Análise de biomarcadores fecais calprotectina e lactoferrina nos pacientes portadores de pancreatite crônica de etiologia alcoólica
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Data
2015-07-31
Autores
Carvente, Claudia Teresa [UNIFESP]
Orientadores
Ferraz, Maria Lucia Cardoso Gomes [UNIFESP]
Tipo
Dissertação de mestrado
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Introdução: A pancreatite crônica é caracterizada por processo inflamatório levando a lesões anatômicas no pâncreas, com substituição do parênquima funcional por tecido fibroso e calcificação. As principais manifestações clínicas de insuficiência pancreática exócrina são a má absorção de gordura (esteatorreia), desconforto e distensão abdominal. Enquanto a insuficiência endócrina resultante da destruição das Ilhotas de Langherans, com redução da secreção de insulina e glucagon leva o aparecimento de diabetes em torno de 10% dos casos de PC de etiologia alcoólica. Pacientes com PC submetidos a tratamento clinico, nutricional e medicamentoso através da reposição com enzimas pancreáticas podem manter alterações dos hábitos intestinais com evacuações pastosas a semilíquidas e até diarreicas. Um dos mecanismos descritos é a presença de atividade inflamatória intestinal. Vários trabalhos têm descritos marcadores fecais, denominados biomarcadores potentes da inflamação da mucosa intestinal, principalmente em pacientes portadores de doença inflamatória intestinal. Objetivo: O objetivo do presente estudo é demonstrar a existência de atividade inflamatória intestinal em pacientes portadores de pancreatite crônica através da determinação dos biomarcadores fecais, lactoferrina e calprotectina. Casuística e Método: Vinte e três pacientes portadores de pancreatite crônica de etiologia alcoólica foram utilizados no estudo. Os pacientes foram separados em cinco grupos no sentido de identificar fatores capazes promover alterações no hábito intestinal. As determinações fecais de lactoferrina e calprotectina fecais foram realizadas através do teste de ELISA com kits específicos. Resultados: Todos os pacientes independentes da natureza dos grupos e subgrupos formados (diabéticos, tabagistas, tratados com reposição de enzimas pancreáticas e quantidade de ingesta alcoólica) apresentaram pequenas diferenças nos parâmetros clínicos e nutricionais, de imagens e laboratoriais quando comparados com os seus grupos controles. Um achado significativo em todos os pacientes foi a presença de atividade inflamatória intestinal, com elevação da calprotectina variando de 283 até 1100 ng/ml (valor de positividade quando > 50ng/ml), média de 632ng/ml, ao passo que a lactoferrina variou sua densidade ótica de 0,032 a 0,998 (valor de positividade: DO > 0,200), média de 0,365, sendo somente positiva em 65,2% dos pacientes. Conclusões: Pacientes portadores de pancreatite crônica podem apresentar diarreia independente da insuficiência pancreática, exócrina e endócrina. A diarreia presente nos pacientes portadores de pancreatite crônica pode apresentar atividade inflamatória intestinal, detectado por níveis elevados de calprotectina e lactoferrina fecais. Existe uma correlação positiva entre a calprotectina e a lactoferrina fecais. A calprotectina foi o marcador mais sensível em diagnosticar atividade inflamatória quando comparada a lactoferrina, uma vez que a lactoferrina é positiva a partir de 478ng/ml de calprotectina. Outras causas de diarreia em pacientes portadores de pancreatite crônica e com atividade inflamatória intestinal devem ser investigadas, como sobrecrescimento bacteriano, doença celíaca ou má absorção de ácidos biliares. Exames séricos como hemoglobina, hematócrito, número de leucócitos e plaquetas, VHS, PCR não são bons marcadores de atividade inflamatória intestinal.
Introduction: Chronic pancreatitis is characterized by an inflammatory process leading to anatomical lesions in the pancreas, with replacement of functional parenchyma by fibrous tissue and calcification. The main clinical manifestations of exocrine pancreatic insufficiency are fat malabsorption (steatorrhea), discomfort and bloating. While endocrine insufficiency resulting from the destruction of Islets of Langerhans, with reduced secretion of insulin and glucagon, leads to the onset of diabetes in approximately 10% of cases of CP of alcoholic etiology. CP patients who have undergone clinical, nutritional and drug treatment through replacement with pancreatic enzymes can maintain changes in bowel habits with bowel movements of soft to semi-liquid constitution and even diarrhea. One of the mechanisms described is the presence of inflammatory bowel activity. Several studies have described fecal markers, called potent biomarkers of inflammation in the intestinal mucosa, especially in patients with inflammatory bowel disease. Objective: The aim of this study is to demonstrate the existence of intestinal inflammatory activity in patients with chronic pancreatitis by determining the fecal biomarkers, lactoferrin and calprotectin. Casuistic and Methods: Twenty-three patients with chronic pancreatitis of alcoholic etiology were used in the study. The patients were divided into five groups with the goal of identifying factors that promote changes in bowel habits. Fecal determinations of fecal calprotectin and lactoferrin were performed by ELISA with specific kits. Results: All patients independent of the nature of the groups and subgroups formed (diabetics, smokers, treated with pancreatic enzyme replacement and amount of alcohol intake) showed small differences in clinical and nutritional parameters, in images and of laboratory nature when compared to their control groups. A significant finding in all patients was the presence of inflammatory bowel activity, with an increase in calprotectin ranging from 283 to 1100 ng/ml (positive value when > 50 ng/ml) average of 632ng/ml, whereas lactoferrin varied its optical density of 0.032 to 0.998 (positive value: OD > 0.200, average of 0.365, being only positive in 65.2 % of patients. Conclusions: Patients with chronic pancreatitis may have diarrhea independent of exocrine and endocrine pancreatic insufficiency. This diarrhea in patients with chronic pancreatitis may present inflammatory bowel activity, detected by high levels of fecal calprotectin and lactoferrin. There is a positive correlation between fecal calprotectin and lactoferrin. Calprotectin was the most sensitive marker in diagnosing inflammatory activity when compared to lactoferrin, since lactoferrin is positive from 478ng/ml of calprotectin. Other causes of diarrhea in patients with chronic pancreatitis and inflammatory bowel activity should be investigated, such as bacterial overgrowth, celiac disease or malabsorption of bile acids. Serum tests such as hemoglobin, hematocrit, white blood cell and platelets count, ESR, CRP are not good markers of inflammatory bowel activity.
Introduction: Chronic pancreatitis is characterized by an inflammatory process leading to anatomical lesions in the pancreas, with replacement of functional parenchyma by fibrous tissue and calcification. The main clinical manifestations of exocrine pancreatic insufficiency are fat malabsorption (steatorrhea), discomfort and bloating. While endocrine insufficiency resulting from the destruction of Islets of Langerhans, with reduced secretion of insulin and glucagon, leads to the onset of diabetes in approximately 10% of cases of CP of alcoholic etiology. CP patients who have undergone clinical, nutritional and drug treatment through replacement with pancreatic enzymes can maintain changes in bowel habits with bowel movements of soft to semi-liquid constitution and even diarrhea. One of the mechanisms described is the presence of inflammatory bowel activity. Several studies have described fecal markers, called potent biomarkers of inflammation in the intestinal mucosa, especially in patients with inflammatory bowel disease. Objective: The aim of this study is to demonstrate the existence of intestinal inflammatory activity in patients with chronic pancreatitis by determining the fecal biomarkers, lactoferrin and calprotectin. Casuistic and Methods: Twenty-three patients with chronic pancreatitis of alcoholic etiology were used in the study. The patients were divided into five groups with the goal of identifying factors that promote changes in bowel habits. Fecal determinations of fecal calprotectin and lactoferrin were performed by ELISA with specific kits. Results: All patients independent of the nature of the groups and subgroups formed (diabetics, smokers, treated with pancreatic enzyme replacement and amount of alcohol intake) showed small differences in clinical and nutritional parameters, in images and of laboratory nature when compared to their control groups. A significant finding in all patients was the presence of inflammatory bowel activity, with an increase in calprotectin ranging from 283 to 1100 ng/ml (positive value when > 50 ng/ml) average of 632ng/ml, whereas lactoferrin varied its optical density of 0.032 to 0.998 (positive value: OD > 0.200, average of 0.365, being only positive in 65.2 % of patients. Conclusions: Patients with chronic pancreatitis may have diarrhea independent of exocrine and endocrine pancreatic insufficiency. This diarrhea in patients with chronic pancreatitis may present inflammatory bowel activity, detected by high levels of fecal calprotectin and lactoferrin. There is a positive correlation between fecal calprotectin and lactoferrin. Calprotectin was the most sensitive marker in diagnosing inflammatory activity when compared to lactoferrin, since lactoferrin is positive from 478ng/ml of calprotectin. Other causes of diarrhea in patients with chronic pancreatitis and inflammatory bowel activity should be investigated, such as bacterial overgrowth, celiac disease or malabsorption of bile acids. Serum tests such as hemoglobin, hematocrit, white blood cell and platelets count, ESR, CRP are not good markers of inflammatory bowel activity.
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CARVENTE, Claudia Teresa. Análise de biomarcadores fecais calprotectina e lactoferrina nos pacientes portadores de pancreatite crônica de etiologia alcoólica. 2015. 101 f. Dissertação (Mestrado em Medicina Translacional) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2015.