Impact of pre-operative weight loss on non-alcoholic fatty liver disease histopathology and insulin resistance in individuals undergoing bariatric surgery: a propensity matched cross-sectional comparison

ABSTRACT BACKGROUND: The effect of weight loss (WL) on histopathological aspects of non-alcoholic fatty liver disease (NAFLD) may provide further insights into the dynamics of hepatic recovery after WL. OBJECTIVE: To analyze the effects of pre-operative WL on insulin resistance- and NAFLD-related histology in individuals undergoing bariatric surgery (BS) with or without pre-operative WL. DESIGN AND SETTING: A matched cross-sectional study was conducted at a public university hospital and a private clinic in Campinas, Brazil. METHODS: An analytical, observational, cross-sectional study was conducted using prospectively collected databases of individuals who underwent BS and liver biopsy at either a public tertiary university hospital (with pre-operative WL) or a private clinic (without pre-operative WL). Random electronic matching by gender, age, and body mass index (BMI) was performed and two paired groups of 24 individuals each were selected. RESULTS: Of the 48 participants, 75% were female. The mean age was 37.4 ± 9.6. The mean BMI was 38.9 ± 2.6 kg/m2. Fibrosis was the most common histopathological abnormality (91.7%). Glucose was significantly lower in the WL group (92 ± 19.1 versus 111.8 ± 35.4 mg/dL; P = 0.02). Significantly lower frequencies of macrovesicular steatosis (58.3% versus 95.8%; P = 0.004), microvesicular steatosis (12.5% versus 87.5%; P < 0.001), and portal inflammation (50% versus 87.5%; P = 0.011) were observed in the WL group. CONCLUSION: Pre-operative WL was significantly associated with lower frequencies of macro- and mi- crovesicular steatosis, portal inflammation, and lower glycemia, indicating an association between the recent trajectory of body weight and histological aspects of NAFLD.

Liver steatosis as a predictor of incident diabetes in adults: a prospective evaluation in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) / Esteatose hepática como preditor de diabetes incidente em adultos: avaliação prospectiva no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) / Esteatosis hepática como predictor de diabetes incidente en adultos: evaluación prospectiva en el Estudio Longitudinal de Salud del Adulto (ELSA-Brasil)

Increasing epidemiological evidence suggests a bidirectional relationship between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes, and that NAFLD may precede and/or promote the development of diabetes. This study aimed to investigate whether liver steatosis is associated with the incidence of diabetes in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The ELSA-Brasil is an occupational cohort study of active or retired civil servants, aged 35-74 years, in six capital cities in Brazil. We excluded participants with diabetes at baseline, those who reported excessive alcohol consumption or with missing information on relevant covariates, and those with self-referred hepatitis or cirrhosis. In total, 8,166 individuals participated, and the mean duration of follow-up was 3.8 years. The Cox proportional regression model was used to estimate the adjusted hazard ratio (HR) for the associations. Abdominal ultrasonography was used to detect liver steatosis. In the follow-up period, the cumulative incidence of diabetes was 5.25% in the whole sample, 7.83% and 3.88% in the groups with and without hepatic steatosis, respectively (p < 0.001). Compared to those without steatosis, individuals with hepatic steatosis had an increased risk of developing diabetes (HR = 1.31; 95%CI: 1.09-1.56) after adjustment for potential confounders, including body mass index (BMI). Hepatic steatosis was an independent predictor of incident diabetes in the ELSA-Brasil cohort study. Physicians should encourage changes in lifestyle and screen for diabetes in patients with fatty liver.

Evidências epidemiológicas crescentes sugerem uma relação bidirecional entre a doença hepática gordurosa não alcoólica (DHGNA) e o diabetes tipo 2 e que a DHGNA pode preceder e/ou promover o desenvolvimento de diabetes. O objetivo deste estudo foi investigar se a esteatose hepática está associada à incidência de diabetes no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). O ELSA-Brasil é um estudo de coorte ocupacional com servidores públicos ativos ou aposentados, com idades entre 35 e 74 anos, de seis capitais do Brasil. Foram excluídos os participantes com diabetes no início do estudo, aqueles que relataram consumo excessivo de álcool ou com falta de informações sobre covariáveis relevantes e indivíduos com hepatite ou cirrose autorreferida. No total, 8.166 indivíduos participaram e o tempo médio de seguimento foi de 3,8 anos. O modelo de regressão proporcional de Cox foi utilizado para estimar a razão de risco (HR) ajustada para as associações. A ultrassonografia abdominal foi utilizada para detectar esteatose hepática. No período de seguimento, a incidência cumulativa de diabetes foi de 5,25% em todo o grupo de participantes e de 7,83% e 3,88% nos grupos com e sem esteatose hepática, respectivamente (p < 0,001). Em comparação com aqueles sem esteatose, os indivíduos com esteatose hepática apresentaram um risco elevado de desenvolver diabetes (HR = 1,31; IC95%: 1,09-1,56) após o ajuste para potenciais fatores de confusão, incluindo o índice de massa corporal (IMC). A esteatose hepática foi um preditor independente de diabetes incidente no ELSA-Brasil. Os médicos devem incentivar mudanças no estilo de vida e a triagem para diabetes para pacientes com fígado gorduroso.

La creciente evidencia epidemiológica sugiere una relación bidireccional entre la enfermedad del hígado graso no alcohólica (EHGNA) y la diabetes tipo 2 y que la EHGNA puede preceder y/o desarrollar la diabetes. El objetivo de este estudio fue investigar si la esteatosis hepática está asociada con la incidencia de diabetes en el Estudio Longitudinal de Salud del Adulto (ELSA-Brasil). ELSA-Brasil es un estudio de cohorte ocupacional, realizado con funcionarios públicos activos o jubilados, con edades entre 35 y 74 años, de seis capitales en Brasil. Se excluyeron a los participantes con diabetes al inicio del estudio, aquellos que informaron consumir excesivamente alcohol o que carecían de información sobre las covariables relevantes, y los individuos con hepatitis o cirrosis autorreportada. En total participaron 8.166 sujetos, y el tiempo medio de seguimiento fue de 3,8 años. Se utilizó el modelo de regresión proporcional de Cox para estimar la razón de riesgo ajustada (HR) en las asociaciones. Se realizó ecografía abdominal para detectar esteatosis hepática. En el periodo de seguimiento, el grupo de participantes tuvo incidencia acumulada de diabetes del 5,25%, y en los grupos con y sin esteatosis hepática fueron del 7,83% y el 3,88%, respectivamente (p < 0,001). Los individuos con enfermedad de hígado graso tuvieron mayor riesgo de desarrollar diabetes (HR = 1,31; IC95%: 1,09-1,56) después de ajustar los posibles factores de confusión, incluido el índice de masa corporal (IMC), en comparación con aquellos sin esteatosis. La esteatosis hepática fue un predictor independiente de diabetes incidente en ELSA-Brasil. Los médicos deben alentar cambios en el estilo de vida y la detección de diabetes a los pacientes con hígado graso.

Potencial efecto terapéutico de los polifenoles obtenidos de la cáscara de granada en la esteatosis hepática

RESUMEN Antecedentes: La enfermedad por hígado graso no alcohólico (EHGNA) tiene una elevada prevalencia a nivel mundial, y puede ir desde la esteatosis simple hasta hepatocarcinoma. Su origen es multifactorial, siendo la dieta poco saludable un factor clave en su patogenia y progresión. Los polifenoles son antioxidantes que han mostrado beneficios en el tratamiento de la EHGNA. Una fuente emergente de estos compuestos son los residuos agroindustriales, entre ellos, la cáscara de granada. La cáscara de granada tiene un alto contenido de polifenoles, específicamente de elagitaninos. Su extracto fenólico (extracto de cáscara de granada; ECG) ha mostrado efectos promisorios a nivel metabólico. Sin embargo, su uso presenta algunas limitantes que deben ser consideradas antes de recomendar su ingesta mediante alimentos funcionales o nutracéuticos para prevención o tratamiento de EHGNA. Objetivo: Discutir a partir de datos obtenidos en estudios in vitro y modelos animales, el potencial terapéutico de los polifenoles obtenidos de la cáscara de granada para prevención y tratamiento de la EHGNA. Metodología: Se realizó una búsqueda bibliográfica en bases de datos PubMed y Web of Science (2015 a la fecha) de estudios en modelos de esteatosis hepática in vitro y en animales, además de ensayos clínicos relacionados. Conclusión: Existen datos promisorios sobre el uso del ECG en alteraciones metabólicas propias de la EHGNA y esteatosis hepática, principalmente a nivel de perfil lipídico. Se deben discutir las dosis y formas de administración, con el fin de mejorar su estabilidad y biodisponibilidad. Se requieren ensayos clínicos controlados que confirmen los efectos en humanos.

ABSTRACT Background: Nonalcoholic fatty liver disease (NAFLD) has a high prevalence worldwide and can range from simple steatosis to hepatocarcinoma. Its causes are multifactorial, with an unhealthy diet being a key factor in its pathogenesis and progression. Polyphenols are antioxidants that have shown benefits in treating NAFLD. An emerging source of these compounds is agro-industrial by-products, including pomegranate peels. Pomegranate peels are high in polyphenols, specifically ellagitannins. Its polyphenolic extract (PPE) has shown promising metabolic benefits. However, its use has some limitations that must be considered before recommending its intake through functional foods or nutraceuticals to prevent or treat NAFLD. Objective: This article aims to discuss, using results from in vitro studies and animal models, the therapeutic potential of polyphenols obtained from pomegranate peels to prevent and treat NAFLD. Methods: A bibliographic search was carried out in PubMed and Web of Science databases (2015 to date) of in vitro and animal model studies of hepatic steatosis, in addition to related clinical trials. Conclusion: There are promising data on the use of PPE in metabolic disorders typical of NAFLD and hepatic steatosis, mainly improving lipid profile. Doses and vehicles of administration should be discussed to improve stability and bioavailability. Controlled clinical trials are required to confirm the effects in humans.

Associação entre aumento de peso e fatores de risco cardiovascular em pacientes com doença hepática gordurosa não alcoólica / Association between weight increase and cardiovascular risk factors in patients with non-alcoholic fat hepatic disease

A Doença Hepática Gordurosa Não Alcoólica (DHGNA) é uma das principais causas de morbimortalidade relacionada ao fígado no mundo e caracteriza-se pela deposição em excesso de lipídios neste órgão. Juntamente com síndrome metabólica, a DHGNA tem forte associação com doença cardiovascular e diabetes mellitus tipo 2. O estudo buscou associar o aumento de peso e fatores de risco cardiovascular com a DHGNA. Tratou-se de um estudo clínico, prospectivo, tipo survey, com abordagem analítica quantitativa. Incluiu-se pacientes de ambos os sexos, de 18 a 70 anos de idade, avaliados pela ultrassonografia abdominal e excluíram-se pacientes com consumo de álcool de ≥ 140g/semana nos homens e ≥70g/semana nas mulheres, portadores de neoplasias malignas do fígado, doenças crônicas do fígado, deficiência cognitiva e em uso regular de drogas indutoras de esteatose hepática. Foram analisados 266 pacientes, 11 atingiram os critérios de exclusão, totalizando uma amostra final de 255. Com relação aos graus da esteatose hepática não alcóolica, 134 pacientes não apresentaram infiltração gordurosa (grau 0), 53 apresentaram grau 1, 57 grau 2 e 11 pacientes grau 3. Aumento na mediana das variáveis pressão arterial sistólica e diastólica, índice de massa corpórea, triglicerídeos e glicemia nos pacientes portadores de DHGNA com significância estatística em relação à gravidade da infiltração gordurosa hepática. A utilização destas variáveis nos pacientes mais vulneráveis para a infiltração gordurosa hepática pode permitir diagnósticos precoces da DHGNA, intervenções terapêuticas imediatas, com o intuito de evitar sua progressão e maiores riscos cardiovasculares e metabólicos.

Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of liver-related morbidity and mortality worldwide and is characterized by excess deposition of lipids in this organ. Along with metabolic syndrome, NAFLD has a strong association with cardiovascular disease and type 2 diabetes mellitus. The study sought to associate weight gain and cardiovascular risk factors with NAFLD. This was a clinical, prospective, survey-type study with a quantitative analytical approach. Patients of both sexes, aged 18 to 70 years, evaluated by abdominal ultrasound were included, and patients with alcohol consumption of ≥ 140g / week in men and ≥70g / week in women with malignant neoplasms of the liver, chronic liver disease, cognitive impairment and regular use of steatosis-inducing drugs. 266 patients were analyzed, 11 reached the exclusion criteria, totaling a final sample of 255. Regarding the degrees of non-alcoholic liver steatosis, 134 patients did not present fatty infiltration (grade 0), 53 had grade 1, 57 grade 2 and 11 grade 3 patients. Increase in the median of the variables systolic and diastolic blood pressure, body mass index, triglycerides and glycemia in patients with NAFLD with statistical significance in relation to the severity of hepatic fatty infiltration. The use of these variables in the most vulnerable patients for hepatic fatty infiltration may allow early diagnosis of NAFLD, immediate therapeutic interventions, in order to prevent its progression and greater cardiovascular and metabolic risks.

The association between serum uric acid to high density lipoprotein-cholesterol ratio and non-alcoholic fatty liver disease: the abund study

SUMMARY OBJECTIVE: Non-alcoholic fatty liver disease, which is characterized by lipid being deposited into hepatocytes, affects nearly one in three adults globally. Inflammatory markers were suggested to be related with hepatic steatosis. Uric acid to HDL cholesterol ratio is proposed as a novel inflammatory and metabolic marker. We aimed to compare Uric acid to HDL cholesterol ratio levels of patients with Non-alcoholic fatty liver disease to those of healthy controls and find out potential correlations between Uric acid to HDL cholesterol ratio and other inflammatory and metabolic markers of Non-alcoholic fatty liver disease. METHODS: Patients with a diagnosis of Non-alcoholic fatty liver disease who were on clinical follow-up in our institution were enrolled in the study as the Non-alcoholic fatty liver disease group, while healthy volunteers were enrolled as the control group. The Uric acid to HDL cholesterol ratio of the groups was compared and potential correlations were studied between Uric acid to HDL cholesterol ratio and fasting blood glucose, transaminases, serum lipids (triglyceride, LDL-cholesterol), weight, and body mass index. RESULTS: The Uric acid to HDL cholesterol ratio of the Non-alcoholic fatty liver disease (13±5%) group was significantly higher compared to the Uric acid to HDL cholesterol ratio of the control (10±4%) group (p<0.001). Uric acid to HDL cholesterol ratio was significantly and positively correlated with fasting blood glucose, transaminases, triglyceride, body weight, waist circumference, hip circumference, and body mass index. A ROC analysis revealed that a Uric acid to HDL cholesterol ratio level greater than 9.6% has 73% sensitivity and 51% specificity in determining Non-alcoholic fatty liver disease. CONCLUSION: Due to the inexpensive and easy-to-assess nature of Uric acid to HDL cholesterol ratio, we suggest that elevated Uric acid to HDL cholesterol ratio levels be considered a useful tool in diagnosing hepatic steatosis.

Research Progress of Quantitative Ultrasound Assessment of Liver Steatosis in Non-alcoholic Fatty Liver Disease / 中国医学科学院学报

The incidence of non-alcoholic fatty liver disease(NAFLD)keeps on rise.Without intervention,it may develop to steatohepatitis,cirrhosis,and even hepatocellular carcinoma.Liver biopsy,the gold standard for evaluating the steatosis severity of NAFLD,is invasive and unsuitable for large-scale screening.In recent years,magnetic resonance imaging(MRI)-related examinations have been used as a gold standard only second to liver biopsy,which still have disadvantages in large-scale application.Ultrasound has the advantages of simple operation,low cost,and safety,and may become an important method for accessing NALFD.This review summarizes the current studies about the diagnosis of liver steatosis by quantitative ultrasound assessment,including controlled attenuation parameters,attenuation imaging,ultrasonic liver/kidney intensity ratio and liver attenuation rate,and integrated backscatter.

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.

Comportamiento de las hepatopatías en el embarazo valoradas por gastroenterología / Behavior of liver diseases in pregnancy valued by Gastroenterology

RESUMEN Introducción: el embarazo supone cambios en la fisiología de la mujer. Estos cambios pueden llevar a la aparición de enfermedades que afectan el hígado como: síndrome de HELLP, colestasis gravídica intrahepática, esteatosis hepática aguda del embarazo, entre otras, que pueden repercutir en el curso de la gestación. Material y métodos: se realizó un estudio observacional, descriptivo, retrospectivo de corte transversal en 52 gestantes que fueron valoradas en gastroenterología por sospecha de hepatopatías durante el embarazo en el año 2018, que constituyeron el universo de estudio, con el objetivo de determinar el comportamiento de las hepatopatías durante la gestación en las embarazadas valoradas por el servicio de Gastroenterología del Hospital Universitario "Comandante Faustino Pérez Hernández" de Matanzas. Se estudiaron las variables: trimestre gestacional, síntomas y signos, resultados analíticos, entidad nosológica, tipo de parto y complicación neonatal. Se elaboró una planilla para la recolección de los datos. Los resultados se analizaron en frecuencias absolutas y porcientos y se expusieron en tablas. Resultados: predominaron las gestantes del tercer trimestre con 61.6 %. El síntoma más frecuente fue el prurito en 33 gestantes (63.6%). La hipertransaminasemia se manifestó en el 100% de las gestantes. La entidad más frecuente fue la hepatitis crónica por virus B en 19 gestantes (36.5%) seguida de la colestasis intrahepática del embarazo con un 25 %. La mayoría de los partos fueron realizados por cesárea (94.2 %). La principal complicación neonatal fue el bajo peso al nacer en 26 (39.4 %). Conclusiones: las hepatopatías propias de la gestación se comportaron con igual frecuencia descrita en la literatura de acuerdo al trimestre que predominó, aunque fue significativa la incidencia de gestantes valoradas con infección por virus de la hepatitis b cuyo diagnóstico se hizo durante el embarazo siendo la principal causa de las complicaciones neonatales observadas (AU).

SUMMARY Introduction: Pregnancy supposes changes in the woman's physiology. These changes can lead to the appearance of illnesses affecting the liver, such as Hellp syndrome, intrahepatic cholestasis gravidarum, acute hepatic steatosis of pregnancy, among others, that can rebound in the course of the gestation. Materials and methods: a cross-sectional retrospective, descriptive, observational study was carried out in 52 pregnant women that were valued in Gastroenterology due to the suspicion of liver diseases during pregnancy in 2018; they were the universe of the study and the aim was determining the behavior of liver diseases during pregnancy in pregnant women valued in the service of Gastroenterology of the university hospital "Comandante Faustino Pérez Hernández" of the province of Matanzas: The studied variables were: gestational trimester, symptoms and signs, analytical results; nosological entity, type of delivery and neonatal complications. A form was draw up to collect data. The results were analyzed in absolute frequencies and percentages and showed in tables. Results: The third semester pregnant women predominated with 61.7 %. Pruritus was the most frequent symptom in 33 pregnant women (63.6 %). High levels of serum transaminases were present in 100 % of the studied women. The most frequent disease was chronic hepatitis caused by virus B in 19 pregnant women (36.5 %), followed by intrahepatic cholestasis of pregnancy with 25 %. Most of deliveries were performed by cesarean (94.2 %). The main neonatal complication was low weight at birth in 26 (39.4 %). Conclusions: liver diseases that are proper of gestation behaved in the same frequency as they are described in literature in relation to the predominating semester, although it was significant the incidence of assessed pregnant women with infection caused by the virus of hepatitis B diagnosed during pregnancy; it was the main cause of the observed neonatal complications (AU).

Esteatosis hepática en pacientes con diabetes tipo 2 y su relación con el control glucémico / Hepatic steatosis in type 2 diabetes patients and its relationship with glycemic control

Introducción: La esteatosis hepática no alcohólica es la enfermedad con mayor frecuencia en el mundo, esta se asocia a diabetes mellitus tipo 2; padecimiento con gran impacto económico-social. Objetivo: Describir el comportamiento de esteatosis hepática en una población de pacientes con diagnóstico de diabetes mellitus tipo 2. Métodos: Se realizó un estudio observacional, descriptivo, transversal en 94 pacientes diabéticos atendidos en el Hospital Clínico Quirúrgico Hermanos Ameijeiras, en el periodo comprendido entre febrero 2016- febrero 2018. Resultados: La esteatosis fue leve en 42,6 por ciento, moderada (44,7 por ciento) y severa en 12,8 por ciento, en ambos casos, con un NAFLD score principalmente indeterminado (72,3 por ciento). Se detectó fibrosis F0-1 en 58,5 por ciento de los pacientes, F2 (29,8 por ciento) y significativa (F3 y F4) en 11,7 por ciento). Se detectó asociación entre ecogenicidad hepática aumentada, patrón hepático difuso y grado severo de esteatosis por ecografía con mayor grado de fibrosis según elastografía. Se detectó relación significativa de niveles elevados de HBA1C con fibrosis significativa medida tanto por NAFLD score como por elastografía. Conclusiones: La esteatosis hepática presente en los pacientes con diabetes mellitus fue principalmente leve a moderada con prevalencia de fibrosis leve, el grado de fibrosis significativa se asoció con ecogenicidad hepática aumentada, patrón hepático difuso, grado severo de esteatosis por ecografía y niveles elevados de hemoglobina glucosilada(AU)

Introduction: Non-alcoholic liver steatosis is the most frequent disease in the world. It is associated with type 2 diabetes mellitus, representing great economic-social impact. Objective: To describe the behavior of hepatic steatosis in a population of patients diagnosed with type 2 diabetes mellitus. Methods: An observational, descriptive, cross-sectional study was conducted in 94 diabetic patients treated at Hermanos Ameijeiras Clinical Surgical Hospital, from February 2016 to February 2018. Results: Steatosis was mild in 42.6 percent, moderate (44.7 percent) and severe in 12.8 percent, with a mainly indeterminate NAFLD score (72.3 percent). F0-1 fibrosis was detected in 58.5 percent of the patients, F2 (29.8 percent) and significant (F3 and F4) in 11.7 percent). Association between increased liver echogenicity, diffuse liver pattern and severe degree of steatosis were ostensible by ultrasound with higher degree of fibrosis according to elastography. Significant relationship of elevated levels of HBA1C with significant fibrosis was detected, measured both by NAFLD score and by elastography. Conclusions: Hepatic steatosis present in patients with diabetes mellitus was mainly mild to moderate with prevalence of mild fibrosis, the degree of significant fibrosis was associated with increased liver echogenicity, diffuse liver pattern, severe degree of steatosis by ultrasound and high levels of hemoglobin. glycosylated(AU)

Prognosis of post-transplant diabetes mellitus in recipients with steatotic donor livers / 中华肝胆外科杂志

Objective To study the risk factors and prognosis of post-transplant diabetes mellitus (PTDM) in recipients with steatotic donor livers.Method The clinical data of 182 patients who underwent liver transplantation from donors with liver steatosis in Tianjin First Central Hospital from June 2002 to December 2010 were retrospectively analyzed.There were sixteen patients with PTDM and one hundred sixtysix without PTDM.The clinical data of these patients were compared and the risk factors were evaluated by COX regression analysis.The 1-,3-,5-year cumulative survival rates were analyzed after liver transplantation.Result The variables which included sex,pretransplant serum creatinine level,model for end-stage liver disease (MELD) score,intraoperative red blood cell transfusion,and post-transplant biliary complications were significantly different between the two groups.Multivariate Cox regression analysis showed that living-donor,pretransplant fasting blood glucose and post-transplant biliary complications could affect the survival time of patients in PTDM group.The 1-,3-and 5-year cumulative survival rates in the PTDM group were 81.3％,68.8％ and 62.5％,which were significantly lower than those in the non-PTDM group (95.2％,86.1％ and 80.7％ respectively,P ＜ 0.05).Conclusions Living-donation,pretransplant fasting blood glucose and post-transplant biliary complications had a worse prognosis in the PTDM group.A comparatively better long-term survival after liver transplantation can be achieved by reducing the risk factors and the occurrence of PTDM.

Dihydroquercetin ameliorates alcoholic liver steatosis through P2x7R-NLRP3 inflammasome pathway / 中国药理学与毒理学杂志

OBJECTIVE Dihydroquercetin(TAX)is the most abundant dihydroflavone found in on-ions,milk thistle and Douglas fir bark.We investigated whether TAX could inhibit the lipid accumulation in alcoholic liver steatosis in vivo and in vitro.METHODS An in vivo model was established by intragas-trically treating mice with ethanol,and an in vitro model was created by treating HepG2 cells with etha-nol.RESULTS TAX regulated Sterol Regulatory Element-binding Protein-1(SREBP1)and Acetyl CoA Carboxylase (ACC) expression via elevating Liver Kinase B1 (LKB1)/ AMP-activated Kinase (AMPK) phosphorylation. Also, TAX upregulated SIRT1 expression, which suppressed by ethanal intake. Suppression of Purinergic 2X7 receptor (P2x7R), nucleotide-binding oligomerization domain-like re-ceptor protein 3(NLRP3)and Cysteine protease-1(caspase-1)cleavage by TAX resulted in the inhibi-tion of Interleukin-1β(IL-1β) production and release. Additionally, TAX reduced lipogenesis and pro-moted lipid oxidation via the regulation of AMPK and ACC in ethanol-treated steatotic HepG2 cell.TAX downregulated IL-1β cleavage response to Lipopolysaccharides (LPS) plus adenosine triphosphate(ATP) stimulation in HepG2 cells. P2x7R deficiency attenuated lipid accumulation with increasing AMPK activity and decreasing SREBP1 expression in ethanol-treated HepG2 cells.CONCLUSION Our data showed that TAX exhibited the inhibitory properties on lipogenesis and hepatoprotective ca-pacity,indicating that TAX has therapeutic potential for preventing alcoholic liver steatosis.

Liver biopsy may facilitate pancreatic graft evaluation: positive association between liver steatosis and pancreatic graft adipose infiltration

OBJECTIVES: The number of pancreatic transplants has decreased in recent years. Pancreatic grafts have been underutilized compared to other solid grafts. One cause of discard is the macroscopic appearance of the pancreas, especially the presence of fatty infiltration. The current research is aimed at understanding any graft-related association between fatty tissue infiltration of the pancreas and liver steatosis. METHODS: From August 2013 to August 2014, a prospective cross-sectional clinical study using data from 54 multiple deceased donor organs was performed. RESULTS: Micro- and macroscopic liver steatosis were significantly correlated with the donor body mass index ([BMI]; p=0.029 and p=0.006, respectively). Positive gamma associations between pancreatic and liver macroscopic and microscopic findings (0.98; confidence interval [CI]: 0.95-1 and 0.52; CI 0.04-1, respectively) were observed. Furthermore, comparisons of liver microscopy findings showed significant differences between severe versus absent (p<0.001), severe versus mild (p<0.001), and severe versus moderate classifications (p<0.001). The area under the receiver operating curve was 0.94 for the diagnosis of steatosis by BMI evaluation using a cut-off BMI of 27.5 kg/m2, which yielded 100% sensitivity, 87% specificity, and 100% negative predictive value. CONCLUSIONS: We observed a positive association of macroscopic and microscopic histopathological findings in steatotic livers with adipose infiltration of pancreatic grafts.

Research advances on effects of ursolic acid and oleanolic acid against hepatic steatosis and fibrosis / 药物评价研究

Anti-oxidation of ursolic acid and oleanolic acid antagonizes oxidative stress-induced lipid peroxidation,inflammatory injury,steatosis,and fibrosis in liver tissue.Ursolic acid and oleanolic acid could block static state hepatic stellate cells activation and proliferation,and promote active state hepatic stellate cells apoptosis,thus decrease expression of collagen,and increase decomposition of extracellular matrix,to produce the effect in prevention and treatment of hepatic fibrosis by obstruction of JAK2-STAT3 signal transduction to inhibit NOX activation.Ursolic acid and oleanolic acid induce expression of detoxification enzymes and effiux transporters to reduce serum levels of bile acids and bilirubin,and liver levels of bile acids in cholestatic animal,thus ameliorating cholestatic liver injury and fibrosis.Ursolic acid and oleanolic acid inhibit occurrence and development of hepatic steatosis via decreasing hyperlipidemia to inhibit lipid out of liver accumulating to liver,inhibiting hepatic lipid synthesis,and improving lipid metabolism.

Effect of dietary supplementation with olive and sunflower oils on lipid profile and liver histology in rats fed high cholesterol diet

Objective To compare the effects of high-monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) against the metabolic disorders elicited by a high-cholesterol diet (HC) in rats. Methods Using in vivo dietary manipulation, rats were fed with different diets containing 4% soybean oil (cholesterol free diet) and 1% HC containing 12% olive oil (HC + OO) enriched with MUFA and 12% sunflower oil (HC + SO) enriched with PUFA for 60 d. Serum lipid levels and hepatic steatosis were evaluated after the treatment period. Results Comparatively, rats treated with HC + OO diet experienced a decrease in the serum LDL-C, VLDL-C and CT levels compared to those fed with HC + SO diet (P < 0.05). Otherwise, HC + OO provoked significant microvesicular steatosis situated in the hepatic acinar zone 1. Conclusions HC + OO diet has high absorption velocity in the acinar zone 1 of liver compared to the HC + SO diet. Based on this, the reduction of the LDL-C, VLDL-C and CT serum levels in the animals treated with HC + OO diet may have been caused by the delay in the FA release to the blood.

Effect of dietary supplementation with olive and sunflower oils on lipid profile and liver histology in rats fed high cholesterol diet

OBJECTIVE@#To compare the effects of high-monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) against the metabolic disorders elicited by a high-cholesterol diet (HC) in rats.@*METHODS@#Using in vivo dietary manipulation, rats were fed with different diets containing 4% soybean oil (cholesterol free diet) and 1% HC containing 12% olive oil (HC + OO) enriched with MUFA and 12% sunflower oil (HC + SO) enriched with PUFA for 60 d. Serum lipid levels and hepatic steatosis were evaluated after the treatment period.@*RESULTS@#Comparatively, rats treated with HC + OO diet experienced a decrease in the serum LDL-C, VLDL-C and CT levels compared to those fed with HC + SO diet (P < 0.05). Otherwise, HC + OO provoked significant microvesicular steatosis situated in the hepatic acinar zone 1.@*CONCLUSIONS@#HC + OO diet has high absorption velocity in the acinar zone 1 of liver compared to the HC + SO diet. Based on this, the reduction of the LDL-C, VLDL-C and CT serum levels in the animals treated with HC + OO diet may have been caused by the delay in the FA release to the blood.

Magnetic Resonance Elastography and Other Magnetic Resonance Imaging Techniques in Chronic Liver Disease: Current Status and Future Directions

Recent advances in the noninvasive imaging of chronic liver disease have led to improvements in diagnosis, particularly with magnetic resonance imaging (MRI). A comprehensive evaluation of the liver may be performed with the quantification of the degree of hepatic steatosis, liver iron concentration, and liver fibrosis. In addition, MRI of the liver may be used to identify complications of cirrhosis, including portal hypertension, ascites, and the development of hepatocellular carcinoma. In this review article, we discuss the state of the art techniques in liver MRI, namely, magnetic resonance elastography, hepatobiliary phase MRI, and liver fat and iron quantification MRI. The use of these advanced techniques in the management of chronic liver diseases, including non-alcoholic fatty liver disease, will be elaborated.

Reducción de la esteatosis hepática, insulino resistencia y pérdida de la defensa antioxidante en ratones alimentados con dieta alta en grasa suplementados con AGPICL n-3 más aceite de oliva extra virgen / Reduction of hepatic steatosis, insulin resistance and loss of antioxidant defense in high fat diet fed mice suplemented with n-3 LCPUFA more extra virgin olive oil

Non-alcoholic fatty liver disease (NAFLD) is directly associated with insulin resistance and oxidative stress. In NAFLD is established a reduction in n-3 LCPUFA (EPA + DHA) levels and hepatic activity of transcription factor PPAR-alpha. EPA and DHA inhibit lipogenesis and stimulate fatty acid oxidation in the liver. Extra virgin olive oil (EVOO) has important antioxidant properties. This study evaluated the prevention of insulin resistance and prevention of depletion of hepatic antioxidant defense inC57BL/6J mice fed high-fat diet (HFD), supplemented with n-3 LCPUFA plus EVOO. HFD generated insulin resistance and hepatic steatosis, together with significant reduction in i) n-3 LCPUFA hepatic levels, ii) DNA binding activity of PPAR-alpha, iii) activity of antioxidant enzymes (catalase and superoxide dismutase), respect to control group (fed with control diet). Supplementation with n-3 LCPUFA plus EVOO prevent development insulin resistance and attenuate increased of fat in liver (p < 0.05), together with a normalization of i) DNA binding activity of PPAR-á, ii) activity of antioxidant enzymes (catalase and superoxide dismutase) and iii) reducing depletion of n-3 LCPUFA levels in liver tissue, compared to the control group (p < 0.05). Supplementation with n-3 LCPUFA plus EVOO reduced hepatic steatosis and prevent development of insulin resistance, along with preserving the antioxidant defense in liver. Projecting the use of this mixture of AGPICL n-3 plus EVOO as a potential treatment of NAFLD.

Impact of hepatic steatosis on liver surgery / 中华肝胆外科杂志

Objective To study the impact of hepatic steatosis on the safety and prognosis of patients who received partial hepatectomy for liver cancer.Methods A retrospective study was conducted on 338 patients who received hepatic resection for liver carcinoma.Results There were 273,44 and 21 patients who had a normal liver,mild steatosis and moderate-to-severe steatosis respectively.There was a significantly higher body mass index in the steatosis group (P ＜ 0.05).The operative time,blood loss,transfusion rate,postoperative hospital stay and ICU stay increased in patients with moderate-severe fatty liver (P ＜ 0.05).Conclusion Mild steatosis had little impact on partial hepatectomy.Moderate-to-severe hepatic steatosis was associated with increased blood loss and perioperative morbidity.

Genome-Wide Analysis of DNA Copy Number Changes in Liver Steatosis.

Aims: Liver steatosis is the most common benign form of non-alcoholic fatty liver disease. It might be a risk factor for hepatocellular carcinoma, either (i) by causing fibrosis, which highly predisposes to hepatoma, or (ii) by being an early precursor of carcinoma, although it is usually considered not to be pre-neoplastic. We investigated the genomic profile of liver samples from patients with fatty liver disease. Study Design & Methodology: Copy number variation was investigated by array-CGH, using the Human Genome 244K catalogue array (Agilent Technologies), and changes validated by quantitative polymerase chain reaction analysis. Results: The analysis of liver biopsies from 17 patients, 10 of whom had histological diagnosis of non-alcoholic fatty liver disease, showed differences in the type of variants in patients with steatosis compared to those without steatosis at several chromosome bands, including 3q29, 6p2, 11q11 and 22q11. Conclusion: The genomic copy number changes we have demonstrated suggest that genomic structural variations may be associated with the pathogenesis or the evolution of steatosis.

Regulatory effect of hydrogen sulfide on adiponectin secretion in fatty liver adipocytes / 中华临床营养杂志

Objective To observe whether hydrogen sulfide modulates adipocytes to secrete adiponectin.Methods Thirty-two male SD rats were randomly divided into normal diet group (n =8),high-fat diet group (n =8),high-fat + cysteine group (n =8),and high-fat + propargylglycine (cystathionine-γ-lyase inhibitor) group (n =8).The fatty liver animal model was established using the high fat diet; meanwhile,L-cysteine was applied to the animals to produce endogenous hydrogen sulfide and propargylglycine to inhibit the production of endogenous hydrogen sulfide.Fatty degeneration of the hver of animals and plasma within the adiponectin concentration was observed after 8 weeks.The omental adipose tissues were excluded and digested using collagenase Ⅰ to isolate fat cells.Sodium hydrosulfide and propargylglycine was applied to stimulate the cells in vitro for 7 days before the detection of the cell supernatant adiponectin content.Results Liver steatosis was established after highfat diet for eight weeks.Steatosis was significantly extenuated after the application of L-cysteine and aggravated by propargylglycine.Plasma hydrogen sulfide and adiponectin levels in fat diet group animals were (21.13 ± 7.06) mmol/L and (3.16 ± 1.15) mg/L respectively,which significantly decreased when compared with the normal diet group with the levels of hydrogen sulfide (29.13 ± 13.06) mmol/L and adiponectin (8.98 ± 2.84) mg/L (P=0.0229,P=0.0062).Hydrogen sulfide [(35.47 ±9.04) mmol/L] and adiponectin [(6.54 ± 1.38) mg/L] levels in the high fat + cysteine group significantly increased (P =0.0032,P =0.0131).However,hydrogen sulfide [(16.65 ±8.79) mmol/L] and adiponectin [(2.50±0.91) mg/L] in high fat + propargylglycine group were significantly decreased (P =0.0191,P =0.0021).Hydrogen sulfide was not significantly differem in the supematam of adipocyte isolated from normal diet group [(26.77 ± 12.65) mmol/L] and from high-fat diet group [(28.76 ±9.09) mmol/L] (P =0.0927),but that in the sodium hydrosulfide and propargylglycine ceils supematants significandy either increased or decreased (P =0.0000,P =0.0000).Adiponectin in the supematants of high-fat diet group and normal diet group adipocyte showed no significant difference [(4.21 ± 1.61) mg/L vs (4.49 ± 1.09) mg/L,P =0.1076)].The levels of adiponectin in sodium hydrosulfide and propargylglycine cell supernatants increased and decreased respectively than that in higher fat diet group cells [(5.77 ±0.86) mg/L vs (4.21 ±1.61) mg/L,P =0.0094; (3.01 ±1.26) mg/L vs (4.21 ± 1.61) mg/L,P =0.0108].Conclusion Hydrogen sulfide promotes adipocytes to secrete adiponectin.