Lychee (Litchi chinensis Sonn) peel flour: effects on hepatoprotection and dyslipidemia induced by a hypercholesterolemic diet

ABSTRACT Dyslipidemias are associated with the incidence of cardiovascular diseases, obesity, diabetes, hypertension and hepatic steatosis, being the cause of morbidity and mortality. This study investigated the effects of lychee peel flour (PF) on serum levels of total cholesterol (TC), low-density lipoprotein (LDL-c), triacylglycerols (TAG) and various parameters related to obesity, in rats fed a hypercholesterolemic diet. Therefore, 20 male rats were used. In the first 21 days, the animals were fed a hypercholesterolemic diet, except for control group. In the following 21 days, their diets were modified, and they received a standard diet (Control); hypercholesterolemic (Hyper); hypercholesterolemic + 5% PF (PF5) and hypercholesterolemic + 10% PF (PF10). The results revealed that PF intake attenuated weight gain, reduced body mass index, glucose and the levels of TAG, TC, LDL-c, hepatic enzymes and leptin, besides the percentage of hepatic lipids, liver lipid peroxidation and frequency of severe steatosis. Histological studies of the aorta did not show the formation of the atheromatous plaque. These results reinforce its potential to reduce the risk of diseases associated with obesity.

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.

Clinical and laboratory characteristics associated with dyslipidemia and liver steatosis in chronic HBV carriers

Introduction Chronic hepatitis B virus (HBV) infection and liver steatosis (LS) are the most common causes of chronic liver disease, and their coexistence is frequently observed in clinical practice. Although metabolic syndrome is the main cause of LS, it has not been associated with HBV infection. The aims of this study were to describe the lipid profile and prevalence of LS among HBV carriers and to identify the characteristics associated with LS in this group. Methods This retrospective cross-sectional study included hepatitis B surface antigen (HBsAg)-positive patients evaluated during 2011 and 2012. Results Of the 83 patients included, the mean age was 46.4±12.5 years, 53% were men, and 9.1% were hepatitis B e antigen (HBeAg) -positive. These patients exhibited the following lipid profile: total cholesterol = 175.4±38.8mg/dL, low-density lipoprotein (LDL) = 113.0±32.7mg/dL, and triglycerides = 91.1±45.2mg/dL. Their fasting glucose was 95.3±14.5g/dL, and fasting insulin was 6.1±5.9µIU/mL. Liver steatosis was observed on abdominal ultrasound in 11.3% of individuals. Factors associated with the presence of LS included higher levels of total cholesterol, prothrombin activity, fasting insulin, and body mass index (BMI) as well as lower levels of aspartate aminotransferase (AST). Conclusions These findings suggest that LS in patients with chronic HBV appears to be a consequence of metabolic alterations and insulin action rather than of viral factors. .

Esteatosis hepática, grasa visceral y alteraciones metabólicas, en individuos con sobrepeso/obesidad aparentemente sanos / Hepatic steatosis, visceral fat and metabolic alterations in apparently healthy overweight/obese individuals

La observación clínica indica que muchos obesos no presentan alteraciones metabólicas importantes, por lo que el objetivo del presente estudio fue comprobar si el sobrepeso/obesidad (SP/OB) simple, no asociado a otros factores de riesgo, se acompañaba de alteraciones metabólicas; o si estaba presente el fenómeno conocido como “paradoja de la obesidad”. A 30 individuos aparentemente sanos de Maracaibo, Venezuela, entre 20 y 59 años de edad, e índice de masa corporal (IMC) superior a 25 kg/m², y a un grupo control de 11 individuos con IMC inferior a 25 kg/m², se les realizó una historia clínica, medida de parámetros antropométricos, determinaciones basales de glicemia, insulina y lípidos, medición ultrasonográfica para esteatosis hepática y ultrasonografía e impedancia bioeléctrica para estimar la grasa visceral. El estudio demostró que solo en un tercio de los individuos con SP/OB, con elevado IMC y circunferencia de cintura (CC), se encontraron concentraciones elevadas de insulina, HOMA-IR y triglicéridos. A pesar de ello, la presencia de esteatosis hepática fue muy elevada (91%) en el grupo SP/OB, si se compara con 9% en el grupo control. La grasa visceral, en el grupo control, estuvo asociada a la CC y a la glicemia; sin embargo, no se relacionó con el IMC, insulina, HOMA-IR o HDLc; mientras que en el grupo SP/OB, aunque estadísticamente elevada en relación al grupo control, reveló una pérdida de estas asociaciones. Los resultados resaltan la importancia de investigar más la presencia de esteatosis hepática en los individuos con SP/OB, que la estimación de la grasa visceral, para identificar sujetos con alto riesgo cardiometabólico.

Clinical observation indicates that many obese individuals do not display important metabolic alterations. Consequently, the objective of this study was to establish whether simple obesity, non concurrent with other important risk factors, was associated with metabolic alterations; or if the phenomenon known as “obesity paradox” was present. A clinical history, measurements of anthropometric and metabolic parameters and estimation of hepatic steatosis and visceral fat, were determined in 30, apparently healthy, individuals from Maracaibo, Venezuela, between 20 and 59 years of age and a body mass index (BMI) above 25 kg/m²,and compared to a lean control group of 11 individuals with BMI less than 25 kg/m². The study demonstrated that only one third of overweight/obese individuals (OW/OB), with high body mass index (BMI) and waist circumference (WC), presented elevated values of insulin, HOMA-IR and triglycerides. Nevertheless, the presence of hepatic steatosis was elevated in the OW/OB group (91%) vs. 9% in the control group. The visceral fat in the lean control group was associated with both, WC and glycemia; however, it was not related to the BMI or insulin, HOMA-IR and HDLc. The visceral fat in the OW/OB group, although elevated in relation to the lean group, revealed a loss of these associations. In the OW/OB it was the BMI that was associated with insulin and HOMA-IR. The results emphasize the importance of investigating for the presence of hepatic steatosis, rather than visceral fat, in individuals with OW/OB, to identify subjects with high cardiometabolic risk.

Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease / Exenatide melhora o diabetes tipo 2 de ocorrência concomitante com doença hepática gordurosa não alcoólica

OBJECTIVE: To investigate the effects of exenatide on blood glucose, body weight and hepatic enzymes in patients with type 2 diabetes mellitus (T2DM) and concomitant non-alcoholic fatty liver disease (NAFLD). SUBJECTS AND METHODS: One hundred and seventeen patients with T2DM and NAFLD were randomly divided into exenatide group and metformin group. Patients were treated with exenatide and metformin, respectively, for 12 weeks. RESULTS: After 12 weeks of treatment, body weight, body mass index (BMI), waist-to-hip ratio, HbA1c, FPG, 2-h PPG, ALT, AST, γ-GT, and hs-CRP were significantly reduced, and the AST/ALT ratio and adiponectin were markedly increased in both groups. BMI, waist-to-hip ratio, 2-h PPG, ALT, AST, γ-GT, and hs-CRP were markedly lower, and AST/ALT ratio and adiponectin in the exenatide group were dramatically higher than in the metformin group. CONCLUSION: Compared with metformin, exenatide is better to control blood glucose, reduces body weight and improves hepatic enzymes, attenuating NAFLD in patients with T2DM concomitant with NAFLD.

OBJETIVO: Investigar os efeitos do exenatide sobre a glicose sérica, peso corporal e enzimas hepáticas em pacientes com diabetes melito tipo 2 (T2DM) e doença hepática gordurosa não alcoólica (DHGNA). SUJEITOS E MÉTODOS: Um total de 117 pacientes com T2DM e DHGNA foi aleatoriamente separado em dois grupos, um tratado com exenatide e um tratado com metformina. Os pacientes foram tratados por 12 semanas. RESULTADOS: Após 12 semanas de tratamento, o peso corporal, índice de massa corporal (IMC), relação cintura-quadril, HbA1c, FPG, glicose pós-prandial, ALT, AST, γ-GT e proteína C-reativa foram significativamente reduzidos, e a relação AST/ALT e a adiponectina aumentaram marcadamente nos dois grupos. O IMC, relação cintura-quadril, glicose pós-prandial, ALT, AST, γ-GT e proteína C-reativa foram marcadamente menores, e a relação AST/ALT e a adiponectina foram dramaticamente mais altas no grupo tratado com exenatide do que no grupo tratado com metformina. CONCLUSÃO: Comparado com a metformina, o exenatide controla melhor a glicose sérica, reduz o peso corporal e melhora as enzimas hepáticas, atenuando a DHGNA em pacientes com T2DM de ocorrência concomitante com a DHGNA.

Relação entre ácido úrico e os componentes da síndrome metabólica e esteatose hepática não alcoólica em crianças e adolescentes com sobrepeso ou obesidade / Association of uric acid levels with components of metabolic syndrome and non-alcoholic fatty liver disease in overweight or obese children and adolescents

OBJETIVO: Verificar a relação entre a concentração de ácido úrico sérico de acordo com a presença ou não de esteatose hepática não alcoólica e/ou síndrome metabólica (SM) em crianças e adolescentes com sobrepeso ou obesidade. MÉTODOS: Estudo transversal desenvolvido no período de abril/2009 a março/2010, incluindo 129 crianças e adolescentes atendidos no Centro de Obesidade Infantil. Foi realizada antropometria, aferição da pressão arterial, dosagem dos exames laboratoriais e o diagnóstico de esteatose hepática por exame ultrassonográfico. Para o diagnóstico de SM, foram utilizados os critérios da National Cholesterol Education Program/Adult Treatment Panel III adaptados para faixa etária. Para avaliação da associação do ácido úrico com os grupos, foi realizado o teste do Qui-quadrado ou Fisher, adotando-se o intervalo de confiança de 95%. Para comparação de médias, utilizou-se o ANOVA One Way. Para o ajuste das variáveis foi utilizada a regressão logística múltipla. Os dados foram processados no SPSS versão 17. RESULTADOS: Níveis elevados de ácido úrico associaram-se significativamente à adolescência, SM e pressão arterial sistólica. O maior quartil de ácido úrico apresentou valores médios significativamente mais elevados de índice de massa corpórea, circunferência abdominal, pressão arterial sistólica, pressão arterial diastólica, triglicerídeos, colesterol total e HOMA-IR, e menor média do colesterol HDL. No modelo final só permaneceram associadas aos níveis de ácido úrico a faixa etária e a presença de síndrome metabólica. CONCLUSÕES: Níveis elevados de ácido úrico estiveram associados à síndrome metabólica e à adolescência, o que não foi observado com a esteatose hepática.

OBJECTIVE: To investigate the association between serum uric acid concentration according to the presence or absence of non-alcoholic fatty liver disease (NAFLD) and/or metabolic syndrome (MS) in overweight or obese children and adolescents. METHODS: This was a cross-sectional study conducted from April of 2009 to March of 2010, including 129 children and adolescents treated at the Center for Childhood Obesity. Anthropometric data, blood pressure measurements, and laboratory test results were obtained, and NAFLD diagnosis was made by ultrasound. The diagnosis of MS was made using the criteria of the National Cholesterol Education Program/Adult Treatment Panel III, adapted to age range. The chi-squared test or or Fisher's test were used to evaluate the association of uric acid with the groups, with a 95% confidence interval. One way analysis of variance (ANOVA) was used for comparison of means. Multiple logistic regression was used for adjustment of variables. The data were analyzed with the Statistical Package for Social Sciences (SPSS), release 17. RESULTS: High levels of uric acid were significantly associated with adolescence, MS, and systolic blood pressure. The highest quartile of uric acid showed significantly higher values of body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, triglycerides, total cholesterol, and homeostatic model assessment index (HOMA-IR), and lower mean values of HDL cholesterol. In the final model, only age range and the presence of MS remained associated with uric acid levels. CONCLUSIONS: High levels of uric acid were associated with MS and adolescence, which was not observed with NAFLD.

Effects of D-002, a mixture of high molecular weight beeswax alcohols, on patients with nonalcoholic fatty liver disease

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is intimately related to insulin resistance and ranges from a benign course to liver fibrosis and cirrhosis. NAFLD management mainly involves dietary modification and weight loss. Although no fully successful pharmacological intervention is available, alternative therapies to treat NAFLD have shown promising results. Experimental studies have shown that D-002, a mixture of beeswax alcohols with antioxidant effects, is hepatoprotective. The aim of this study was to investigate the efficacy and safety of D-002 in patients with NALFD. METHODS: Fifty patients with NAFLD were randomized to receive a placebo or D-002 (100 mg/day) for 24 weeks. The primary endpoint was a significant ultrasonography-detected reduction of liver fat infiltration versus a placebo. Secondary endpoints were decreases in the homeostatic model assessment (HOMA) index, insulin levels, serum liver enzymes, increases in plasma total antioxidant status (TAS) and improved clinical symptoms versus the placebo recipients. RESULTS: At randomization, all indicators were comparable in both groups. At study completion, seven (28.0%) D-002-patients, but none of the placebo recipients, exhibited a normal liver echo pattern on ultrasonography (p < 0.01). Also, D-002 significantly reduced (p < 0.01 vs. baseline and placebo) the HOMA index and insulin levels and increased the TAS, but did not affect other parameters. The proportion of D-002-patients (12/25, 48.0%) showing symptom improvement was higher (p < 0.001) than that of the placebo group (1/25, 4.0%). The treatment was safe and well tolerated. Three patients in each group withdrew from the study. CONCLUSIONS: D-002 (100 mg/day) improved ultrasonographic findings, indicators of insulin resistance, plasma TAS and clinical evolution on NAFLD patients. Further studies, however, are needed to confirm these results.

AssociaþÒo entre índice glicÛmico e carga glicÛmica dietéticos e doenþa hepática gordurosa nÒo alcoólica em idosos / [Relationship between dietary glycemic index and glycemic load and nonalcoholic fatty liver disease in elderly].

OBJECTIVE: To investigate if there is an association between glycemic index (GI) and glycemic load (GL) of the diet and the presence of nonalcoholic fatty liver disease (NAFLD) in the elderly. METHODS: Retrospective study, composed of 229 patients seen at the Outpatient Clinic of Arterial Hyperten- sion in a public hospital, 103 carriers and 126 noncarriers of NAFLD. Food intake was analyzed to GI and GL. RESULTS: We found a high prevalence of inadequate dietary GI, with an average of 62.0 +/- 6.3 among patients with NAFLD and 62.5 +/- 6.5 among patients without NAFLD. The same occurred with the GL, 101.7 +/- 33.3 and 101.4 +/- 40.2, respectively, between carriers and noncarriers of the disease. There was no statistical difference between the values of GI and GL found in the diet of patients with and without NAFLD. CONCLUSION: In the evaluated group there was no association between GI and GL dietetic with NAFLD, but the findings put all of the patients at higher risk for the development of chronic diseases.

Relação entre o estado nutricional de vitamina a e a regressão da esteatose hepática após gastroplastia em Y- de- Roux para tratamento da obesidade classe III / Relationship of the nutritional status of vitamin a and the regression of hepatic steatosis after Roux-en-Y gastric bypass surgery for treatment of class III obesity

RACIONAL: A vitamina A participa de várias funções primordiais no organismo humano e as suas concentrações séricas podem estar diminuídas nas doenças crônicas não transmissíveis. OBJETIVO: Avaliar a relação entre o estado nutricional da vitamina A, e a regressão da esteatose hepática em indivíduos submetidos à gastroplastia em Y-de-Roux para tratamento da obesidade classe III. MÉTODOS: Foram estudados 30 pacientes obesos classe III, de ambos os sexos, com esteatose hepática, submetidos à gastroplastia em Y-de-Roux. Seis meses após a operação, os pacientes foram submetidos à ultrassonografia abdominal e distribuídos em dois grupos: grupo 1 - pacientes com esteatose detectada na ultrassonografia e grupo 2 - pacientes sem esteatose detectada na ultrassonografia. No pré-operatório e seis meses após a operação foram realizadas análises antropométricas e exames bioquímicos: insulina basal, glicemia, Homeostasis Model Assessment Index (HOMA IR), colesterol, HDL, LDL, triglicerídeos, AST, ALT, Gama-GT, albumina, bilirrubina total, retinol, e beta caroteno. RESULTADOS: A média de perda de peso foi de 35,05 + 10,47 (p<0,01) e a diminuição no Índice de Massa Corporal (IMC) de 11,6 + 4,99 Kg/m² (p<0,01). Após seis meses, todos os exames bioquímicos apresentaram diminuição significativa das concentrações (p<0,05). O grupo 2 (sem esteatose) apresentou no pós-operatório, concentrações significativamente inferiores (p<0,05), nas variáveis: peso, IMC, AST, ALT, gama GT, HOMA IR, insulina basal. As concentrações séricas de albumina apresentaram valores médios aproximados, sem diferença significativa nos dois tempos avaliados. Observaram-se concentrações séricas mais elevadas de retinol e de β-caroteno e redução menor em relação as concentrações do pré-operatório nos pacientes sem esteatose, porém sem diferença estatística. CONCLUSÃO: Adequado estado nutricional de vitamina A pode contribuir na regressão da esteatose hepática em pacientes submetidos à Gastroplastia em Y-de-Roux para tratamento da obesidade classe III.

BACKGROUND: Vitamin A participates in several essentials functions in the human body and their serum concentrations may be decreased in non-transmissible diseases. AIM: To assess the relationship of the nutritional status of Vitamin A through the serum concentrations of retinol and beta carotene, with regression of hepatic steatosis in individuals who undergone Roux-en-Y gastric bypass surgery for treatment of class III obesity. METHODS: Were included 30 individuals, male and female, submitted to Roux-en-Y gastric bypass for treatment of class III obesity, who were diagnosed through an abdominal ultrasonography as presenting hepatic steatosis. From the result of an ultrasonography screened six months after the surgical procedure those subjects were divided into two groups: group 1 - patients with steatosis detected in the ultrasonography (16 subjects) and group 2 - patients without steatosis detected in the ultrasonography (14 subjects). Before and six months after the surgery, were carried out anthropometrical analyses and biochemical exams (basal insulin, glicemy, Homeostasis Model Assessment Index (HOMA IR), cholesterol, HDL, LDL, triglycerides, AST, ALT, Gamma-GT, albumin, total bilirubin, retinol, and beta carotene. RESULTS: The individuals presented an average weight loss of 35.05 + 10.47 (p<0.01) and a decrease in the Body Mass Index (BMI) of 11.6 + 4.99 Kg/m² (p<0.01). After six months, all the biochemical exams presented a significant decrease in their basal concentrations (p<0.05). In the post-operative period the group 2 (without steatosis) presented concentrations significantly lower (p<0.05) in the following variables: weight, BMI, AST, ALT, Gamma-GT, HOMA IR, basal insulin. The albumin serum concentrations presented close average values, with no significant difference in the two periods evaluated. In the assessment of retinol and beta carotene, higher serum concentrations and a small decrease in relation to the concentrations of the pre-operative period in the group without steatosis were observed, however, no statistical difference was found. CONCLUSION: An adequate nutritional status of vitamin A might contribute in the improvement of the hepatic esteatosis after Roux-en-Y gastric bypass for class III obesity treatment.

Associação entre doença hepática gordurosa não alcoólica e marcadores de lesão/função hepática com componentes da síndrome metabólica em indivíduos obesos classe III / Association between non-alcoholic fatty liver disease and liver function/injury markers with metabolic syndrome components in class III obese individuals

OBJETIVO: Investigar a associação entre doença hepática gordurosa não alcoólica (DHGNA) e os marcadores de lesão e função hepática com os componentes da síndrome metabólica (SM) em indivíduos obesos classe III. MÉTODOS: A população estudada foi constituída por 144 pacientes com obesidade classe III (IMC > a 40 kg/m²). A SM foi identificada segundo o critério do NCEP ATP III, por meio da determinação do perfil lipídico, glicemia e insulina basal. Foram quantificados ainda os marcadores de função e lesão hepática. A resistência à insulina (RI) foi verificada pelo índice HOMA-IR e o diagnóstico da DHGNA por ressonância magnética. Os cálculos estatísticos foram realizados pelo programa estatístico SPSS na versão 13.0. A associação foi verificada pelo teste Mann-Whitney e qui-quadrado, com nível de significância de 5%. RESULTADOS: Foi encontrada associação significativa entre o diagnóstico de SM e DHGNA (χ² = 6,84; p = 0,01). Quanto aos componentes diagnósticos para SM, constatou-se associação positiva e significativa entre HDL-c (p = 0,05), circunferência da cintura (p < 0,05) e hipertensão arterial (χ² = 4,195; p = 0,041) com a DHGNA. O índice HOMA-IR (p < 0,001) também apresentou associação positiva com a doença hepática. CONCLUSÃO: Constatouse associação positiva e significativa entre DHGNA e componentes da SM em indivíduos obesos classe III, sugerindo a necessidade e importância do monitoramento desses componentes para rastreamento da DHGNA.

OBJECTIVE: To investigate the association between non-alcoholic fatty liver disease (NAFLD) and liver function/injury markers with components of metabolic syndrome (MS) in class III obese individuals. METHODS: The study population consisted of 144 patients with class III obesity (body mass index [BMI] > 40 kg/m²). MS was diagnosed according to the National Cholesterol Education Program - Adult Treatment Panel III (NCEP ATP III) criteria, by determining the lipid profile, blood glucose and basal insulin. Liver function/injury markers were also quantified. Insulin resistance (IR) was measured by HOMA-IR and NAFLD diagnosis was established by magnetic resonance imaging (MRI). Statistical calculations were performed by SPSS version 13.0. The association was assessed by the Mann-Whitney and Chi-square tests, with a level of significance set at 5%. RESULTS: There was a significant association between the diagnosis of MS and NAFLD (χ² = 6.84, p = 0.01). As for the diagnostic components of MS, there was a positive and significant association between HDL-C (p = 0.05), waist circumference (p < 0.05) and hypertension (χ² = 4.195, p = 0.041) with NAFLD. HOMA-IR (p < 0.001) also showed a positive association with liver disease. CONCLUSION: A positive and significant association between NAFLD and components of metabolic syndrome in class III obese individuals was observed, suggesting the need and importance of monitoring these components for NAFLD screening.

Peroxisome proliferator-activated receptor delta agonist attenuates hepatic steatosis by anti-inflammatory mechanism

Although peroxisome proliferator receptor (PPAR)-alpha and PPAR-gamma agonist have been developed as chemical tools to uncover biological roles for the PPARs such as lipid and carbohydrate metabolism, PPAR-delta has not been fully investigated. In this study, we examined the effects of the PPAR-delta agonist GW0742 on fatty liver changes and inflammatory markers. We investigated the effects of PPAR-delta agonist GW0742 on fatty liver changes in OLETF rats. Intrahepatic triglyceride contents and expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and monocyte chemo-attractant protein-1 (MCP-1) and also, PPAR-gamma coactivator (PGC)-1alpha gene were evaluated in liver tissues of OLETF rats and HepG2 cells after GW0742 treatment. The level of TNF-alpha and MCP-1 was also examined in supernatant of Raw264. 7 cell culture. To address the effects of GW0742 on insulin signaling, we performed in vitro study with AML12 mouse hepatocytes. Rats treated with GW0742 (10 mg/kg/day) from 26 to 36 weeks showed improvement in fatty infiltration of the liver. In liver tissues, mRNA expressions of TNF-alpha, MCP-1, and PGC-1alpha were significantly decreased in diabetic rats treated with GW0742 compared to diabetic control rats. We also observed that GW0742 had inhibitory effects on palmitic acid-induced fatty accumulation and inflammatory markers in HepG2 and Raw264.7 cells. The expression level of Akt and IRS-1 was significantly increased by treatment with GW0742. The PPAR-delta agonist may attenuate hepatic fat accumulation through anti-inflammatory mechanism, reducing hepatic PGC-1alpha gene expression, and improvement of insulin signaling.

Gluco-lipidic indices in treated hypothyroidism associated with nonalcoholic fatty liver disease / Índices glicolipídicos no hipotireoidismo tratado associado à doença hepática gordurosa não-alcoólica

CONTEXT: Thyroid hormones may interfere with regulation of lipid and carbohydrate metabolism as well as with severity of nonalcoholic fatty liver disease (NAFLD), however results are still debated. OBJECTIVES: Retrospective evaluation of clinical and metabolic correlations between hypothyroidism and NAFLD was the target. METHODS: Clinical, biochemical and histological investigation of 103 NAFLD patients exhibiting drug-treated hypothyroidism was conducted. RESULTS: Steatosis was present in 32.0 percent of the population and nonalcoholic steatohepatitis in 68.0 percent. Females were the majority in both groups, with age of 50.0 ± 1.5 and 56.0 ± 1.1 years, respectively. Hypothyroidism was not rare (15.5 percent), and multivariate analysis confirmed positive correlation with this disease for insulin (r = 0.213, P = 0.03), glucose homeostasis index "HOMA" (r = 0.221, P = 0.02), aspartate aminotransferase (r = 0.234, P = 0.01) and triglycerides above 150 mg/dL (r = 0.233, P = 0.01). No association between hypothyroidism and steatohepatitis could be established. CONCLUSION: A link could be identified between hypothyroidism and markers of glucose and lipid homeostasis, but not with severity of NAFLD. The lack of correlation with liver biopsy requires further studies.

CONTEXTO: Os hormônios tireoidianos podem interferir na regulação do metabolismo de lipídios e carboidratos e também na gravidade da doença hepática gordurosa não-alcoólica (DHGNA), porém os resultados ainda são debatidos. OBJETIVOS: Avaliar retrospectivamente correlações clínicas e metabólicas entre hipotireoidismo e DHGNA. MÉTODOS: Em 103 pacientes com DHGNA confirmada por biopsia e também hipotireoidismo recebendo tratamento, procedeu-se à investigação clínica, bioquímica e histológica. RESULTADOS: A esteatose foi observada em 32,0 por cento e a esteatohepatite não-alcoólica em 68,0 por cento da população. O sexo feminino foi mais frequente nas duas circunstâncias, com idade média de 50,0 ± 1,5 e 56,0 ± 1,1 anos, respectivamente. O hipotireoidismo não foi raro (15,5 por cento), sendo que na análise multivariada insulina (r = 0,213, P = 0,03), índice de homeostase glicídica HOMA (r = 0,221, P = 0,02), aspartato aminotransferase (r = 0,234, P = 0,01) e triglicerídeos acima de 150 mg/dL (r = 0,233, P = 0,01) foram correlacionados positivamente com hipotireoidismo. A associação entre hipotireoidismo e esteatohepatite não pôde ser estabelecida neste estudo. CONCLUSÃO: O hipotireoidismo vinculou-se à piora de alguns marcadores do metabolismo glicolipídico, porém não a lesões histológicas mais avançadas. A falta de correlação com a biopsia do fígado requer maiores estudos.

The Relationship between Normal Serum Uric Acid and Nonalcoholic Fatty Liver Disease

The objective of the present study was to determine the relationship between serum uric acid (SUA) level and the presence of nonalcoholic fatty liver disease (NAFLD). We analyzed data of 9,019 Koreans who visited a health check up center. The SUA levels of all of these subjects were within the normal range. The participants were divided into 4 groups according to the quartiles of the SUA levels for both sexes. Hepatic steatosis was diagnosed on the basis of ultrasonographic findings. Multivariate logistic regression modeling was performed across the SUA quartiles. The presence of NAFLD and metabolic abnormalities were found significantly in subjects with high-normal SUA levels. After adjustment for age, metabolic components, and the liver-function test, the adjusted odds ratio (OR, 95% CIs) for the presence of NAFLD in the subjects with the highest SUA level was 1.46 (1.17-1.82) for men and 2.13 (1.42-3.18) for women, as compared to the subjects with the lowest SUA level. Our results suggest that increased SUA concentrations, even within the normal range, are independently associated with the presence of NAFLD.

Paraoxonase-1 activity, malondialdehyde and glutathione peroxidase in non-alcoholic fatty liver disease and the effect of atorvastatin

The prevalence of non-alcoholic fatty liver disease [NAFLD] appears to be increasing. The aim of the present study was to investigate the relationship between hepatic antioxidant paraoxonase 1 [PON1] activity, lipid peroxidation and antioxidant enzymes in patients with NAFLD and the effect of atorvastatin. This study was conducted on 50 patients with NAFLD and 20 normal subjects matched for age and sex. All of them were subjected to the following investigations: abdominal ultraso-nography, serum PON1 activity level, liver function tests, serum lipid profile, fasting and postprandial blood glucose and serum levels of malondialdehyde [MDA] and glutathione peroxidase [GP]. NAFLD patients were further randomly classified into two groups [25 patients each], groups Ia and Ib. Only group la received atorvastatin 40 mg tablet for 8 months. Obesity, dyslipidaemia and impaired glucose tolerance were prevalent in group I. There was a significant decrease in serum PON1 activity with a significant increase in MDA and GP activity [i.e., there is a significant increase in lipid peroxidation rate] in group I compared with group II. After atorvastatin therapy, there was a significant increase in serum PNO1 activity and significant decrease in serum MDA levels. Patients with NAFLD show enhanced oxidative stress which may lead to non-alcoholic steatohepatitis [NASH]. Reduced PON1 activity and increased MDA could be considered a biochemical marker for lipid peroxidation, which require follow-up in patients with NAFLD. Atorvastatin may have a role in prevention of, or delay, the transformation of liver steatosis into NASH

Clinical characteristics associated with hepatic steatosis on ultrasonography in patients with elevated alanine aminotransferase / Características clínicas associadas a esteatose hepática à ultrassonografia em pacientes com alanina aminotransferase elevada

CONTEXT AND OBJECTIVE: The main causes of hepatic steatosis (HS) are alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD). Although liver biopsy is the gold standard for NAFLD diagnosis, the finding of abnormal aminotransferases in abstinent individuals, without known liver disease, suggests the diagnosis of NAFLD in 80-90 percent of the cases. Identification of clinical factors associated with HS on abdominal ultrasound may enable diagnoses of fatty liver non-invasively and cost-effectively. The aim here was to identify clinical variables associated with HS in individuals with elevated alanine aminotransferase (ALT) levels. DESIGN AND SETTING: Cross-sectional study in a single tertiary care center. METHODS: Individuals with elevated ALT, serologically negative for hepatitis B and C, were evaluated by reviewing medical files. Patients who did not undergo abdominal ultrasonography were excluded. RESULTS: Among 94 individuals included, 40 percent presented HS on ultrasonography. Compared with individuals without HS, those with fatty liver were older (P = 0.043), with higher body mass index (BMI) (P = 0.003), diabetes prevalence (P = 0.024), fasting glucose levels (P = 0.001) and triglycerides (P = 0.003). Multivariate analysis showed that BMI (odds ratio, OR = 1.186; 95 percent confidence interval, CI: 1.049-1.341; P = 0.006) and diabetes mellitus (OR = 12.721; 95 percent CI: 1.380-117.247; P = 0.025) were independently associated with HS. CONCLUSIONS: Simple clinical findings such as history of diabetes and high BMI may predict the presence of HS on ultrasonography in individuals with elevated ALT and negative serological tests for hepatitis.

CONTEXTO E OBJETIVO: Doença hepática alcoólica e doença hepática esteatótica não alcoólica (DHENA) são as principais causas de esteatose hepática (EH). Apesar de a biópsia hepática ser o método de escolha para diagnóstico DHENA, o achado de aminotransferases elevadas em indivíduos abstêmios, sem doença hepática conhecida, sugere o diagnóstico de DHENA em 80-90 por cento dos casos. A identificação de variáveis clínicas associadas à EH na ultrassonografia abdominal pode permitir o diagnóstico de DHENA de forma não invasiva e custo-efetiva. O objetivo foi identificar variáveis clínicas associadas à EH em indivíduos com níveis elevados de alanina aminotransferase (ALT). TIPO DE ESTUDO E LOCAL: Estudo transversal em um único centro de atendimento terciário. MÉTODOS: Indivíduos com ALT elevada e sorologias negativas para os vírus de hepatite B e C foram avaliados por meio de revisão de prontuários. Os pacientes não submetidos à ultrassonografia foram excluídos. RESULTADOS: Foram incluídos 94 indivíduos, 40 por cento deles com EH à ultrassonografia. Quando comparados aos indivíduos sem EH, aqueles com EH apresentaram maior prevalência de diabetes (P = 0,024), maiores idade (P = 0,043) e índice de massa corpórea (IMC) (P = 0,003), glicemia de jejum mais elevada (P = 0,001) e triglicerídeos mais elevados (P = 0,003). A análise multivariada evidenciou que o IMC (odds ratio, OR = 1,186, 95 por cento intervalo de confiança, IC 1,049-1,341, P = 0,006) e o diabetes mellitus (OR = 12,721, 95 por cento IC 1,380-117,247, P = 0,025) foram associadas independentemente à EH. CONCLUSÕES: Achados clínicos simples como história de diabetes e o IMC elevado podem predizer a presença de EH à ultrassonografia de indivíduos com ALT elevada e sorologias negativas para hepatite.

Association of hypoadiponectinemia with non-alcoholic fatty liver disease in urban south Indians - (CURES - 81).

Background & objective: Association between adiponectin and non-alcoholic fatty liver disease (NAFLD) has been reported in west. Studies in Indian population are lacking. This study was undertaken to assess the association of hypoadiponectinemia with NAFLD in Asian Indians. Method: In this cross-sectional study, subjects were randomly selected from Phase 5 of the Chennai Urban Rural Epidemiology Study (CURES), an epidemiological study based on a representative population of Chennai in south India. One hundred twenty one subjects without NAFLD and 72 subjects with NAFLD were selected. NAFLD was diagnosed by ultrasonography. Serum adiponectin levels were measured using radioimmunoassay. Insulin resistance was calculated using Homeostasis Assessment model (HOMA-IR). Results: Serum adiponectin values were significantly lower in subjects with NAFLD compared to those without [5.6 μg/ml (95% Confidence Interval (CI) 5.0 - 6.3 μg/ml] vs 7.4 μg/ml (95% CI: 6.7 - 8.1 μg/ml, P<0.01). Adiponectin levels decreased with increasing severity of NAFLD. Subjects with moderate to severe steatosis had significantly lower adiponectin levels (5.1μg/ml, 95% CI: 4.1- 6.4 μg/ml) compared to subjects with mild steatosis (5.9 μg/ml, 95% CI: 5.0 - 6.9 μg/ml; P<0.001) and subjects without NAFLD (7.3 μg/ml, 95% CI: 6.6 - 8.0 μg/ml; P<0.01). Multiple logistic regression analysis revealed adiponectin to be negatively associated with NAFLD [Odds Ratio (OR): 0.865, 95% Confidence Interval (CI): 0.792- 0.944, P=0.001]. This remained statistically significant even after adjusting for confounding factors age, gender, body mass index, insulin resistance, waist circumference, total cholesterol, triglycerides and glucose intolerance (OR: 0.873, 95% CI: 0.793 - 0.961; P=0.005). Interpretation & conclusion: NAFLD is associated with lower serum adiponectin levels independent of conventional cardiovascular risk factors in Asian Indians known to have high prevalence of diabetes and coronary artery disease.

Insulin resistance index (HOMA-IR) in the differentiation of patients with non-alcoholic fatty liver disease and healthy individuals / Índice de resistência insulínica (HOMA-IR) na diferenciação entre pacientes com doença hepática gordurosa não-alcoólica e indivíduos saudáveis

CONTEXT: Due to its good correlation to glycemic clamp, HOMA-IR has been widely utilized as insulin resistance index in clinical and epidemiological studies involving non-alcoholic fatty liver disease carriers. However, values used for this parameter have shown large variability. OBJECTIVE: To identify the HOMA-IR cut value that best distinguishes non-diabetic non-alcoholic fatty liver disease patients from a control group. METHODS: One hundred sixteen non-alcoholic fatty liver disease patients were studied, diagnosed by clinical, biochemical, and liver image or biopsy criteria, and 88 healthy individuals, without any liver disease and testing for oral glucose tolerance within normality. These groups did not differ in age and gender. All were submitted to oral glucose tolerance test and blood samples were collected for glucose and insulin measurements by immunofluorometric method. HOMA-IR was calculated according to the formula: fasting insulin (µU/L) x fasting glucose (nmol/L)/22.5. RESULTS: NAFLD patients showed higher insulin, glycemia, and HOMA-IR values than control group, even when excluding glucose intolerant and diabetes mellitus patients by their glycemic curves. HOMA-IR 75th percentile for control group was 1.78 and the best area under the curve index was obtained for HOMA-IR values of 2.0 [AUC= 0.840 (0.781-0.899 CI 95 percent), sensitivity (Se): 85 percent, specificity (Sp): 83 percent] while value 2.5 showed best specificity without important loss in sensitivity [AUC=0,831 (0.773-0.888) Se = 72 percent, Sp = 94 percent]. CONCLUSION: HOMA-IR values above or equal to 2.0 or 2.5 show enhanced diagnostic value in distinguishing non-alcoholic fatty liver disease carriers from control group individuals.

CONTEXTO: Pela sua boa correlação com o "clamp" glicêmico, o HOMA-IR tem sido largamente utilizado como índice de resistência insulínica em estudos clínicos e epidemiológicos em pacientes com doença hepática gordurosa não-alcoólica. Porém os valores utilizados para esse parâmetro têm sido muito variáveis. OBJETIVO: Identificar o valor de corte do HOMA-IR que melhor diferencie pacientes com doença hepática gordurosa não-alcoólica não-diabéticos, de um grupo controle. MÉTODOS: Foram estudados 116 pacientes com doença hepática gordurosa não-alcoólica, diagnosticados por critérios clínicos, bioquímicos e de imagem ou biopsia hepática e 88 indivíduos saudáveis, sem doença hepática e com teste de tolerância oral à glicose dentro da normalidade. Esses grupos não diferiam quanto à idade e gênero. Todos foram submetidos ao teste de tolerância oral à glicose e coletadas amostras de sangue para dosagem de glicemia e de insulina através de método imunofluorimétrico. Foi feito o cálculo do HOMA-IR de acordo com fórmula = insulina de jejum (µU/L) x glicemia de jejum (nmol/L)/22.5. RESULTADOS: Os pacientes com doença hepática gordurosa não-alcoólica apresentaram valores mais elevados de insulina, glicemia e HOMA-IR que o grupo controle, mesmo quando excluídos os pacientes com diagnóstico de intolerância à glicose ou de diabetes mellitus pela curva glicêmica. O percentil 75 para HOMA-IR no grupo controle foi de 1.78 e o melhor índice de área sob a curva foi obtido para os valores de HOMA-IR de 2,0 [ASC = 0,840 (0,781-0,899 IC95 por cento), sensibilidade: 85 por cento, especificidade: 83 por cento] enquanto o valor de 2,5 foi o que apresentou melhor especificidade, sem perda importante de sensibilidade [ASC = 0,831 (0.773-0.888) sensibilidade: 72 por cento, especificidade: 94 por cento] . CONCLUSÃO: Valores de HOMA-IR acima ou iguais a 2.0 ou 2.5 mostram elevado valor diagnóstico na distinção entre os doentes com doença hepática gordurosa não-alcoólica...

Evaluation of the nonalcoholic fat liver disease fibrosis score for patients undergoing bariatric surgery / Avaliação do escore de fibrose hepática para doença hepática gordurosa não-alcoólica em pacientes submetidos a cirurgia bariátrica

CONTEXT: Morbidly obese patients have an increased risk for nonalcoholic fat liver disease. Its severe form, nonalcoholic steatohepatitis may cause liver fibrosis. The diagnosis of advanced fibrosis has great value during the pre operative evaluation for bariatric surgery. Currently, liver biopsy is the gold standard for diagnosis of liver fibrosis. OBJECTIVE: To evaluate the nonalcoholic fat liver disease fibrosis score in morbidly obese patients undergoing Roux-en-Y gastric bypass in our population. METHODS: One hundred fifty-eight morbidly obese patients that had undergone bariatric surgery were included. Age, body mass index, hyperglycemia, platelet count, albumin and AST/ALT ratio were applied to the score formula. Scores above 0.676 were indicative of advanced liver fibrosis and scores under -1,455 absence of advanced liver fibrosis. These scores were compared to liver biopsy findings. RESULTS: The presence of advanced fibrosis could be diagnosed with good accuracy, with a positive predictive value of 83.7 percent. The score had a higher accuracy to exclude advanced fibrosis with a negative predictive value of 97 percent. Twenty-five patients (16 percent) had scores between the cutoffs points and were identified as indeterminate. The score sensibility and specificity was 83 percent and 97 percent respectively. CONCLUSIONS: The nonalcoholic fat liver disease fibrosis score has high accuracy to identify and exclude advanced liver fibrosis in morbidly obese patients subjected to bariatric surgery.

CONTEXTO: Pacientes com obesidade mórbida apresentam risco significativo para doença hepática gordurosa não-alcoólica e para suas formas mais graves, a esteatohepatite e a cirrose hepática. O diagnóstico de tais alterações é importante, principalmente na avaliação pré-operatória de cirurgia bariátrica. Até o momento, a biopsia hepática é o procedimento com maior precisão para tal diagnóstico. OBJETIVO: Avaliar o escore de fibrose hepática em doença hepática gordurosa não-alcoólica em pacientes com obesidade mórbida na população brasileira. MÉTODOS: Foram incluídos 158 pacientes com obesidade mórbida submetidos a cirurgia bariátrica. Idade, índice de massa corporal, hiperglicemia, albumina, contagem de plaquetas e razão AST/ALT foram aplicados à fórmula do escore de fibrose. Valores acima de 0,676 indicavam fibrose avançada e abaixo de - 1,455 indicavam ausência de fibrose. Estes valores foram comparados com os achados de biopsia hepática realizados no intra-operatório. RESULTADOS: A presença de fibrose avançada foi diagnosticada com boa precisão, valor preditivo positivo de 83,7 por cento. O escore teve melhor precisão para excluir fibrose avançada, com valor preditivo negativo de 97,2 por cento. Em 25 pacientes (16 por cento) o escore resultou indeterminado entre os pontos de corte. A sensibilidade e a especificidade do escore foram de 83 por cento e 97 por cento, respectivamente. CONCLUSÃO: O escore de fibrose para doença hepática gordurosa não-alcoólica apresenta elevada precisão para reconhecer e excluir fibrose avançada em pacientes com obesidade mórbida submetidos a cirurgia bariátrica.

Serum prohepcidin levels in chronic hepatitis C, alcoholic liver disease, and nonalcoholic fatty liver disease / 대한간학회지

BACKGROUND/AIMS: Patients with various chronic liver diseases frequently have increased body iron stores. Prohepcidin is an easily measurable precursor of hepcidin, which is a key regulator of iron homeostasis. This study investigated the serum prohepcidin levels in patients with various chronic liver diseases with various etiologies. METHODS: Serum prohepcidin levels were measured in patients with chronic hepatitis C (CH-C) (n=28), nonalcoholic fatty liver disease (NAFLD) (n=24), and alcoholic liver disease (ALD) (n=22), and in healthy controls (n=25) using commercial ELISA. Serum interleukin 6 (IL-6) levels and blood iron indices were also measured. RESULTS: The serum levels of both prohepcidin and IL-6 were significantly higher in CH-C patients than in healthy controls, and there was a positive correlation between the IL-6 and prohepcidin levels (r=0.505, p=0.020). The prohepcidin levels in ALD patients did not differ from those in controls, despite their significantly elevated IL-6 levels. There was a tendency for a negative correlation between serum prohepcidin levels and transferrin saturation in ALD patients (r=-0.420, p=0.051). Neither prohepcidin nor IL-6 was significantly elevated in the NAFLD group, despite the presence of elevated serum iron and ferritin levels. CONCLUSIONS: The role of prohepcidin may differ in different human liver diseases. In the setting of CH-C, both the serum prohepcidin and IL-6 levels were significantly elevated and were positively correlated with each other.

Fibras solúveis no tratamento da doença hepática gordurosa não-alcoólica: estudo piloto / Non alcoholic fatty liver disease: treatment with soluble fibres

O presente estudo piloto avaliou a eficácia de fibras solúveis no tratamento da doença hepática gordurosa não-alcoólica. Foram incluídos 12 pacientes que receberam 10 g/dia de fibras solúveis oral por 3 meses. Após o tratamento, observou-se redução nos valores do índice de massa corporal, circunferência da cintura e resistência à insulina em 100 por cento dos casos, redução nos níveis de colesterol em 66,7 por cento e normalização de ALT, AST e GGT em 75 por cento. Os resultados sugerem que a utilização de fibras solúveis pode colaborar no controle de fatores de risco e das enzimas hepáticas em pacientes com doença hepática gordurosa não-alcoólica e estimulam a realização de estudos controlados envolvendo controle histológico.

The pilot study evaluated the efficiency of oral soluble fibers to treat patients with nonalcoholic fatty liver disease. Twelve patients received 10 g/day of soluble fibers during 3 months. After the treatment 100 percent of patients presented reduction in body mass index, waist circumference and insulin resistance index. In 66.7 percent of the patients were observed reduction of the cholesterol levels and 75 percent presented normal liver enzymes (AST, ALT, and GGT). The present study suggests that oral soluble fibers may be useful to control risk factors and liver enzymes in patients with nonalcoholic fatty liver disease. However, future studies with histological controls are considered necessary.