Niveles tensionales en niños y adolescentes con esteatosis hepática / Tensional levels in children and adolescents with hepatic steatosis

Introducción: la enfermedad hepática no alcohólica (EHNA) constituye un desorden multifactorial cuyos elementos de riesgo se pueden aludir a la obesidad, el sedentarismo y el componente genético. Objetivo: evaluar los niveles tensionales en niños y adolescentes con esteatosis hepática por sonografía de 5-18 años en el Hospital Regional Universitario Dr. Arturo Gullón. Métodos y técnicas: se realizó un estudio descriptivo de corte transversal y fuente primaria. La muestra estuvo compuesta por de 106 participantes. Se realizó sonografía abdominal para determinar la presencia de esteatosis hepática y se midió la presión arterial sistólica abdominal para determinar la presencia de esteatosis hepática y se midió la presión arterial sistólica y diastólica, IMC, talla y pruebas de laboratorio. Para el análisis estadístico se empleó chi-cuadrado. Resultados: el sexo predominante en la tensión arterial sistólica fue el femenino con un 44.9 % en estadio prehipertensión, mientras que el masculino fue el sexo predominante en presión arterial diastólica con un 49.1 %. Se evidenció que los individuos con IMC del percentil 90 se encontraban en estadio prehipertensión en el percentil. El perfil lipídico (colesterol, HDL, LDL, triglicéridos) y las transaminasas (SGOT y SGPT) mostraron relación con niveles tensionales elevados con predominio en la TAD. Los valores elevados de glicemia presentan relación con las cifras aumentadas de la tensión arterial sistólica. Conclusión: el estudio mostró que existe una relación entre la esteatosis hepática no alcohólica y el riesgo de desarrollar hipertensión arterial. Presentando relación estadísticamente significativa entre los niveles tensionales elevados y el perfil bioquímico estudiado, así como al IMC de los pacientes evaluados en la investigación

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disorder whose risks factors can be attributed to obesity, sedentary lifestyle and a genetic component. Objective: To evaluate blood pressure levels in children and adolescent aged 5-18 years old with hepatic steatosis using ultrasound at the Dr. Arturo Grullón Regional University Hospital. Methods and Techniques: A descriptive cross-sectional study of primary source were carried out. The sample of the study consisted in 106 participants. Abdominal ultrasono-graphy was performed to determine the presence of hepatic steatosis and systolic and diastolic blood pressure, BMI, height and laboratory tests were measured. Chi square was used in the statistical analysis of the data. Results: The predominant sex in systolic blood pressure was female with 44.9% in prehypertension stage, while male was the predominant sex in diastolic blood pressure with 49.1%. It was evidenced that individuals with BMI ≥90thpercentile were in the prehypertensive stage at the percentile. The lipid profile (cholesterol, HDL-C, LDL-C, triglycerides) and transaminases (SGOT ad SGPT) showed a relationship with high blood pressure levels with a predo-minance in DBP. Elevated glucose levels are related to an increase in systolic blood pressure. Conclusion: The study showed that there is a relationship between nonalcoholic fatty liver disease and the risk of developing high blood pressure. Presenting a statistically significant relationship between the elevated blood pres-sure levels and the biochemical profile studied, as well the BMI of the patients evaluated in this research

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.

Evaluation of nonalcoholic fatty liver disease using magnetic resonance in obese children and adolescents / Avaliação de doença hepática gordurosa não alcoólica utilizando ressonância em crianças e adolescentes obesos

Abstract Objective: To determine the frequency of nonalcoholic fatty liver disease using nuclear magnetic resonance as a noninvasive method. Methodology: This was a cross-sectional study conducted on 50 children and adolescents followed up at an outpatient obesity clinic. The subjects were submitted to physical examination, laboratory tests (transaminases, liver function tests, lipid profile, glycemia, and basal insulin) and abdominal nuclear magnetic resonance (calculation of hepatic, visceral, and subcutaneous fat). Results: Nonalcoholic fatty liver disease was diagnosed in 14 (28%) participants, as a severe condition in eight (percent fat >18%), and as non-severe in four (percent fat from 9% to 18%). Fatty liver was associated with male gender, triglycerides, AST, ALT, AST/ALT ratio, and acanthosis nigricans. Homeostasis model assessment of insulin resistance and metabolic syndrome did not show an association with fatty liver. Conclusion: The frequency of nonalcoholic fatty liver disease in the present population of children and adolescents was lower than that reported in the international literature. It is suggested that nuclear magnetic resonance is an imaging exam that can be applied to children and adolescents, thus representing an effective noninvasive tool for the diagnosis of nonalcoholic fatty liver disease in this age range. However, further national multicenter studies with longitudinal design are needed for a better analysis of the correlation between nonalcoholic fatty liver disease and its risk factors, as well as its consequences.

Resumo Objetivo: Determinar a frequência da doença hepática gordurosa não alcoólica utilizando ressonância magnética nuclear como um método não invasivo. Metodologia: Este foi um estudo transversal realizado em 50 crianças e adolescentes acompanhadas em uma Clínica Ambulatorial de Obesidade. Os indivíduos foram submetidos a exame físico, testes de laboratório (transaminases, testes de função hepática, perfil lipídico, glicemia e insulina basal) e ressonância magnética nuclear abdominal (cálculo da gordura hepática, visceral e subcutânea). Resultados: A doença hepática gordurosa não alcoólica foi diagnosticada em 14 (28%) participantes, como uma condição grave em oito (percentual de gordura > 18%) e não grave em quatro (percentual de gordura de 9 a 18%). Fígado gorduroso foi associado a sexo masculino, triglicerídeos, aspartato aminotransferase (AST), alanina aminotransferase (ALT), proporção de AST/ALT e acanthosis nigricans. O Modelo de Avaliação da Homeostase de Resistência à Insulina e a síndrome metabólica não mostraram associação com fígado gorduroso. Conclusão: A frequência da doença hepática gordurosa não alcoólica na população atual de crianças e adolescentes foi inferior à relatada na literatura internacional. Sugerimos que a ressonância magnética nuclear seja um exame de imagem que pode ser aplicado em crianças e adolescentes, representando, assim, uma ferramenta não invasiva eficaz no diagnóstico de doença hepática gordurosa não alcoólica nessa faixa etária. Contudo, estudos multicêntricos nacionais adicionais de modelo longitudinal são necessários para uma melhor análise da correlação entre a doença hepática gordurosa não alcoólica e seus fatores de risco, bem como suas consequências.

Association of alanine aminotransferase concentration with cardiometabolic risk factors in children and adolescents: the CASPIAN-V cross-sectional study

ABSTRACT BACKGROUND: It has been suggested that the levels of some liver enzymes, and especially alanine aminotransferase (ALT), might be correlatable with cardiometabolic risk factors. We investigated the relationship between ALT concentration and cardiometabolic risk factors among children and adolescents. DESIGN AND SETTING: This nationwide study in Iran was conducted within the framework of the fifth survey of a national surveillance program known as the Childhood and Adolescence Surveillance and PreventIon of Adult Non-communicable disease study (CASPIAN-V). METHODS: The participants comprised 4200 students aged 7-18 years, who were recruited through multi-stage random cluster sampling in 30 provinces in Iran. Physical examinations and laboratory tests were conducted in accordance with standard protocols. RESULTS: Overall, 3843 students (participation rate: 91.5%) completed the survey. Mean ALT levels were significantly higher in individuals with dyslipidemia, in terms of elevated total cholesterol (TC) or LDL-cholesterol or triglycerides (TG), excess weight and dyslipidemia. Some cardiometabolic risk factors were associated with higher levels of ALT, with the following odds ratio (OR) and 95% confidence interval (CI):metabolic syndrome (OR: 1.013; 95% CI: 1.001-1.025); elevated TC (OR: 1.060; 95% CI: 1.039-1.081), elevated LDL (OR: 1.031; 95% CI: 1.016-1.046), elevated TG (OR: 1.056; 95% CI: 1.040-1.072) and dyslipidemia (OR: 1.051; 95% CI: 1.034-1.068). CONCLUSION: This large population-based study revealed that some cardiometabolic risk factors were significantly associated with ALT levels. These findings suggest that an association with fatty liver is an underlying mechanism for development of cardiometabolic risk factors.

Correlações entre características da doença hepática gordurosa não-alcoólica e os níveis de adipocinas e citocinas inflamatórias em indivíduos submetidos à cirurgia bariátrica / Correlation between nonalcoholic fatty liver disease features and levels of adipokines and inflammatory cytokines among morbidly obese individuals

ABSTRACT BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the commonest hepatopathy worldwide. OBJECTIVE: To investigate the correlations between NAFLD histopathological features and the levels of adipokines (adiponectin, leptin, and resistin) and circulating inflammatory markers (interleukin-6 [IL-6], interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-α], and C-reactive protein [CRP]). METHODS: This is an exploratory cross-sectional study, which enrolled 19 women with obesity who underwent bariatric surgery. Biochemical characteristics evaluated included the levels of adiponectin, leptin, resistin, IL-6, IL-8, TNF-α, and CRP. NAFLD was assessed through histological examination of liver biopsies carried out during the surgical procedures. RESULTS: The mean age of the study group was 37.3±8.2 years old; mean BMI was 36.2±2.5 kg/m2. Among individuals with liver fibrosis, the levels of IL-8 were significantly higher (24.4 ± 9.7 versus 12.7 ± 6.6; P=0.016726). The intensity of fibrosis presented a significant negative correlation with the levels of adiponectin (R= -0.49379; P=0.03166); i.e. the higher the levels of adiponectin, the lower the intensity of fibrosis. The intensity of steatohepatitis presented a significant negative correlation with the levels of adiponectin (R= -0.562321; P=0.01221); this means that the higher the levels of adiponectin, the lower the intensity of steatohepatitis. CONCLUSION: Adiponectin levels were inversely correlated with the severity of fibrosis and steatohepatitis, whereas IL-8 levels were higher in individuals with liver fibrosis among individuals with obesity and NAFLD undergoing bariatric surgery. The use of these markers to assess NAFLD may bring significant information within similar populations.

RESUMO CONTEXTO: A doença hepática gordurosa não-alcoólica (DHGNA) é a hepatopatia mais comum no mundo. OBJETIVO: Investigar correlações entre as apresentações histopatológicas da DHGNA e os níveis de adipocinas (adiponectina, leptina e resistina) e marcadores sistêmicos de inflamação (interleucina-6 [IL-6], interleucina-8 [IL-8], fator de necrose tumoral alfa [TNF-α] e proteína C reativa [PCR]). MÉTODOS: Estudo transversal exploratório envolvendo 18 mulheres com obesidade submetidas à cirurgia bariátrica. As características bioquímicas avaliadas incluíram os níveis de adiponectina, leptina, resistina, IL-6, IL-8, TNF-α e PCR. A DHGNA foi avaliada através de exams histológicos de biópsias hepáticas realizadas durantes as cirurgias. RESULTADOS: A idade média foi 37,3±8,2 anos; o índice de massa corporal (IMC) médio foi 36,2±2,5 kg/m2. Entre os indivíduos com fibrose hepática, os níveis de IL-8 foram significativamente mais altos (24,4±9,7 versus 12,7±6,6; P=0,016726). A intensidade da fibrose apresentou uma correlação negativa significativa com os níveis de adiponectina (R= -0,49379; P=0,03166), demonstranso que, quanto maiores os níveis de adiponectina, menor a intensidade da fibrose. A intensidade da esteato-hepatite apresentou uma correlação negativa significativa com os níveis de adiponectina (R= -0,562321; P=0,01221), demonstrando que quanto mais altos os níveis de adiponectina, menor a intensidade da esteato-hepatite. CONCLUSÃO: Os níveis de adiponectina correlacionaram-se negativamente com a severidade da fibrose e da esteato-hepatite, enquanto os níveis de IL-8 foram maiores entre os indivíduos com fibrose hepática. O uso destes marcadores pode trazer informações significativas sobre a DHGNA em populações com obesidade.

Medição do parâmetro de atenuação controlada: um marcador substituto da esteatose hepática em pacientes com doença hepática gordurosa não alcoólica na modificação do estilo de vida - acompanhamento de um estudo prospectivo / Measurement of controlled attenuation parameter: a surrogate marker of hepatic steatosis in patients of nonalcoholic fatty liver disease on lifestyle modification - a prospective follow-up study

ABSTRACT BACKGROUND: Liver biopsy is a gold standard method for hepatic steatosis assessment. However, liver biopsy is an invasive and painful procedure and can cause severe complications therefore it cannot be frequently used in case of follow-up of patients. Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease (NAFLD). To evaluate hepatic steatosis, transient elastography with controlled attenuation parameter (CAP) measurement is an option now days. OBJECTIVE: Aim of this study is to evaluate role of measurement of controlled attenuation parameter, a surrogate marker of hepatic steatosis in patients of nonalcoholic fatty liver disease on lifestyle modification. METHODS: In this study, initially 37 participants were included who were followed up after 6 months with transient elastography, blood biochemical tests and anthropometric measurements. The results were analyzed by Multivariate linear regression analysis and paired samples t-test (Dependent t-test) with 95% confidence interval. Correlation is calculated by Pearson correlation coefficients. RESULTS: Mean CAP value for assessing hepatic steatosis during 1st consultation (278.57±49.13 dB/m) was significantly improved (P=0.03) after 6 months of lifestyle modification (252.91±62.02 dB/m). Only fasting blood sugar (P=0.008), weight (P=0.000), body mass index (BMI) (P=0.000) showed significant positive correlation with CAP. Only BMI (P=0.034) and weight (P=0.035) were the independent predictor of CAP value in NAFLD patients. CONCLUSION: Lifestyle modification improves the hepatic steatosis, and CAP can be used to detect the improvement of hepatic steatosis during follow-up in patients with NAFLD on lifestyle modification. There is no relation between CAP and Fibroscan score in NAFLD patients. Only BMI and weight can predict CAP value independently.

RESUMO CONTEXTO: A biópsia hepática é o método padrão-ouro para avaliação de esteatose hepática. No entanto, é um procedimento invasivo e doloroso que pode causar complicações graves e, portanto, não pode ser usado com frequência em caso de acompanhamento dos pacientes. A avaliação não invasiva de esteatose e fibrose é de crescente relevância na doença hepática gordurosa não alcoólica (DHGNA). Para avaliar a esteatose hepática, a elastografia transitória com parâmetro de atenuação controlada (PAC) é uma opção atual. OBJETIVO: O objetivo deste estudo foi de avaliar o papel da medição do PAC, um marcador substituto da esteatose hepática em pacientes da doença hepática gordurosa não alcoólica, com modificação do estilo de vida. MÉTODOS: Foram incluídos inicialmente neste estudo 37 participantes acompanhados por 6 meses com elastografia transitória, testes bioquímicos no sangue, e medidas antropométricas. Os resultados foram analisados por análise de regressão linear multivariada e emparelhado em amostras-teste t (teste t-dependente) com intervalo de confiança de 95%. A correlação foi calculada pelos coeficientes de correlação de Pearson. RESULTADOS: O valor do PAC para avaliar esteatose hepática durante a primeira consulta (278,57±49,13 dB/m) foi significativamente melhorado (P=0,03) após 6 meses de modificação do estilo de vida (252,91±62,02 dB/m). Somente a glicemia de jejum (P=0,008), o peso (valor de P=0,000), o índice de massa corporal (IMC) (P=0,000) mostraram correlação positiva significativa com PAC. Apenas o IMC (P=0,034) e o peso (P=0,035) foram o preditores independentes de valor de PAC em pacientes com DHGNA. CONCLUSÃO: A modificação do estilo de vida melhora a esteatose hepática, e o PAC pode ser usado para detectar a melhoria da esteatose hepática durante o seguimento em pacientes com DHGNA. Não existe relação entre o PAC e o escore do Fibroscan em pacientes com DHGNA. Só o IMC e o peso podem prever o valor do PAC independentemente.

Testosterone, Sex Hormone-Binding Globulin and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

ABSTRACT Introduction and aim. Endogenous sex hormones are associated with the risk of diabetes and metabolic syndrome. Recent studies suggested the role of these hormones in nonalcoholic fatty liver disease (NAFLD). We conducted a systematic review and meta-analysis of observational studies investigating the association between sex hormones and NAFLD. Material and methods. A comprehensive search of the databases of the MEDLINE and EMBASE was performed from inception through April 2016. The inclusion criterion was the observational studies that assessed the association of serum total testosterone (TT) and sex-hormone binding globulin (SHBG) and NAFLD. We calculated pooled effect estimates of TT and SHBG with 95% confidence intervals (Cl) comparing between subjects with and without NAFLD by using random-effects model. Results. Sixteen trials comprising 13,721 men and 5,840 women met the inclusion criteria. TT levels were lower in men with NAFLD (MD = -2.78 nmol/l, 95%CI -3.40 to -2.15, I2 = 99%) than in those without. Men with higher TT levels had lower odds of NAFLD whereas higher TT levels increased the odds of NAFLD in women. In both sexes, SHBG levels were lower in patients with NAFLD than controls and this inverse association was stronger in women than men and higher SHBG levels were associated with reduced odds of NAFLD. Conclusion. Our meta-analysis demonstrated a sex-dependent association between TT and NAFLD. Lower TT levels are associated with men with NAFLD and inversely associated with women with NAFLD, whereas higher SHBG levels are associated with lower NAFLD odds in both men and women.

Hyperferritinemia in patients with nonalcoholic fatty liver disease / Hiperferritinemia em pacientes com doença hepática gordurosa não alcoólica

Summary Objective: In liver diseases, hyperferritinemia (HYF) is related to injured cells in acquired and genetic conditions with or without iron overload. It is frequent in patients with nonalcoholic fatty liver disease (NAFLD), in which it is necessary to define the mean of HYF to establish the better approach for them. The present study evaluated the significance of elevated ferritin in patients with NAFLD and steatohepatitis (NASH). Method: The review was performed using search instruments of indexed scientific material, including MEDLINE (by PubMed), Web of Science, IBECS and LILACS, to identify articles published in Portuguese, English and Spanish, from 2005 to May, 2016. Studies eligible included place and year of publication, diagnose criteria to NAFLD, specifications of serum ferritin measurements and/or liver histopathologic study. Exclusion criteria included studies with patients with alcohol consumption ≥ 20 g/day and other liver diseases. Results: A total of 11 from 30 articles were selected. It included 3,564 patients and they were cross-sectional, retrospective, case series and case-control. The result's analyses showed in 10 of these studies a relationship between ferritin elevated serum levels and NAFLD/NASH with and without fibrosis and insulin resistance. Conclusion: Hyperferritinemia in patients with NAFLD/NASH is associated more frequently with hepatocellular injury than hemochromatosis. These data suggest the relevance to evaluate carefully HYF in patients with NAFLD/NASH to establish appropriate clinical approach.

Resumo Objetivo: A hiperferritinemia (HPF) está associada à agressão hepatocelular nas doenças do fígado e à sobrecarga de ferro, em doenças genéticas e adquiridas. A HPF é frequente em pacientes com doença hepática gordurosa não alcoólica (DHGNA) e é necessário definir seu significado para estabelecer as melhores condutas para esses indivíduos. Esta revisão avaliou o significado da HPF em portadores de DHGNA e esteato-hepatite não alcoólica (EHNA). Método: A busca de artigos foi realizada através do PubMed (Medline), Web of Science e Lilacs, e foram selecionados aqueles publicados em português, inglês e espanhol de 2005 a maio de 2016. Os artigos foram elegíveis quando informavam data e local da publicação, critérios diagnósticos para DHGNA, especificações das dosagens de ferritina sérica e/ou estudo histopatológico. Foram excluídos os artigos cujos pacientes relataram ingestão alcoólica ≥ 20 g/dia ou eram portadores de outras doenças do fígado. Resultados: Foram selecionados 11 de 30 artigos, totalizando 3.564 pacientes. Os artigos eram de corte transversal, retrospectivos, série de casos e caso-controles. Em dez artigos, observou-se correlação entre alteração de ferritina e DHGNA/EHNA com e sem fibrose hepática e resistência à insulina. Conclusão: Hiperferritinemia em pacientes com DHGNA/EHNA se associa com maior frequência à agressão hepatocelular do que com sobrecarga de ferro hepático. Os resultados da revisão sugerem a necessidade de um maior cuidado na interpretação da elevação da ferritina sérica em pacientes com DHGNA/EHNA para o estabelecimento de condutas clínicas apropriadas.

Differences in Hepatic Expression of Iron, Inflammation and Stress-Related Genes in Patients with Nonalcoholic Steatohepatitis

Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. We have previously shown that hepatic reticuloendothelial system (RES) iron deposition is associated with an advanced degree of nonalcoholic steatohepatitis (NASH) in humans. In this study, we aimed to determine differentially expressed genes related to iron overload, inflammation and oxidative stress pathways, with the goal of identifying factors associated with NASH progression. Seventy five patients with NAFLD were evaluated for their biochemical parameters and their liver tissue analyzed for NASH histological characteristics. Gene expression analysis of pathways related to iron homeostasis, inflammation and oxidative stress was performed using real-time PCR. Gene expression was compared between subjects based on disease status and presence of hepatic iron staining. We observed increased gene expression of hepcidin (HAMP) (2.3 fold, p = 0.027), transmembrane serine proteinase 6 (TMPRSS6) (8.4 fold, p = 0.003), signal transducer and activator of transcription 3 (STAT3) (5.5 fold, p = 0.004), proinflammatory cytokines; IL-1β (2.7 fold, p = 0.046) and TNF-α (3.8 fold, p = 0.001) in patients with NASH. TMPRSS6, a negative regulator of HAMP, is overexpressed in patients with NASH and HIF1α (hypoxia inducible factor-1) is downregulated. NAFLD patients with hepatic iron deposition exhibited higher hepcidin expression (3.1 fold, p = 0.04) but lower expression of cytokines. In conclusion, we observed elevated hepatic HAMP expression in patients with NASH and in NAFLD patients who had hepatic iron deposition, while proinflammatory cytokines displayed elevated expression only in patients with NASH, suggesting a regulatory role for hepcidin in NAFL to NASH transition and in mitigating inflammatory responses.

Parámetros metabólicos en pacientes con esteatosis hepática no alcohólica y diabetes tipo 2 controlados versus no controlados / Metabolic parameters in patients with steatosis non alcoholic liver and controlled diabetes type 2 versus uncontrolled diabetes type 2

La esteatosis hepática no alcohólica (EHNA) está ampliamente distribuida a nivel mundial y es más frecuente en sujetos con dislipidemia, síndrome metabólico, obesos y con DM2 (34-74%). Sin embargo, la prevalencia de cirrosis por EHNA en la población general no se conoce, lo que es aún materia de investigación en nuestro medio. Objetivo: Determinar si existe diferencia significativa entre los parámetros metábólicos de esteatosis hepática no alcohólica en pacientes con diabetes tipo 2 de reciente diagnóstico controlados y no controlados. Material y métodos: Estudio retrospectivo de tipo caso control, realizado en el Hospital Guillermo Almenara Irigoyen, Lima - Perú, durante los meses de noviembre de 2014 a febrero de 2015. Constó de231 pacientes: 147 pacientes con DM2 de diagnóstico reciente con mal control glicémico y EHNA y 84 pacientes con DM2 de diagnóstico reciente con adecuado control y EHNA. Para el análisis estadístico se utilizó las pruebas de Levene para evaluar homogenidad de varianzas intragrupos y prueba paramétrica de t de student para muestras independientes. Resultados: Luego de aplicar la prueba de homogeneidad de Levene y el t de student para igualdad de medias los parámetros metabólicos significativos fueron el nivel de triglicéridos, el nivel de HbA1C, la dosis de metformina y el género. Conclusiones: Es importante en pacientes diabéticos diagnosticar EHGNA en forma temprana para un control más estricto, no sólo de la glucosa sérica sino de otros parámetros metabólicos, principalmente, los triglicéridos lo cual apoya fuertemente el concepto existente de "múltiples hits " que considera que la EHGNA afecta la homeostasis de la glucosa, y podría ser el punto de partida de nuevas investigaciones que permitan mejorar las intervenciones para reducir la progresión de la cirrosis en pacientes diabéticos y también retrasar la progresión de la diabetes mellitus en pacientes con esteatohepatitis no alcohólica.

Non-alcoholic fatty liver (NASH) is widely distributed around the world and is more common in subjects with dyslipidemia, metabolic syndrome obese and DM2 (34-74%). However, the prevalence of cirrhosis by NASH in general population is unknown which is still subject of research. Objective: To determine if there are significant differences between metabolic parameters of non-alcoholic fatty liver in controlled versus uncontrolled diabetes type 2 of recent diagnosis. Material and methods: retrospective case-control study, performed in the Hospital Guillermo Almenara Irigoyen, Lima, Peru from November 2014 to February 2015.This study included 231 patients: 147 patients (NASH with DM2 of recent diagnosis and poor control) and 84 patients (NASH with DM2 ofrecent diagnosis and adequate control). Statistical analysis: Levene test for evaluating homogeneity of variances intra groups and parametric test for independent samples. Results: After applying Levene test of homogeneity and student test, significant metabolic parameters were the triglycerides, HbA1C level, metformin dose and gender. Conclusions: It is important in diabetic patients to diagnose NASH early for a tighter control, not only of glucose but other metabolic parameters mainly triglycerides which strongly supports existing concept of "multiple hits" which considers NASH affects glucose homeostasis, and it could be the starting point of new research to improve interventions for decreasing progression from to cirrhosis in diabetic patients and also to delay progression of diabetes mellitus in patients with non alcoholic steatohepatitis.

FT3/FT4 ratio predicts non-alcoholic fatty liver disease independent of metabolic parameters in patients with euthyroidism and hypothyroidism

OBJECTIVE: This study was performed to evaluate the effects of metabolic parameters and thyroid dysfunction on the development of non-alcoholic fatty liver disease (NAFLD). METHODS: The current study evaluated a total of 115 patients, 75 female and 40 male. Physical examination and anthropometric measurements were applied to all participants. Hypothyroidism was considered at a thyroid stimulating hormone level ≥ 4.1 mIU/L. Patients with euthyroidism and patients with hypothyroidism were compared. Abdominal ultrasonography was used to diagnose non-alcoholic fatty liver disease. The participants were further compared with regard to the presence of non-alcoholic fatty liver disease. Logistic regression modeling was performed to identify the relationship between non-alcoholic fatty liver disease and independent variables, such as metabolic parameters and insulin resistance. RESULTS: Non-alcoholic fatty liver disease was identified in 69 patients. The mean waist circumference, body mass index, fasting plasma insulin, HOMA-IR (p<0.001) and FT3/FT4 ratio (p=0.01) values were significantly higher in the patients with NAFLD compared to those without it. Multivariate regression analysis revealed that FT3/FT4 ratio, waist circumference and insulin resistance were independent risk factors for non-alcoholic fatty liver disease. CONCLUSION: Insulin resistance, enlarged waist circumference, elevated body mass index, higher FT3/FT4 ratio and hypertriglyceridemia are independent risk factors for NADLF, whereas hypothyroidism is not directly related to the condition.

Prevalence and Factors Associated with Nonalcoholic Fatty Liver Disease in a Nonobese Korean Population

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is an emerging problem in Asia, but little is known about the disease in the nonobese population. The aims of this study were to investigate the prevalence of NAFLD and the factors associated with it in a nonobese Korean population and to compare the clinical characteristics of nonobese and obese subjects with NAFLD. METHODS: This cross-sectional study used data from 2,058 subjects who participated in a medical checkup program. RESULTS: The prevalence of NAFLD was 12.4% (213/1,711) in the nonobese population. A higher body mass index (BMI), higher homeostasis model assessment of insulin resistance (HOMA-IR) values, higher alanine aminotransferase (ALT) levels, triglyceride concentrations 150 mg/dL, and hyperuricemia were independently associated with the presence of NAFLD in the nonobese subjects. Compared with the obese subjects with NAFLD, the nonobese subjects with NAFLD were composed of a higher proportion of females and had lower BMIs, smaller waist circumferences, lower HOMA-IR values, and fewer metabolic irregularities. CONCLUSIONS: Higher BMIs, HOMA-IR values, ALT levels, hypertriglyceridemia, and hyperuricemia were associated with NAFLD in the nonobese subjects. Clinicians should be particularly aware of the possibility of NAFLD in nonobese Asian people.

The serum vitamin D level is inversely correlated with nonalcoholic fatty liver disease

BACKGROUND/AIMS: A low vitamin D level has been associated with metabolic syndrome and diabetes. However, an association between a low vitamin D level and nonalcoholic fatty liver disease (NAFLD) has not yet been definitively established. This study aimed to characterize the relationship between a vitamin D level and NAFLD in Korea. METHODS: A cross-sectional study involving 6,055 health check-up subjects was conducted. NAFLD was diagnosed on the basis of typical ultrasonographic findings and a history of alcohol consumption. RESULTS: The subjects were aged 51.7±10.3 years (mean±SD) and 54.7% were female. NAFLD showed a significant inverse correlation with the vitamin D level after adjusting for age and sex [odds ratio (OR)=0.85, 95% confidence interval (CI)=0.75-0.96]. The age- and sex-adjusted prevalence of NAFLD decreased steadily with increasing vitamin D level [OR=0.74, 95% CI=0.60-0.90, lowest quintile (≤14.4 ng/mL) vs highest quintile (≥28.9 ng/mL), p for trend 20 ng/mL) [OR=0.86, 95% CI=0.75-0.99] and the quintiles of the vitamin D level in a dose-dependent manner (p for trend=0.001). CONCLUSIONS: The serum level of vitamin D, even when within the normal range, was found to be inversely correlated with NAFLD in a dose-dependent manner. Vitamin D was found to be inversely correlated with NAFLD independent of known metabolic risk factors. These findings suggest that vitamin D exerts protective effects against NAFLD.

INFLUENCE OF OXIDATIVE STRESS AND OBESITY IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS / Influência do estresse oxidativo e obesidade em pacientes com esteatohepatite não alcoólica

BackgroundNonalcoholic steatohepatitis is considered the hepatic manifestation of metabolic syndrome and it is particularly associated to the insulin resistance, hypertension, obesity and abnormalities in lipid and glucose metabolism.ObjectiveConsidering the importance of obesity and oxidative stress in the pathophysiology of nonalcoholic steatohepatitis, this study aimed to evaluate the presence and association of the obesity and oxidative stress in this pathology.MethodsFifteen outpatients with nonalcoholic steatohepatitis (nonalcoholic steatohepatitis group), diagnosed according to the histopathological findings from the liver biopsy, and 15 body mass index-matched subjects (non nonalcoholic steatohepatitis group) without nonalcoholic steatohepatitis were included. All volunteers were registered in a Brazilian University Hospital. Nutritional assessment (weight, height, body mass index and waist circumference) and biochemical analysis (fasting glucose, liver enzymes, lipid profile, leptin, superoxide dismutase, glutathione peroxidase, vitamins C and E, catalase and 8-isoprostane) were performed for all the participants. The student t test was used for statistical analysis, with P<0.05 as the significant factor.ResultsNonalcoholic steatohepatitis patients had higher fasting glucose, hepatic enzymes (serum aspartate aminotransaminase, alanine aminotransaminase, gamma glutamyl transferase, alkaline phosphatase), triglycerides and superoxide dismutase and lower glutathione peroxidase values than non nonalcoholic steatohepatitis individuals.ConclusionThis paper demonstrates that only the presence of obesity is not enough to trigger alterations in all the studied biomarkers. Despite the majority of oxidative stress markers being found to be similar in both conditions, the nonalcoholic steatohepatitis subjects could be slightly more affected than the non nonalcoholic steatohepatitis individuals.

ContextoEsteatohepatite não alcoólica é considerada uma manifestação hepática da síndrome metabólica e está particularmente associada com a resistência insulínica, hipertensão, obesidade, anormalidades no metabolismo lipídico e da glicose.ObjetivoConsiderando a importância da obesidade e do estresse oxidativo na fisiopatogenia da esteatohepatite não alcoólica, o objetivo deste estudo foi avaliar a associação e presença da obesidade e do estresse oxidativo nesta patologia.MétodosQuinze pacientes com esteatohepatite não alcoólica (grupo esteatohepatite não alcoólica), diagnosticados de acordo com os achados histopatológicos da biópsia hepática, e 15 indivíduos sem esteatohepatite não alcoólica com sobrepeso/obesidade (grupo sem esteatohepatite não alcoólica) foram incluídos. Todos os voluntários eram acompanhados em Hospital Universitário Brasileiro. Avaliação nutricional (peso, altura, índice de massa corporal e circunferência abdominal) e bioquímica (glicemia de jejum, enzimas hepáticas, lipidograma, leptina, superóxido dismutase, glutationa peroxidase, vitaminas C e E, catalase e 8-isoprostano) foram realizadas em todos os indivíduos. O teste t de Student foi usado para análise estatística considerando o P≤0,05 como significativo.ResultadosIndivíduos do Grupo esteatohepatite não alcoólica apresentaram valores significativamente maiores de glicemia, AST, ALT, Gama GT, fosfatase alcalina, triglicérides e superóxido dismutase e menor valor de glutationa peroxidase, quando comparados ao Grupo sem esteatohepatite não alcoólica.ConclusãoEste artigo demonstra que somente a presença da obesidade não é suficiente para provocar alterações nos biomarcadores estudados. Apesar da maioria dos marcadores de estresse oxidativo apresentarem-se similar nas duas condições, os pacientes com esteatohepatite não alcoólica podem apresentar-se levemente mais afetados que os indivíduos sem esteatohepatite não alcoólica.

Physical activity as a protective factor for development of non-alcoholic fatty liver in men / Atividade física como fator de proteção para o desenvolvimento de esteatose hepática não alcoólica em homens / Atividade física como fator de proteção para o desenvolvimento de esteatose hepática não alcoólica em homens

Objective To determine the impact of physical activity on the prevalence of fatty liver, metabolic and cardiovascular disease in adult men. Methods This study evaluated 1,399 men (40.7±8.18 years) with body mass index of 26.7kg/m2 (±3.4) who participated in the Protocol of Preventive Health Check-up at Hospital Israelita Albert Einstein from January to October 2011. We conducted tests of serum blood glucose, total cholesterol, LDL, HDL, triglycerides, reactive c-protein, aspartate transaminase, alanine transaminase and gamma-glutamyl transpeptidase. The statistical analysis comprised in the comparison of mean and standard deviation. The analysis of variance was based in two paths of two way ANOVA, Student’s t-test, Mann Whitney U test, Wald test and χ2. We considered a significance level at p<0.05 and correlation of univariate Poison with 95% confidence interval. Results Fatty liver was diagnosed in 37.0% of the sample. Triglyceride levels of active men with fatty liver were 148.2±77.6mg/dL while inactive men with fatty liver had 173.4±15.6mg/dL. The remaining serum levels were normal. Inactive individuals showed higher values than active. In addition, inactive individuals have 10.68 times higher risk of developing fatty liver compared with active. Conclusion Physical activity improves metabolic parameters such as triglycerides, weight control, HDL, which interfere in the development of fatty liver. Physically active individuals had lower fatty liver prevalence regardless of values of body composition and lipid profile, leading the conclusion that physical activity has a protective role against development of fatty liver. .

Objetivo Determinar o impacto do nível de atividade física na prevalência de esteatose hepática, perfil metabólico e comportamento cardiovascular em homens adultos. Métodos Foram avaliados 1.399 homens (40,7±8,18 anos) com índice massa corporal de 26,7kg/m2 (±3,4) pelo protocolo da Revisão Continuada de Saúde do Hospital Israelita Albert Einstein entre janeiro a outubro de 2011. Foram realizadas análise séricas de glicose sanguínea, colesterol total e séries, triglicerídeos, PCR, ALT, AST e Gama GT. A análise estatística utilizada consistiu na comparação de média e desvio padrão. A análise de variância de dois caminhos ANOVA two way, teste t de Student, teste U Mann Whitney, teste de Wald e teste χ2, sendo o nível de significância p<0,05 e correlação univariada de Poison, com intervalo de confiança de 95%. Resultados Os resultados demonstraram que 37,0% da amostra apresentou diagnóstico de esteatose hepática. Homens ativos com esteatose hepática apresentaram níveis de triglicerídeos de 148,2±77,6mg/dL enquanto os inativos com esteatose hepática apresentaram 173,4±15,6mg/dL. Os demais níveis séricos apresentaram-se dentro dos padrões considerados saudáveis, porém os inativos apresentaram todos os valores superiores, em relação aos ativos. Apontou-se que indivíduos inativos apresentam 10,68 vezes maior risco em desenvolver esteatose hepática em relação aos ativos. Conclusão A atividade física melhora os indicadores metabólicos, como triglicérides, controle de peso, HDL, que interferem no desenvolvimento de esteatose hepática, mostrando que indivíduos fisicamente ativos apresentaram menor prevalência de esteatose hepática independentemente dos valores de composição corporal e perfil lipídico, concluindo que a atividade física apresenta papel protetor no desenvolvimento de esteatose hepática. .

Vitamin D Status and Bone Mineral Density in Obese Children with Nonalcoholic Fatty Liver Disease

Whether nonalcoholic fatty liver disease (NAFLD) is related to vitamin D and bone health in obese children is unknown. The aim of this study was to evaluate vitamin D status and bone mineral density (BMD) in obese children according to their condition within the NAFLD spectrum. Anthropometric data, laboratory tests, and abdominal ultrasonography were obtained from 94 obese children. The subjects were divided into three groups according to NAFLD spectrum: normal liver, simple steatosis, and nonalcoholic steatohepatitis (NASH). Although there were no differences in vitamin D levels between the three groups, these groups showed significant differences in highly sensitive C-reactive protein (P=0.044), homeostasis model assessment of insulin resistance (HOMA-IR) (P=0.02), hepatic fibrosis scores (P<0.05), and trunk fat percentage (P=0.025). Although there were significant differences in BMDs, the age-matched BMD z-scores were not significantly different between the three groups. Serum vitamin D levels were negatively correlated with age (r=-0.368, P=0.023), serum uric acid levels (r=-0.371, P=0.022), fibrosis 4 (FIB4) (r=-0.406, P=0.011), and HOMA-IR (r=-0.530, P=0.001) in obese children with NASH. Multiple regression analysis for vitamin D in the NASH group revealed age and HOMA-IR as significant factors. In conclusion, inflammatory markers, hepatic fibrosis scores, trunk fat, and insulin resistance may reflect the spectrum of NAFLD in obese children, whereas vitamin D levels and BMD may not. In patients with NASH, however, low serum vitamin D is associated with hepatic fibrosis and insulin resistance, but not with bone health status.

EFFECT OF HELICOBACTER PYLORI ERADICATION ON HEPATIC STEATOSIS, NAFLD FIBROSIS SCORE AND HSENSI IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS: a MR imaging-based pilot open-label study / O efeito da erradicação do Helicobacter pylori na esteatose hepática, no escore de fibrose na DHNA e o HSENSI em pacientes com esteatohepatite não alcoólica: um estudo piloto aberto baseado em ressonância magnética

Context Limited clinical data suggest Helicobacter pylori (Hp) infection may contribute to nonalcoholic fatty liver disease (NAFLD) pathogenesis. Objectives The effect of Hp eradication on hepatic steatosis (magnetic resonance imaging), nonalcoholic fatty liver disease fibrosis score and HSENSI (Homocysteine, serum glutamic oxaloacetic transaminase, Erythrocyte sedimentation rate, nonalcoholic steatohepatitis Index) in nonalcoholic steatohepatitis patients. Methods Thirteen adult patients with biopsy-proven nonalcoholic steatohepatitis, asymptomatic for gastrointestinal disease, underwent 13C urea breath test; Hp positive patients received eradication therapy until repeat test become negative. Hepatic fat fraction, standard biochemical tests and calculation of nonalcoholic fatty liver disease fibrosis score and HSENSI were performed at baseline and month 12. Results Hepatic fat fraction was similar for between and within group comparisons. Nonalcoholic fatty liver disease fibrosis score showed a non-significant trend towards decrease in Hp(+) [-0.34 (-1.39-0.29) at baseline and -0.24 (-0.99-0.71) at month 12; P = 0.116], whereas increase in Hp(-) group [-0.38 (-1.72-0.11) and -0.56 (-1.43-0.46), respectively; P = 0.249]. HSENSI was significantly decreased only in Hp(+) group [1.0 (1.0-2.0) at baseline and 1.0 (0-1.0) at month 12; P = 0.048]. Conclusions Hp eradication had no long-term effect on hepatic steatosis, but showed a trend towards improvement in nonalcoholic fatty liver disease fibrosis score and HSENSI. These results warrant larger studies with paired biopsies. .

Contexto Dados clínicos limitados sugerem que infecção por Helicobacter pylori (Hp) pode contribuir para a patogênese da doença hepática gordurosa não alcoólica. Objetivos Verificar o efeito da erradicação do Hp na esteatose hepática pela ressonância magnética, na pontuação da fibrose na doença hepática gordurosa não alcoólica e no HSENSI (homocisteína, transaminase glutâmico oxalacética no soro, taxa de sedimentação de eritrócitos, Indice NASH na esteatohepatite não-alcoólica) em pacientes com esteato-hepatite não alcoólica. Métodos Treze pacientes adultos com esteato-hepatite não alcoólica comprovada por biópsia, assintomáticos para a doença gastrointestinal, submetidos ao 113C teste respiratório da ureia 13C. Pacientes Hp positivos receberam terapia de erradicação até repetição do teste tornar-se negativa. A fração de gordura hepática, testes bioquímicos padrão e cálculo da pontuação da fibrose e esteatose hepática HSENSI foram realizados no início e no mês 12. Resultados A fração de gordura hepática foi similar entre e dentro das comparações entre os grupos. A pontuação da fibrose na doença hepática gordurosa não alcoólica mostrou uma tendência não significativa para diminuição no grupo Hp (+) [-0,34 (-1,39-0,29) no início do estudo e -0,24 (-0,99-0,71) no 12 mês; P = 0,116], enquanto aumentaram no grupo Hp (-) [-0.38 (-1,72-0,11) e -0,56 (-1,43-0,46), respectivamente; P = 0,249]. O HSENSI diminuiu significativamente apenas no grupo Hp (+) [1,0 (1,0-2,0) na linha de base e 1,0 (0-1,0) no 12º mês; P = 0,048]. Conclusões A erradicação do Hp não teve efeito ...

Association of adult weight gain and nonalcoholic fatty liver in a cross-sectional study in Wan Song Community, China

Our objective was to examine associations of adult weight gain and nonalcoholic fatty liver disease (NAFLD). Cross-sectional interview data from 844 residents in Wan Song Community from October 2009 to April 2010 were analyzed in multivariate logistic regression models to examine odds ratios (OR) and 95% confidence intervals (CI) between NAFLD and weight change from age 20. Questionnaires, physical examinations, laboratory examinations, and ultrasonographic examination of the liver were carried out. Maximum rate of weight gain, body mass index, waist circumference, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, fasting blood glucose, cholesterol, triglycerides, uric acid, and alanine transaminase were higher in the NAFLD group than in the control group. HDL-C in the NAFLD group was lower than in the control group. As weight gain increased (measured as the difference between current weight and weight at age 20 years), the OR of NAFLD increased in multivariate models. NAFLD OR rose with increasing weight gain as follows: OR (95%CI) for NAFLD associated with weight gain of 20+ kg compared to stable weight (change <5 kg) was 4.23 (2.49-7.09). Significantly increased NAFLD OR were observed even for weight gains of 5-9.9 kg. For the “age 20 to highest lifetime weight” metric, the OR of NAFLD also increased as weight gain increased. For the “age 20 to highest lifetime weight” metric and the “age 20 to current weight” metric, insulin resistance index (HOMA-IR) increased as weight gain increased (P<0.001). In a stepwise multivariate regression analysis, significant association was observed between adult weight gain and NAFLD (OR=1.027, 95%CI=1.002-1.055, P=0.025). We conclude that adult weight gain is strongly associated with NAFLD.