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BACKGROUND AND AIMS: The relationship between obesity and nonalcoholic fatty liver disease (NAFLD) has long been established, and the prevalence of both conditions has grown together. Recent interest in NAFLD in nonobese individuals has led to an increasing number of studies, especially in Asia. Despite the fact that the prevalence of NAFLD in Latin America is one of the highest in the world, there is a lack of information on lean NAFLD populations from the region. The aim of the present study was to assess the risk of metabolic comorbidities across the whole body mass index spectrum when nonalcoholic steatohepatitis (NASH) was first diagnosed in a Latin American population. METHODS: A single-center, cross-sectional study on Colombian patients newly diagnosed with NAFLD, within the time frame of 2010-2020, compared their metabolic biochemical profile, liver enzymes, risk of prevalent metabolic abnormalities, and liver disease. RESULTS: Data from 300 patients were collected. Ninety-two percent of the patients were men and the median patient age was 47 (IQR 20) years. We found no significant differences in the biochemical, metabolic profile, or liver enzyme plasma concentration between lean, overweight, and obese individuals. Obese patients had significantly higher LDL cholesterol, and a higher risk of dyslipidemia (OR 1.86, 95% CI 1.14-3.05). Every 1kg increase in body weight increased the risk of having NASH by 2% (95% CI 2-4). CONCLUSIONS: We evaluated the metabolic risk across the entire body mass index spectrum in a Colombian cohort with NAFLD and presented the characteristics of what we believe is the first Latin American lean NAFLD population to be described.
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AIM: To analyze the scientific evidence regarding to the effect of the Mediterranean diet on the imaging tests and biopsy characteristics in subjects with non-alcoholic fatty liver disease (NAFLD). METHODS: A bibliographic search was carried out in this narrative review in Pubmed and Web of Science databases, considering studies published between 2011 and 2020, in English or Spanish, randomized clinical trials and observational studies in patients with a diagnosis of NAFLD, in subjects over 18years of age of both sexes. RESULTS: In the observational studies found, an inverse association between adherence to a Mediterranean diet and liver damage stands out, while in the intervention studies with measurement of liver biopsy a 4.4% reduction in intrahepatic lipids and with magnetic resonance a reduction between 4.2 and 10.2% was found. In experimental studies with ultrasound measurement, the proportion of people with moderate (6-16%) and severe (25%) degree decreased and the studies with transient elastography showed a decrease in liver stiffness between 0.5 and 2.1kPa. CONCLUSIONS: The Mediterranean diet contributes to the treatment of NAFLD, which is manifested in the liver and histological imaging tests characteristics.
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Dieta Mediterrânea , Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Biópsia , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/terapiaRESUMO
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disorder commonly attributed to fatty acid deposition that can induce hepatic necroinflammation, defined as nonalcoholic steatohepatitis (NASH). It is strongly associated with obesity. Laparoscopic sleeve gastrectomy (LSG) is a favorable surgical modality for the treatment of morbid obesity. AIM: Our study evaluated the impact of LSG on patients with NAFLD and morbid obesity, 3 months after the operation, through clinical and biochemical characteristics, clinico-biochemical indices, and imaging parameters. PATIENTS AND METHODS: Morbidly obese patients with NAFLD±NASH underwent LSG. They were thoroughly evaluated clinically (body weight, body mass index, waist circumference) and biochemically (transaminases and triglycerides), as well as through the fatty liver index (FLI), the hepatic steatosis index (HSI), and ultrasound elastography imaging studies (liver stiffness measurement [LSM] and the controlled attenuation parameter [CAP]), before and 3 months after the LSG. RESULTS: Twenty-six obese patients with NAFLD underwent LSG that resulted in a significantly high reduction in all the parameters analyzed, except for liver transaminases. CONCLUSION: LSG is considered an efficient surgical modality for the treatment of morbidly obese patients with NAFLD.
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INTRODUCCIÓN: La enfermedad del hígado graso no alcohólico (EHGNA) es la forma más común de enfermedad hepática. A nivel celular se caracteriza por la acumulación de triglicéridos (TG) en forma de gotas lipídicas (GL) dando lugar a esteatosis e inflamación. Entre los factores relevantes para la síntesis de TG se encuentran las enzimas DGAT1/2 que catalizan la etapa final de la síntesis de TG, y la proteína FABP4 que transporta lípidos intracelulares y se expresa en modelos de enfermedad hepática dependiente de obesidad. Por otra parte, TNF-α es una reconocida citoquina involucrada en el proceso inflamatorio en la EHGNA. La medicina popular del norte de Chile ha utilizado la planta Lampaya medicinalis Phil. (Verbenaceae) para el tratamiento de algunas enfermedades inflamatorias. OBJETIVO: Evaluar el efecto de un extracto hidroalcóholico de lampaya (EHL) sobre la esteatosis y expresión de marcadores de inflamación en hepatocitos tratados con ácidos grasos. Diseño experimental: Estudio in vitro en cultivos de la línea celular humana HepG2 tratadas con ácido oleico (AO) y ácido palmítico (AP). MÉTODOS: Se incubó hepatocitos HepG2 con AO/AP por 24 horas en presencia o no de EHL. Se evaluó la presencia de GL y el contenido de TG intracelulares por Oil Red O y Nile Red, respectivamente. La expresión de DGAT1/2, FABP4 y TNF-α fue evaluada por qPCR. RESULTADOS: Los hepatocitos tratados con AO/AP mostraron un aumento en las GL y TG, así como una mayor expresión de DGAT2 en comparación al control. El cotratamiento con EHL revirtió los efectos inducidos por AO/AP. CONCLUSIONES: EHL revierte el incremento en las GL, TG y en la expresión de DGAT2 inducido por AO/AP en células HepG2. Estos hallazgos sugieren un efecto hepatoprotector de la Lampaya contra la esteatosis, y apoyarían su uso complementario en el tratamiento de patologías con componente inflamatorio como la EHGNA.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. At the cellular level, it is characterized by the accumulation of triglycerides (TG) in the form of lipid droplets (LD), which leads to steatosis and inflammation. Among relevant factors for TG synthesis are the enzymes DGAT1/2 catalyzing the final stage of TG synthesis, and the protein FABP4 which transports intracellular lipids and is expressed in cell models of obesity-dependent liver disease. Additionally, TNF-α is a cytokine involved in the inflammatory process associated to NAFDL. Lampaya medicinalis Phil. (Verbenaceae) is a plant used in folk medicine in northern Chile to treat some inflammatory diseases. OBJECTIVE: To evaluate the effect of the hydroalcoholic extract of lampaya (HEL) on steatosis and the expression of inflammatory markers in hepatocytes treated with fatty acids. Study design: In vitro study in cultures of the human HepG2 cell line treated with oleic acid (OA) and palmitic acid (PA). METHODS: HepG2 hepatocytes were incubated with OA/PA for 24 hours in the presence and absence of HEL. The formation of LD and the accumulation of intracellular TG were assessed by Oil Red O and Nile Red, respectively. The expression of DGAT1/2, FABP4 and TNF-α was assessed by qPCR. RESULTS: The treatment with OA/PA increased the levels of LD and TG as well as the expression of DGAT2 in HepG2 hepatocytes compared to control cells. HEL cotreatment counteracted OA/PA-induced effects. CONCLUSIONS: HEL prevents the increase in LD and TG levels and DGAT2 expression induced by OA/PA in HepG2 cells. These findings suggest that lampaya may have a protective effect against hepatic steatosis, which would support its complementary use in the treatment of pathologies associated with inflammation, such as NAFLD.
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Humanos , Extratos Vegetais/farmacologia , Hepatócitos/efeitos dos fármacos , Verbenaceae/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Triglicerídeos/análise , Técnicas In Vitro , Extratos Vegetais/uso terapêutico , Sobrevivência Celular , Reação em Cadeia da Polimerase , Técnicas de Cultura de Células , Ácido Oleico , Etanol/química , Células Hep G2/efeitos dos fármacos , InflamaçãoRESUMO
Se estima que aproximadamente 100 trillones de microorganismos (incluidos bacterias, virus y hongos) residen en el intestino humano adulto y que el total del material genético del microbioma es 100 veces superior al del genoma humano. Esta comunidad, conocida como microbioma se adquiere al momento del nacimiento a través de la flora comensal de la piel, vagina y heces de la madre y se mantiene relativamente estable a partir de los dos años desempeñando un papel crítico tanto en el estado de salud como en la enfermedad. El desarrollo de nuevas tecnologías, como los secuenciadores de próxima generación (NGS), permiten actualmente realizar un estudio mucho más preciso de ella que en décadas pasadas cuando se limitaba a su cultivo. Si bien esto ha llevado a un crecimiento exponencial en las publicaciones, los datos sobre las poblaciones Latinoamérica son casi inexistentes. La investigación traslacional en microbioma (InTraMic) es una de las líneas que se desarrollan en el Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). Esta se inició en 2018 con la línea de cáncer colorrectal (CCR) en una colaboración con el Colorectal Cancer Research Group del Leeds Institute of Medical Research en el proyecto Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents. A fines de 2019 se cumplió el objetivo de comprobar la factibilidad de la recolección, envío y análisis de muestras de MBF en 5 continentes, incluyendo muestras provenientes de la Argentina, Chile, India y Vietnam. Luego de haber participado de capacitaciones en Inglaterra, se ha cumplido con el objetivo de la etapa piloto, logrando efectivizar la recolección, envío y análisis metagenómico a partir de la secuenciación de la región V4 del ARNr 16S. En 2019, la línea de enfermedad de hígado graso no alcohólico se sumó a la InTraMic iniciando una caracterización piloto en el marco de una colaboración con el laboratorio Novartis. Los resultados de ese estudio, así como el de cáncer colorrectal, están siendo enviados a publicación. En 2020, con la incorporación de la línea de trasplante alogénico de células progenitoras hematopoyéticas, fue presentado un proyecto para un subsidio del CONICET que ha superado la primera etapa de evaluación. En el presente artículo se brinda una actualización sobre la caracterización taxonómica de microbioma y se describen las líneas de investigación en curso. (AU)
It is estimated that approximately 100 trillion microorganisms (including bacteria, viruses, and fungi) reside in the adult human intestine, and that the total genetic material of the microbiome is 100 times greater than that of the human genome. This community, known as the microbiome, is acquired at birth through the commensal flora of the mother's skin, vagina, and feces and remains relatively stable after two years, playing a critical role in both the state of health and in disease. The development of new technologies, such as next-generation sequencers (NGS), currently allow for a much more precise study of it than in past decades when it was limited to cultivation. Although this has led to exponential growth in publications, data on Latin American populations is almost non-existent. Translational research in microbiome (InTraMic) is one of the lines developed at the Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). This started in 2018 with the Colorectal Cancer Line (CRC) in a collaboration with the Colorectal Cancer Research Group of the Leeds Institute of Medical Research in the project "Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents". At the end of 2019, the objective of verifying the feasibility of collecting, sending and analyzing MBF samples on 5 continents, including samples from Argentina, Chile, India and Vietnam, was met. After having participated in training in England, the objective of the pilot stage has been met, achieving the collection, delivery and metagenomic analysis from the sequencing of the V4 region of the 16S rRNA. In 2019, the non-alcoholic fatty liver disease line joined InTraMic, initiating a pilot characterization in the framework of a collaboration with the Novartis laboratory. The results of that study, as well as that of colorectal cancer, are being published. In 2020, with the incorporation of the allogeneic hematopoietic stem cell transplantation line, a project was presented for a grant from the CONICET that has passed the first stage of evaluation. This article provides an update on the taxonomic characterization of the microbiome and describes the lines of ongoing research. (AU)
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Humanos , Pesquisa Translacional Biomédica/organização & administração , Microbioma Gastrointestinal/genética , Transplante Homólogo , Vietnã , Aztreonam/uso terapêutico , RNA Ribossômico 16S/análise , Neoplasias Colorretais/genética , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/epidemiologia , Classificação/métodos , Transplante de Células-Tronco Hematopoéticas , Metagenômica , Pesquisa Translacional Biomédica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/tendências , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Microbioma Gastrointestinal/fisiologia , Índia , América Latina , Sangue OcultoRESUMO
Existe evidencia que en pacientes con enfermedad de hígado graso no alcohólica (EHGNA) hay aumento del estrés oxidativo hepático y que esta entidad puede también ser un marcador temprano de ateroesclerosis en personas sanas. Establecer la relación entre el espesor de íntima media carotídea (EIMC) y la placa de ateroma, con la EHGNA, como un marcador precoz de ateroesclerosis subclínica independiente de los factores de riesgo cardiometabólicos clásicos. Estudio clínico no experimental, transversal, analítico. 40 sujetos distribuidos en 2 grupos: sin EHGNA y con EHGNA, diagnosticados por ultrasonido hepático, a quienes se les determinó el EIMC. Para el análisis de los resultados se calculó la media y la desviación estándar, U de Mann-Whitney y la prueba chi-cuadrado (p <0,05). Prevalencia de EHGNA 64, %. En el grupo con EHGNA 80% grado I, 20% grado II, y ninguno grado III. La media del EIMC fue mayor en el grupo con EHGNA. Se encontraron 14 individuos (35%) con EIMC > 0,8 mm; 17 individuos (40%) con placa ateromatosa carotídea, y 20 individuos (50%) con una o ambas características, en su mayoría, se encontraron en el grupo con EHGNA (p=0,004). Los pacientes con EHGNA tienen un incremento en el EIMC, y por consiguiente, del riesgo de enfermedad cardiovascular. Así, la detección de EHGNA por ultrasonido podría ser un marcador temprano de ateroesclerosis
There is evidence that in patients who have Nonalcoholic Fatty Liver Disease (NFLD), there is an increase of hepatic oxidative stress, and this entity could be an early marker of atherosclerosis in healthy people. To establish the relationship between carotid intimamedia thickness (CMT), atheroma plaque and NFLD as a possible early marker of subclinic atherosclerosis independently of the classical cardiometabolic factors. Our sample consisted of 40 subjects, divided in two groups: with and without NFLD diagnosed by hepatic ultrasound. CIMT was done in all. For statistical analysis we applied median, standard deviation, U de Mann-Whitney and chi-square. Prevalence of NFLD was 64%. In the group with NFLD 80% had stage I. 20% stage II. Median of CMT was higher in the group with NFLD. 14 subjects (40 %) had a CMT > 0,8 mm; 17 (40%) had atheromatous plaque and 20 (50%) both. (p=0,004). Patients with NFLD have a higher CMT, and, thereforea higher risk of CVD. Hepatic Ultrasound could help as an early marker of atherosclerosis