Benito-Boíllos, A. (Alberto)
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- Clinical usefulness of abdominal bioimpedance (ViScan) in the determination of visceral fat and its application in the diagnosis and management of obesity and its comorbidities(Elsevier, 2018) Valenti, V. (Víctor); Colina, I. (Inmaculada); Ramirez, B. (Beatriz); Benito-Boíllos, A. (Alberto); Catalan, V. (Victoria); Frühbeck, G. (Gema); Moncada, R. (Rafael); Silva, C. (Camilo); Gomez-Ambrosi, J. (Javier); Salvador, J. (Javier); Rodriguez, A. (Amaia); Gil, M.J. (María José); Romero, S. (Sonia); González-Crespo. I. (Ignacio)Background & aims: Visceral adipose tissue (VAT) has been shown to be profoundly responsible of most of the obesity-associated metabolic derangements. The measurement of VAT usually implies the use of imaging techniques such as magnetic resonance imaging or computed tomography (CT). Our aim was to evaluate the accuracy of the determination of VAT by means of abdominal bioimpedance (BIA) with the ViScan device in comparison with CT and its clinical usefulness in the management of obesity. Methods: We studied a sample of 140 subjects (73 males/67 females) with BMI ranging from 17.7 to 50.4 kg/m2 to evaluate the accuracy of the ViScan in comparison to CT to determine VAT. To further analyze ViScan's clinical usefulness we studied a separate cohort (n = 2849) analyzing cardiometabolic risk factors. Furthermore, we studied the ability of the ViScan to detect changes in VAT after weight gain (n = 107) or weight loss (n = 335). The study was performed from October 2009 through June 2015. Results: ViScan determines VAT with a good accuracy in individuals with a CT-VAT up to 200 cm2, and then with lower precision with increasing body mass, exhibiting a moderate-high correlation with CT-VAT (r = 0.75, P < 0.001). Importantly, VAT determination with the ViScan exhibits better correlations with several cardiometabolic risk factors such as glucose, triglycerides, HDL-cholesterol and markers of fatty liver than anthropometric measurements such as BMI or waist circumference. ViScan is able to detect VAT variations after body weight changes. Conclusions: Since the possibility of measuring VAT by imaging techniques is not always available, abdominal BIA represents a good alternative to estimate VAT, allowing the identification of patients with increased VAT-related cardiometabolic risk and a better management of obese patients.
- 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.
- A new animal model of atrophy–hypertrophy complex and liver damage followingYttrium‐90 lobar selective internal radiation therapy in rabbits(Nature Research, 2022) Berasain, C. (Carmen); Páramo-Alfaro, M. (María); Peñuelas-Sanchez, I. (Ivan); Benito-Boíllos, A. (Alberto); Quincoces, G. (Gemma); Collantes-Martínez, M. (María); Sangro, B. (Bruno); Iñarrairaegui, M. (Mercedes); Bilbao, J.I. (José I.); Santamaría, E. (Eva); Idoate, M.A. (Miguel Ángel); Quiroga, J. (Jorge); Argemí, J. (Josepmaria); Rodriguez, M. (Macarena)Lobar selective internal radiation therapy (SIRT) is widely used to treat liver tumors inducing atrophy of the treated lobe and contralateral hypertrophy. The lack of animal model has precluded further investigations to improve this treatment. We developed an animal model of liver damage and atrophy–hypertrophy complex after SIRT. Three groups of 5–8 rabbits received transportal SIRT with Yttrium 90 resin microspheres of the cranial lobes with diferent activities (0.3, 0.6 and 1.2GBq), corresponding to predicted absorbed radiation dose of 200, 400 and 800 Gy, respectively. Another group received non-loaded microspheres (sham group). Cranial and caudal lobes volumes were assessed using CT volumetry before, 15 and 30 days after SIRT. Liver biochemistry, histopathology and gene expression were evaluated. Four untreated rabbits were used as controls for gene expression studies. All animals receiving 1.2GBq were euthanized due to clinical deterioration. Cranial SIRT with 0.6GBq induced caudal lobe hypertrophy after 15 days (median increase 34% -ns-) but produced signifcant toxicity. Cranial SIRT with 0.3GBq induced caudal lobe hypertrophy after 30 days (median increase 82%, p = 0.04). No volumetric changes were detected in sham group. Transient increase in serum transaminases was detected in all treated groups returning to normal values at 15 days. There was dose-dependent liver dysfunction with bilirubin elevation and albumin decrease. Histologically, 1.2GBq group developed permanent severe liver damage with massive necrosis, 0.6 and 0.3GBq groups developed moderate damage with infammation and portal fbrosis at 15 days, partially recovering at 30 days. There was no diference in the expression of hepatocyte function and diferentiation genes between 0.3GBq and control groups. Cranial SIRT with 0.3GBq of 90Y resin microspheres in rabbits is a reliable animal model to analyse the atrophy–hypertrophy complex and liver damage without toxicity.
- 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).
- Liver resection and transplantation following Yttrium-90 radioembolization for primary malignant liver tumors: a 15-year single-center experience(2023) Rotellar, F. (Fernando); Pardo-Sanchez, F. (Fernando); Ortega-Montes, A. (Ana); Lopez-Olaondo, L. (Luis); Benito-Boíllos, A. (Alberto); Zozaya-Larequi, G. (Gabriel); Hidalgo, F. (Francisco); Martinez-de-la-Cuesta, A. (Antonio); Sangro, B. (Bruno); Ponz-Sarvise, M. (Mariano); Iñarrairaegui, M. (Mercedes); Bilbao, J.I. (José I.); Herrero, J.I. (José Ignacio); Marti-Cruchaga, P. (Pablo); Rodriguez-Fraile, M. (Macarena); Rodríguez-Rodríguez, J. (Javier); Aliseda, D. (Daniel)Simple Summary Radioembolization is a locoregional therapy used in primary liver malignancies with different applications depending on the treatment goal. The aim of this retrospective study was to evaluate postoperative and long-term survival outcomes of patients with unresectable or high biological risk HCC and ICC treated with RE that were finally rescued to liver surgery with curative intent. In a cohort of 34 patients, we assessed that liver resection and transplantation after RE seem safe and feasible with adequate short-term outcomes. Moreover, long-term outcomes after RE and LR were optimal, with a 10-year OS rate greater than 50% for HCC and ICC patients. On the other hand, the 10-year OS rates from RE were also greater than 50% for patients with HCC downstaged or bridged to LT. Radioembolization (RE) may help local control and achieve tumor reduction while hypertrophies healthy liver and provides a test of time. For liver transplant (LT) candidates, it may attain downstaging for initially non-candidates and bridging during the waitlist. Methods: Patients diagnosed with HCC and ICC treated by RE with further liver resection (LR) or LT between 2005-2020 were included. All patients selected were discarded for the upfront surgical approach for not accomplishing oncological or surgical safety criteria after a multidisciplinary team assessment. Data for clinicopathological details, postoperative, and survival outcomes were retrospectively reviewed from a prospectively maintained database. Results: A total of 34 patients underwent surgery following RE (21 LR and 13 LT). Clavien-Dindo grade III-IV complications and mortality rates were 19.0% and 9.5% for LR and 7.7% and 0% for LT, respectively. After RE, for HCC and ICC patients in the LR group, 10-year OS rates were 57% and 60%, and 10-year DFS rates were 43.1% and 60%, respectively. For HCC patients in the LT group, 10-year OS and DFS rates from RE were 51.3% and 43.3%, respectively. Conclusion: Liver resection after RE is safe and feasible with optimal short-term outcomes. Patients diagnosed with unresectable or high biological risk HCC or ICC, treated with RE, and rescued by LR may achieve optimal global and DFS rates. On the other hand, bridging or downstaging strategies to LT with RE in HCC patients show adequate recurrence rates as well as long-term survival.
- 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.
- Use of Machine-Learning Algorithms in Intensified Preoperative Therapy of Pancreatic Cancer to Predict Individual Risk of Relapse(MDPI AG, 2019) Chopitea, A. (Ana); Larrea-Leoz, B. (Blanca); Rotellar, F. (Fernando); Benito-Boíllos, A. (Alberto); Baudin, V. (Vicky); Carranza, O. (Omar); Arbea-Moreno, L. (Leire); Pardo, F. (Fernando); Subtil, J.C. (José Carlos); Ponz-Sarvise, M. (Mariano); Mejías-Sosa, L.D. (Luis D.); Sala-Elarre, P. (Pablo); Rodríguez-Rodríguez, J. (Javier); Iragorri-Barberena, Y. (Yohana); Yu, K.H. (Kenneth H.); Oyaga-Iriarte, E. (Esther)Background: Although surgical resection is the only potentially curative treatment for pancreatic cancer (PC), long-term outcomes of this treatment remain poor. The aim of this study is to describe the feasibility of a neoadjuvant treatment with induction polychemotherapy (IPCT) followed by chemoradiation (CRT) in resectable PC, and to develop a machine-learning algorithm to predict risk of relapse. Methods: Forty patients with resectable PC treated in our institution with IPCT (based on mFOLFOXIRI, GEMOX or GEMOXEL) followed by CRT (50 Gy and concurrent Capecitabine) were retrospectively analyzed. Additionally, clinical, pathological and analytical data were collected in order to perform a 2-year relapse-risk predictive population model using machine-learning techniques. Results: A R0 resection was achieved in 90% of the patients. After a median follow-up of 33.5 months, median progression-free survival (PFS) was 18 months and median overall survival (OS) was 39 months. The 3 and 5-year actuarial PFS were 43.8% and 32.3%, respectively. The 3 and 5-year actuarial OS were 51.5% and 34.8%, respectively. Forty-percent of grade 3-4 IPCT toxicity, and 29.7% of grade 3 CRT toxicity were reported. Considering the use of granulocyte colony-stimulating factors, the number of resected lymph nodes, the presence of perineural invasion and the surgical margin status, a logistic regression algorithm predicted the individual 2-year relapse-risk with an accuracy of 0.71 (95% confidence interval [CI] 0.56-0.84, p = 0.005). The model-predicted outcome matched 64% of the observed outcomes in an external dataset. Conclusion: An intensified multimodal neoadjuvant approach (IPCT + CRT) in resectable PC is feasible, with an encouraging long-term outcome. Machine-learning algorithms might be a useful tool to predict individual risk of relapse. A small sample size and therapy heterogeneity remain as potential limitations.
- 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.