Objetivos: Quantificar a ingestão dietética de adultos portadores de hepatopatia crônica correlacionando-a ao estado nutricional, e comparar diferentes métodos de avaliação nutricional nesta população, especialmente métodos de avaliação funcional (dinamometria - FAM - e espessura do músculo adutor do polegar - MAP) e a avaliação global do Royal Free Hospital (RFH-GA). Materiais e métodos: Foram avaliados 97 pacientes ambulatoriais do Hospital de Clínicas de Porto Alegre, com diagnóstico de hepatopatia crônica (41 hepatite crônica – HCr - e 56 cirróticos - CIR) entre abril de 2009 e janeiro de 2010. Foi realizada avaliação nutricional através de inquérito alimentar (R24h), antropometria - Índice de massa corporal (IMC) e circunferência muscular do braço (CMB), avaliação subjetiva global (ASG), FAM, RFH-GA e MAP. Resultados: Pacientes do grupo HCr apresentaram maior ingestão calórica total (p=0,005) e maior ingestão proteica (p<0,0001) que os pacientes CIR. Houve relação entre RFH-GA (p<0,001) e FAM (p<0,05) e ingestão de calorias e proteínas. A prevalência de desnutrição no grupo HCr e no grupo CIR foi, de acordo com RFH-GA (51,2 vs 84% - p=0,002), FAM (61 vs 82,1% - p=0,02), ASG (14,6 vs 32,1% - p=0,048), MAP (7,3vs 14,3% - p=NS), CMB (4,9 vs 14,3% - p=NS) e IMC (2,4 vs 3,6% - p=NS). Houve concordância moderada entre FAM e RFH-GA (k=0,43). Conclusão: Pacientes portadores de hepatopatia crônica, mesmo não cirróticos, têm ingestão energética e proteica inadequadas. Desnutrição é frequente nos dois grupos, especialmente na cirrose. FAM e RFH-GA são os métodos que identificaram maior prevalência de desnutrição nesta população e apresentam concordância entre si. A ingestão insuficiente de calorias e proteinas foi associada ao diagnóstico de DPC pela RFH-GA e FAM. / Background/aims: Objectives: To quantify the dietary intake of adults with chronic liver disease and correlate the nutritional status. Compare different methods of nutritional assessment in this population, in special methods of functional evaluation (hand grip streght – HG and The thickness of the adductor pollices muscle - APM) and the Royal Free Hospital global assessment (RFH-GA). Methods: 97 patients at the Hospital de Clinicas de Porto Alegre, diagnosed with chronic liver disease (41 chronic hepatitis - CH - and 56 cirrhotic - CIR) between April 2009 and January 2010 was assessed. Nutritional assessment was carried out by dietary recall (24HR), anthropometry (body mass index - BMI - body and arm muscle circumference - AMC), subjective global assessment (SGA), HG, RFH-GA and APM. Results: CH group patients had higher total caloric intake (p = 0.005) and higher protein intake (p <0.0001) than patients CIR. There was a relationship between the RFH-GA (p <0.001) and HG (p <0.001) and intake of calories and proteins. The prevalence of malnutrition in the CH group and the CIR group was by RFH-GA (51.2 vs. 84% - p = 0.002), HG (61 vs 82.1% - p = 0.02), SGA (14.6 vs. 32.1% - p = 0.048), APM (7.3 vs 14.3% - p> 0.05), MAC (4.9 vs 14.3% - p> 0.05) and BMI (2.4 vs. 3.6% - p> 0.05). There was moderate agreement between HG and RFH-GA (k = 0.43). Conclusion: Patients HC and CIR have energy and protein intake inadequate. Malnutrition is common in both groups, especially in the second. RFH-GA and HG are the best methods to identify malnutrition in this population and usually correlate with each other. The insufficient intake of calories and protein contributed to the diagnosis of malnutrition by RFH-GA and HG.

Introdução: Doentes Hepáticos mesmo após o Transplante de Fígado (TF) apresentam heranças fisiopatológicas que podem influenciar na diminuição da Capacidade Funcional (CF). Objetivo: Traçar o perfil dos pacientes pós TF em relação à CF, e definir quais os melhores exercícios físicos para compor futuro programa de condicionamento físico dos pacientes, tanto antes como depois do TF. Métodos: Estudo transversal com 52 pacientes submetidos ao TF entre os anos de 2002 e 2013. Foi realizado o Teste de Caminhada de 6 minutos (TC6). Resultados: 51,9% dos pacientes eram homens, sendo a média de idade da amostra 58 + 10,26 anos. Entre os participantes, 48,1% eram hipertensos, 42,3% obesos e 40,4% tinham diabetes tipo II. Tacrolimus é o medicamento mais utilizado em 84,6% dos pacientes. O DPTC6 média total foi de 497 + 90 metros, onde os homens andavam distância média mais alta que as mulheres (531 + 70 e 460 + 95 metros respectivamente). Sexo e Idade foram significativas (p=0,002 e p=0,011), evidenciando que a média do TC6 é maior em homens mais jovens do que em mulheres, independentemente do tempo transcorrido após o TF (p>0,05). Em relação a prática de exercícios físicos, apesar de não ser estatisticamente significativa, evidenciou-se que praticantes possuem melhores DPTC6. Conclusão: A DPTC6 por pacientes já submetidos ao Transplante de Fígado no Hospital de Clínicas de Porto Alegre, é indicativa de boa capacidade funcional, principalmente entre os pacientes mais jovens, os do sexo masculino e praticantes de exercícios físicos. / Introduction: The pathophysiological profile of patients with liver disease may impact functional capacity even after liver transplantation (LT). Objective: To describe functional capacity after LT in a group of Brazilian patients. Methods: This cross-sectional study included 52 patients submitted to LT between 2002 and 2013. Functional capacity was determined using the six-minute walk test (6MWT). Results: The mean age of the overall sample was 58 ± 10.26 years, and 51.9% were male. Hypertension was detected in 48.1%, obesity in 42.3%, and type 2 diabetes in 40.4%. Tacrolimus was the most used medicine (84.6% of patients). The mean distance traveled in the 6MWT was 497 + 90 m (531 ± 70 m for males vs. 460 ± 95 m for females). Gender and age were significantly associated with 6MWT results (p=0.002 and p=0.011), showing a higher mean 6MWT distance in younger men than in women, regardless of the time elapsed since LT (p<0.05). In relation to physical exercise, physically active individuals had more favorable 6MWT results; however, this association was not statistically significant. Conclusion: The present group of LT patients had good functional capacity as measured by the 6MWT, especially younger patients, male patients, and physically active patients.

Objetivos: Quantificar a ingestão dietética de adultos portadores de hepatopatia crônica correlacionando-a ao estado nutricional, e comparar diferentes métodos de avaliação nutricional nesta população, especialmente métodos de avaliação funcional (dinamometria - FAM - e espessura do músculo adutor do polegar - MAP) e a avaliação global do Royal Free Hospital (RFH-GA). Materiais e métodos: Foram avaliados 97 pacientes ambulatoriais do Hospital de Clínicas de Porto Alegre, com diagnóstico de hepatopatia crônica (41 hepatite crônica – HCr - e 56 cirróticos - CIR) entre abril de 2009 e janeiro de 2010. Foi realizada avaliação nutricional através de inquérito alimentar (R24h), antropometria - Índice de massa corporal (IMC) e circunferência muscular do braço (CMB), avaliação subjetiva global (ASG), FAM, RFH-GA e MAP. Resultados: Pacientes do grupo HCr apresentaram maior ingestão calórica total (p=0,005) e maior ingestão proteica (p<0,0001) que os pacientes CIR. Houve relação entre RFH-GA (p<0,001) e FAM (p<0,05) e ingestão de calorias e proteínas. A prevalência de desnutrição no grupo HCr e no grupo CIR foi, de acordo com RFH-GA (51,2 vs 84% - p=0,002), FAM (61 vs 82,1% - p=0,02), ASG (14,6 vs 32,1% - p=0,048), MAP (7,3vs 14,3% - p=NS), CMB (4,9 vs 14,3% - p=NS) e IMC (2,4 vs 3,6% - p=NS). Houve concordância moderada entre FAM e RFH-GA (k=0,43). Conclusão: Pacientes portadores de hepatopatia crônica, mesmo não cirróticos, têm ingestão energética e proteica inadequadas. Desnutrição é frequente nos dois grupos, especialmente na cirrose. FAM e RFH-GA são os métodos que identificaram maior prevalência de desnutrição nesta população e apresentam concordância entre si. A ingestão insuficiente de calorias e proteinas foi associada ao diagnóstico de DPC pela RFH-GA e FAM. / Background/aims: Objectives: To quantify the dietary intake of adults with chronic liver disease and correlate the nutritional status. Compare different methods of nutritional assessment in this population, in special methods of functional evaluation (hand grip streght – HG and The thickness of the adductor pollices muscle - APM) and the Royal Free Hospital global assessment (RFH-GA). Methods: 97 patients at the Hospital de Clinicas de Porto Alegre, diagnosed with chronic liver disease (41 chronic hepatitis - CH - and 56 cirrhotic - CIR) between April 2009 and January 2010 was assessed. Nutritional assessment was carried out by dietary recall (24HR), anthropometry (body mass index - BMI - body and arm muscle circumference - AMC), subjective global assessment (SGA), HG, RFH-GA and APM. Results: CH group patients had higher total caloric intake (p = 0.005) and higher protein intake (p <0.0001) than patients CIR. There was a relationship between the RFH-GA (p <0.001) and HG (p <0.001) and intake of calories and proteins. The prevalence of malnutrition in the CH group and the CIR group was by RFH-GA (51.2 vs. 84% - p = 0.002), HG (61 vs 82.1% - p = 0.02), SGA (14.6 vs. 32.1% - p = 0.048), APM (7.3 vs 14.3% - p> 0.05), MAC (4.9 vs 14.3% - p> 0.05) and BMI (2.4 vs. 3.6% - p> 0.05). There was moderate agreement between HG and RFH-GA (k = 0.43). Conclusion: Patients HC and CIR have energy and protein intake inadequate. Malnutrition is common in both groups, especially in the second. RFH-GA and HG are the best methods to identify malnutrition in this population and usually correlate with each other. The insufficient intake of calories and protein contributed to the diagnosis of malnutrition by RFH-GA and HG.

A hepatopatia da fibrose cística (FC) é uma complicação grave sendo descrita como terceira causa de morte nestes pacientes. Sua prevalência é muito variável, desde 14,3% até 41% em crianças e adolescentes. A discrepância entre os diferentes estudos clínicos se deve à forma utilizada para o diagnóstico da hepatopatia (características clínicas, bioquímicas e/ou ultra-sonográficas), à idade dos pacientes selecionados, ao tipo de estudo empregado (transversal ou longitudinal) e também, à falta de um marcador específico e sensível de disfunção hepatobiliar. Em 1995, Williams et al, elaboraram um escore ultra-sonográfico que mostrou boa relação com as alterações laboratoriais hepáticas pretendendo, desta forma, graduar o nível da lesão hepática. O escore foi elaborado por meio da avaliação do padrão do parênquima hepático, do contorno do fígado e do grau de ecogenicidade periportal. Quanto aos marcadores não invasivos para diagnosticar a doença hepática, vários tem sido estudados, entre eles o ácido hialurônico (AH).O AH é o maior mucopolissacarídeo componente da matriz extracelular, é encontrado na maioria dos tecidos e fluidos corporais, particularmente abundante em tecido conectivo frouxo. É sintetizado na membrana citoplasmática de fibroblastos e de outras células, sendo que uma pequena parte é metabolizada neste local. Através dos vasos linfáticos chega à corrente sanguínea e é rapidamente eliminada pelo fígado, ao nível do sinusóide hepático. Neste estudo buscamos relacionar as alterações ultra-sonográficas com o nível sérico de AH e, desta forma, realizar o diagnóstico precoce da hepatopatia da FC. Foi realizado um estudo transversal em 57 pacientes com FC, todos caucasóides, que apresentavam uma média de idade de 10,2 + 4,9 anos. A avaliação constou de dados clínicos, laboratoriais e ultra-sonográficos. Os pacientes foram classificados de acordo com um escore ultra-sonográfico em:Grupo 1 (G1) – ausência de doença hepática: escore 3; - Grupo 2 (G2) – doença hepática moderada: escore 4 – 6; - Grupo 3 (G3) – doença hepática grave: escore 7 - 9. O nível sérico do ácido hialurônico foi medido através da técnica de ELISA (Enzyme Linked Immunoassay) e comparado com 23 controles saudáveis. Vinte e nove pacientes foram incluídos no G1, dezoito pacientes no G2 e dez pacientes no G3. Os pacientes do sexo masculino apresentaram escore ultra-sonográfico mais alterado (P= 0,018). O nível sérico da ALT e da AST foram consideravelmente mais elevados no G3 do que no G1. O nível sérico da GGT foi mais elevado no G3 do que no G1 e G2. A porcentagem do volume expiratório forçado no primeiro segundo (%VEF1) apresentou uma correlação positiva fraca com o escore Z P/I (r= 0,31/P= 0,031). O nível sérico de AH variou de 1,8 a 45 ng/mL (mediana= 13,9), apresentou uma mediana semelhante entre os grupos 1,2,3 e o grupo controle (P= 0,431), entre os grupos 1,2 e 3 (P= 0,24) e também, quando comparado cada grupo com o grupo controle (todos P> 0,1). Não houve correlação entre o nível sérico de AH e o escore ultra-sonográfico (P= 0,164). Desta forma, concluímos que o AH isoladamente não se mostrou um marcador da hepatopatia causada pela fibrose cística. / Cystic fibrosis (CF) liver disease (LD) is a serious complication, being described as the third cause of death in these patients. Its prevalence varies widely, from 14.3% to 41.0% in children and adolescents. The discrepancy shown by the various clinical studies is due to the method employed for the diagnosis of LD (clinical, biochemical and/or ultrasonographic characteristics), the age of selected patients, the type of study (crosssectional or longitudinal) and the absence of a specific and sensitive marker. In 1995, WILLIAMS et al, developed an ultrasonographic score that showed a good relation to liver biochemical alterations, in order to measure the liver involvement. The score was elaborated through an evaluation of three cardinal features of hepatic ultrasound in CF: coarseness of the parenchyma, nodularity of the liver edge and increased periportal echogenicity. Regarding non-invasive markers to diagnose the hepatic disease, several have been studied, among them the hyaluronic acid (HA). Hyaluronic acid is a major mucopolysaccharide in the extracellular matrix, found in most body tissues and fluids, particularly abundant in loose connective tissue. It is synthetized in the cytoplasmatic membrane of fibroblasts and other cells, with a small part being metabolized there. Through the lymph vessels, it reaches the bloodstream and is rapidly eliminated by the liver, at the hepatic sinusoid level. In this study, we attempted to correlate the ultrasound findings with HA serum level, and thus, obtain the early diagnosis of CFLD. A cross-sectional study was performed with 57 patients with CF, all white individuals presenting mean age of 10.2 + 4.9 years. The evaluation considered clinical, laboratorial and ultrasonographic data. The patients were classified according to an ultrasonographic score into: - Group 1 (G1) – absence of liver disease: score 3- Group 2 (G2) – moderate liver disease: score 4 – 6; - Group 3 (G3) – severe liver disease: score 7 - 9. HA serum level was measured by ELISA (Enzyme Linked Immunoassay) in the CF patients and 23 healthy controls. Twenty-nine patients were included in G1, 18 in G2 and 10 in G3. The male patients presented an ultrasonographic score with more alterations (P= 0,018). The serum levels of ALT and AST in G3 were considerably higher than in G1. The serum level of GGT in G3 was higher than in G1 and G2. The percent of forced expiratory volume in the first second (%FEV1) presented a small positive correlation with Z score W/A (r= 0.31/P= 0.031). HA serum level ranged from 1.8 to 45 ng/mL (mean = 13.9), and presented a similar mean value between Groups 1,2,3 and the control group (P= 0.431), among Groups 1,2 and 3 (P= 0.24), as well as when comparing each group to the control group (all P> 0.1). There was no correlation between HA serum level and ultrasonographic score (P= 0.164). Thus, we concluded that HA lonely cannot be considered as a marker of liver disease caused by cystic fibrosis.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O transplante ortotÃpico de fÃgado à o Ãnico tratamento eficaz para as doenÃas hepÃticas terminais. Atà recentemente, o Estado do CearÃ, com uma populaÃÃo estimada de 7 milhÃes de habitantes, nÃo oferecia esta opÃÃo terapÃutica. Hà trÃs anos foi iniciado um programa de transplante hepÃtico experimental em suÃnos no Hospital UniversitÃrio da Universidade Federal do Cearà com a finalidade de reunir e treinar uma equipe multidisciplinar em torno de um projeto comum. Em 17 de maio de 2002, todo esse esforÃo foi coroado pela realizaÃÃo com sucesso do primeiro transplante de fÃgado do CearÃ. Desde entÃo, foram realizados 6 transplantes de fÃgado com preservaÃÃo da veia cava, tÃcnica conhecida pelo nome de piggyback. A idade mÃdia foi de 39,5 anos. Cinco pacientes eram do sexo masculino e um do sexo feminino. A etiologia da doenÃa hepÃtica foi cirrose pelo virus C em 5 pacientes e doenÃa de Wilson em uma paciente, que foi transplantada de urgÃncia por falÃncia hepÃtica aguda. A mÃdia de transfusÃo foi de 2,6 concentrados de hemÃcias por paciente. O tempo de isquemia fria do enxerto foi em mÃdia de 7,5 horas e a permanÃncia hospitalar mÃdia foi de 17 dias. Todos os pacientes foram extubados dentro das 6 primeiras horas pÃs-transplante. Cinco pacientes evoluÃram com normalizaÃÃo das enzimas hepÃticas e das bilirrubinas, bem como do tempo de protrombina representada pelo INR e receberam alta entre o 10o e o 16o dia de pÃs-operatÃrio. Um paciente apresentou grande elevaÃÃo de AST e ALT, caracterizando uma disfunÃÃo primÃria do enxerto, seguida por hemorragia digestiva alta e Ãbito no 8o dia. ConcluÃndo, o sucesso tÃcnico dos transplantes de fÃgado realizados foi de 100%, sendo que a sobrevida inicial maior que 30 dias foi de 83,3%. Assim, pode-se considerar consolidada a etapa de implantaÃÃo do programa de transplante de fÃgado no Estado do CearÃ. / The orthotopic liver transplantation is the only effective treatment for the end-stage liver diseases. The state of CearÃ, with a population of about seven million inhabitants did not offer, until recently, this therapeutic modality. In 1999 an experimental liver transplantation program in pigs was initiated in the University Hospital of the Federal University of Cearà with the objective to group and train a multidisciplinary team in this procedure. On May 17th 2002, all these efforts were rewarded with the successful fulfillment of the first liver transplantation. Since then were realized six liver transplants with inferior caval vein preservation, a technical variant called piggyback. The patients average age was 39.5 years and five of the recipients were men. The etiology of the liver failure was virus C cirrhosis in five patients and WilsonÂs disease in one. This patient had a clinical presentation of acute hepatic failure and priority for transplantation. There were an average of 2.6 packed red blood cells per patient, the graft cold ischemia time was in average 7.5 hours and the mean hospitalization time 17 days. All patients were weaned from ventilation until six hours of post transplant. Five patients presented normalization of the hepatic transaminases and bilirrubins as well as the prothrombin time and left the hospital between the 10th and 16th day. One patient had an acute increased in hepatic enzymes, characterizing a primary graft dysfunction, and presented variceal and diffused bleeding, dying at the 8th post operative day. Concluding, there was a 100% technical success, and an initial survival (more than 30 days) of 83,3%. After these successful results, the liver transplant program was consolidated as a therapeutic option in the State of CearÃ.

Orientadores: Elza Cotrim Soares, Sarah Monte Alegre / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T22:40:52Z (GMT). No. of bitstreams: 1 Fioravante_Milena_M.pdf: 3241616 bytes, checksum: 06a63b1444ac4ae94958e122343557c9 (MD5) Previous issue date: 2011 / Resumo: Os objetivos deste estudo foram avaliar a perda de peso, a composição corporal e o gasto energético de repouso de pacientes durante o tratamento da hepatite crônica C com Interferon peguilado (PEG IFN) e ribavirina, comparando com os resultados obtidos antes do tratamento. Após seleção de 56 indivíduos, com o diagnóstico de hepatite crônica C, encaminhados para o ambulatório de hepatites virais no Gastrocentro da Unicamp, o presente estudo avaliou, prospectivamente, 42 pacientes que preencheram os critérios previamente estabelecidos. O estudo foi realizado em dois tempos diferentes: o primeiro, antes de iniciar o tratamento, e o segundo na 12ª semana de tratamento que consistia no uso semanal de injeções de PEG IFN alfa-2a (180 ?g) ou PEG IFN alfa-2b (1,5 ?g/kg) e ribavirina (1000 ou 1250 mg/dia). A avaliação do estado nutricional incluiu avaliação antropométrica de peso e altura para cálculo do índice de massa corporal (IMC), circunferência do braço, dobra cutânea tricipital, circunferência muscular do braço e circunferência abdominal. A composição corporal foi analisada por bioimpedância elétrica (BIA), sendo estimados os valores de massa magra em kilogramas e porcentagem de gordura corporal. O gasto energético de repouso de cada indivíduo foi obtido pelo método da calorimetria indireta e o consumo alimentar avaliado por recordatório de 24 horas e questionário de freqüência alimentar. Os exames laboratoriais foram aproveitados do prontuário médico. A amostra de indivíduos, com média de idade igual a 46,3 anos, foi composta por 30 (71,4%) homens e 12 (28,6%) mulheres. No momento basal do estudo, 40,5% dos pacientes eram eutróficos, 33,3% tinham sobrepeso e 26,2% apresentavam algum grau de obesidade. Os indivíduos apresentaram perda de peso significativa durante o tratamento (79,1 ± 15,6 vs. 75,7 ± 15 kg; p<0,001) com conseqüente redução de IMC (27,5 ± 5,2 vs. 26,3 ± 5 kg/m²; p<0,001), circunferência do braço (32,6 ± 3,8 vs. 31,3 ± 3,7 cm; p<0,001), dobra cutânea tricipital (18 ± 8,1 vs. 15,6 ± 7 mm; p<0,001), circunferência muscular do braço (27 ± 2,9 vs. 26,5 ± 2,8; p=0,008) e circunferência abdominal (97,8 ± 14,3 vs. 95,5 ± 14,1 cm; p<0,001). A perda de peso deu-se com redução significativa de gordura corporal (29 ± 8,2 vs. 26,7 ± 7,8%; p<0,001), sem redução de massa magra (55,6 ± 10 vs. 55 ± 10,2 kg; p=0,210). Houve redução significativa no consumo alimentar (2131 ± 890 vs. 1834 ± 699 kcal; p=0,012), avaliado pelo recordatório de 24 horas. Porém, não houve alteração no gasto energético de repouso (1168,2 ± 303 vs. 1151,3 ± 249 kcal; p=0,670) e no gasto energético de repouso corrigido pela massa magra (20,9 ± 3,7 vs. 21,1 ± 3,7 kcal/kg; p=0,864). Em conclusão, os pacientes com hepatite crônica C submetidos ao tratamento com interferon e ribavirina apresentaram importante perda de peso, observando-se redução significativa do consumo calórico, porém sem alteração do gasto energético de repouso. Mais estudos podem ser necessários para tentar elucidar as verdadeiras causas de perda de peso nesses pacientes / Abstract: The aim of this study was to evaluate weight loss, body composition and resting energy expenditure (REE) in patients during treatment of chronic hepatitis C with pegylated interferon (PEG IFN) and ribavirin, compared with the results obtained before treatment. After selection of 56 individuals with chronic hepatitis C, this study evaluated prospectively 42 patients who met the established criteria. The study was conducted at two different times: the first, before starting treatment, and the second at 12 weeks of treatment, which consisted in using weekly injections of PEG IFN alfa-2a (180 ?g) or PEG IFN alfa-2b (1,5 ?g/kg) and ribavirin (1000 or 1250 mg/d). The assessment of nutritional status included anthropometric measurements of body height and weight to calculate body mass index (BMI), arm circumference, triceps skinfoldthickness, arm muscle circumference and waist circumference. Body composition was determined by bioelectrical impedance analysis (BIA) and estimated values of fat free mass (FFM) in kilograms and percentage of body fat. The REE of each individual was obtained by indirect calorimetry and food intake assessed by 24- hour recall and food frequency questionnaire. Laboratory tests were drawn from medical records. The sample of individuals consisted of 30 (71.4%) men and 12 (28.6%) women. At baseline, 40.5% were eutrophic, 33.3% were overweight and 26.2% had some degree of obesity. Subjects had significant weight loss during treatment(79.1 ± 15.6 vs. 75.7 ± 15 kg, p <0.001) with consequent decrease in BMI (27.5 ± 5.2 vs. ± 26.3 5 kg / m², p <0.001), arm circumference (32.6 ± 3.8 vs. 31.3 ± 3.7 cm, p <0.001), triceps skinfold thickness (18 ± 8.1 vs. 15, 6 ± 7 mm, p <0.001), arm muscle circumference (27 ± 2.9 vs. 26.5 ± 2.8, p = 0.008) and waist circumference (97.8 ± 14.3 vs. 95.5 ± 14.1 cm, p <0.001). This weight decrease was accompanied by significant decrease in body fat (29 ± 8.2 vs. 26.7 ± 7.8%, p <0.001) and there was no decrease in FFM (55.6 ± 10 vs. ± 55 10.2 kg, p = 0.210). There was significant decrease in energy intake (2131 ± 890 vs. 1834 ± 699 kcal, p = 0.012) assessed by 24-hour recall. However, there was no change in REE (1168.2 ± 303 vs. 1151.3 ± 249 kcal; p=0.670) and REE corrected for FFM (20.9 ± 3.7 vs. 21.1 ± 3.7 kcal/kg; p=0.864). Our study of individuals with hepatitis C treatment showed that these patients had a significant weight loss and this was not associated with changes in energy expenditure. However, we observed a significant reduction in energy intake, pointing to a possible need for intervention measures to reduce damage / Mestrado / Ciencias Basicas / Mestre em Clinica Medica

No description available.

<p>Functioning as a “powerhouse”, the liver adapts to the metabolic needs of the body by maintaining a homeostatic balance. Prolactin receptor (PRLR) has been found to have a copious existence in the liver. Having established a well-defined role in both reproductive and endocrine systems, the role of this transmembrane protein in hepatocytes is yet to be elucidated. Due to its abundant nature, we hypothesized that PRLR is required for maintaining hepatic homeostasis and plays a role in liver diseases. To test this hypothesis, we defined two specific aims. The first was to explore whether PRLR loss-of-function affects liver structure and function in physiological conditions. The second was to determine whether PRLR is associated with liver pathology. We deleted the <i>Prlr</i> gene specifically in hepatocytes using a virus-based approach and evaluated liver function, transcriptome, and activities of downstream signaling molecules. Due to the absence of PRLR, we found that the urea cycle was disrupted, concomitant with excessive accumulation of urea in the blood; 133 genes exhibited differential expression, largely associated with hepatocyte structure, metabolism, and inflammation; and the activities of STAT3 and 5 were reduced. The results signify that PRLR indeed plays a homeostatic role in the liver. We also used <i>Prlr</i>^+/- mice to assess whether the loss of one allele of the <i>Prlr</i> gene alters maternal hepatic adaptations to pregnancy. As a result, in the pre-pregnancy state and during the first half of gestation, the expression of maternal hepatic PRLR protein was reduced approximately by half owing to <i>Prlr</i> insufficiency. However, during the second half of pregnancy, we observed compensatory upregulation of this molecule, leading to minimal interference in STAT 3 and 5 signaling and liver size. Contrary to a previous study in the breast and ovary, our results suggest that one allele of <i>Prlr</i> may be sufficient for the maternal liver to respond to this physiological stimulus (pregnancy). Furthermore, we examined the expression and activity of PRLR in fatty as well as cholestatic livers. Using a high fat diet, we induced non-alcoholic fatty liver disease (NAFLD). Strikingly and for the first time, we discovered that the short isoform of PRLR (PRLR-S) was completely inactivated in response to NAFLD, whereas the long isoform remained unchanged. This finding strongly suggests the involvement of PRLR-S in lipid metabolism. We also postulate that PRLR-L may be the major regulator of STAT signaling in the liver, consistent with other reports. Lastly, we induced extrahepatic cholestasis via bile duct ligation (BDL) in mice. As this liver disease progressed, the expression of both isoforms of PRLR generally declined and was surprisingly accompanied by increased STAT 3 and 5 activity. The data suggests that PRLR participates in this disease progression, with a disconnection between PRLR signaling and STAT proteins. Collectively, our preliminary studies suggest that PRLR signaling is required to maintain liver homeostasis and more prominently, is involved in liver diseases, especially NAFLD. These findings lay a foundation for our future studies.</p>

Indiana University-Purdue University Indianapolis (IUPUI) / Functioning as a “powerhouse”, the liver adapts to the metabolic needs of the body by maintaining a homeostatic balance. Prolactin receptor (PRLR) has been found to have a copious existence in the liver. Having established a well-defined role in both reproductive and endocrine systems, the role of this transmembrane protein in hepatocytes is yet to be elucidated. Due to its abundant nature, we hypothesized that PRLR is required for maintaining hepatic homeostasis and plays a role in liver diseases. To test this hypothesis, we defined two specific aims. The first was to explore whether PRLR loss-of-function affects liver structure and function in physiological conditions. The second was to determine whether PRLR is associated with liver pathology. We deleted the Prlr gene specifically in hepatocytes using a virus-based approach and evaluated liver function, transcriptome, and activities of downstream signaling molecules. Due to the absence of PRLR, we found that the urea cycle was disrupted, concomitant with excessive accumulation of urea in the blood; 133 genes exhibited differential expression, largely associated with hepatocyte structure, metabolism, and inflammation; and the activities of STAT3 and 5 were reduced. The results signify that PRLR indeed plays a homeostatic role in the liver. We also used Prlr+/- mice to assess whether the loss of one allele of the Prlr gene alters maternal hepatic adaptations to pregnancy. As a result, in the pre-pregnancy state and during the first half of gestation, the expression of maternal hepatic PRLR protein was reduced approximately by half owing to Prlr insufficiency. However, during the second half of pregnancy, we observed compensatory upregulation of this molecule, leading to minimal interference in STAT 3 and 5 signaling and liver size. Contrary to a previous study in the breast and ovary, our results suggest that one allele of Prlr may be sufficient for the maternal liver to respond to this physiological stimulus (pregnancy). Furthermore, we examined the expression and activity of PRLR in fatty as well as cholestatic livers. Using a high fat diet, we induced non-alcoholic fatty liver disease (NAFLD). Strikingly and for the first time, we discovered that the short isoform of PRLR (PRLR-S) was completely inactivated in response to NAFLD, whereas the long isoform remained unchanged. This finding strongly suggests the involvement of PRLR-S in lipid metabolism. We also postulate that PRLR-L may be the major regulator of STAT signaling in the liver, consistent with other reports. Lastly, we induced extrahepatic cholestasis via bile duct ligation (BDL) in mice. As this liver disease progressed, the expression of both isoforms of PRLR generally declined and was surprisingly accompanied by increased STAT 3 and 5 activity. The data suggests that PRLR participates in this disease progression, with a disconnection between PRLR signaling and STAT proteins. Collectively, our preliminary studies suggest that PRLR signaling is required to maintain liver homeostasis and more prominently, is involved in liver diseases, especially NAFLD. These findings lay a foundation for our future studies.

No description available.