Accuracy of computer-aided ultrasound as compared with magnetic resonance imaging in the evaluation of nonalcoholic fatty liver disease in obese and eutrophic adolescents

AbstractObjective:To compare the accuracy of computer-aided ultrasound (US) and magnetic resonance imaging (MRI) by means of hepatorenal gradient analysis in the evaluation of nonalcoholic fatty liver disease (NAFLD) in adolescents.Materials and Methods:This prospective, cross-sectional study evaluated 50 adolescents (aged 11–17 years), including 24 obese and 26 eutrophic individuals. All adolescents underwent computer-aided US, MRI, laboratory tests, and anthropometric evaluation. Sensitivity, specificity, positive and negative predictive values and accuracy were evaluated for both imaging methods, with subsequent generation of the receiver operating characteristic (ROC) curve and calculation of the area under the ROC curve to determine the most appropriate cutoff point for the hepatorenal gradient in order to predict the degree of steatosis, utilizing MRI results as the gold-standard.Results:The obese group included 29.2% girls and 70.8% boys, and the eutrophic group, 69.2% girls and 30.8% boys. The prevalence of NAFLD corresponded to 19.2% for the eutrophic group and 83% for the obese group. The ROC curve generated for the hepatorenal gradient with a cutoff point of 13 presented 100% sensitivity and 100% specificity. As the same cutoff point was considered for the eutrophic group, false-positive results were observed in 9.5% of cases (90.5% specificity) and false-negative results in 0% (100% sensitivity).Conclusion:Computer-aided US with hepatorenal gradient calculation is a simple and noninvasive technique for semiquantitative evaluation of hepatic echogenicity and could be useful in the follow-up of adolescents with NAFLD, population screening for this disease as well as for clinical studies.

Prevalence and sonographic changes compatible with fatty liver disease in patients referred for abdominal ultrasound examination in Aracaju, SE

Abstract Objective: To estimate the prevalence and evaluate sonographic findings compatible with changes consistent with hepatic steatosis in patients referred for abdominal ultrasonography at four reference centers in Aracaju, SE, Brazil. Materials and Methods: Prospective, descriptive survey, with analytical and quantitative approach, comprising abdominal ultrasonography scans performed with a convex, dynamic 3.75 MHz transducer. Liver dimensions and parenchymal echotexture were evaluated, classifying hepatic steatosis into grades (1, 2 or 3). The SPSS® 22.0 software was used for statistical analysis, adopting p < 0.05 as significance level. Results: A total of 800 individuals (561 women and 239 men) were evaluated. The prevalence of steatosis was 29.1%, and the male patients were most affected, presenting with more advanced grades of disease (p = 0.021), as follows: 119 grade 1 (51.0%); 94 grade 2 (40.4%); and 20 grade 3 (8.6%). The median age patients' was 46 years. Conclusion: In the present study sample, the prevalence of hepatic steatosis was high, particularly in the male patients. Ultrasonography is suggested as a first choice for the diagnosis of this condition, considering its wide availability, low cost and absence of side effects or risks to the patient.

A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid

In order to determine the effect of ursodeoxycholic acid on nonalcoholic fatty liver disease, 30 patients with body mass indices higher than 25, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyltransferase (gamma-GT) at least more than 1.5 times the upper limit of normality, and hepatic steatosis demonstrated by ultrasonography were randomized into two groups of 15 patients to receive placebo or 10 mg kg-1 day-1 ursodeoxycholic acid for three months. Abdominal computed tomography was performed to quantify hepatic fat content, which was significantly correlated with histological grading of steatosis (r s = -0.83, P < 0.01). Patient body mass index remained stable for both groups throughout the study, but a significant reduction in mean (± SEM) serum levels of ALT, AST and gamma-GT was observed only in the treated group (ALT = 81.2 ± 9.7, 44.8 ± 7.7, 48.1 ± 7.7 and 52.2 ± 6.3 IU/l at the beginning and after the first, second and third months, respectively, N = 14, P < 0.05). For the placebo group ALT values were 66.4 ± 9.8, 54.5 ± 7, 60 ± 7.6 and 43.7 ± 5 IU/l, respectively. No alterations in hepatic lipid content were observed in these patients by computed tomography examination (50.2 ± 4.2 Hounsfield units (HU) at the beginning versus 51.1 ± 4.1 HU at the third month). These results show that ursodeoxycholic acid is able to reduce serum levels of hepatic enzymes in patients with nonalcoholic fatty liver disease, but this effect is not related to modifications in liver fat content.

Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87% accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100%), but with reduction in diagnostic sensitivity (64%). When compared with the criteria of Ratziu et al. [Gastroenterology (2000) 118: 1117-1123] for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70%). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.

Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7) or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7) for 4 weeks. The control group (N = 7) was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4) and a decrease in respiratory control rate (RCR) in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1) when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively), P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

Beneficial effects of exercise training (treadmill) on insulin resistance and nonalcoholic fatty liver disease in high-fat fed C57BL/6 mice

C57BL/6 mice develop signs and symptoms comparable, in part, to the human metabolic syndrome. The objective of the present study was to evaluate the effects of exercise training on carbohydrate metabolism, lipid profile, visceral adiposity, pancreatic islet alterations, and nonalcoholic fatty liver disease in C57BL/6 mice. Animals were fed one of two diets during an 8-week period: standard (SC, N = 12) or very high-fat (HF, N = 24) chow. An exercise training protocol (treadmill) was then established and mice were divided into SC and HF sedentary (SC-Sed, HF-Sed), exercised groups (SC-Ex, HF-Ex), or switched from HF to SC (HF/SC-Sed and HF/SC-Ex). HF/HF-Sed mice had the greatest body mass (65% more than SC/SC-Sed; P < 0.0001), and exercise reduced it by 23% (P < 0.0001). Hepatic enzymes ALP (+80%), ALT (+100%) and AST (+70%) were higher in HF/HF mice than in matched SC/SC. Plasma insulin was higher in both the HF/HF-Sed and HF/SC-Sed groups than in the matched exercised groups (+85%; P < 0.001). Pancreatic islets, adipocytes and liver structure were greatly affected by HF, ultimately resulting in islet β-cell hypertrophy and severe liver steatosis. The HF group had larger islets than the SC/SC group (+220%; P < 0.0001), and exercise significantly reduced liver steatosis and islet size in HF. Exercise attenuated all the changes due to HF, and the effects were more pronounced in exercised mice switched from an HF to an SC diet. Exercise improved the lipid profile by reducing body weight gain, visceral adiposity, insulin resistance, islet alterations, and fatty liver, contributing to obesity and steatohepatitis control.

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

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

Mitochondrial Alterations in Nonalcoholic Fatty Liver Disease. Pediatric Case Description of Three Submitted Sequential Biopsies

Nonalcoholic fatty liver disease (NAFLD) is a clinical-pathological syndrome that encompasses a wide spectrum of morphologic alterations, ranging from simple hepatic steatosis to a more severe stage, known as nonalcoholic steatohepatitis (NASH). The purpose of this clinical report was to contribute to the understanding of mitochondrial alterations in NAFLD. The child (13-month-old) underwent initial biopsy in the year 2000 and was diagnosed with diffuse macro and microvesicular steatosis. Two additional biopsies were performed in 2001 and 2004. A high percentage of microvesicular steatosis was observed in the biopsies performed in 2000 and 2001. Mitochondrial size was slightly increased in the biopsy performed in the year 2000, significantly increased in 2001 and decreased in 2004. The presence of "mitochondrial hypertrophy" in the hepatocytes of an asymptomatic pediatric patient whose disease presentation was typical of NAFLD, excluding other pathological processes, allowed us to suspect that such a defect was considered the primary mitochondrial disorder.

Exercise counteracts fatty liver disease in rats fed on fructose-rich diet

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nonalcoholic fatty liver disease and metabolic syndrome in postmenopausal women

Nonalcoholic fatty liver disease (NAFLD) is considered the most common cause of chronic liver disease in the Western countries. NAFLD includes a spectrum ranging from a simple steatosis to a nonalcoholic steatohepatitis (NASH) which is defined by the presence of inflammatory infiltrate, cellular necrosis, hepatocyte ballooning, and fibrosis and cirrhosis that can eventually develop into hepatocellular carcinoma. Studies emphasize the role of insulin resistance, oxidative stress, pro-inflammatory cytokines, adipokines in the development and progression of NAFLD. It seems to be independently associated with type II diabetes mellitus, increased triglycerides, decreased HDL-cholesterol, abdominal obesity and insulin resistance. These findings are in accordance with the criteria used in the diagnosis of metabolic syndrome (MetS). Here, we will discuss the current knowledge on the epidemiology, pathophysiology and diagnosis of NAFLD and the association of metabolic syndrome in postmenopausal women.

Evaluation of Clinical and Inflammatory Markers of Nonalcoholic Fatty Liver Disease in Postmenopausal Women with Metabolic Syndrome

Background: The aim of this study was to assess clinical and inflammatory markers in nonalcoholic fatty liver disease (NAFLD) in postmenopausal women with metabolic syndrome.Methods: This cross-sectional study included 180 Brazilian women (age >= 45 years and amenorrhea >= 12 months). Metabolic syndrome was diagnosed by the presence of at least three of the following indicators: Waist circumference (WC) > 88 cm, triglycerides (TGs) >= 150 mg/dL, high-density lipoprotein (HDL) < 50 mg/dL; blood pressure >= 130/85 mmHg; and glucose >= 100 mg/dL. NAFLD was diagnosed by abdominal ultrasound. Participants were divided into three groups: Metabolic syndrome alone (n = 53); metabolic syndrome + NAFLD (n = 67); or absence of metabolic syndrome or NAFLD (control, n = 60). Clinical, anthropometric, and biochemical variables were quantified. The inflammatory profile included adiponectin, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Data were submitted to statistical analysis using a Tukey test, analysis of variance (ANOVA), chi-squared, Pearson correlation, and logistic regression (odds ratio, OR).Results: Women with metabolic syndrome + NAFLD, abdominal obesity, high glucose, and insulin resistance by HOMA-IR were compared to women with metabolic syndrome alone and controls (P < 0.05). High values of IL-6 and TNF-alpha and low values of adiponectin were observed among women with metabolic syndrome alone or metabolic syndrome + NAFLD when compared to controls (P < 0.05). In multivariate analysis, the variables considered as risk of NAFLD development were: High systolic blood pressure (SBP) [(OR 1.02, 95% confidence interval (CI) 1.0-1.04]; large WC (OR 1.07, 95% CI 1.01-1.13); insulin resistance (OR 3.81, 95% CI 2.01-7.13); and metabolic syndrome (OR 8.68, 95% CI 3.3-24.1). Adiponectin levels reduced NAFLD risk (OR 0.88, 95% CI 0.80-0.96).Conclusion: In postmenopausal women, metabolic syndrome, abdominal obesity, and insulin resistance were risk markers for the development of NAFLD, whereas higher adiponectin values indicated a protection marker.

Non-alcoholic fatty liver disease and its associated risk factors in Brazilian postmenopausal women

Objective To evaluate the prevalence and risk factors of non-alcoholic fatty liver disease (NAFLD) in postmenopausal women.Methods A cross-sectional study was carried involving 188 women (age >= 45 years and amenorrhea >= 12 months) attending the outpatient unit in south-eastern Brazil. Exclusion criteria were liver disease (hepatitis B and C, cholestatic disease, liver insufficiency), use of drugs that affect liver metabolism; alcoholics; AIDS or cancer history; and morbid obesity. NAFLD was diagnosed by abdominal ultrasound. Clinical, anthropometric (body mass index, waist circumference) and biochemical variables were measured.Results Of the 188 women, 73 (38.8%) had NAFLD. Blood pressure, waist circumference, body mass index, LDL cholesterol, triglycerides and glucose were significantly higher in NAFLD patients when compared with women without NAFLD (control group) (p < 0.05). HOMA-IR values indicated insulin resistance only in the NAFLD group (6.1 +/- 4.6 vs. 2.4 +/- 1.4 in control group, p < 0.05). Metabolic syndrome was detected in 93.1% of the women affected by NAFLD, and 46.1% of the control group (p < 0.05). In multivariate analysis, adjusted for age and weight, the variables considered at risk for the development of NAFLD, were: high waist circumference (odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01-1.13), insulin resistance (OR 3.81, 95% CI 2.01-7.13), and presence of metabolic syndrome (OR 8.68, 95% CI 3.3-24.1).Conclusion NAFLD showed a high prevalence among postmenopausal women. The presence of metabolic syndrome, abdominal obesity and IR were indicators of risk for the development of NAFLD.