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A nutrigenetic tool for precision dietary management of non-alcoholic fatty liver disease deeming insulin resistance markers.
Perez-Diaz-Del-Campo, N, Riezu-Boj, JI, Marin-Alejandre, BA, Monreal, JI, Elorz, M, Herrero, JI, Benito-Boillos, A, Milagro, FI, Bugianesi, E, Tur, JA, et al
Panminerva medica. 2022;(4):485-496
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) development is linked to insulin resistance and influenced by environmental factors, but it also underlined a genetic predisposition. The aim of this research was to build a predictive model based on genetic and hepatic health information, deeming insulin resistance markers in order to personalize dietary treatment in overweight/obese subjects with NAFLD. METHODS A 6-month nutritional intervention was conducted in 86 overweight/obese volunteers with NAFLD randomly assigned to 2 energy-restricted diets: the American Heart Association (AHA) diet and the Fatty Liver in Obesity (FLiO) diet. Individuals were genotyped using a predesigned panel of 95 genetic variants. A Genetic Risk Score (GRS) for each diet was computed using statistically relevant SNPs for the change on Fatty Liver Index (FLI) after 6-months of nutritional intervention. Body composition, liver injury and insulin resistance markers, as well as physical activity and dietary intake were also assessed. RESULTS Under energy restriction, both the AHA and FLiO diets induced similar significant improvements on body composition, insulin resistance markers, hepatic health and dietary and lifestyle outcomes. The calculated score included in the linear mixed regression model was able to predict the change of FLI adjusted by diet, age and sex. This model allowed to personalize the most suitable diet for 72% of the volunteers. Similar models were also able to predict the changes on Triglycerides and Glucose (TyG) Index and retinol-binding protein 4 (RBP4) levels depending on diet. CONCLUSIONS Models integrating genetic screening and insulin resistance markers can be useful for the personalization of NAFLD weight loss treatments.
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Effects of two personalized dietary strategies during a 2-year intervention in subjects with nonalcoholic fatty liver disease: A randomized trial.
Marin-Alejandre, BA, Cantero, I, Perez-Diaz-Del-Campo, N, Monreal, JI, Elorz, M, Herrero, JI, Benito-Boillos, A, Quiroga, J, Martinez-Echeverria, A, Uriz-Otano, JI, et al
Liver international : official journal of the International Association for the Study of the Liver. 2021;(7):1532-1544
Abstract
BACKGROUND AND OBJECTIVES Nonalcoholic fatty liver disease (NAFLD) management is focused on lifestyle modifications, but long-term maintenance is a challenge for many individuals. This study aimed to evaluate the long-term effects of two personalized energy-restricted dietary strategies on weight loss, metabolic and hepatic outcomes in overweight/obese subjects with NAFLD. METHODS Ninety-eight subjects from the Fatty Liver in Obesity (FLiO) study (NCT03183193) were randomly assigned to the American Heart Association (AHA) or the FLiO dietary group in a 2-year controlled trial. Anthropometry, body composition (DXA), biochemical parameters and hepatic status (ultrasonography, Magnetic Resonance Imaging, and elastography) were assessed at baseline, 6, 12 and 24 months. RESULTS Both the AHA and FLiO diets significantly reduced body weight at 6 (-9.7% vs -10.1%), 12 (-6.7% vs -9.6%), and 24 months (-4.8% vs -7.6%) with significant improvements in body composition, biochemical and liver determinations throughout the intervention. At the end of the follow-up, the FLiO group showed a greater decrease in ALT, liver stiffness and Fatty Liver Index, among others, compared to AHA group, although these differences were attenuated when the analyses were adjusted by weight loss percentage. The FLiO group also showed a greater increase in adiponectin compared to AHA group. CONCLUSIONS The AHA and FLiO diets were able to improve body weight and body composition, as well as metabolic and hepatic status of participants with overweight/obesity and NAFLD within a 2-year follow-up. These findings show that both strategies are suitable alternatives for NAFLD management. However, the FLiO strategy may provide more persistent benefits in metabolic and hepatic parameters.
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Ultrasound/Elastography techniques, lipidomic and blood markers compared to Magnetic Resonance Imaging in non-alcoholic fatty liver disease adults.
Cantero, I, Elorz, M, Abete, I, Marin, BA, Herrero, JI, Monreal, JI, Benito, A, Quiroga, J, Martínez, A, Huarte, MP, et al
International journal of medical sciences. 2019;(1):75-83
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) may progress to steatohepatitis, cirrhosis and complicated hepatocellular carcinoma with defined differential symptoms and manifestations. OBJECTIVE To evaluate the fatty liver status by several validated approaches and to compare imaging techniques, lipidomic and routine blood markers with magnetic resonance imaging in adults subjects with non-alcoholic fatty liver disease. MATERIALS AND METHODS A total of 127 overweight/obese with NAFLD, were parallelly assessed by Magnetic Resonance Imaging (MRI), ultrasonography, transient elastography and a validated metabolomic designed test to diagnose NAFLD in this cross-sectional study. Body composition (DXA), hepatic related biochemical measurements as well as the Fatty Liver Index (FLI) were evaluated. This study was registered as FLiO: Fatty Liver in Obesity study; NCT03183193. RESULTS The subjects with more severe liver disease were found to have worse metabolic parameters. Positive associations between MRI with inflammatory and insulin biomarkers were found. A linear regression model including ALT, RBP4 and HOMA-IR was able to explain 40.9% of the variability in fat content by MRI. In ROC analyses a combination panel formed of ALT, HOMA-IR and RBP4 followed by ultrasonography, ALT and metabolomic test showed the major predictive ability (77.3%, 74.6%, 74.3% and 71.1%, respectively) for liver fat content. CONCLUSIONS A panel combination including routine blood markers linked to insulin resistance showed highest associations with MRI considered as a gold standard for determining liver fat content. This combination of tests can facilitate the diagnosis of early stages of non-alcoholic liver disease thereby avoiding other invasive and expensive methods.
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Association between Sleep Disturbances and Liver Status in Obese Subjects with Nonalcoholic Fatty Liver Disease: A Comparison with Healthy Controls.
Marin-Alejandre, BA, Abete, I, Cantero, I, Riezu-Boj, JI, Milagro, FI, Monreal, JI, Elorz, M, Herrero, JI, Benito-Boillos, A, Quiroga, J, et al
Nutrients. 2019;11(2)
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Inadequate sleep has been associated with poor health outcomes such as obesity and type 2 diabetes. The relevance of sleep patterns in the onset or progression of non-alcoholic fatty liver disease (NAFLD) is poorly understood. The aim of this cross-sectional study was to investigate the association between sleep characteristics and liver health in obese people with NAFLD compared to normal weight people without NAFLD. 94 overweight or obese patients with NAFLD and 40 normal weight people without NAFLD were enrolled in the study. Measures of liver health such as liver stiffness and levels of liver enzymes were assessed, along with sleep features evaluated using a Sleep Quality Index (SQI). A higher prevalence of short sleep duration and poor sleep quality were found in people with NAFLD. Sleep disturbance or sleep quality predicted up to 20.3% and 20.4% of the variability of liver stiffness, respectively, after adjusting for other factors. The authors of the study suggest that sleep disruption may be contributing to the development of NAFLD, and/or the alteration of the liver may be affecting sleep patterns. Consequently, sleep may be a modifiable behaviour to consider in the prevention and management of NAFLD.
Abstract
The relevance of sleep patterns in the onset or evolution of nonalcoholic fatty liver disease (NAFLD) is still poorly understood. Our aim was to investigate the association between sleep characteristics and hepatic status indicators in obese people with NAFLD compared to normal weight non-NAFLD controls. Ninety-four overweight or obese patients with NAFLD and 40 non-NAFLD normal weight controls assessed by abdominal ultrasonography were enrolled. Hepatic status evaluation considered liver stiffness determined by Acoustic Radiation Force Impulse elastography (ARFI) and transaminases. Additionally, anthropometric measurements, clinical characteristics, and biochemical profiles were determined. Sleep features were evaluated using the Pittsburgh Sleep Quality Index (PSQI). Hepatic status parameters, anthropometric measurements, and clinical and biochemical markers differed significantly in NAFLD subjects compared to controls, as well as sleep efficiency, sleep disturbance score, and sleep quality score. In the NAFLD group, a higher prevalence of short sleep duration (p = 0.005) and poor sleep quality (p = 0.041) were found. Multivariate-adjusted odds ratio (95% confidence interval) for NAFLD considering sleep disturbance was 1.59 (1.11⁻2.28). Regression models that included either sleep disturbance or sleep quality predicted up to 20.3% and 20.4% of the variability of liver stiffness, respectively, and after adjusting for potential confounders. Current findings suggest that sleep disruption may be contributing to the pathogenesis of NAFLD as well as the alteration of the liver may be affecting sleep patterns. Consequently, sleep characteristics may be added to the list of modifiable behaviors to consider in health promotion strategies and in the prevention and management of NAFLD.
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The Metabolic and Hepatic Impact of Two Personalized Dietary Strategies in Subjects with Obesity and Nonalcoholic Fatty Liver Disease: The Fatty Liver in Obesity (FLiO) Randomized Controlled Trial.
Marin-Alejandre, BA, Abete, I, Cantero, I, Monreal, JI, Elorz, M, Herrero, JI, Benito-Boillos, A, Quiroga, J, Martinez-Echeverria, A, Uriz-Otano, JI, et al
Nutrients. 2019;(10)
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. NAFLD management is mainly focused on weight loss, but the optimal characteristics of the diet demand further investigation. This study aims to evaluate the effects of two personalized energy-restricted diets on the liver status in overweight or obese subjects with NAFLD after a 6 months follow-up. Ninety-eight individuals from the Fatty Liver in Obesity (FLiO) study were randomized into two groups and followed different energy-restricted diets. Subjects were evaluated at baseline and after 6 months. Diet, anthropometry, body composition, and biochemical parameters were evaluated. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, and determination of transaminases. Both dietary groups significantly improved their metabolic and hepatic markers after the intervention, with no significant differences between them. Multivariate regression models evidenced a relationship between weight loss, adherence to the Mediterranean Diet (MedDiet), and a decrease in liver fat content, predicting up to 40.9% of its variability after 6 months. Moreover, the antioxidant capacity of the diet was inversely associated with liver fat content. Participants in the group with a higher adherence to the MedDiet showed a greater reduction in body weight, total fat mass, and hepatic fat. These results support the benefit of energy-restricted diets, high adherence to the MedDiet, and high antioxidant capacity of the diet for the management of NAFLD in individuals with overweight or obesity.
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Fruit Fiber Consumption Specifically Improves Liver Health Status in Obese Subjects under Energy Restriction.
Cantero, I, Abete, I, Monreal, JI, Martinez, JA, Zulet, MA
Nutrients. 2017;9(7)
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Non-alcoholic-fatty-liver-disease (NAFLD) is the most common cause of chronic liver disease in Western countries, affecting 20–30% of the general adult population. The causes of NAFLD are related to lifestyle factors such as unbalanced diets and/or overnutrition as well as sedentary lifestyles. NAFLD is associated with obesity, diabetes, and metabolic syndrome (MS). This study aimed to evaluate the influence of two calorie-restricted diets on non-invasive markers and scores of liver damage in obese individuals with MS after six months of follow-up and to assess the role of fibre content in metabolic outcomes. Seventy obese adults were evaluated at baseline and after six months of calorie-restricted diets (American Heart Association (AHA) and RESMENA dietary groups). Both diets had the same energy restriction (−30% of the individual’s requirements). Dietary records, body composition and routine laboratory measurements for liver status were analysed. Although adherence to the dietary strategies was similar, resulting in no differences in macronutrient distribution, a variety of markers of liver damage were lower in those individuals who had a higher fibre intake. Fibre derived from fruit had a particularly beneficial impact, suggesting that not only energy restriction but also other dietary components positively influence liver health. The authors concluded that these results support the design of dietary patterns based on the consumption of insoluble fibre and fibre from fruits in the context of energy restriction for the management of obese patients suffering fatty liver disease.
Abstract
The prevalence of non-alcoholic-fatty-liver-disease (NAFLD) is associated with obesity, diabetes, and metabolic syndrome (MS). This study aimed to evaluate the influence of two energy-restricted diets on non-invasive markers and scores of liver damage in obese individuals with features of MS after six months of follow-up and to assess the role of fiber content in metabolic outcomes. Seventy obese individuals from the RESMENA (Reduction of Metabolic Syndrome in Navarra) study were evaluated at baseline and after six months of energy-restricted nutritional intervention (American Heart Association (AHA) and RESMENA dietary groups). Dietary records, anthropometrical data, body composition by dual energy X-ray absorptiometry (DXA), and routine laboratory measurements were analyzed by standardized methods. Regarding liver status, cytokeratin-18 fragments and several non-invasive scores of fatty liver were also assessed. The RESMENA strategy was a good and complementary alternative to AHA for the treatment of obesity-related comorbidities. Participants with higher insoluble fiber consumption (≥7.5 g/day) showed improvements in fatty liver index (FLI), hepatic steatosis index (HIS), and NAFLD liver fat score (NAFLD_LFS), while gamma-glutamyl transferase (GGT) and transaminases evidenced significant improvements as a result of fruit fiber consumption (≥8.8 g/day). Remarkably, a regression model evidenced a relationship between liver status and fiber from fruits. These results support the design of dietary patterns based on the consumption of insoluble fiber and fiber from fruits in the context of energy restriction for the management of obese patients suffering fatty liver disease.