizado pelo baixo nível de testosterona, perda de libido, atrofia testicular, impotência e ginecomastia. Sabe-se que a testosterona tem uma grande influência sobre a composição da gordura corporal e massa muscular no homem. Testosterona sérica total (T) e testosterona livre (FT) estão diminuídas em pacientes com cirrose hepática avançada. Também estes pacientes têm globulina de ligação ao hormônio sexual (SHBG) aumentada antes do transplante hepático ortotópico (THO). Objetivo: Determinar a influência do transplante hepático ortotópico nos níveis de testosterona total, testosterona livre e SHBG em pacientes cirróticos do sexo masculino e também determinar a relação dessas mudanças com o escore MELD (Model for End-stage Liver Disease). Métodos: Em um estudo prospectivo, os níveis séricos de testosterona (T), testosterona livre (FT) e globulina de ligação ao hormônio sexual (SHBG) de 30 pacientes adultos do sexo masculino com doença hepática em estágio final foram medidos duas a quatro horas antes e seis meses após transplante hepático (THO). O MELD foi determinado no dia do THO. Para esta análise, pontos extras não foram adicionados para pacientes com hepatocarcinoma. A etiologia da cirrose e a média do escore MELD determinaram a subdivisão do grupo em C (etiologia alcoólica), D (etiologia não alcoólica), A (MELD ? 18) e B (MELD > 18). Resultados: Os níveis de SHBG reduziram após o transplante hepático no grupo geral (p 0,007), nos grupos A (p 0,008) e C (p 0,03). Os níveis de testosterona livre aumentaram no grupo D (p 0,004) e A (p 0,03). Não houve mudança significativa nos níveis de testosterona total após o transplante hepático. Conclusões: O transplante hepático reduz os níveis de SHBG, principalmente em pacientes com MELD ? 18 e etiologia alcoólica da cirrose. O transplante hepático aumenta os níveis de testosterona livre em pacientes com MELD ?18 e pacientes com etiologia não alcoólica da cirrose. Não há mudança significativa nos níveis de testosterona total após o transplante hepático. Não há mudança significativa no perfil hormonal em pacientes com MELD>18. Palavras-Chave: Transplante hepático. Testosterona. Cirrose. Escore MELD.Abstract: Hypogonadism is a common clinical situation in male cirrhotic patients and is characterized by low serum testosterone level, loss of libido, small testes, impotence and gynecomastia. It has been known that testosterone affects the body fat composition and muscle mass in the male. Serum total testosterone (T) and free testosterone (FT) are decreased in patients with advanced liver cirrhosis. Also these patients have sex hormone-binding globulin (SHBG) increased before orthotopic liver transplantation. Objective: To determine the influence of orthotopic liver transplantation in serum levels of total testosterone, free testosterone and SHBG in male cirrhotic patients and also to determine the relationship of these changes with MELD score (Model for End-stage Liver Disease). Methods: In a prospective study, serum levels of testosterone (T), free testosterone (FT) and sex hormone-binding globulin (SHBG) of 30 male adult patients with end-stage liver disease were measured two to four hours before and six months after orthotopic liver transplantation. MELD was determined on the day of the transplantation. For this analysis, extra points were not added for patients with hepatocarcinoma. The etiology of cirrhosis and the mean value of MELD determined the subdivision of the group in C (alcoholic etiology), D (non alcoholic etiology), A (MELD ?18) and B (MELD >18). Results: SHBG levels decreased after liver transplantation in general group (p 0,007), in A (p 0,008) and C (p 0,03) groups. Free testosterone levels increased in D (p 0,004) and A (p 0,03) groups. There was no significant change in total testosterone levels after liver transplantation. Conclusions: The liver transplantation decreases SHBG levels, especially in patients with MELD ?18 and alcoholic etiology of cirrhosis. The liver transplantation increases free testosterone levels in patients with MELD ?18 and patients with non alcoholic etiology of cirrhosis. There is no significant change in total testosterone levels after liver transplantation. There is no significant change in hormonal profile in patients with MELD >18. Keywords: Liver transplantation. Testosterone. Cirrhosis. MELD Score

O impacto do transplante hepático nos níveis de testosterona e sua correlação com o MELD

Orientador: Prof. Dr. Júlio Cezar Uili CoelhoDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Clínica Cirúrgica. Defesa: Curitiba, 28/08/2015Inclui referências : f. 33-36Área de concentração : Avaliação anátomo-funcional dos transplantesResumo: O hipogonadismo é uma situação clínica comum em pacientes do sexo masculino com cirrose hepática e é caracterizado pelo baixo nível de testosterona, perda de libido, atrofia testicular, impotência e ginecomastia. Sabe-se que a testosterona tem uma grande influência sobre a composição da gordura corporal e massa muscular no homem. Testosterona sérica total (T) e testosterona livre (FT) estão diminuídas em pacientes com cirrose hepática avançada. Também estes pacientes têm globulina de ligação ao hormônio sexual (SHBG) aumentada antes do transplante hepático ortotópico (THO). Objetivo: Determinar a influência do transplante hepático ortotópico nos níveis de testosterona total, testosterona livre e SHBG em pacientes cirróticos do sexo masculino e também determinar a relação dessas mudanças com o escore MELD (Model for End-stage Liver Disease). Métodos: Em um estudo prospectivo, os níveis séricos de testosterona (T), testosterona livre (FT) e globulina de ligação ao hormônio sexual (SHBG) de 30 pacientes adultos do sexo masculino com doença hepática em estágio final foram medidos duas a quatro horas antes e seis meses após transplante hepático (THO). O MELD foi determinado no dia do THO. Para esta análise, pontos extras não foram adicionados para pacientes com hepatocarcinoma. A etiologia da cirrose e a média do escore MELD determinaram a subdivisão do grupo em C (etiologia alcoólica), D (etiologia não alcoólica), A (MELD ? 18) e B (MELD > 18). Resultados: Os níveis de SHBG reduziram após o transplante hepático no grupo geral (p 0,007), nos grupos A (p 0,008) e C (p 0,03). Os níveis de testosterona livre aumentaram no grupo D (p 0,004) e A (p 0,03). Não houve mudança significativa nos níveis de testosterona total após o transplante hepático. Conclusões: O transplante hepático reduz os níveis de SHBG, principalmente em pacientes com MELD ? 18 e etiologia alcoólica da cirrose. O transplante hepático aumenta os níveis de testosterona livre em pacientes com MELD ?18 e pacientes com etiologia não alcoólica da cirrose. Não há mudança significativa nos níveis de testosterona total após o transplante hepático. Não há mudança significativa no perfil hormonal em pacientes com MELD>18. Palavras-Chave: Transplante hepático. Testosterona. Cirrose. Escore MELD.Abstract: Hypogonadism is a common clinical situation in male cirrhotic patients and is characterized by low serum testosterone level, loss of libido, small testes, impotence and gynecomastia. It has been known that testosterone affects the body fat composition and muscle mass in the male. Serum total testosterone (T) and free testosterone (FT) are decreased in patients with advanced liver cirrhosis. Also these patients have sex hormone-binding globulin (SHBG) increased before orthotopic liver transplantation. Objective: To determine the influence of orthotopic liver transplantation in serum levels of total testosterone, free testosterone and SHBG in male cirrhotic patients and also to determine the relationship of these changes with MELD score (Model for End-stage Liver Disease). Methods: In a prospective study, serum levels of testosterone (T), free testosterone (FT) and sex hormone-binding globulin (SHBG) of 30 male adult patients with end-stage liver disease were measured two to four hours before and six months after orthotopic liver transplantation. MELD was determined on the day of the transplantation. For this analysis, extra points were not added for patients with hepatocarcinoma. The etiology of cirrhosis and the mean value of MELD determined the subdivision of the group in C (alcoholic etiology), D (non alcoholic etiology), A (MELD ?18) and B (MELD >18). Results: SHBG levels decreased after liver transplantation in general group (p 0,007), in A (p 0,008) and C (p 0,03) groups. Free testosterone levels increased in D (p 0,004) and A (p 0,03) groups. There was no significant change in total testosterone levels after liver transplantation. Conclusions: The liver transplantation decreases SHBG levels, especially in patients with MELD ?18 and alcoholic etiology of cirrhosis. The liver transplantation increases free testosterone levels in patients with MELD ?18 and patients with non alcoholic etiology of cirrhosis. There is no significant change in total testosterone levels after liver transplantation. There is no significant change in hormonal profile in patients with MELD >18. Keywords: Liver transplantation. Testosterone. Cirrhosis. MELD Score

TESTOSTERONE CHANGES IN PATIENTS WITH LIVER CIRRHOSIS BEFORE AND AFTER ORTHOTOPIC LIVER TRANSPLANTATION AND ITS CORRELATION WITH MELD

Context Hypogonadism is a common clinical situation in male patients with liver cirrhosis. Objectives The aim of the present study was to evaluate the effects of orthotopic liver transplantation on testosterone, free testosterone and sex hormone-binding globulin in male with advanced liver disease and also to determine the relationship of these changes with Model for End-stage Liver Disease (MELD) score. Methods In a prospective study, serum levels of testosterone, free testosterone and sex hormone-binding globulin of 30 male adult patients with end-stage liver disease were measured 2 to 4 hours before and 6 months after orthotopic liver transplantation. Results Total testosterone levels increased after orthotopic liver transplantation and the number of patients with normal testosterone levels increased from 18 to 24. Free testosterone mean level in the pre-transplant group was 7.8 pg/mL and increased to 11.5 pg/mL (P = 0.10) and sex hormone-binding globulin level decreased after orthotopic liver transplantation returning to normal levels in MELD &#8804;18 - group (A) (P<0.05). Conclusions Serum level changes of testosterone, free testosterone and sex hormone-binding globulin are more pronounced in cirrhotic males with MELD &#8804;18. Serum levels of testosterone and free testosterone increase and serum levels of sex hormone-binding globulin decrease after orthotopic liver transplantation

Change in platelet count in patients with hypersplenism subjected to liver transplantation

CONTEXT: Most patients subjected to liver transplantation presents hypersplenism, which is reversed after the operation. However, some patients remain with moderate to intense hypersplenism. OBJECTIVES: To study the effect of liver transplantation on platelet count in patients with hypersplenism. METHOD: Of a total of 233 patients who underwent liver transplantation, 162 were excluded from the present study because of occurrence of steroid-resistant rejection, absence of hypersplenism before the transplantation, absence of follow-up for at least 2 years or incomplete exams data. The electronic study protocols of the remaining 71 patients were reviewed to determine the demographics, etiology of cirrhosis, and results of pathologic examination of the explanted liver. Serial platelet count was obtained from the study protocol on the day before liver transplantation and 1, 2, 4, and 6 months and 1 year after liver transplantation. Statistical analysis was performed using the Student's t-test, chi-square test, and Spearman's correlation test. RESULTS: Posttransplant platelet count at all time intervals was significantly higher than the pretransplant value (P100,000/mm³) in 58 patients (81.7%) 1 month after liver transplantation. Twelve patients (16.9%) remained with thrombocytopenia 1 year after liver transplantation. Three patients (4.2%) had recurrence of thrombocytopenia within 1 year after liver transplantation. There was no correlation between pretransplant platelet count and the Child-Pugh class or the MELD score. CONCLUSION: Liver transplantation reverses hypersplenism in most patients

The immunological response and post-treatment survival of DC-vaccinated melanoma patients are associated with increased Th1/Th17 and reduced Th3 cytokine responses

Artículo de publicación ISIIntroduction Immunization with autologous dendritic cells (DCs) loaded with a heat shock-conditioned allogeneic melanoma cell lysate caused lysate-specific delayed type hypersensitivity (DTH) reactions in a number of patients. These responses correlated with a threefold prolonged long-term survival of DTH? with respect to DTH- unresponsive patients. Herein, we investigated whether the immunological reactions associated with prolonged survival were related to dissimilar cellular and cytokine responses in blood. Materials and methods Healthy donors and melanoma patient’s lymphocytes obtained from blood before and after vaccinations and from DTH biopsies were analyzed for T cell population distribution and cytokine release. Results/discussion Peripheral blood lymphocytes from melanoma patients have an increased proportion of Th3 (CD4? TGF-b?) regulatory T lymphocytes compared with healthy donors. Notably, DTH? patients showed a threefold reduction of Th3 cells compared with DTH- patients after DCs vaccine treatment. Furthermore, DCs vaccination resulted in a threefold augment of the proportion of IFN-c releasing Th1 cells and in a twofold increase of the IL-17-producing Th17 population in DTH? with respect to DTH- patients. Increased Th1 and Th17 cell populations in both blood and DTH-derived tissues suggest that these profiles may be related to a more effective anti-melanoma response. Conclusions Our results indicate that increased proinflammatory cytokine profiles are related to detectable immunological responses in vivo (DTH) and to prolonged patient survival. Our study contributes to the understanding of immunological responses produced by DCs vaccines and to the identification of follow-up markers for patient outcome that may allow a closer individual monitoring of patients