Nonalcoholic fatty liver disease in women with polycystic ovary syndrome: associated factors and noninvasive fibrosis staging in a single Brazilian center

ABSTRACT Objective Polycystic ovary syndrome (PCOS) is a recognized risk factor for nonalcoholic fatty liver disease (NAFLD). The aims of this study were to investigate the prevalence and factors associated with NAFLD in women with PCOS and evaluate noninvasive indices of hepatic fibrosis in patients with PCOS and NAFLD. Subjects and methods Patients with PCOS (n = 87) and women without PCOS (n = 40; controls) were included. NAFLD was diagnosed by abdominal ultrasonography after exclusion of alcohol consumption and viral or autoimmune liver disease. Anthropometric, clinical and metabolic variables, homeostasis model assessment of insulin resistance (HOMA-IR) index, lipid accumulation product (LAP), FIB-4 index, NAFLD score, and transient elastography (TE; FibroScan) were obtained in subsets of patients with PCOS and NAFLD. Results A total of 87 patients with PCOS were included (mean age: 34.4 ± 5.7 years, mean body mass index [BMI]: 34.7 ± 4.7 kg/m 2 ). NAFLD was present in 67 (77.0%) patients with PCOS versus 21 of 40 (52.5%) controls (p = 0.005). Women with PCOS and liver steatosis, compared with their NAFLD-free counterparts, had higher values of BMI, waist circumference, triglycerides, total cholesterol, alanine and aspartate aminotransferases, and γ-glutamyltransferase, along with higher frequencies of obesity, metabolic syndrome, and insulin resistance. NAFLD was independently associated with waist circumference, serum triglycerides, and alanine aminotransferase levels. The FIB-4 index was not compatible with advanced fibrosis in any of the evaluated patients, while NAFLD score and TE were compatible with advanced liver fibrosis in 1 of 26 (3.8%) and 3 of 25 (12%) patients, respectively. Conclusion Women with PCOS had a high risk of NAFLD, and a combination of both was associated with central obesity, dyslipidemia, insulin resistance, and metabolic syndrome. Noninvasive methods suggested low rates of severe hepatic fibrosis in Brazilian women with PCOS. Arch Endocrinol Metab. 2020;64(3):235-42

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.

Bypass vs. sleeve and its effects in non-alcoholic fatty liver disease: what is the best technique? / Bypass vs. sleeve e seus resultados na doença hepática gordurosa não alcoólica: qual a melhor técnica?

ABSTRACT Background: Strongly associated with obesity, non-alcoholic fatty liver disease is considered the hepatic manifestation of the metabolic syndrome. It presents as simple steatosis and steatohepatitis, which can progress to cirrhosis and its complications. Among the therapeutic alternatives is bariatric surgery. Aim: To compare the effect of the two most frequent bariatric procedures (sleeve and bypass) on liver disease regarding to epidemiological, demographic, clinical and laboratory parameters. Methods: The results of intraoperative and 12 months after surgery liver biopsies were used. The NAFLD activity score (NAS) was used to assess and compare the stages of liver disease. Results: Sixteen (66.7%) patients underwent Bypass procedure and eight (33.3%) Sleeve. It was observed that the variation in the NAFLD activity score was significantly greater in the Bypass group than in Sleeve (p=0.028) and there was a trend regarding the variation in fibrosis (p=0.054). Conclusion: Both surgical techniques were effective in improving the hepatic histology of most operated patients. When comparing sleeve and bypass groups, bypass showed better results, according to the NAS score.

RESUMO Racional: Fortemente associada à obesidade, a doença hepática gordura não alcoólica é considerada a manifestação hepática da síndrome metabólica. Ela apresenta-se como esteatose simples e esteato-hepatite, podendo evoluir para cirrose e suas complicações. Entre as alternativas terapêuticas está a cirurgia bariátrica. Objetivo: Comparar o efeito sobre a doença hepática dos dois procedimentos bariátricos mais frequentes - sleeve e bypass - e comparar dados epidemiológicos, demográficos, parâmetros clínicos e laboratoriais. Métodos: Utilizou-se o resultado das biópsias hepáticas realizadas no intra-operatório e 12 meses após a operação. O NAFLD activity score foi utilizado para avaliar e comparar os estágios da doença hepática. Resultados: Dezesseis (66,7%) pacientes foram submetidos ao bypass e oito (33,3%) ao sleeve. Observou-se melhora significativa no IMC e glicemia nas duas técnicas cirúrgicas enquanto que os níveis de fosfatase alcalina, ferritina, Gama-GT e TGP reduziram com significância apenas no grupo bypass. A redução no NAFLD activity score foi significativamente maior no grupo bypass que no sleeve (p=0,040). Conclusão: Ambas as técnicas foram eficazes em promover a melhora da histologia hepática da maior parte dos pacientes operados. Quando comparadas o bypass apresentou melhores resultados.

Insulin-like growth factor binding protein-1, non-alcoholic fatty liver disease, and its relationship with fructose consumption in children with obesity

Background Over consumption of added sugar is associated with obesity, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR). Objective The objective of the study was to study the insulin-like growth factor binding protein-1 (IGFBP-1) and NAFLD and their relationship with fructose consumption in children with obesity. Methods A cross-sectional study was carried out in children 6-11 years old with obesity. Anthropometric measurements, fructose consumption, glucose, lipid profile, insulin, and IGFBP-1 levels were evaluated; the homeostatic model assessment of IR (HOMA-IR) was used. NAFLD was evaluated by ultrasound. Results We studied 83 children with a mean age of 9.2 ± 1.3 years. About 93% of the girls presented IR and lower levels of IGFBP-1 (p = 0.0001). The group with the lower levels of IGFBP-1 had higher HOMA-IR (p = 0.000002); IGFBP-1 was associated with fructose consumption (r = −0.25; p = 0.03), body mass index (BMI) (r=−0.42; p = 0.02), and HOMA-IR (r=−0.61; p = 0.002). About 81% of the children were classified as having mild or moderate/severe NAFLD, and these groups had higher HOMA-IR (p = 0.036) and fructose consumption (p = 0.0014). Conclusions The girls had more metabolic alterations. The group with lower levels of IGFBP-1 (hepatic IR) was associated with higher BMI, HOMA-IR, and fructose consumption; the group with higher severity of NAFLD showed higher HOMA-IR and fructose consumption.

Could semiquantitative analysis of real-time ultrasound elastography distinguish more liver parenchyma alterations of nonalcoholic fatty liver disease in patients with polycystic ovary syndrome?

ABSTRACT Objective: Nonalcoholic fatty liver disease is the commonest diffuse liver disease, of which women with polycystic ovary syndrome are at an increased risk. The aim of the present study was to assess the diagnostic value of the semiquantitative strain parameters of real-time ultrasound elastography for nonalcoholic fatty liver disease in patients with polycystic ovary syndrome. Subjects and methods: Thirty-five polycystic ovary syndrome patients with nonalcoholic fatty liver disease, 70 polycystic ovary syndrome patients without nonalcoholic fatty liver disease, and 70 healthy female controls of reproductive age were included. All participants underwent ultrasonic examination and semiquantitative analysis of real-time ultrasound elastography of the liver. Results: Main semi quantitative strain parameters, such as average strain value, differed significantly among groups polycystic ovary syndrome with nonalcoholic fatty liver disease, polycystic ovary syndrome without nonalcoholic fatty liver disease, and control (87.02 ± 10.16 vs. 96.31 ± 11.44 vs. 104.49 ± 7.28, p < 0.001). Clinical and laboratory parameters differed significantly between the two subgroups with low or high average strain value. For diagnostic value of average strain value for elevated aminotransferase, the area under the curve was 0.808 (range 0.721-0.895). In multiple linear regression analysis, polycystic ovary syndrome, waist circumference, and metabolic syndrome were stand-alone independent factors associated with average strain value among subjects without nonalcoholic fatty liver disease. Conclusion: Semiquantitative real-time ultrasound elastography analysis could distinguish liver parenchyma alterations in patients with polycystic ovary syndrome more sensitively. The diagnostic value of the proposed method for nonalcoholic fatty liver disease need further research.

Tendências temporais da prevalência de Helicobacter pylori em Itajaí - SC: um estudo retrospectivo de 25 anos baseado em banco de dados endoscópicos / Time trends of helicobacter pylori prevalence in itajaí - sc: a retrospective study of 25 years based on endoscopic database

ABSTRACT BACKGROUND: The bacterium Helicobacter pylori is strongly associated with the development of gastric adenocarcinoma. Currently, the prevalence in developed countries is 40%, but this value increases considerably in developing countries, which can reach rates bigger than 90%. OBJECTIVE: The objective of this study was to determine the mean and annual prevalence of Helicobacter pylori infection in patients from Itajaí during the period from July 1992 to April 2016, as well as the gender and age groups most affected. METHODS: After consent of the clinical director of the Gastroclinica Itajaí and confidentiality commitment about the research, the database of the Endoscopy Service of the clinic was evaluated. All the patients who underwent their first upper digestive endoscopy with urease test and/or histological analysis were included. The data were submitted to statistical analysis of prevalence by gender, age group and years of study, with subsequent correction through the confidence interval. RESULTS: The mean prevalence of Helicobacter pylori infection thru all years of study was 50.07%. With the calculation of the annual prevalences, it was evident the gradual reduction of infection in the population of Itajaí, that was 81.3% in 1992, declining to 33% in the year of 2016. When classifying the prevalence of infection by gender, it was higher in males (53.59%), and gender distribution by age group showed no statistically significant difference among genders between the ages of 40 and 80 years. In relation to the age group, the highest prevalence was in the group between 40 and 49 years. CONCLUSION: Although this study is retrospective and based on endoscopic database analysis, without access to clinical data of patients such as prior use of proton pump inhibitor and antibiotics to endoscopy, its results are important because they may reflect the current panorama of Helicobacter pylori infection in the city under study, where it has been presenting a gradual reduction of prevalence over the years, with current rates similar to that of developed countries (33%). Future studies are needed to confirm our data.

RESUMO CONTEXTO: A bactéria Helicobacter pylori associa-se fortemente ao desenvolvimento do adenocarcinoma gástrico. Atualmente, a prevalência em países desenvolvidos é de 40%, porém esse valor cresce consideravelmente em países em desenvolvimento, que chegam a alcançar taxas de até 90%. OBJETIVO: O objetivo desta pesquisa foi determinar a prevalência média e anual da infecção por Helicobacter pylori nos pacientes de Itajaí durante o período de julho de 1992 a abril de 2016, assim como o sexo e as faixas etárias mais acometidas. MÉTODOS: Após consentimento do diretor técnico da Gastroclínica Itajaí e comprometimento de sigilo em relação à pesquisa, foi avaliada a base de dados do Serviço de Endoscopia da clínica. Foram selecionados todos os pacientes que realizaram pela primeira vez o exame de endoscopia digestiva alta com teste da urease e/ou análise histológica. Os dados obtidos foram submetidos à análise estatística de prevalência por sexo, faixa etária e anos do estudo, com posterior correção dos dados através do intervalo de confiança. RESULTADOS: A prevalência média da infecção por Helicobacter pylori em todos os anos de estudo foi de 50,07%. Com o cálculo das prevalências anuais, ficou evidente a redução gradual da infecção na população de Itajaí, que era de 81,3% em 1992, passando a 33% no ano de 2016. Ao classificar a prevalência da infecção por gênero, foi maior no sexo masculino (53,59%) e a distribuição dos gêneros por faixa etária não mostrou diferença estatisticamente significativa entre os sexos entre as idades de 40 a 80 anos. Em relação à faixa etária, a maior prevalência foi no grupo entre 40 e 49 anos. CONCLUSÃO: Embora este estudo seja retrospectivo e baseado em análise de banco de dados de endoscopias digestivas, sem acesso a dados clínicos de pacientes como uso prévio de nibidor de bomba de próton e antibióticos à endoscopia, seus resultados são importantes, pois podem refletir o panorama atual da infecção por Helicobacter pylori no município em estudo, que vem apresentando uma redução gradual da prevalência ao longo dos anos, com taxas atuais semelhantes às dos países desenvolvidos (33%). Estudos futuros são necessários para confirmar nossos dados.

Correlação entre a circunferência do pescoço e resistência a insulina em pacientes com DHGNA / The correlation of neck circumference and insulin resistance in nafld patients

ABSTRACT BACKGROUND: Insulin resistance, especially that induced by obesity, plays a central role in the development of non-alcoholic fatty liver disease. Although the evaluation of overweight patients is important, the nutritional assessment tools used in clinical practice have limitations. Neck circumference (NC), from this, becomes a viable and low-cost alternative, which seems to be related to the accumulation of fat in the hepatic tissue. OBJECTIVE: To evaluate the association between NC and metabolic alterations in patients with non- alcoholic fatty liver disease. METHODS: A cross-sectional study performed in 82 patients, of whom 76 underwent liver biopsy. We performed weight, height, abdominal circumference and NC measures. Values of NC ≥42 cm and ≥36 cm were considered as altered for men and women, respectively. Laboratory tests and liver biopsy result were collected in the participants' charts. We evaluated fasting blood glucose levels, insulin, glycosylated hemoglobin, triglycerides, total cholesterol, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), ferritin, alkaline phosphatase, gamma glutamyltransferase, albumin, total bilirubin, direct bilirubin, glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase and the HOMA-IR index. RESULTS: We evaluated eighty-two patients. Patients with altered NC had increased body mass index (P=0.043), abdominal circumference (P=0.007), insulin (P=0.003) and HOMA-IR (P=0.029) when compared to those with adequate NC. NC was significantly correlated with reduced levels of high-density cholesterol (HDL-C) in men (r= -042, P<0.05), increased insulin levels in men and female (rs=0.47; P<0.05 and rs=0.51; P<0.01, respectively), as well as higher HOMA-IR index both males (rs=0.49; P<0.01) and female (rs=0.30; P<0.05). There was no significant association between NC and liver outcomes (r=0.145; P=0.36). CONCLUSION: NC is associated with the HOMA-IR index in patients with non-alcoholic fatty liver disease. NC can be used in the screening of insulin resistance in these patients, considering that insulin resistance plays a key role in the progression of the disease.

RESUMO CONTEXTO: A resistência à insulina, em especial a induzida pela obesidade, desempenha papel central no desenvolvimento da doença hepática gordurosa não alcoólica (DHGNA). Embora seja importante a avaliação de pacientes com excesso de peso, as ferramentas de avaliação nutricional utilizadas na prática clínica apresentam limitações. A circunferência do pescoço, a partir disso, torna-se uma alternativa viável e de baixo custo, a qual parece estar relacionada ao acúmulo de gordura no tecido hepático. OBJETIVO: Avaliar a associação entre a circunferência do pescoço (CP) e as alterações metabólicas em pacientes com DHGNA. MÉTODOS: Estudo transversal realizado em 82 pacientes, dos quais 76 foram submetidos à biópsia hepática. Foram realizadas as medidas de peso, altura, circunferência abdominal e CP. Valores de CP ≥42 cm e ≥36 cm foram considerados alterados para homens e mulheres, respectivamente. Os exames laboratoriais e o resultado da biópsia hepática foram coletados dos prontuários dos participantes. Foram avaliados os níveis glicêmicos em jejum, insulina, hemoglobina glicosilada, triglicerídeos, colesterol total, lipoproteína de alta densidade (HDL-C), lipoproteína de baixa densidade (LDL-C), ferritina, fosfatase alcalina, gama glutamiltransferase, albumina, bilirrubina total, bilirrubina direta, transaminase glutâmico-oxalacética, transaminase glutâmico-pirúvica e o índice HOMA-IR. RESULTADOS: Foram avaliados 82 pacientes. Os pacientes com CP alterada apresentaram aumento do índice de massa corporal (P=0,043), circunferência abdominal (P=0,007), insulina (P=0,003) e HOMA-IR (P=0,029) quando comparados àqueles com CP adequada. A CP foi significativamente correlacionada com níveis reduzidos de colesterol de alta densidade (HDL-C) em homens (r= -042, P<0,05), aumento dos níveis de insulina em homens e mulheres (rs=0,47, P<0,05 e rs = 0,51; P<0,01, respectivamente), bem como maior índice HOMA-IR, tanto do sexo masculino (rs=0,49; P<0,01) quanto do feminino (rs=0,30; P<0,05). Não houve associação significativa entre CP e os desfechos hepáticos (r=0,145, P=0,36). CONCLUSÃO: A CP está associada com o índice HOMA-IR em pacientes com DHGNA. A CP pode ser utilizada no rastreamento da resistência à insulina nesses pacientes, considerando que a resistência à insulina desempenha um papel fundamental na progressão da doença.

Nonalcoholic fatty liver disease and bariatric surgery: a comprehensive review / Doença hepática gordurosa não alcoólica e cirurgia bariátrica: uma revisão abrangente

ABSTRACT CONTEXT AND OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) has been increasingly diagnosed worldwide and is now recognized as a source of public health concern. It comprises a wide spectrum of histological features that range from simple steatosis to severe forms of fibrosis, steatohepatitis and even cirrhosis. The impact of bariatric surgery on the course of NAFLD in individuals with obesity has been extensively studied. DESIGN AND SETTING: Narrative review; public university hospital. METHODS: A comprehensive review was conducted based on an online search on the electronic databases MEDLINE and LILACS using the MeSH terms "fatty liver" and "bariatric surgery". RESULTS: The exact mechanisms that lead to improvement in NAFLD following bariatric surgery are not completely understood. Since Roux-en-Y gastric bypass (RYGB) is the bariatric surgical procedure most performed worldwide, it is also the one from which the effects on NAFLD have been most studied, although there is also consistent evidence regarding the effects from gastric banding, sleeve gastrectomy and biliopancreatic diversions. CONCLUSION: According to the currently available evidence, bariatric surgery leads to significant improvement in NAFLD. Further research, especially by means of randomized controlled trials enrolling larger cohorts of individuals, is needed to determine the optimal procedure for this group of subjects.

RESUMO CONTEXTO E OBJETIVO: A doença hepática gordurosa não alcoólica (DHGNA) tem sido diagnosticada com maior frequência em todo o mundo na atualidade, sendo agora reconhecida como motivo de preocupação em saúde pública. Abrange um amplo espectro de alterações histológicas que variam desde a simples esteatose até formas graves de fibrose, esteato-hepatite e até cirrose. O impacto da cirurgia bariátrica sobre o curso da DHGNA em indivíduos com obesidade tem sido profundamente estudado. TIPO DE ESTUDO E LOCAL: Revisão narrativa; hospital universitário público. MÉTODOS: Uma revisão abrangente da literatura foi conduzida baseada na pesquisa on-line nas bases de dados eletrônicas MEDLINE e LILACS por meio dos termos MeSH "fígado gorduroso" e "cirurgia bariátrica". RESULTADOS: Os mecanismos exatos que levam à melhora da DHGNA após a cirurgia bariátrica não são completamente conhecidos. Como o bypass gástrico em Y de Roux é a cirurgia bariátrica mais realizada em todo o mundo, é também o procedimento cujos efeitos sobre DHGNA foram mais estudados, embora haja também evidências consistentes sobre os efeitos de banda gástrica, gastrectomia vertical e derivações biliopancreáticas. CONCLUSÃO: De acordo com as evidências atualmente disponíveis, a cirurgia bariátrica leva à melhora significativa da DHGNA. Mais estudos, especialmente por meio de ensaios clínicos randomizados e controlados, recrutando coortes maiores de indivíduos, são necessários para determinar o melhor procedimento para esse grupo de pacientes.

Assessment of left ventricular diastolic function in nonalcoholic fatty liver disease

Background: Nonalcoholic fatty liver disease [NAFLD] is a spectrum of fat-associated liver conditions that can result in end stage liver disease. NAFLD patients when compared to control subjects have a higher prevalence of atherosclerosis which is independent of obesity and other established risk factors. Recent studies have identified NAFLD as a risk factor for early subclinical abnormalities in myocardial metabolism as well as in cardiac structure and function. In particular, it has been shown that NAFLD is associated with left ventricular hypertrophy and impaired diastolic function

The Objective: The aim of this study is to assess left ventricular diastolic function in NAFLD patients

Patients and Methods: The study included thirty Egyptian NAFLD patients their age between 20 and 45 years old, and twenty healthy control subjects who were age and sex matched. Full medical history, complete physical examination and laboratory tests were done in form of ALT, AST, total cholesterol, LDL, HDL, triglyceride, hemoglobin A1C, creatinine, urea and CBC. Abdominal ultrasonography and transthoracic echocardiography also were done

Results: NAFLD patients had higher diastolic blood pressures, increased body mass indices, ALT, AST and glycated hemoglobin A1C more than controls. Also in our study the mean of E, E/A ratio, DT, lateral E/e and septal E/e is significant higher in NAFLD patients than control group. The mean of lateral e and septal e is lower in NAFLD patients than control group

Conclusion: Patients with NAFLD had significant impairment on diastolic function in the non-diabetic and normotensive NAFLD patients compared to the controls as measured by two-dimensional echocardiography Doppler imaging in addition to tissue Doppler imaging

Efeito quimiopreventivo da ß-ionona nas fases de iniciação e seleção/promoção da hepatocarcinogênese associada ao desenvolvimento de esteatose hepática não alcoólica em ratos Wistar / Chemopreventive effect of ß-ionone in the phases of initiation and selection/promotion of hepatocarcinogenesis associated with the development of non-alcoholic steatosis in Wistar rats

O câncer é um dos principais problemas de saúde pública no mundo. Dentre as neoplasias primárias que acometem o fígado, o carcinoma hepatocelular (HCC) é a mais frequente. Diversos fatores de risco predispõem ao HCC, entre eles a doença hepática gordurosa não-alcoólica (NAFLD). Segundo estudos prévios do grupo, a ß-ionona (BI), presente em uvas e aromatizantes de vinho, apresenta potencial quimiopreventivo da hepatocarcinogênese. Além disso, a ßI parece atuar na redução da colesterolemia podendo, assim, influenciar a NAFLD. Desta forma pretendeu-se, neste projeto, avaliar o desenvolvimento da NAFLD e sua influência nas etapas de iniciação e seleção/promoção da hepatocarcinogênese em ratos Wistar submetidos ao modelo do hepatócito resistente (RH), além da atividade quimiopreventiva da ßI, nessas condições experimentais em ratos. Para isso, os animais foram alocados em 6 grupos experimentais: RH iniciação (n=11), NAFLD iniciação (n=15), BI iniciação (n=15), RH seleção/promoção (n=11), NAFLD seleção promoção (n=15) e BI seleção/promoção (n=15). Na fase de iniciação os animais do grupo NAFLD receberam, diariamente, emulsão hipercalórica até a sexta semana do experimento um dia antes da administração de DEN. Já na fase de seleção/promoção os animais do grupo NAFLD receberam a emulsão hipercalórica, a partir de um dia após a DEN. Os animais dos grupos RH da iniciação e da seleção/promoção servem como controles e receberam, diariamente, 1mL/100g peso corpóreo de água até a sexta semana do experimento e um dia após a DEN, respectivamente. Na fase de iniciação, após 13 semanas os animais do grupo NAFLD não demonstraram sinais de esteatose, apresentaram maiores níveis séricos de triacilglicerol, colesterol total e LDL comparados ao grupo RH (P<0,05). O grupo NAFLD apresentou maior porcentagem de nódulos macroscópicos, bem como maior número e porcentagem de área hepática de lesões pré neoplásicas persistentes (pLPN) comparado ao grupo RH (P<0,05). Já o grupo BI apresentou menor número de pLPN e maior número de lesões em remodelação e uma maior porcentagem de área hepática de rLPN (p<0,05). Em relação a proliferação celular, o grupo NAFLD apresentou maior número de células em sourrounding, pLPN e rLPN comparada ao grupo RH e o grupo BI menor número em pLPN comparada a NAFLD. Já na fase de seleção/promoção foi possível observar o grupo NAFLD tem maiores valores de focos de inflamação, hepatócitos balonizados e grau de esteatose hepática em relação ao grupo BI, assim como maiores níveis séricos de triacilgliceróis, colesterol total e LDL (p<0,05). O grupo NAFLD apresentou maior porcentagem de nódulos macroscópicos <1, maior número, menor tamanho médio de pLPN comparados ao grupo RH (p<0,05). O grupo BI apresentou menor número e menor porcentagem de área em pLPN e maior porcentagem de área em rLPN (p<0,05). Em relação a proliferação celular, o grupo NAFLD apresentou maior número de células em sourrounding, pLPN e rLPN comparada ao grupo RH (p<0,05). Na expressão gênica, o grupo BI apresentou maior expressão de HMGCR em relação grupo NAFLD (p<0,05), O grupo NAFLD apresentou maior expressão de INSIG1 em relação ao grupo RH (p<0,05) e tendência na expressão de INSIG 2

Cancer is a major public health problems in the world. Among the primary neoplasm affecting the liver, hepatocellular carcinoma (HCC) is the most frequent. Several risk factors predispose to HCC, including the non-alcoholic fatty liver disease (NAFLD). According to previous studies of the group, ß-ionone (BI), present in grapes and flavors of wine, it presents potential chemopreventive of hepatocarcinogenesis. Furthermore, ßI appears to act in reducing blood cholesterol and may thus influence NAFLD. In this way it was intended in this project, evaluate the development of NAFLD and its influence on the steps of initiation and selection/promotion of hepatocarcinogenesis in Wistar rats resistant hepatocyte model (HR), and the chemopreventive activity of ßI, these experimental conditions in rats. For this, the animals were divided into 6 groups: RH initiation (n = 11), NAFLD initiation (n = 15), BI initiation (n = 15), HR selection / promotion (n = 11), NAFLD selection promotion ( n = 15) and BI selection / promotion (n = 15). In the inception phase of the NAFLD group animals received daily calorie emulsion until the sixth week of the experiment one day prior to DEN administration. In the selection / promotion stage NAFLD group of animals received hypercaloric emulsion, from one day after the DEN. The animals of groups HR and selection of initiation / promotion serve as controls and received daily 1mL / 100g body weight of water until the sixth week of the experiment, and one day after DEN respectively. In the initiation phase, after 13 weeks the animals of group NAFLD showed no signs steatosis, had higher serum levels of triglyceride, total cholesterol and LDL compared to the HR group (P <0.05). The NAFLD showed higher prevalence of macroscopic nodules as well as higher number and percentage of liver area of persistent pre-neoplastic lesions (pLPN) compared to the HR group (P <0.05). But the BI group had fewer pLPN and higher number of lesions in remodeling and a higher percentage of liver area rLPN (p <0.05). In relation to cell proliferation, the NAFLD group had a higher number of cells in sourrounding, pLPN and rLPN compared to the RH group and the lowest number in pLPN BI group compared to NAFLD. In the selection / promotion layer was observed NAFLD group has the highest values of inflammation foci, balonizados hepatocytes and hepatic steatosis grade in relation to BI group as well as higher serum levels of triglyceride, total cholesterol and LDL (p <0 , 05). The NAFLD showed higher prevalence of macroscopic nodules <1, more, smaller average size pLPN compared to the HR group (p <0.05). The BI group had fewer and smaller percentage area in pLPN and higher percentage of area rLPN (p <0.05). In relation to cell proliferation, the NAFLD group had a higher number of cells in sourrounding, pLPN and rLPN compared to the HR group (p <0.05). In gene expression, the BI group showed higher expression of HMGCR regarding NAFLD group (p <0.05), the NAFLD group had higher expression of INSIG1 against the RH group (p <0.05) and a tendency in the expression of INSIG 2

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.

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...

Controversias en el diagnóstico de enfermedad por hígado graso no alcohólico / Controversies in the diagnosis of non-alcoholic fatty liver disease

There has been an increase in the prevalence of nonalcoholic fatty liver disease (NAFLD) throughout the western world and especially in Latin America. This condition is associated with metabolic syndrome, risk of diabetes, cardiovascular risk and extrahepatic cancer. However, in patients with NAFLD, risk of mortality from diseases affecting the liver does not exceed 5 percent in contrast to 60 percent when advanced fibrosis is present. Only 10 to 20 percent of patients with NAFLD have non-alcoholic steatohepatitis (NASH), a condition that can potentially progress to fibrosis and cirrhosis. The non-invasive diagnostic tools for discriminating current patients at risk of progression to advanced fibrosis are sub-optimal. Clinical variables and routine laboratory tests help in detecting NAFLD but do not allow discrimination of NASH patients. New diagnostic tools could allow prediction of NASH such as markers of oxidative stress, inflammatory markers and markers of apoptosis. Regarding liver fibrosis biomarkers, there are indirect markers that are related to the degree of liver function and direct markers that reflect the dynamics of extracellular matrix. Imaging methods such as ultrasound-based elastography, (ARFI) and magnetic resonance elastography have shown a good correlation with the degree of fibrosis. Finally various predictor models that combine clinical and laboratory variables have a very good correlation with the degree of fibrosis. Although there is still some controversy on its clinical utility, liver biopsy still plays a role in NAFLD severity assessment for initiation of drug therapy.

Se ha registrado un aumento en la prevalencia de la enfermedad por hígado graso no alcohólico HGNA (NAFLD, por su sigla en inglés) en todo el mundo occidental y especialmente en Latinoamérica. Esta condición se relaciona con síndrome metabólico, riesgo de diabetes, riesgo cardiovascular y cáncer extrahepático. Sin embargo, en pacientes con HGNA el riesgo de mortalidad por enfermedades que afectan al hígado no supera el 5 por ciento en contraste con 60 por ciento cuando hay fibrosis avanzada. Sólo 10 a 20 por ciento de los pacientes presenta esteatohepatitis no alcohólica EHNA (NASH, por su sigla en inglés), una condición que potencialmente puede progresar a fibrosis y cirrosis. Las herramientas de diagnóstico no invasivo actuales para discriminar pacientes con riesgo de progresión a fibrosis avanzada son subóptimas. Las variables clínicas y exámenes de laboratorio habituales ayudan en la detección de HGNA,pero no permiten discriminar pacientes con EHNA. Nuevas herramientas diagnósticas podrían permitir predecir EHNA como marcadores de estrés oxidativo, marcadores de inflamación y de apoptosis. De los marcadores de fibrosis existen los indirectos que se relacionan con el grado de función hepática, marcadores directos que reflejan la dinámica de la matriz extracelular. Los métodos de imagen como la elastografía por ultrasonido (ARFI), elastografía por resonancia magnética, han demostrado una buena correlación con el grado de fibrosis. Finalmente, diversos índices que combinan variables clínicas y de laboratorio tienen una muy buena correlación con el grado de fibrosis. La biopsia aun cumple un rol a pesar de la controversia en su real necesidad para iniciar tratamiento.

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.

Grading scale o visceral adipose tissue thicknss and their relation to the noonalcoholic fatty liver disease / Escala de classificação da espessura do tecido adiposo visceral e sua relação com a doença gordurosa hepática não alcoólica

Context The mesenteric fat is drained by the portal system, being related to the metabolic syndrome which is an impor­tant risk factor for non-alcoholic fatty liver disease (NAFLD). Objectives Graduate of visceral fat thickness and correlate with the NAFLD degree through ultrasonography method. Methods We studied 352 subjects for age, gender, measures of subcutaneous fat thickness and visceral fat thickness as well as the presence and degree of liver fatty. Was analyzed the independent relationship between visceral fat thickness and NAFLD, and linear regression analysis was used in order to predict the visceral fat thickness from subcutaneous fat thickness. Results The mean age of 225 women (63.9%) and 127 men (36.1%) was 47.5 ± 14.0 (18-77) years, 255 subjects had normal examinations, 97 had NAFLD thus distributed, 37 grade 1, 32 grade 2, and 28 grade 3. The subcutaneous fat thickness ranged from 0.26 to 3.50 cm with a mean of 1.3 ± 0.6 cm and visceral fat thickness ranged from 0.83 to 8.86 cm with a mean of 3.6 ± 1.7 cm. Linear regression showed that for every increase of 1 cm in subcutaneous fat thickness the visceral fat thickness will increase 0.9 cm. Conclusions The visceral fat thickness measured by ultrasonography is a useful and seems to be able to help estimate the risk of NAFLD. .

Contexto A gordura mesentérica é drenada pelo sistema venoso portal, estando relacionada à síndrome metabólica, que é um importante fator de risco para doença de infiltração gordurosa do fígado. Objetivos Graduar a espessura do tecido adiposo visceral e correlacionar com o grau de doença de infiltração gordurosa do fígado através do exame ultrassonográfico. Métodos Foram estudados 352 indivíduos, avaliando-se idade, gênero, medidas da espessura da gordura subcutânea e tecido adiposo visceral, a presença e o grau de doença de infiltração gordurosa do fígado. Foi analisada a relação independente entre tecido adiposo visceral e doença de infiltração gordurosa do fígado, e a regressão linear foi utilizada para prever a tecido adiposo visceral pela espessura da gordura subcutânea. Resultados A idade média de 225 (63,9%) mulheres e 127 (36,1%) homens foi 47,5 ± 14,0 (18-77) anos, 255 indivíduos apresentaram exames normais, 97 apresentaram doença de infiltração gordurosa do fígado assim distribuídos: 37 grau 1, 32 grau 2 e 28 grau 3. A espessura da gordura subcutânea variou de 0,26 e 3,50 cm, com uma média de 1,3 ± 0,6 cm e a tecido adiposo visceral variou de 0,83 a 8,86 cm, com uma média de 3,6 ± 1,7 cm. A regressão linear demonstrou que para cada aumento de 1 cm da espessura da gordura subcutânea o tecido adiposo visceral aumentará 0,9 cm. Conclusão O tecido adiposo visceral medido por ultrassonografia é um instrumento útil e parece ser capaz de estimar o risco de doença de infiltração gordurosa do fígado. .

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.

Effect and the probable mechanisms of silibinin in regulating insulin resistance in the liver of rats with non-alcoholic fatty liver

Our previous study has shown that reduced insulin resistance (IR) was one of the possible mechanisms for the therapeutic effect of silibinin on non-alcoholic fatty liver disease (NAFLD) in rats. In the present study, we investigated the pathways of silibinin in regulating hepatic glucose production and IR amelioration. Forty-five 4- to 6-week-old male Sprague Dawley rats were divided into a control group, an HFD group (high-fat diet for 6 weeks) and an HFD + silibinin group (high-fat diet + 0.5 mg kg-1·day-1 silibinin, starting at the beginning of the protocol). Both subcutaneous and visceral fat was measured. Homeostasis model assessment-IR index (HOMA-IR), intraperitoneal glucose tolerance test and insulin tolerance test (ITT) were performed. The expression of adipose triglyceride lipase (ATGL) and of genes associated with hepatic gluconeogenesis was evaluated. Silibinin intervention significantly protected liver function, down-regulated serum fat, and improved IR, as shown by decreased HOMA-IR and increased ITT slope. Silibinin markedly prevented visceral obesity by reducing visceral fat, enhanced lipolysis by up-regulating ATGL expression and inhibited gluconeogenesis by down-regulating associated genes such as Forkhead box O1, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Silibinin was effective in ameliorating IR in NAFLD rats. Reduction of visceral obesity, enhancement of lipolysis and inhibition of gluconeogenesis might be the underlying mechanisms.