Elorz, M. (Mariana)
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- Association of the SH2B1 rs7359397 gene polymorphism with steatosis severity in subjects with obesity and non-alcoholic fatty liver disease(MDPI, 2020) Martinez, J.A. (José Alfredo); Riezu-Boj, J.I. (José Ignacio); Benito-Boíllos, A. (Alberto); Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Milagro-Yoldi, F.I. (Fermín Ignacio); Marin-Alejandre, B.A. (Bertha Araceli); Herrero, J.I. (José Ignacio); Monreal, J.I. (José Ignacio); Elorz, M. (Mariana); Abete, I. (Itziar); Cantero-González, I. (Irene); Pérez-Díaz-Campo, N. (Nuria) delNon-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. Some genetic variants might be involved in the progression of this disease. The study hypothesized that individuals with the rs7359397 T allele have a higher risk of developing severe stages of NAFLD compared with non-carriers where dietary intake according to genotypes could have a key role on the pathogenesis of the disease. SH2B1 genetic variant was genotyped in 110 overweight/obese subjects with NAFLD. Imaging techniques, lipidomic analysis and blood liver biomarkers were performed. Body composition, general biochemical and dietary variables were also determined. The SH2B1 risk genotype was associated with higher HOMA-IR p equal 0.001; and Fatty Liver Index (FLI) p equal 0.032. Higher protein consumption (p equal 0.028), less mono-unsaturated fatty acid and fiber intake (p equal 0.045 and p equal 0.049, respectively), was also referred to in risk allele genotype. Lipidomic analysis showed that T allele carriers presented a higher frequency of non-alcoholic steatohepatitis (NASH) (69.1/100 vs. 44.4/100; p equal 0.006). In the genotype risk group, adjusted logistic regression models indicated a higher risk of developing an advanced stage of NAFLD measured by FLI (OR 2.91) and ultrasonography (OR 4.15). Multinomial logistic regression models showed that risk allele carriers had higher liver fat accumulation risk (RRR 3.93) and an increased risk of NASH (RRR 7.88). Consequently, subjects carrying the T allele were associated with a higher risk of developing a severe stage of NAFLD. These results support the importance of considering genetic predisposition in combination with a healthy dietary pattern in the personalized evaluation and management of NAFLD.
- 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(MDPI AG, 2019) Huarte-Muniesa, M.P. (Maria Pilar); Benito-Boíllos, A. (Alberto); Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Marin-Alejandre, B.A. (Bertha Araceli); Martinez-Echeverria, A. (Ana); Uriz-Otano, J.I. (Juan Isidoro); Herrero, J.I. (José Ignacio); Martinez, A. (Alfredo); Monreal, J.I. (José Ignacio); Quiroga, J. (Jorge); Elorz, M. (Mariana); Abete, I. (Itziar); Cantero-González, I. (Irene)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.
- Inflammatory markers as diagnostic and precision nutrition tools for metabolic dysfunction-associated steatotic liver disease: Results from the Fatty Liver in Obesity trial(Elsevier, 2024) Martinez, J.A. (José Alfredo); Riezu-Boj, J.I. (José Ignacio); Tobaruela-Resola, A.L. (Ana Luz); Benito-Boíllos, A. (Alberto); Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Mogna-Peláez, P. (Paola); Milagro-Yoldi, F.I. (Fermín Ignacio); Herrero, J.I. (José Ignacio); Elorz, M. (Mariana); Abete, I. (Itziar)Background & aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern. The disease is silent, and its diagnosis is often delayed. Inflammatory markers constitute an interesting tool to act as subrogate, non-invasive markers. This study aimed to evaluate the changes of inflammatory markers throughout a two-year dietary intervention in subjects presenting MASLD, to determine which of the markers are suitable to predict the disease, and act as a customizing tool for MASLD's dietary treatment. Methods: Ninety-eight subjects with MASLD and forty-five controls from the Fatty Liver in Obesity (FLiO) Study were analyzed. MASLD was diagnosed and graded by ultrasound. The MASLD subjects were randomly assigned to two different dietary strategies, the American Heart Association (AHA diet) or a dietary strategy based on the Mediterranean pattern, which was specially designed for the study (FLiO diet), and then followed for two years. Hepatic status was additionally assessed through Magnetic Resonance Imaging (MRI), elastography, and determination of transaminases. Results & discussion: Inflammatory markers improved throughout the intervention in the MASLD sub- jects and managed to reach similar levels to controls, especially at 6 and 12 months. Additionally, leptin, adiponectin, M30, and LECT2 managed to significantly diagnose the disease at all time marks of the intervention, making them candidates for subrogate non-invasive markers of the disease. Moreover, baseline chemerin, leptin, LECT2, and M65 were used to build a predictive score to achieve greater weight loss, and therefore, which strategy could be more useful for MASLD ‘s treatment. The predictive score was significantly able assign a specific diet to 55% of the study participants, meaning that the remaining 45% could achieve the same amount of weight loss following either diet equally. Conclusion: Inflammatory markers constitute a potential non-invasive tool to be used in MASLD screening and could also constitute an interesting tool for MASLD's treatment customization, being able to predict the effectiveness of a dietary strategy based on the initial inflammatory state of each subject. Trial registration: www.clinicaltrials.gov (NCT03183193).
- Predictive value of serum ferritin in combination with alanine aminotransferase and glucose levels for noninvasive assessment of NAFLD: Fatty liver in obesity (FLiO) study(MDPI AG, 2020) Martinez, J.A. (José Alfredo); Benito-Boíllos, A. (Alberto); Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Marin-Alejandre, B.A. (Bertha Araceli); Galarregui-Miquelarena, C. (Cristina); Herrero, J.I. (José Ignacio); Monreal, J.I. (José Ignacio); Elorz, M. (Mariana); Abete, I. (Itziar); Cantero-González, I. (Irene); Pérez-Díaz-Campo, N. (Nuria) delThe identification of affordable noninvasive biomarkers for the diagnosis and characterization of nonalcoholic fatty liver disease (NAFLD) is a major challenge for the research community. This study aimed to explore the usefulness of ferritin as a proxy biomarker of NAFLD condition, alone or in combination with other routine biochemical parameters. Subjects with overweight/obesity and ultrasound-confirmed liver steatosis (n = 112) from the Fatty Liver in Obesity (FLiO) study were assessed. The hepatic evaluation considered magnetic resonance imaging, ultrasonography, and credited routine blood liver biomarkers. Anthropometry and body composition, dietary intake (by means of a validated 137-item food frequency questionnaire), and specific biochemical markers were also determined. Serum ferritin levels were analyzed using a chemiluminescent microparticle immunoassay kit. Lower serum ferritin concentrations were associated with general better liver health and nutritional status. The evaluation of ferritin as a surrogate of liver damage by means of quantile regression analyses showed a positive association with alanine aminotransferase (ALT) (β = 19.21; p ≤ 0.001), liver fat content (β = 8.70; p = 0.008), and hepatic iron (β = 3.76; p ≤ 0.001), after adjusting for potential confounders. In receiver operating characteristic (ROC) analyses, the panel combination of blood ferritin, glucose, and ALT showed the best prediction for liver fat mass (area under the curve (AUC) 0.82). A combination of ferritin and ALT showed the higher predictive ability for estimating liver iron content (AUC 0.73). This investigation demonstrated the association of serum ferritin with liver health as well as with glucose and lipid metabolism markers in subjects with NAFLD. Current findings led to the identification of ferritin as a potential noninvasive predictive biomarker of NAFLD, whose surrogate value increased when combined with other routine biochemical measurements (glucose/ALT).
- Association between Different Animal Protein Sources and Liver Status in Obese Subjects with Non-Alcoholic Fatty Liver Disease: Fatty Liver in Obesity (FLiO) Study(MDPI AG, 2019) Benito-Boíllos, A. (Alberto); Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Marin-Alejandre, B.A. (Bertha Araceli); Herrero, J.I. (José Ignacio); Martinez, A. (Alfredo); Monreal, J.I. (José Ignacio); Elorz, M. (Mariana); Abete, I. (Itziar); Cantero-González, I. (Irene); Recaredo, G. (Gregorio)Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Obesity and unhealthy dietary habits are described as risk factors for NAFLD. The aim of this study was to investigate the association between the consumption of different animal protein sources and hepatic status in NAFLD adults. A total of 112 overweight/obese participants with NAFLD from Fatty Liver in Obesity (FLiO) study were evaluated at baseline. Diet, body composition, and biochemical variables were evaluated. Hepatic status was also assessed by Magnetic Resonance Imaging, ultrasonography, and elastography. Red meat consumption showed a positive relationship with liver iron content (r = 0.224; p = 0.021) and ferritin concentration (r = 0.196; p = 0.037). Processed meat consumption exhibited a positive association with liver iron content (r = 0.308; p = 0.001), which was also found in the quantile regression (β = 0.079; p = 0.028). Fish consumption was related with lower concentration of ferritin (r = -0.200; p = 0.034). This association was further evidenced in the regression model (β = -0.720; p = 0.033). These findings suggest that the consumption of different animal protein sources differentially impact on liver status in obese subjects with NAFLD, showing fish consumption as a healthier alternative for towards NAFLD features.
- Ultrasound/Elastography techniques, lipidomic and blood markers compared to Magnetic Resonance Imaging in non-alcoholic fatty liver disease adults(Ivyspring International Publisher, 2019) Martinez, J.A. (José Alfredo); Huarte-Muniesa, M.P. (Maria Pilar); Benito-Boilos, A. (Alberto); Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Marin-Alejandre, B.A. (Bertha Araceli); Kearney, J. (J.); Uriz-Otano, J.I. (Juan Isidoro); Herrero, J.I. (José Ignacio); Martínez, A. (Ana); Monreal, J.I. (José Ignacio); Quiroga, J. (Jorge); Elorz, M. (Mariana); Abete, I. (Itziar); Cantero-González, I. (Irene)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.
- Effects of two personalized dietary strategies during a 2-year intervention in subjects with nonalcoholic fatty liver disease: a randomized trial(2021) Martinez, J.A. (José Alfredo); Huarte-Muniesa, M.P. (Maria Pilar); Benito-Boíllos, A. (Alberto); Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Marin-Alejandre, B.A. (Bertha Araceli); Martinez-Echeverria, A. (Ana); Uriz-Otano, J.I. (Juan Isidoro); Herrero, J.I. (José Ignacio); Monreal, J.I. (José Ignacio); Quiroga, J. (Jorge); Elorz, M. (Mariana); Abete, I. (Itziar); Cantero-González, I. (Irene); Pérez-Díaz-Campo, N. (Nuria) delBackground 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.
- Interplay of glycemic index, glycemic load, and dietary antioxidant capacity with insulin resistance in subjects with a cardiometabolic risk profile(MDPI AG, 2018) Martinez, J.A. (José Alfredo); Benito-Boíllos, A. (Alberto); Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Marin-Alejandre, B.A. (Bertha Araceli); Galarregui-Miquelarena, C. (Cristina); Herrero, J.I. (José Ignacio); Monreal, J.I. (José Ignacio); Elorz, M. (Mariana); Abete, I. (Itziar); Cantero-González, I. (Irene)Background: Dietary total antioxidant capacity (TAC), glycemic index (GI), and glycemic load (GL) are accepted indicators of diet quality, which have an effect on diet–disease relationships. The aim of this study was to evaluate potential associations of dietary TAC, GI, and GL with variables related to nutritive status and insulin resistance (IR) risk in cardiometabolic subjects. Methods: A total of 112 overweight or obese adults (age: 50.8 ± 9 years old) were included in the trial. Dietary intake was assessed by a validated 137-item food frequency questionnaire (FFQ), which was also used to calculate the dietary TAC, GI, and GL. Anthropometrics, blood pressure, body composition by dual-energy X-ray absorptiometry (DXA), glycemic and lipid profiles, C-reactive protein (CRP), as well as fatty liver quantification by magnetic resonance imaging (MRI) were assessed. Results: Subjects with higher values of TAC had significantly lower circulating insulin concentration and homeostatic model assessment of insulin resistance (HOMA-IR). Participants with higher values of HOMA-IR showed significantly higher GI and GL. Correlation analyses showed relevant inverse associations of GI and GL with TAC. A regression model evidenced a relationship of HOMA-IR with TAC, GI, and GL. Conclusion: This data reinforces the concept that dietary TAC, GI, and GL are potential markers of diet quality, which have an impact on the susceptible population with a cardiometabolic risk profile.
- Association between sleep disturbances and liver status in obese subjects with nonalcoholic fatty liver disease: a comparison with healthy controls(MDPI, 2019) Martinez, J.A. (José Alfredo); Riezu-Boj, J.I. (José Ignacio); Huarte-Muniesa, M.P. (Maria Pilar); Benito-Boilos, A. (Alberto); Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Milagro-Yoldi, F.I. (Fermín Ignacio); Marin-Alejandre, B.A. (Bertha Araceli); Martinez-Echeverria, A. (Ana); Uriz-Otano, J.I. (Juan Isidoro); Herrero, J.I. (José Ignacio); Monreal, J.I. (José Ignacio); Quiroga, J. (Jorge); Elorz, M. (Mariana); Abete, I. (Itziar); Cantero-González, I. (Irene)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.
- Síndrome de Pseudomeigs en paciente con tumor de Krukenberg(Ediciones Universidad de Navarra, 2007) Herraiz-Bayod, M.J. (Maite J.); Idoate, M.A. (Miguel Ángel); Elorz, M. (Mariana)e presenta el caso de una mujer de 51 años con antecedente de Linfoma no Hodking y adenocarcinoma gástrico con células en anillo de sello. Acude a nuestro centro por llevar 20 meses con disnea por derrame pleural, linfedema en ambas piernas y ascitis. Se detectan en la TC y en la ecografía dos masas anexiales bilaterales, que se biopsian. El diagnóstico histológico es metástasis ovárica bilateral por adenocarcinoma de células en anillo de sello (tumor de Krukenberg). Esta paciente presenta un síndrome de Pseudomeigs, que comprende un tumor maligno de ovario asociado con ascitis y derrame pleural con citología maligna negativa. En pacientes oncológicos con ascitis y derra- me pleural benignos se debería considerar en el diagnóstico diferencial el síndrome de PseudoMeigs. INGLÉS: We report the case of a fiftyone-year-old woman with a past medical history of Linfoma no Hodking and a gastric adenocarcinoma with signet ring cells. She came to our institution with a twenty month history of dysnea secondary to pleural effussion, bilateral lower extremity edema and probably had ascitis. On CT and US two bilateral pelvic masses were found and biopsied. The anatomopathological analysis showed bilateral ovarian implants from signet ring cell adenocarcinoma (Krukenberg tumor). This patient developed a PseudoMeigs syndrome consisting on malignant ovarian tumor asociated with ascitis and pleural effusion without malignant cells. Oncological patients who present with ascitis and benign pleural effusion, the diagnosis of PseudoMeigs syndrome should be considered.