Interaction between mucus layer and gut microbiota in non-alcoholic fatty liver disease: Soil and seeds / 中华医学杂志(英文版)

The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells, as well as acts as the "mucus layer-soil" for intestinal flora adhesion and colonization. Its structural and functional integrity is crucial to human health. Intestinal mucus is regulated by factors such as diet, living habits, hormones, neurotransmitters, cytokines, and intestinal flora. The mucus layer's thickness, viscosity, porosity, growth rate, and glycosylation status affect the structure of the gut flora colonized on it. The interaction between "mucus layer-soil" and "gut bacteria-seed" is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Probiotics, prebiotics, fecal microbiota transplantation (FMT), and wash microbial transplantation are efficient methods for managing NAFLD, but their long-term efficacy is poor. FMT is focused on achieving the goal of treating diseases by enhancing the "gut bacteria-seed". However, a lack of effective repair and management of the "mucus layer-soil" may be a reason why "seeds" cannot be well colonized and grow in the host gut, as the thinning and destruction of the "mucus layer-soil" is an early symptom of NAFLD. This review summarizes the existing correlation between intestinal mucus and gut microbiota, as well as the pathogenesis of NAFLD, and proposes a new perspective that "mucus layer-soil" restoration combined with "gut bacteria-seed" FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.

Obesidad e hígado graso: el rol del pediatra / Obesity-fatty liver: the role of the pediatrician

La enfermedad hepática grasa no alcohólica pediátrica (EHGNA) es la causa más frecuente en niños y adolescentes de enfermedad hepática crónica que no puede ser atribuida a otras causas genéticas, infecciosas, tóxicas o nutricionales. Puede evolucionar desde una esteatosis simple hasta un cuadro de esteatohepatitis no alcohólica, y progresar a fibrosis avanzada, cirrosis y riesgo aumentado de carcinoma hepatocelular. Su tratamiento consiste en el cambio en el estilo de vida, mediante la promoción de la disminución de peso con la incorporación de una dieta saludable y el aumento de actividad física. Para lograr este objetivo, es fundamental el acompañamiento familiar. Estas medidas beneficiarán la calidad de vida física, psíquica y social de estos niños. El objetivo de esta comunicación es sensibilizar a la comunidad pediátrica acerca de la importancia del manejo de estos pacientes y su entorno familiar, comprometiéndose en la modificación de los factores de riesgo socioeconómicos, para lograr una mejor calidad de vida de las futuras generaciones.

Pediatric nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adolescents that cannot be attributed to other genetic, infectious, toxic or nutritional causes. It can evolve from simple steatosis to nonalcoholic steatohepatitis, and can progress to advanced fibrosis, cirrhosis, and an increased risk of hepatocellular carcinoma. Its treatment consists of a change in lifestyle, promoting weight loss with the incorporation of a healthy diet and increased physical activity. To achieve this goal, family support is essential. These measures will benefit the physical, mental and social quality of life of these children. The objective of this communication is to sensitize the pediatric community about the importance of managing these patients and their family environment, committing to modifying socioeconomic risk factors, to achieve a better quality of life for future generations.

The therapeutic impact of probiotics on nonalcoholic fatty liver disease in pediatrics: a systematic review / Impacto terapêutico dos probióticos na doença hepática gordurosa não alcoólica em pediatria: uma revisão sistemática

ABSTRACT Objective: Evaluate the effects of probiotics use, compared with placebo, in pediatric patients with non-alcoholic fatty liver disease (NAFLD), using laboratorial and ultrasonographic parameters as outcomes. Methods: A systematic review of the literature was performed through MEDLINE and Lilacs databases. The articles selected were randomized controlled clinical trials published until November 2018, without any language restriction, dealing with pediatric patients with NAFLD. Patients were divided into 2 groups. One group received probiotic therapy and the other group, only received placebo. The primary outcome evaluated was the difference between the serum levels of alanine aminotransferase (ALT) before and after receiving probiotics or placebo. The secondary outcomes evaluated were the serum aspartate aminotransferase levels, body mass index, serum triglycerides, waist circumference and level of liver steatosis on the ultrasonography. Results: A total of 46 articles were recovered, and 3 articles were included in the qualitative analysis, totaling 128 patients. Two trials revealed a significant decrease of alanine aminotransferase levels after treatment with probiotics (Lactobacillus rhamnosus for 8 weeks; Bifidobacterium+Lactobacillus for 12 weeks), when compared to the placebo. The other variables did not show a statistically significant difference between both groups. Conclusions: Probiotic therapy has contributed to the reduction of ALT serum levels in pediatric patients with nonalcoholic fatty liver disease, which is in line with results found by other authors in scientific literature. Regarding the secondary outcomes, the use of probiotics did not show benefits or damages compared to placebo.

RESUMO Objetivo: Avaliar os efeitos do uso de probióticos em comparação com placebo, em pacientes pediátricos portadores de doença hepática gordurosa não alcoólica (DHGNA), utilizando parâmetros laboratoriais e ultrassonográficos como desfecho. Métodos: Revisão sistemática da literatura por meio das bases de dados Sistema Online de Busca e Análise de Literatura Médica (MEDLINE) e Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs). Foram selecionados ensaios clínicos controlados randomizados publicados até novembro de 2018, sem restrição de língua, com pacientes pediátricos portadores de DHGNA, divididos em dois grupos. Um grupo foi submetido à terapia probiótica e outro grupo recebeu somente placebo. O desfecho primário avaliado foi a comparação dos níveis de alanina aminotransferase (ALT) ao início e no fim do seguimento entre os grupos probiótico e placebo. Os desfechos secundários avaliados foram os níveis de aspartato aminotransferase sérico, índice de massa corpórea, triglicerídeos totais séricos, circunferência abdominal e grau de esteatose hepática à ultrassonografia abdominal. Resultados: Foram recuperados 46 artigos, sendo três incluídos na análise qualitativa, totalizando 128 pacientes. Dois estudos demonstraram redução significativa dos níveis de ALT com o uso de probiótico (Lactobacillus rhamnosus, por oito semanas; Bifidobacterium+Lactobacillus, por 12 semanas), em comparação ao placebo. As demais variáveis avaliadas não evidenciaram diferença estatisticamente significante ente os dois grupos. Conclusões: O uso de probióticos representou redução nos níveis séricos de ALT na esteatose hepática na infância, indo ao encontro dos resultados obtidos por outros autores da literatura científica vigente. No que se refere às variáveis de desfecho secundário, não foi demonstrado benefício ou dano do tratamento de probióticos em relação ao placebo.

Aspectos relevantes de la enfermedad por hígado graso no alcohólico / Relevant aspects of nonalcoholic fatty liver disease

La enfermedad por hígado graso no alcohólico (EHGNA) es una condición que incluye desde la esteatosis hepática simple y la esteatohepatitis, hasta la cirrosis hepática y eventualmente el carcinoma hepatocelular. La diabetes tipo 2 y la obesidad son los principales factores asociados a la EHGNA. Su prevalencia en la población general se ha descrito entre el 20% y el 30%. Estos pacientes tienen un riesgo aumentado de mortalidad y presentan mayor incidencia que la población general de complicaciones hepáticas y cardiovasculares. La asociación de diferentes factores promueve la acumulación de ácidos grasos en el parénquima hepático, generando un estado de estrés, con formación de radicales de oxígeno y liberación de citoquinas inflamatorias que determinan la progresión de la enfermedad. Aunque existen diferentes pruebas no invasivas para el diagnóstico y estadificación de esta entidad, la biopsia hepática es la única prueba que permite identificar de manera fiable la presencia de inflamación, además del grado de fibrosis. El tratamiento actual de la EHGNA se basa en los cambios de estilo de vida del paciente, que han demostrado ser efectivos, incluso para revertir la fibrosis. Desafortunadamente, la adherencia a las medidas generales es muy pobre, de ahí la necesidad de contar con estrategias farmacológicas. Hasta el momento, no contamos con medicamentos aprobados por las agencias regulatorias para esta entidad, y los únicos fármacos recomendados por las sociedades internacionales son la pioglitazona y la vitamina E, que no están exentas de efectos adversos. Actualmente se encuentran bajo investigación diferentes medicamentos que buscan reducir la actividad inflamatoria sin aumento de la fibrosis, o mejoría de la fibrosis sin deterioro de la esteatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is a condition that ranges from simple hepatic steatosis and steatohepatitis, to liver cirrhosis and eventually hepatocellular carcinoma. Type 2 diabetes and obesity are the main factors associated with NAFLD. The prevalence in the general population has been described between 20% and 30%. These patients are at increased risk of mortality and have a higher incidence than the general population of liver and cardiovascular complications. The association of different factors promotes the accumulation of fatty acids in the liver parenchyma, generating a state of stress, with the formation of oxygen radicals and the release of inflammatory cytokines that determine the progression of the disease. Although there are different non-invasive tests for the diagnosis and staging of this condition, liver biopsy is the only test that reliably identifies the presence of inflammation, in addition to the degree of fibrosis. The current treatment of NAFLD is based on changes in the patient's lifestyle, which have been shown to be effective, including in reversing fibrosis. Unfortunately, adherence to general measures is very poor, hence the need for pharmacological strategies. So far, we do not have drugs approved by the regulatory agencies for this disease, and the only drugs recommended by international societies are pioglitazone and vitamin E, which are not exempt from adverse effects. Currently, different drugs are under investigation that seek to reduce inflammatory activity without increasing fibrosis, or improvement of fibrosis without deterioration of steatohepatitis.

Síndrome metabólico, hígado graso no alcohólico y hepatocarcinoma / Metabolic syndrome, nonalcoholic fatty liver disease and hepatocellular carcinoma

En las últimas décadas, los cambios en el estilo de vida pro-vocaron un incremento en la prevalencia del síndrome meta-bólico y que la enfermedad por hígado graso no alcohólico (nonalcoholic fatty liver disease, NAFLD sus siglas en inglés) se convierta en la enfermedad hepática crónica más fre-cuente en todo el mundo. Los componentes del síndrome metabólico no son sólo altamente prevalentes en pacientes con hígado graso no alcohólico, sino que a la vez aumentan el riesgo de desarrollarlo. Esta relación bidireccional ha sido claramente establecida. Asimismo se considera que NAFLD podría ser el componente hepático del síndrome metabólico. Aunque NAFLD se considera principalmente una enfermedad benigna, puede progresar a fibrosis hepática grave y carcino-ma hepatocelular (CHC), incluso se encontraría este último en hígados no cirróticos. El objetivo de esta revisión es determinar los procesos fisio-patológicos comunes a estas entidades, cuáles son las estra-tegias diagnósticas recomendadas y cuáles las intervenciones terapéuticas actualmente aprobadas.

Análisis crítico del tratamiento de la enfermedad hepática grasa no alcohólica / Management of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFDL) includes fatty liver or simple steatosis, characterized by lipid deposits in hepatocytes and more advanced stages such as steatohepatitis (NASH) and non-alcoholic cirrhosis. Physical inactivity, hypercaloric and unbalanced diet together with aging play a key role in the pathogenesis of NAFLD and are strongly associated with metabolic and physical activity continue to be major components in prevention and first-line treatment to attenuate or reverse NAFLD. Dietary patterns, their composition and weight reduction would be the most relevant nutritional aspects in NAFDL treatment. Physical exercise, moderate to intense, aerobic and resistance type contributes to weight loss, improves metabolic control and body composition. Pharmacological therapy can be useful in clinical circumstances that require it and needs a medical evaluation when there is no adherence and success in non-pharmacological interventions.

Suppression of high fat diet-induced liver cell injury by swim exercise / Supresión de lesión en células de hígado inducida por dieta alta en grasas con ejercicio de natación

SUMMARY: The rapid rise in obesity, particularly among children is a major public health concern that adversely affects vital organs including the liver. We sought to investigate the effect of exercise on the healing of liver cells from damage induced by high fat diet (HFD) in a rat model of hepatic steatosis. Rats were randomly divided into four groups (n=6 in each group); control group fed on a low fat diet (LFD), LFD plus exercise group (LFD+EX), model group fed on HFD, and swim exercise treated group (HFD+EX). Training swim exercise started from the 11th week up until the end of week 15. Liver index and body mass index (BMI) were determined, and harvested liver tissues were examined using basic histological staining and visualised under light microscopy. In addition, collected blood samples were assayed for biomarkers of liver injury. Histological images from the model group showed accumulation of lipid droplets in the hepatocytes (steatosis) and damaged liver cells that were inhibited by swimming exercise. Compared to control groups, HFD caused an increase in BMI and liver weight but not in liver index. In addition, HFD significantly (p<0.05) increased liver injury biomarkers; high-sensitivity C-reactive protein (hsCRP) and alkaline phosphatase (ALP) that were effectively (p<0.05) decreased by swimming exercise. Furthermore, a negative correlation between these biomarkers and the antioxidant and anti-inflammatory protein adiponectin was observed. Thus, HFD-induced hepatic steatosis is treated by swim exercise.

RESUMEN: El aumento de la obesidad, especialmente entre los niños, es un problema importante en la salud pública que afecta negativamente los órganos vitales, incluyendo el hígado. En este estudio se investigó el efecto del ejercicio en la curación de las células del hígado y el daño inducido por la dieta alta en grasas (HFD) en un modelo de rata de esteatosis hepática. Las ratas se dividieron aleatoriamente en cuatro grupos (n = 6 en cada grupo); grupo control, alimentado con una dieta baja en grasas (LFD); grupo de ejercicio LFD más (LFD + EX); grupo modelo alimentado con HFD; y grupo tratado con ejercicio de natación (HFD + EX). El entrenamiento con ejercicio de natación comenzó a partir de la semana 11 hasta el final de la semana 15. Se determinaron el índice hepático y el índice de masa corporal (IMC). Los tejidos hepáticos recolectados se examinaron mediante tinción histológica básica y se visualizaron con microscopía óptica. Además, se analizaron las muestras de sangre recogidas para identificar biomarcadores de lesión hepática. Las imágenes histológicas del grupo modelo mostraron acumulación de gotitas de lípidos en los hepatocitos (esteatosis) y células hepáticas dañadas que fueron inhibidas por el ejercicio de natación. En comparación con los grupos control, HFD causó un aumento en el IMC y el peso del hígado, pero no en el índice de hígado. Además, HFD aumentó significativamente (p <0.05) los biomarcadores de lesiones hepáticas; la proteína C reactiva de alta sensibilidad (hsCRP) y la fosfatasa alcalina (ALP) disminuyeron efectivamente (p <0.05) con el ejercicio de natación. Además, se observó una correlación negativa entre estos biomarcadores y la proteína antioxidante y antiinflamatoria adiponectina. Por lo tanto, la esteatosis hepática inducida por HFD puede ser tratada mediante el ejercicio de natación.

Current management of non-alcoholic fatty liver disease / Atualidades no tratamento da doença hepática gordurosa não alcoólica

SUMMARY Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic accumulation of lipid in patients who do not consume alcohol in amounts generally considered harmful to the liver. NAFLD is becoming a major liver disease in Eastern countries and it is related to insulin resistance and metabolic syndrome. Treatment has focused on improving insulin sensitivity, protecting the liver from oxidative stress, decreasing obesity and improving diabetes mellitus, dyslipidemia, hepatic inflammation and fibrosis. Lifestyle modification involving diet and enhanced physical activity associated with the treatment of underlying metabolic are the main stain in the current management of NAFLD. Insulin-sensitizing agents and antioxidants, especially thiazolidinediones and vitamin E, seem to be the most promising pharmacologic treatment for non-alcoholic steatohepatitis, but further long-term multicenter studies to assess safety are recommended.

RESUMO A doença hepática gordurosa não alcoólica (DHGNA) é caracterizada pela deposição significativa de lipídios nos hepatócitos de pacientes que não apresentam história de ingestão alcoólica significativa. É a doença do fígado mais prevalente em populações ocidentais e existe forte associação da DHGNA com a resistência à insulina (RI) e com a síndrome metabólica. O tratamento objetiva reduzir a RI, o estresse oxidativo, a obesidade, a dislipidemia bem como a inflamação e a fibrose hepáticas. O tratamento atual baseia-se principalmente em modificações do estilo de vida, que incluem dieta e prática regular de exercícios físicos, associadas ao tratamento de todos os componentes da síndrome metabólica. Quanto ao tratamento medicamentoso da esteato-hepatite não alcoólica, os agentes insulino-sensibilizantes e os antioxidantes parecem os mais promissores, especialmente as tiazolidinodionas e a vitamina E, mas faltam estudos multicêntricos avaliando sua segurança a longo prazo.

Nonalcoholic fatty liver disease brazilian society of hepatology consensus

ABSTRACT The prevalence of obesity-related metabolic syndrome has rapidly increased in Brazil, resulting in a high frequency of nonalcoholic fatty liver disease, that didn't receive much attention in the past. However, it has received increased attention since this disease was identified to progress to end-stage liver diseases, such as cirrhosis and hepatocellular carcinoma. Clinical practice guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease have not been established in Brazil. The Brazilian Society of Hepatology held an event with specialists' members from all over Brazil with the purpose of producing guideline for Nonalcoholic Fatty Liver Disease based on a systematic approach that reflects evidence-based medicine and expert opinions. The guideline discussed the following subjects: 1-Concepts and recommendations; 2-Diagnosis; 3-Non-medical treatment; 4-Medical treatment; 5-Pediatrics - Diagnosis; 6-Pediatrics - Non-medical treatment; 7-Pediatrics - Medical treatment; 8-Surgical treatment.

RESUMO A prevalência de obesidade relacionada à síndrome metabólica tem crescido no Brasil, que implicou em uma maior frequência de doença hepática gordurosa não alcoólica, não havia recebido muita atenção no passado. Contudo, essa atenção tem merecido interesse cada vez maior desde que se observou o elevado potencial de progressão para formas mais graves dessa doença como cirrose e carcinoma hepatocelular. No Brasil ainda não havia sido proposta nenhuma diretriz para orientar o diagnóstico e tratamento da doença hepática gordurosa não alcoólica. A Sociedade Brasileira de Hepatologia realizou então um evento que reuniu especialistas de todo o Brasil com o objetivo de propor uma diretriz para a doença hepática gordurosa não alcoólica baseada em evidências científicas e opiniões de especialistas nesse tema. A diretriz final é composta dos seguintes temas: 1-Conceitos e recomendações; 2-Diagnóstico; 3-Tratamento não medicamentoso; 4-Tratamento medicamentoso; 5-Diagnóstico em Pediatria; 6-Tratamento não medicamentoso em Pediatria; 7-Tratamento medicamentoso em Pediatria; 8-Tratamento cirúrgico.

Esteatohepatitis no alcohólica (EHNA) / Non alcoholic steatohepatitis (NASH)

En la presente revisión mostramos lo último sobre la etiología, epidemiología, fisiopatología, historia natural, cuadro clínico, tratamiento y complicaciones de la esteatohepatitis no alcohólica...

In this review we show you all the advances in ethiology, epidemiology, phisiopatology, natural history, clinic aspects, treatment and complications of non alcoholic steatohepatitis...

Microbiota e hígado graso: potencial terapéutico / Microbiota and fatty liver: therapeutic potencial

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, characterized by accumulation of fat on the liver parenchyma with a heterogeneous clinical presentation. In recent years its prevalence and incidence has been increasing in association with the rise in obesity and its comorbidities, becoming one of the main causes of cirrhosis. The cause of NAFLD is multifactorial, and currently the role of intestinal microbiota and its interaction with the metabolic syndrome and NAFLD has become of interest. Different pathophysiological phenomena have emerged, the main being intestinal dysbiosis, loss of intestinal barrier, bacterial translocation, with activation of inflammation and oxidative stress, and production of active metabolites, such as ethanol. The management of this factor seems promising and adds to the classic approach of changes in lifestyle. Probiotics are the most studied tool and show evidence of effectiveness, however further studies are needed.

La enfermedad por hígado graso no alcohólico (EHGNA) es la manifestación hepática del síndrome metabólico,caracterizándose por acumulación de grasa a nivel del parénquima con una heterogénea presentación clínica. En los últimos años su prevalencia e incidencia ha ido en aumento, en asociación al aumento de la obesidad y sus comorbilidades, transformándose en una de las principales etiologías de cirrosis hepática. La causa de la EHGNA es multifactorial, siendo de interés en la actualidad el rol de la microbiota intestinal y su interacción con el síndrome metabólico y la EHGNA. Distintos fenómenos fisiopatológicos se han planteado, siendo los principales la disbiosis intestinal, la pérdida de la barrera intestinal, la translocación bacteriana con activación de la cascada de la inflamación y estrés oxidativo y la producción de metabolitos activos como el etanol. El manejo de este factor parece promisorio y se agrega al clásico enfrentamiento de cambios en estilo de vida. Los probióticos son la herramienta más estudiada y disponen de evidencia de efectividad, pero con necesidad de mayores estudios.

Guía de práctica clínica para la enfermedad hepática grasa no alcohólica / Clinical practice guideline for nonalcoholic fatty liver disease

Objetivo: brindar una guía de práctica clínica basada en la evidencia más reciente para el diagnóstico y tratamiento de la enfermedad hepática grasa no alcohólica teniendo en cuenta la efectividad y seguridad de las intervenciones dirigidas a pacientes, personal asistencial, administrativo y entes gubernamentales de cualquier servicio de atención en Colombia. Materiales y métodos: esta guía fue desarrollada por un equipo multidisciplinario con apoyo de la Asociación Colombiana de Gastroenterología, el Grupo Cochrane ITS y el Instituto de Investigaciones Clínicas de la Universidad Nacional de Colombia. Se desarrollaron preguntas clínicas relevantes y se realizó la búsqueda de guías nacionales e internacionales en bases de datos especializadas. Las guías existentes fueron evaluadas en términos de calidad y aplicabilidad; una guía cumplió los criterios de adaptación, por lo que se decidió adaptar 3 preguntas clínicas. El Grupo Cochrane realizó la búsqueda sistemática de la literatura. Las tablas de evidencia y recomendaciones fueron realizadas con base en la metodología GRADE. Las recomendaciones de la guía fueron socializadas en una reunión de expertos con entes gubernamentales y pacientes. Resultados: se desarrolló una guía de práctica clínica basada en la evidencia para el diagnóstico y tratamiento de la enfermedad hepática grasa no alcohólica en Colombia. Conclusiones: el diagnóstico y manejo oportuno de la enfermedad hepática grasa no alcohólica contribuirá a disminuir la carga de la enfermedad en Colombia, así como de las enfermedades asociadas.

Objective: To provide a clinical practice guideline with the latest evidence for diagnosis and treatment of nonalcoholic fatty liver disease for patients, caregivers, administrative and government bodies at all levels of care in Colombia. Materials and Methods: This guide was developed by a multidisciplinary team with the support of the Colombian Association of Gastroenterology, Cochrane STI Group and Clinical Research Institute of the Universidad Nacional de Colombia. Relevant clinical questions were developed and the search for national and international guidelines in databases was performed. Existing guidelines were evaluated about quality and applicability. One guideline met the criteria for adaptation, so the group decided to adapt 3 clinical questions. Systematic literature searches were conducted by the Cochrane Group. The tables of evidence and recommendations were made based on the GRADE methodology. The recommendations of the guide were socialized in a meeting of experts with government agencies and patients. Results: An evidence-based Clinical Practice Guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease was developed for the Colombian context. Conclusions: The opportune detection and appropriate management of nonalcoholic fatty liver disease would contribute to the burden of the disease in Colombia.

Hígado graso no alcohólico / Non-alcoholic fatty liver disease

La esteatosis hepática no alcohólica es la acumulación excesiva de grasa en el hígado, en ausencia de causas secundarias y constituye la etiología frecuente de enfermedad hepática crónica sin terapia efectiva demostrada. La enfermedad incluye esteatosis, inflamación, fibrosis/cirrosis y hepatocarcinoma. El fenómeno inicial ocurre en la grasa corporal, con hipertrofia adipocitaria, liberación de adipoquinas y citoquinas pro-inflamatorias, que inducirán resistencia a la insulina. Este fenómeno provocará liberación de ácidos grasos a la circulación, captados por hepatocitos. En su evaluación clínica existen diferentes algoritmos con múltiples variables, limitando la biopsia hepática solo a casos excepcionales. Es esencial modificar el estilo de vida y bajar de peso. En diabéticos, metformina y pioglitazona son de primera elección. Los bloqueadores de la angiotensina son útiles en hipertensos con EHNA. Para prevenir la progresión de la enfermedad y en pacientes no diabéticos, asociar vitamina E. Las estatinas pueden utilizarse dada la asociación con patología cardiovascular.

Nonalcoholic fatty liver disease is characterized by excessive hepatic fat accumulation in the abscence of secundary causes. It is the most common cause of chronic liver disease. The spectrum ranges from benign steatosis, steatohepatitis, cirrhosis and hepatocarcinoma. The initial event is the hyperthofied adipocytes, and the release of adipokines and chemokines, that induce insulin resistance, and then free fatty acids into the circulation that accumulate in the liver. Algorithms have been proposed to target liver biopsy only to select patients. Lifestyle modifications to achieve weight loss are essential for all patients with NAFLD. For diabetics treatment should be with metformin and pioglitazone if glycaemic control is not achieved. Angiotensin receptor blockers are the antihypertensive agent of choice in patients with nonalcoholic steatohepatitis (NASH). If lifestyle changes and metabolic syndrome are unsuccessful in preventing disease progression, vitami E should be considered, also in non-diabetic patients with advance (NASH).

Enfermedad hepática por depósito de grasa / Hepatic disease due to fat deposit

La enfermedad hepática por depósito de grasa adquiere cada vez una importancia mayor como entidad y, al mismo tiempo, como factor de riesgo aislado o asociado al síndrome metabólico. Con el objetivo de actualizar algunos aspectos relacionados con esta hepatopatía, tales como su actual nomenclatura y nuevo enfoque etiopatogénico, se efectuó la presente revisión bibliográfica desde una perspectiva clínica, la que incluye datos elementales sobre la fisiopatología y las características de presentación de la entidad, así como las principales armas utilizadas en su diagnóstico, control o terapéutica. Se demuestra, además, que la visión sobre el tema ha cambiado en los últimos años y constituye fuente de investigación en múltiples grupos prestigiosos por las particularidades de su evolución.

The hepatic disease due to fat deposit acquires greater importance as entity and, at the same time, as isolated or associated risk factor to the metabolic syndrome. With the objective of updating some aspects related to this hepatopathy, such as its current nomenclature and new etiopathogenic approach; the present literature review was carried out from a clinical perspective, which includes elementary data on the pathophysiology and the presentation characteristics of the entity, as well as the main tools used in its diagnosis, control or therapy. It is also demonstrated, that the vision on the topic has changed in the last years and it constitutes an investigation source in multiple noted groups due to the particularities of its clinical course.

Nonalcoholic fatty liver disease: a cohort study focusing on treatment response to nutritional counseling / A doença hepática gordurosa não-alcoólica: um estudo de coorte com foco na resposta ao tratamento com orientação nutricional

BACKGROUND: Nonalcoholic fatty liver disease is the leading cause of liver pathology. The mainstay of management is weight loss. Our aim was to evaluate responses to nutritional counseling in long-term patients with this condition. METHODS: A prospective cohort study with consecutive inclusion of 105 subjects with nonalcoholic fatty liver disease who received individualized low-calories diet counseling (1400 to 1600 kcal/day according to gender) every three months for 24 months. Weight loss of 5% or more was considered as a therapeutic response. RESULTS: Out of 105 patients, 45 (42.9%) did not return for a second evaluation. Mean age was 55 ± 9 years, 81.6% were women and mean body mass index was 31.9 (23.8-44.9) kg/m2. Follow-up time was 6.5 (3.2-26.9) months and median appointment number was 3 (2-11). Metabolic syndrome and hypercholesterolemia were more common in women. The number of subjects who lost more than 5% weight was: 5/20 (25%) at 6-months; 3/15 (33%) at 12 months; 3/18 (17%) at 18 months and 4/13 (31%) at the end of follow up. The median body weight loss at 6, 12, 18 and 24 months decreased significantly. CONCLUSIONS: Adherence to nutritional counseling is poor in patients with nonalcoholic fatty liver disease. Only a very small proportion of patients reached the targeted body loss of weight on long term.

RESUMO OBJETIVOS: A doença hepática gordurosa não alcoólica éa principal causa de patologia hepática. Essencial para seu manejo éa perda de peso. Nosso objetivo foi avaliar as respostas a aconselhamento nutricional em pacientes crônicos com esta condição. METODOS: Estudo prospectivo de coorte com inclusão consecutiva de 105 indivíduos com doenca hepática gordurosa não alcoólica que receberam dieta individualizada de baixa caloria (1400-1600kcal/dia, de acordo com o sexo) e aconselhamento a cada 3 meses, durante 24 meses. A perda de peso de 5% ou mais foi considerada como resposta terapêutica adequada. RESULTADOS: Dos 105 pacientes, 45 (42,9%) não voltaram para uma segunda avaliação. A média de idade foi de 55 ± 9 anos, 81,6% eram mulheres e o índice de massa corporal foi de 31,9 (23,8-44,9) kg/m2. O tempo de seguimento foi de 6,5 (3,2-26,9) meses e número médio de entrevistas foi de 3 (2-11). A síndrome metabólica e a hipercolesterolemia foram mais comuns em mulheres. O número de indivíduos que perderam mais de 5% em peso foi: 5/20 (25%) em 6 meses; 3/15 (33%) aos 12 meses; 3/18 (17%) e aos 18 meses 4/13 (31%) no final do seguimento. A perda de peso corporal média aos 6, 12, 18 e 24 meses diminuiu significativamente. CONCLUSÕES: A adesão ao aconselhamento nutricional épobre em pacientes com doenca hepática gordurosa não alcoólica. Apenas uma pequena proporcão de pacientes que atingiu a perda de peso corporal programada a longo prazo.

Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver and is associated with obesity and insulin resistance. Activin A is a member of the transforming growth factor beta (TGF)-β superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin. Exercise is an important therapeutic strategy to reduce the metabolic effects of obesity. We evaluated the pattern of activin A and follistatin liver expression in obese rats subjected to swimming exercise. Control rats (C) and high-fat (HF) diet-fed rats were randomly assigned to a swimming training group (C-Swim and HF-Swim) or a sedentary group (C-Sed and HF-Sed). Activin βA subunit mRNA expression was significantly higher in HF-Swim than in HF-Sed rats. Follistatin mRNA expression was significantly lower in C-Swim and HF-Swim than in either C-Sed or HF-Sed animals. There was no evidence of steatosis or inflammation in C rats. In contrast, in HF animals the severity of steatosis ranged from grade 1 to grade 3. The extent of liver parenchyma damage was less in HF-Swim animals, with the severity of steatosis ranging from grade 0 to grade 1. These data showed that exercise may reduce the deleterious effects of a high-fat diet on the liver, suggesting that the local expression of activin-follistatin may be involved.

Efecto del tratamiento con extracto de propóleos rojo oral en la esteatohepatitis no alcohólica / Effect of treatment with oral red propolis extract on nonalcoholic teatohepatitis

Introducción: la esteatohepatitis no alcohólica es frecuente y puede evolucionar hacia la cirrosis. Sus opciones de tratamiento farmacológico son poco eficaces. Se conoce que los propóleos tienen acción antioxidante y antiinflamatoria y se han reportado efectos beneficiosos de los propóleos. Objetivo: identificar los cambios histológicos hepáticos en pacientes con esteatohepatitis tratados con extracto hidroalcohólico al 5 por ciento de propóleos rojo oral cubano durante un año. Métodos: se realizó un ensayo clínico aleatorizado, a doble ciegas, con grupo control, en 40 individuos de ambos sexos, entre 20 y 65 años, con índice de Kleiner entre 6 y 8, divididos en 2 grupos: propóleos y placebo. Las pruebas estadísticas aplicadas fueron chi-cuadrado y la prueba no paramétrica. Resultados: el Kleiner total en el grupo propóleos se redujo de 6 ± 0,65 a 3,15 ± 071 y en el grupo placebo de 6 ± 0,65 a 6,1 ± 0,97. En el grupo propóleos se redujeron la esteatosis, inflamación, balonamiento y fibrosis y los cambios en las enzimas hepáticas y las lipoproteínas plasmáticas fueron favorables. Conclusiones: el propóleos rojo puede ser una alternativa terapéutica para detener la progresión de la esteatohepatitis...

Introduction: nonalcoholic steatohepatitis is a common condition which may lead to cirrhosis. The existing drug therapy options are not very effective. It is a well known fact that propolis has an antioxidant and antiinflammatory effect. Reports on the benefits of propolis may be found in the literature. Objective: identify histological hepatic changes in patients with steatohepatitis treated with 5 percent hydroalcoholic oral extract of Cuban red propolis for a year. Methods: a double-blind randomized controlled clinical trial was conducted with 40 patients of both sexes aged 20-65 with 6-8 Kleiner index, who were divided in 2 groups: propolis and placebo. Statistical analysis was based on chi-square and nonparametric tests. Results: total Kleiner decreased from 6 ± 0.65 to 3.15 ± 071 in the propolis group and from 6±0.65 to 6.1±0.97 in the placebo group. In the propolis group there was also a decrease in steatosis, inflammation, ballooning and fibrosis. Changes in liver enzymes and plasmatic lipoproteins were favorable. Conclusions: red propolis may be a therapeutic alternative to stop the progress of esteatohepatitis...

Duodenal jejunal bypass attenuates non-alcoholic fatty liver disease in western diet-obese rats

PURPOSE:To evaluate the effects of duodenal-jejunal bypass (DJB) on serum and hepatic profiles of obese rats fed on a western diet (WD).METHODS:Twenty eight male Wistar rats were fed a standard rodent chow diet (CTL group) or WD ad libitum. After 10 weeks, WD rats were submitted to sham (WD SHAM) or duodenal-jejunal bypass (WD DJB). Body weight, fat pad depots, glycemia, insulinemia, HOMA-IR, TyG, lipids profile and hepatic analyses were evaluated two months after surgery.RESULTS:The WD SHAM group presented greater obesity, hyperglycemia, hyperinsulinemia, insulin resistance, hypertriglyceridemia and hepatic steatosis than the CTL group. WD DJB rats presented decreased serum glucose and insulin resistance, when compared to WD SHAM animals, without changes in insulinemia. In addition, DJB surgery normalized serum TG and attenuated TG accumulation and steatosis in the liver of the WD DJB group. Hepatic ACC and FAS protein expressions were similar in all groups.CONCLUSION:Duodenal-jejunal bypass attenuates hepatic parameters of non-alcoholic fatty liver disease in obese rats fed on a western diet.

Pharmacological and antioxidant actions of garlic and/or onion in non-alcoholic fatty liver disease [NAFLD] in rats

Non-alcoholic fatty liver disease [NAFLD] includes a broad spectrum of fat-induced liver injury, ranging from mild steatosis to cirrhosis and liver failure. This study investigates the hepatoprotective properties of garlic and onion in NAFLD rat model. Ninety male Sprague-Dawley rats were randomly divided into 9 groups; normal [I], NAFLD induced with high fat diet [HFD; II], NAFLD switched to regular diet [RD; III], NAFLD-HFD or NAFLD-RD treated with garlic [IV, V] onion [VI, VII] or the combined garlic+onion [VIII, IX] respectively. A NAFLD rat model was established by feeding the animals with a high-fat diet for 12 wk. These animals were then treated with garlic or/and onion or vehicle for 8 wk [weeks 13-20] and then killed to obtain serum samples and liver tissues. Liver histology, lipids, parameters of oxidative stress, TNF-alpha and TGF-p were measured. The liver in NAFLD-HFD showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration. Serum levels of ALT, AST, ALP, leptin, cholesterol, triglycerides, TNF-alpha, TGF-P and hepatic MDA were significantly increased [P<0.05] compared with normal group. This was accompanied with reduction of hepatic GSH, GR, GPx, GST, SOD and serum adiponectin. These changes were to a less degree in NAFLD-RD group. Combined administration of garlic+onion produced a better and significant decrease in liver steatosis, serum liver enzymes, oxidative markers and lipid peroxidation versus each one alone. In the same time, NAFLD-induced inflammation was also mitigated via reduction of TNF-alpha and TGF-P. In addition, these results were better in the group IX versus group VIII

Histological study on the effect of metformin on high-fat-diet-induced liver injury in adult male albino rats

Changes in lifestyle and food habits increase the prevalence of nonalcoholic fatty liver disease [NAFLD]. It is a chronic condition that has no or few symptoms. It may be accompanied by inflammation and insulin resistance. Moreover, it is closely linked to diabetes. Metformin is an antidiabetic agent that can improve insulin resistance. The study was conducted to investigate the effect of metformin on liver injury induced by a high-fat diet. The study lasted for 12 weeks. Thirty-six adult male albino rats were used and divided into four groups. Group I was the control group. Group II rats received metformin. Group III rats were fed a high-fat diet for induction of NAFLD. Group IV rats were fed a high-fat diet for induction of NAFLD and then administered metformin orally in the last 4 weeks of the study. Liver specimens were processed for light and electron microscopic examination. Moreover, liver weight index was determined, and biochemical, morphometric, and statistical studies were performed. Induction of NAFLD [group III] resulted in severe insulin resistance. Hepatocytes showed macrovesicular and microvesicular steatosis, ballooning, and lobular inflammation. The number of positive cells and the reaction for tumor necrosis factor-alpha in group III apparently increased as compared with group IV. Lipid droplets, loss of mitochondrial cristae, and dispersion of rER were detected in group III. Metformin improved insulin resistance, and liver histological changes were fewer than those in group III. Metformin can greatly improve liver histological changes associated with a model of NAFLD