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Consistently, lipid storage contributes substantially to the liver triglyceride pool and liver steatosis.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">5</span></a> Its spectrum varies from simple steatosis to nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">6</span></a> In spite of high prevalence of NAFLD, little is known about its pathogenesis. Recent studies suggest that both environmental and genetic factors are involved in the progression and development of NAFLD.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Neuropeptide Y (NPY) is a 36-amino acid peptide neurotransmitter. It is expressed by chromaffin cells as well as noradrenergic cells.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">7</span></a> It has been proposed that increased NPY signaling due to high NPY expression in the hypothalamus contributes to the development of diabetes mellitus type 2, obesity and insulin resistance.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">8–9</span></a> The <span class="elsevierStyleItalic">NPY</span> gene has four exons and it is located at 7p15.1. The main genetic variant in this gene is rs16147 (G-399A).<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">10</span></a> This genetic variant is associated with changes in NPY expression. According previous studies might be responsible for more than half of the variation in the expression of NPY in vivo.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">11</span></a> The association between NPY rs16147 SNP and metabolic syndrome (MetS) has seldom been reported. To our knowledge, only one previous have explored the importance of rs16147:T>C for regulation of NPY gene expression and brain function in 314 young adults.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">12</span></a> Recently, receptors of NPY have beed related to NAFLD fibrosis. Of note, in vitro study has demonstrated a reduced expression of Y1, Y4 and Y5 NPY receptors, whereas patients with NAFLD and advanced fibrosis (F4 or cirrhosis) had high expression of Y1, Y4 and Y6 NPY receptors in the liver of patients with NAFLD without fibrosis.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">13</span></a> Given the limited information about the relation of the polymorphisms of <span class="elsevierStyleItalic">NPY</span> gene with NAFLD, we aimed to evaluate the influence of polymorphism rs16147 of NPY gene on liver histology and biochemical parameters in patients with obesity and NAFLD.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Subjects and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Subjects</span><p id="par0015" class="elsevierStylePara elsevierViewall">The study group consisted of eighty nine Caucasian subjects with obesity. Participants were selected according to the following inclusion criteria: body mass index<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>, persistently elevated liver enzyme (<span class="elsevierStyleItalic">ALT</span> alanine amino transferase<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>UI/L or <span class="elsevierStyleItalic">AST</span> aspartate amino transferase<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>31<span class="elsevierStyleHsp" style=""></span>UI/L) with an abdominal ultrasound showing fatty liver. Exclusion criteria were significant alcohol consumption (>30<span class="elsevierStyleHsp" style=""></span>g/day in males and >20<span class="elsevierStyleHsp" style=""></span>g/day in females), hepatitis B, C, cytomegalovirus, Epstein Barr infections, non-organ-specific autoantibodies, diabetes mellitus, medication (blood-pressure lowering medication and statins), hereditary defects (iron and copper storage diseases and alpha 1-antitrypsin deficiency) and medication that might induce steatosis (glucocorticoids, estrogens, tamoxifen or valproic acid). All participants signed an informed consent. This protocol was conducted according to the guidelines laid down in the Declaration of Helsinki, the local ethics committee (HCUVA) approved all procedures involving patients and patient data were codified to guarantee anonymity.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Liver histology</span><p id="par0020" class="elsevierStylePara elsevierViewall">The diagnosis of NAFLD was confirmed in all patients by percutaneous liver biopsy performed with a Menghini-type biopsy needle. The biopsy site was located in the seventh or eighth intercostal space in the mid-axillary line. The site was further confirmed with ultrasonography. Skin, subcutaneous tissue, muscles, and peritoneum were infiltrated with the local anesthetic (procainamide 1%, 1<span class="elsevierStyleHsp" style=""></span>ml at most). Vim–Silverman needle (short trocar and cannula) was introduced until the needle reached the liver. Then, trocar was removed and the 1<span class="elsevierStyleHsp" style=""></span>cm long biopsy punched out by the introduction of a longer cannula split longitudinally that turned around to cut the liver piece. Biopsied liver was withdrawn through the cannula. Liver samples were sectioned, and stained with hematoxylin–eosin and Manson's trichrome. NAFLD was defined histologically by the presence of minimum 5% of steatosis on liver biopsy. Steatosis was scored as 1 (5–33%), 2 (34–66%), or 3 (>66%). Lobular inflammation was scored as 0 (presence of no inflammation), 1 (<2 foci per 200× field), 2 (2–4 foci per 200× field), or 3 based on >4 foci per 200× field. Ballooning was scored as 0 (no balloon cell), 1(few balloon cells), and 2 (many cells/prominent ballooning cells). A case presenting with at least grade 1 of each of the two features (ballooning, and lobular inflammation) and steatosis (NAS score) was classified as non alcoholic steatohepatitis (NASH).<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">14</span></a> Fibrosis was scored as 0 (no fibrosis), 1 (perisinusoidal or periportal), 2 (perisinusoidal and portal/periportal), 3 (bridging) and 4 (cirrhosis). To minimize inter-observer variability, liver biopsy specimens were read by the same pathologist using the SAF (Steatosis, Activity, Fibrosis) score which assesses the grade of steatosis (S, from S0 to S3), the grade of activity (A from A0 to A4 by adding grades of ballooning and lobular inflammation, both from 0 to 2) and the stage of fibrosis (F from F0 to F4).<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Genotyping and biochemical parameters</span><p id="par0025" class="elsevierStylePara elsevierViewall">DNA was extracted using commercial kit extraction (Biorad, LA, CA). Primers were designed with the Sequenom Assay Design v4 (SEQUENOM, Inc., San Diego, CA). Genotyping for the rs16147 polymorphism was performed by chain reaction real time analysis. This polymerase chain reaction (PCR) was carried out with 20–25<span class="elsevierStyleHsp" style=""></span>ng of genomic DNA, 0.1–0.15<span class="elsevierStyleHsp" style=""></span>μl each of oligonucleotide primer for rs16147 (primer forward: 5′-ACGTTGGATGCACAAAGAGGATTCAGGTGC-3′ and reverse 5′-ACGTTGGATGAGCCCAGACGATTCTTGTC-3′ in a 2-μl final volume (Termociclador Lifetecnologies, LA, CA). DNA was denatured at 85<span class="elsevierStyleHsp" style=""></span>°C for 5<span class="elsevierStyleHsp" style=""></span>min; this was followed by 45 cycles of denaturation at 95<span class="elsevierStyleHsp" style=""></span>°C for 15<span class="elsevierStyleHsp" style=""></span>s, and annealing at 58.1<span class="elsevierStyleHsp" style=""></span>°C for 45<span class="elsevierStyleHsp" style=""></span>s). The PCRs were run in a 2-μl final volume containing 0.1<span class="elsevierStyleHsp" style=""></span>μl of iPLEx Termination mix (Bio-Rad<span class="elsevierStyleSup">®</span>, San Diego, CA) with hot start Taq DNA polymerase. Hardy Weinberg equilibrium was calculated with a statistical test (Chi-square). The variant of NPY gene was in Hardy Weinberg equilibrium (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.21).</p><p id="par0030" class="elsevierStylePara elsevierViewall">Blood samples were collected in Na-EDTA tubes from patients after 12<span class="elsevierStyleHsp" style=""></span>h fast. All samples were frozen at −80<span class="elsevierStyleHsp" style=""></span>°C until laboratory testing. Insulin was assessed by radioimmunoassay (RIA) (RIA Diagnostic Corporation, Los Angeles, CA) with a sensitivity of 0.5<span class="elsevierStyleHsp" style=""></span>mUI/L (normal range 0.5–30<span class="elsevierStyleHsp" style=""></span>mUI/L)<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a> and the homeostasis model assessment for insulin resistance (HOMA-IR) was calculated using the next formula (fasting insulin<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>fasting glucose concentrations/22.5).<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">16</span></a> Plasma glucose levels, total cholesterol, triglyceride concentrations, HDL cholesterol, alanine amino transferase, aspartate aminotransferase activity and Gama glutamine transferase were measured by enzymatic colorimetric assay Hitachi 902 analyser (Hitachi Ltd., Tokyo, Japan). LDL cholesterol was calculated using Friedewald formula.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">17</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Resistin was measured by Enzyme-Linked Immunoabsorbent Assay (ELISA) (Biovendor Laboratory, Inc., Brno, Czech Republic) with a sensitivity of 0.2<span class="elsevierStyleHsp" style=""></span>ng/ml and a normal range of 4–12<span class="elsevierStyleHsp" style=""></span>ng/ml.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">18</span></a> Leptin was measured by ELISA (Diagnostic Systems Laboratories, Inc., Texas, USA) with a sensitivity of 0.05<span class="elsevierStyleHsp" style=""></span>ng/ml and a normal range of 10–100<span class="elsevierStyleHsp" style=""></span>ng/ml.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a> Adiponectin was measured by ELISA (R&D systems, Inc., Minneapolis, USA) with a sensitivity of 0.246<span class="elsevierStyleHsp" style=""></span>ng/ml and a normal range of 8.65–21.43<span class="elsevierStyleHsp" style=""></span>ng/ml.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Anthropometric measurements</span><p id="par0040" class="elsevierStylePara elsevierViewall">Body weight was assessed to an accuracy of 10<span class="elsevierStyleHsp" style=""></span>g and body mass index calculated as body weight in kg/(height in m<span class="elsevierStyleSup">2</span>). Waist and hip circumferences to derive waist-to hip ratio (WHR) were measured, too. Bioimpedance was used to determine total body fat mass with an accuracy of 10<span class="elsevierStyleHsp" style=""></span>g<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">21</span></a> (Akern, EFG, It). Resistance and reactance were used to calculate total body water, fat and fat-free mass.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Sample size was calculated to detect a 15% of differences in percentage of steatohepatitis between genotype groups in a dominant model. Data are expressed as mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation or as frequencies for categorical variables. Categorical variables were analyzed with the Chi-square test, with Yates correction as necessary, and Fisher's test. Continuous variables with normal distribution were analyzed with a two-tailed Student's <span class="elsevierStyleItalic">t</span>-test. Non-parametric variables were analyzed with the Mann–Whitney <span class="elsevierStyleItalic">U</span> test. Logistic regression analysis was used to test the association of rs16147 with liver histology (steatosis, fibrosis, ballooning and lobulillar inflammation as independent dichotomy variables, presence vs. absence) adjusted by sex, age, waist circumference and BMI. It was calculate OR and 95% confidence interval (CI). The genotype distribution was tested for deviation from Hardy–Weinberg equilibrium by a Chi-square test with 1 df (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05). The statistical analysis was performed for the combined <span class="elsevierStyleItalic">GA</span> and <span class="elsevierStyleItalic">AA</span> as a group and GG genotype as second group, with a dominant model. The statistical package was SPSS 15.0 (IL, USA). A <span class="elsevierStyleItalic">p</span>-value under 0.05 was considered statistically significant.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">Eighty nine patients gave informed consent and were enrolled in the study. The mean age was 45.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.5 years and the mean body mass index (BMI) 37.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.0<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>). All subjects were weight stable during the 12 weeks period preceding the study (body weight change, 0.16<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.1<span class="elsevierStyleHsp" style=""></span>kg).</p><p id="par0055" class="elsevierStylePara elsevierViewall">Thirty two were men (35.2%) and 57 women (64.8%). Twenty three patients (25.0%) had the genotype GG (wild type group) and sixty six patients (75%) patients GA (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>39) or AA (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>27) (mutant type group). The allelic frequency of A was 0.53. Age and gender distribution were similar in all groups.</p><p id="par0060" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> details the anthropometric variables. No differences were reported between both genotype groups.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> details the classic biochemical parameters. Lipid profile, levels of adipokines, liver biochemistry and glucose metabolism did not show statistical differences.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the histological findings according genotype. Patients with A allele presented a lower percentage of lobulillar inflammation and steatohepatitis (lobulillar inflammation plus ballooning) than patients in the wild type group. Patients with A allele showed lower SAF score than non-A allele carriers (5.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.7 points vs. 4.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.1 points; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01). In the analysis of this score performed without fibrosis (NAS score), the same differences were also detected (4.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.8 points vs. 3.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.8 points; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Finally, logistic regression analysis indicated that subjects with A-allele carriers presented lower probability of lobulillar inflammation (OR 0.11, 95% CI 0.02–0.84, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03) and steatohepatitis (OR 0.39, 95% CI 0.14–0.86, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04) after adjusting by age, sex and BMI. If the BMI is replaced by the waist circumference, the adjustment models are not modified.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">The main finding of this cross-sectional study was the beneficial effect of A allele on liver histology. This effect was independent of anthropometric and biochemical anthropometric and biochemical parameters. Carriers of A allele exhibited lower percentage of steatohepatitis and lobulillar inflammation than non A allele carriers.</p><p id="par0085" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">NPY</span> gene is highly polymorphic, some SNPs (single nucleotide polymorphism) of this gene have been associated with obesity and cardiovascular risk in some<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">22–23</span></a> but not all studies.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">24</span></a> The differences of these studies with our design is important; firstly, the population of the previous studies is no a Caucasian population and secondly, the inclusion criteria in some studies are very different from ours. For example, patients of this study<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">24</span></a> had a documented coronary artery disease; however the patients in our study had no coronary disease. The age of the populations studied can also be an important factor in the findings found in the literature. For example, Zain et al.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">25</span></a> reported that A allele of rs16147 is associated with increased risk of obesity, whereas A allele of rs5574 is associated with a reduced risk of obesity. Olza et al.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">26</span></a> reported similar results with rs16147 in a pediatric population. Hohmann et al.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a> reported a positive an increasing association between NPY promoter polymorphism and BMI during the course of development child growth, too. However, all these findings have not been replicated in the adult population.<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">28,29</span></a> Finally, the samples evaluated are not comparable, and in the particular case of our population of obese adults with cardiovascular risk, other genetic and environmental factors may be involved in our findings.</p><p id="par0095" class="elsevierStylePara elsevierViewall">To our knowledge, this research is the first to study the effect of this polymorphism of the <span class="elsevierStyleItalic">NPY</span> gene on liver histology in NAFLD subjects. Our results show that the A allele influence on lobulillar inflammation and steatohepatitis independently of body weight, age and sex. A previous study evaluating the NPY pathway has shown that patients with NAFLD presented a positive correlation between saturated fatty acid intake and NPY levels.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">30</span></a> Perhaps an interaction between the dietary intake in our study participants and the NPY pathway could explain our histopathological findings. On the other hand, in our study did not observe between a relationship between adipokine levels and this SNP. Nevertheless, a negative correlation between NPY and adiponectinemia in NAFLD obese adolescents has been reported.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">31</span></a> Mutschler et al.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a> reported an interaction of this SNP with leptin levels in females, too.</p><p id="par0100" class="elsevierStylePara elsevierViewall">The precise molecular mechanisms underlying our observed association between rs16147 and liver histology are unclear. Molecular studies have been developed to NPY after its discovery as an orexigenic neuropeptide, since those initial studies, NPY has also been found to affect energy expenditure independent of food intake.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">32</span></a> Perhaps this effect on energy expenditure can influence the accumulation of fat at the body and specifically in the liver tissue at the liver level. Another potential hypothesis is the level of expression of different subtypes of NPY receptors in the liver at the hepatic level. Sigala et al.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">13</span></a> have reported a relationship between expression of different types of NPY receptors and liver fibrosis. Since NAFLD patients without fibrosis had reduced expression of Y1, Y4 and Y5 NPY receptors, whereas patients with NAFLD with cirrhosis had high expression of Y1, Y4 and Y6 NPY receptors in an in vitro study.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">13</span></a> Other in vitro study<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">33</span></a> has shown the proliferative effects of NPY on hepatic stellate cells.</p><p id="par0105" class="elsevierStylePara elsevierViewall">A strength of our study, it is the use of liver biopsy as a diagnostic method for NALFLD. Our study has some limitations. First, we did not measure serum NPY levels in order to evaluate their direct effects on hepatic histology. Secondly, there are uncontrolled non-genetic factors such as exercise, hormone levels, and other lifestyle factors that could influence the relationships observed in our study, none of which were taken to account in the present study. For example, different studies of dietary intervention<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">34,35</span></a> have shown that the metabolic response to diet is modulated depending on the presence of the allele A. Thirdly, other variants of this gene or other genes that are in imbalance can influence the results obtained in our findings. Fourthly, the difficulties in generalizing the results to other populations of patients with non-alcoholic fatty liver disease, such as patients without significant obesity (the mean BMI of the included patients was >35<span class="elsevierStyleHsp" style=""></span>kg or with diabetes (comorbidity frequently associated with NAFLD). Finally, our study cannot prove causality due to its cross-sectional design.</p><p id="par0110" class="elsevierStylePara elsevierViewall">In conclusion, A variant of the polymorphism rs16147 of <span class="elsevierStyleItalic">NPY</span> gene is independently associated with a lower percentage of steatohepatitis and lobulillar inflammation in obesity subjects with proven biopsy NAFLD. Therefore, future studies are necessary to find out if it is necessary to evaluate different polymorphisms in the patient with NAFLD at the time of diagnosis and before initiating the treatment.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Funding</span><p id="par0115" class="elsevierStylePara elsevierViewall">There is no financial support.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflict of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">There is no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1196398" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and rationale" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1114886" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1196399" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y justificación" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1114885" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Subjects and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Subjects" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Liver histology" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Genotyping and biochemical parameters" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Anthropometric measurements" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-05-17" "fechaAceptado" => "2018-10-16" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1114886" "palabras" => array:5 [ 0 => "Adipokines" 1 => "Obesity" 2 => "NPY" 3 => "RS16147" 4 => "Non-alcoholic fatty liver disease" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1114885" "palabras" => array:5 [ 0 => "Adipoquinas" 1 => "Obesidad" 2 => "NPY" 3 => "RS16147" 4 => "Enfermedad por hígado graso no alcohólico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and rationale</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">This study was intended to assess the influence of the rs16147 variant of the <span class="elsevierStyleItalic">NPY</span> gene on liver histology in patients with non-alcoholic fatty liver disease (NAFLD).</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Eighty-nine patients with NAFLD were recruited into the study. Serum chemistry tests were done including lipid profile, transaminases, adipokines, and insulin resistance. Genotype of polymorphism (rs161477) of the <span class="elsevierStyleItalic">NPY</span> gene was studied.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Twenty-three patients (25.0%) had the GG genotype (wild type) and sixty-six patients (75%) the GA (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>39) or AA (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>27) (mutant) types. Patients with A allele had a lower percentage of lobular inflammation and steatohepatitis (lobular inflammation plus ballooning) than those with wild genotype. Patients with A allele showed lower SAF (Steatosis, Activity, Fibrosis) scores than non-A allele carriers (5.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.7 points vs. 4.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.1 points; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01). In the analysis without fibrosis (NAS score), the same differences were detected (4.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.8 points vs. 3.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.8 points; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01). In the logistic regression analysis A allele carriers showed lower odds for inflammation (OR 0.11, 95% CI 0.02–0.84, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03) and steatohepatitis (OR 0.39, 95% CI 0.14–0.86, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04) after adjusting for age, sex, and body mass index.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A variant of polymorphism rs16147 of the <span class="elsevierStyleItalic">NPY</span> gene is independently associated to a lower percentage of steatohepatitis and lobular inflammation in obese subjects with biopsy-proven NAFLD.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and rationale" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y justificación</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El objetivo de nuestro estudio fue estudiar la influencia de la variante rs16147 del gen <span class="elsevierStyleItalic">NPY</span> en la histología hepática en pacientes con enfermedad de hígado graso no alcohólico (NAFLD).</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se reclutó una muestra de 89 pacientes con NAFLD. Se realizó un análisis bioquímico del suero que incluyó perfil lipídico, transaminasas, adipoquinas y resistencia a la insulina. Se estudió el genotipo de polimorfismo (rs161477) del gen <span class="elsevierStyleItalic">NPY</span>.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Un total de 23 pacientes (25,0%) presentaron el genotipo GG (genotipo salvaje) y 66 pacientes (75%) GA (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>39) o AA (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>27) (genotipo mutante). Los pacientes con alelo A presentaron un menor porcentaje de inflamación lobulillar y esteatohepatitis que los pacientes con genotipo salvaje. Los pacientes con alelo A mostraron una puntuación más baja de SAF (esteatosis, actividad, fibrosis) que los no portadores de alelos A (5,4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2,7 puntos vs. 4,1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1,1 puntos, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,01). En el análisis realizado sin fibrosis (solo puntaje NAS), también se detectaron las mismas diferencias (4,5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1,8 puntos vs. 3,4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1,8 puntos, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,01). En el análisis de regresión logística a presencia del alelo A a una menor probabilidad de presentar con inflamación lobulillar (OR 0,11, IC 95%: 0,02-0,84; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,03) y esteatohepatitis (OR 0,39, IC 95%: 0,14-0,86, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,04) después de ajustar por edad, sexo e índice de masa corporal.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La variante del polimorfismo rs16147 del gen <span class="elsevierStyleItalic">NPY</span> se asocia de forma independiente con un menor porcentaje de esteatohepatitis e inflamación lobulillar en sujetos obesos con NAFLD diagnosticado con biopsia.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes y justificación" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">BMI: body mass index. WC: waist circumference. No statistical differences between groups. Parameters expressed in (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation).</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GG (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>22) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(GA or AA) (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>66) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI (kg/m<span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Weight (kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">129.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>31.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">126.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>23.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">WC (cm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">122.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">119.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fat mass (kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2042461.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Anthropometric variables.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">LDL: low density lipoprotein. HDL: high density lipoprotein. Ch: cholesterol. TG: triglycerides. HOMA-IR: homeostasis model assessment. <span class="elsevierStyleItalic">ALT</span>: alanine amino transferase. <span class="elsevierStyleItalic">AST</span>: aspartate amino transferase. GGT: gamma glutamil transferase. No statistical differences between groups. Parameters expressed in mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GG (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>22) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(GA or AA) (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>66) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glucose (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">101.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">103.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total ch. (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">168.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>38.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">166.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>39.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LDL-ch. (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">97.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>20.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">99.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HDL-ch. (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TG (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">180.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>71.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">160.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>72.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Insulin (UI/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HOMA-IR (UI/L<span class="elsevierStyleHsp" style=""></span>*<span class="elsevierStyleHsp" style=""></span>mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adiponectin (ng/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Resistin (ng/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leptin (ng/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>31.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>26.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ALT (UI/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AST (UI/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>24.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GGT (UI/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">102.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>33.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>26.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2042460.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Biochemical parameters.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Steatosis grade 3 (> 66%).</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Chi square test, *<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 (%) frequencies in each genotype group.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GG (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>22) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(GA or AA) (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>66) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Steatosis grade 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22.0% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ballooning \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58.2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.31 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lobular inflammation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">95.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Steatohepatitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70.8% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40.8% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fibrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50.0% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47.8% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.85 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2042459.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Histological parameters (frequencies).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:35 [ 0 => array:3 [ "identificador" => "bib0180" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. 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Caldwell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jhep.2003.50193" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2003" "volumen" => "37" "paginaInicial" => "1202" "paginaFinal" => "1219" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12717402" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0215" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Expressions of neuropeptide Y and Y1 receptor in subcutaneous and visceral fat tissues in normal weight and obese humans and their correlations with clinical parameters and peripheral metabolic factors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. Sitticharoon" 1 => "S. Chatree" 2 => "M. 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Year/Month | Html | Total | |
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2024 November | 2 | 0 | 2 |
2024 October | 22 | 8 | 30 |
2024 September | 25 | 7 | 32 |
2024 August | 20 | 2 | 22 |
2024 July | 27 | 2 | 29 |
2024 June | 15 | 6 | 21 |
2024 May | 26 | 16 | 42 |
2024 April | 28 | 6 | 34 |
2024 March | 28 | 9 | 37 |
2024 February | 34 | 14 | 48 |
2024 January | 7 | 9 | 16 |
2023 December | 14 | 9 | 23 |
2023 November | 12 | 11 | 23 |
2023 October | 15 | 18 | 33 |
2023 September | 15 | 20 | 35 |
2023 August | 17 | 14 | 31 |
2023 July | 7 | 12 | 19 |
2023 June | 13 | 10 | 23 |
2023 May | 37 | 15 | 52 |
2023 April | 48 | 7 | 55 |
2023 March | 25 | 10 | 35 |
2023 February | 32 | 17 | 49 |
2023 January | 8 | 18 | 26 |
2022 December | 17 | 15 | 32 |
2022 November | 17 | 15 | 32 |
2022 October | 19 | 15 | 34 |
2022 September | 17 | 9 | 26 |
2022 August | 17 | 8 | 25 |
2022 July | 19 | 5 | 24 |
2022 June | 23 | 7 | 30 |
2022 May | 59 | 4 | 63 |
2022 April | 51 | 6 | 57 |
2022 March | 118 | 9 | 127 |
2022 February | 108 | 6 | 114 |
2022 January | 96 | 5 | 101 |
2021 December | 37 | 14 | 51 |
2021 November | 86 | 7 | 93 |
2021 October | 25 | 9 | 34 |
2021 September | 32 | 8 | 40 |
2021 August | 11 | 6 | 17 |
2021 July | 18 | 11 | 29 |
2021 June | 10 | 6 | 16 |
2021 May | 17 | 8 | 25 |
2021 April | 35 | 23 | 58 |
2021 March | 13 | 6 | 19 |
2021 February | 17 | 6 | 23 |
2021 January | 21 | 12 | 33 |
2020 December | 16 | 6 | 22 |
2020 November | 24 | 7 | 31 |
2020 October | 20 | 5 | 25 |
2020 September | 20 | 9 | 29 |
2020 August | 14 | 7 | 21 |
2020 July | 19 | 7 | 26 |
2020 June | 18 | 1 | 19 |
2020 May | 14 | 7 | 21 |
2020 April | 12 | 3 | 15 |
2020 March | 21 | 3 | 24 |
2020 February | 14 | 4 | 18 |
2020 January | 16 | 3 | 19 |
2019 December | 17 | 10 | 27 |
2019 November | 8 | 1 | 9 |
2019 October | 9 | 8 | 17 |