Effect of Vitamin D Serum Levels and GC Gene Polymorphisms in Liver Fibrosis Due to Chronic Hepatitis C

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Sustained virologic response at post-treatment week 12 among patients treated in the first 12 months of the PEI HCV treatment program (n = 84). Individual proportions are presented. Patients received: 12 weeks paritaprevir/ritonavir/ombitasvir/dasabuvir with ribavirin (n = 73) or without ribavirin (n = 7); 24 weeks paritaprevir / ritonavir / ombitasvir / dasabuvir with ribavirin (n = 4). ^ One loss to follow-up; 1 unrelated death after therapy. SVR12: sustained virologic response at post-treatment week 12. Tx: treatment." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Jordan W. Francheville, Robin Rankin, Jeremy Beck, Connie Hoare, Stefanie Materniak, Greg German, Lisa Barrett, Natalie Bunimov-Wall, Daniel Smyth" "autores" => array:9 [ 0 => array:2 [ "nombre" => "Jordan W." 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"documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2017;16:734-41" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 111 "formatos" => array:3 [ "EPUB" => 13 "HTML" => 58 "PDF" => 40 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Outcomes for Cirrhotic Patients with Hepatitis C Virus 1b Treated with Asunaprevir and Daclatasvir Combination" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "734" "paginaFinal" => "741" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1112 "Ancho" => 1471 "Tamanyo" => 147065 ] ] "descripcion" => array:1 [ "en" => "Change from baseline ALT levels during ASV + DCV treatment in cirrhot-ic and non-cirrhotic groups. * Treatment was stopped due to ALT elevation." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Akihiro Tamori, Hoang Hai, Sawako Uchida-Kobayashi, Masaru Enomoto, Ritsuzo Kozuka, Hiroyuki Motoyama, Etsushi Kawamura, Atsushi Hagihara, Yuga Teranishi, Kanako Yoshida, Hiroyasu Morikawa, Yoshiki Murakami, Norifumi Kawada" "autores" => array:13 [ 0 => array:2 [ "nombre" => "Akihiro" "apellidos" => "Tamori" ] 1 => array:2 [ "nombre" => "Hoang" "apellidos" => "Hai" ] 2 => array:2 [ "nombre" => "Sawako" "apellidos" => "Uchida-Kobayashi" ] 3 => array:2 [ "nombre" => "Masaru" "apellidos" => "Enomoto" ] 4 => array:2 [ "nombre" => "Ritsuzo" "apellidos" => "Kozuka" ] 5 => array:2 [ "nombre" => "Hiroyuki" "apellidos" => "Motoyama" ] 6 => array:2 [ "nombre" => "Etsushi" "apellidos" => "Kawamura" ] 7 => array:2 [ "nombre" => "Atsushi" "apellidos" => "Hagihara" ] 8 => array:2 [ "nombre" => "Yuga" "apellidos" => "Teranishi" ] 9 => array:2 [ "nombre" => "Kanako" "apellidos" => "Yoshida" ] 10 => array:2 [ "nombre" => "Hiroyasu" "apellidos" => "Morikawa" ] 11 => array:2 [ "nombre" => "Yoshiki" "apellidos" => "Murakami" ] 12 => array:2 [ "nombre" => "Norifumi" "apellidos" => "Kawada" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119304326?idApp=UINPBA00004N" "url" => "/16652681/0000001600000005/v1_201905301208/S1665268119304326/v1_201905301208/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "titulo" => "Effect of Vitamin D Serum Levels and GC Gene Polymorphisms in Liver Fibrosis Due to Chronic Hepatitis C" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "742" "paginaFinal" => "748" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Laura A. Azevedo, Ursula Matte, Themis R. Silveira, Jacqueline W. Bonfanti, Juliana P. Bruch, Mário R. Álvares-da-Silva" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Laura A." "apellidos" => "Azevedo" "email" => array:1 [ 0 => "laura.alencastro@ufrgs.br" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] 1 => array:3 [ "nombre" => "Ursula" "apellidos" => "Matte" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "**" "identificador" => "aff2" ] 1 => array:2 [ "etiqueta" => "***" "identificador" => "aff3" ] ] ] 2 => array:3 [ "nombre" => "Themis R." "apellidos" => "Silveira" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "***" "identificador" => "aff3" ] ] ] 3 => array:3 [ "nombre" => "Jacqueline W." "apellidos" => "Bonfanti" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "****" "identificador" => "aff4" ] ] ] 4 => array:3 [ "nombre" => "Juliana P." "apellidos" => "Bruch" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] ] ] 5 => array:3 [ "nombre" => "Mário R." "apellidos" => "Álvares-da-Silva" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "****" "identificador" => "aff4" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Graduate Program in Gastroenterology and Hepatology Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil" "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Department of Genetics; Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil" "etiqueta" => "**" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Graduate Program in Child and Adolescence Health, Universidade Federal do Rio Grande do Sul; Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil" "etiqueta" => "***" "identificador" => "aff3" ] 3 => array:3 [ "entidad" => "Department of Internal Medicine, Universidade Federal do Rio Grande do Sul; Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil" "etiqueta" => "****" "identificador" => "aff4" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 785 "Ancho" => 999 "Tamanyo" => 91809 ] ] "descripcion" => array:1 [ "en" => "Median 25(OH)D serum levels of the enrolled patients according to investigation month." ] ] ] "textoCompleto" => "IntroductionLiver fibrosis is defined by extracellular matrix (ECM) accumulation with consequent loss of liver function, due to acute or chronic damage.<a class="elsevierStyleCrossRef" href="#bib0010">1</a> Chronic hepatitis C (CHC) leads to liver fibrosis and 20-30% of patients progress to cirrhosis after 25-30 years of infection.<a class="elsevierStyleCrossRef" href="#bib0015">2</a> Several factors influence the evolution of CHC and formation of liver fi-brosis, such as age, obesity, virus C genotype, alcohol consumption, duration of infection, presence of viral co-infections and metabolic disorders.<a class="elsevierStyleCrossRef" href="#bib0015">2</a>Vitamin D has been associated with chronic liver diseases and low vitamin levels may contribute to progression of CHC.<a class="elsevierStyleCrossRef" href="#bib0020">3</a> Vitamin D is mainly synthesized in the skin by 7-dehydrocholesterol redutase (DHCR7) in pre-vitamin D, which is converted into vitamin D by isomeri-zation. Vitamin D and its metabolites circulate bounded to vitamin D-binding protein (GC-globulin). Vitamin D goes under hydroxylation in the liver by cytochrome P450 enzymes forming 25-hydroxyvitamin D (25(OH)D) and is used to evaluate vitamin D status. The metabolite 25(OH)D is hydroxylated by CYP27B1 in the kidney, producing 1,25-dihydroxyvitamin D (1,25(OH)D), the active form that binds to vitamin D receptor (VDR).<a class="elsevierStyleCrossRef" href="#bib0025">4</a> Vitamin D deficiency is a risk factor for all-cause mortality in the general population<a class="elsevierStyleCrossRef" href="#bib0030">5</a> as well as for cirrhotic patients.<a class="elsevierStyleCrossRef" href="#bib0035">6</a>GC-globulin is coded by GC gene. The three protein isoforms are coded by different alleles, which are formed by single nucleotide polymorphisms (SNPs). Polymorphism rs7041 has two alternative alleles, containing either A or C, and polymorphism rs4588 has either G or T. Each person carries two copies of the GC gene; therefore possible genotypes for rs7041 are AA, AC or CC, for example. Different SNPs at the same gene are inherited together forming a haplotype. For rs7041 and rs4588 possible haplo-types are CT, CG or AT. These two SNPs are responsible for the three major circulating isoforms of GC-globulin Gc1F (CT), Gc1S (CG) and Gc2rs (AT).<a class="elsevierStyleCrossRef" href="#bib0040">7</a> The Gc-2 iso-form is described to have the lowest affinity for its ligand.<a class="elsevierStyleCrossRef" href="#bib0045">8</a> The three common haplotype variants combined form CT-CT, CT-CG, CG-CG, CG-AT, CT-AT and AT-AT.It is known that several polymorphisms involved in the vitamin D metabolism are associated with its serum con-centrations.<a class="elsevierStyleCrossRefs" href="#bib0050">9,10</a> The aim of this study was to evaluate the influence of vitamin D serum levels and GC polymorphisms in the severity of liver fibrosis in patients with chronic hepatitis C genotype 1.Material and MethodsThis was a cross-sectional study that enrolled 132 adult patients with chronic hepatitis C genotype 1 attended at the outpatient Clinic of Gastroenterology Division at Hospital de Clínicas de Porto Alegre, Brazil, from June 2013 to February 2015. Hepatitis C virus infection was confirmed by anti-HCV ELISA 3 and by detection of viral RNA by polymerase chain reaction (HCV RNA PCR). Patients infected by the human immunodeficiency virus (HIV) or hepatitis B virus (HBV), alcohol abusers (> 40g/ day), chronic renal injured, liver transplanted, decompen-sated cirrhotic and those with hepatocellular carcinoma (HCC) or in immunosuppressive or antiviral treatment were excluded. Both naïve and previously PEG-INF treated patients were included.At the time of the enrollment patients had a blood withdraw for vitamin D serum levels determination and geno-typic analysis. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl-transferase (GGT), platelets, glucose, cholesterol and body mass index (BMI) were extracted from patient's chart from the previous 6 months. Severity of fibrosis was evaluated by the last liver biopsy done by the outpatients Clinic routine. Liver biopsies were evaluated by the same pathologist and scored with METAVIR system.<a class="elsevierStyleCrossRef" href="#bib0060">11</a> Serum 25(OH)D levels were determined using a chemoluminescent immunoassay on a Liaison automatic analyzer (Dia-Sorin). Vitamin D levels below 10 ng/mL were considered severe deficiency; 10 to 20 ng/mL deficiency; 20 to 30 ng/ mL insufficiency; and above 30 ng/mL sufficiency.<a class="elsevierStyleCrossRef" href="#bib0065">12</a> Date of sample collection was categorized into two seasons, Summer/autumn (December-May) and Winter/spring (June-November). The study was conducted according to the principles of the Declaration of Helsinki and was approved by the hospital Ethical Committee. All patients gave written informed consent to participate in the study.Genotypic analysisThe genomic DNA was extracted from whole blood EDTA using Wizard® Genomic DNA Purification Kit (Promega) according to manufacturer's instructions. The polymorphisms rs7041 and rs4588 from the GC gene were identified using hydrolysis probes (TaqMan Assays; ABI), IDs: C_3133594_30 and C_8278879_10, respectively. A total of 10 ng of DNA was used in a final reaction volume of 12.5 μL for real-time PCR on StepOne™ System (Thermo Fisher).Statistical analysisCategorical variables are presented as frequencies. Continuous variables with normal distribution are presented as mean and standard deviation and variables with non-normal distribution as median and interquartile range (P25-P75). To check the normal distribution of the variables, a Sha-piro-Wilk test was applied. Associations between continuous variables were carried out with T test, Mann-Whitney or Kruskall-Wallis as appropriated and associations between categorical variables were evaluated with Fisher's exact test. Stepwise multiple linear regression analysis with a forward approach using a cutoff value of 0.05 was performed to identify independent predictors of 25(OH)D levels. Step-wise logistic regression analysis with a forward approach using a cutoff value of 0.05 was performed to identify independent predictors of liver fibrosis. Variables included in the model were sex, age, fibrosis (none/mild or severe), diabetes mellitus, BMI, ALT, AST, GGT, cholesterol, glucose, platelets, rs4588 and rs7041 haplotypes (AT/AT + AG/ AT vs. others), season of blood withdrawn (Summer/Autumn vs. Winter/Spring). For analysis purposes none/mild fibrosis was considered as METAVIR F0, F1 and F2 and severe fibrosis as METAVIR F3 and F4 (cirrhosis). A χ2 test was employed to verify whether the proportions of the two polymorphisms were distributed in accordance with the Hardy-Weinberg Equilibrium. Haplotypes for rs7041 and rs4588 were statistically reconstructed using the PHASE program, version 2.1, which implements a Bayesian statistical method for haplotyping reconstructing from genotype data.<a class="elsevierStyleCrossRefs" href="#bib0070">13,14</a> Statistical analysis was performed using SPSS 20.0 (SPSS Inc, Chicago, Il, USA). Significance level was set at α< 0.05.ResultsPatient featuresDemographical, clinical, biochemical and genotypic features of enrolled patients are described in <a class="elsevierStyleCrossRef" href="#t0010">table 1</a>. Patients’ age varied from 26 to 74 years. The majority of patients were cirrhotic (33.3%). Median 25(OH)D levels were 19.9 ng/mL (14.0 - 29.4). Fifty percent of patients presented deficiency or severe deficiency of vitamin D.<elsevierMultimedia ident="t0010"></elsevierMultimedia>Genotypes and alleles frequencies of rs7041 and rs4588 were in Hardy Weinberg Equilibrium. The most frequent genotypes were AC for rs7041 and GG for rs4588 (<a class="elsevierStyleCrossRef" href="#t0015">Table 2</a>). Finally, for haplotypes, GC/TA, GC/GC and GC/GC were the most common ones.<elsevierMultimedia ident="t0015"></elsevierMultimedia>Predictors of 25(OH)D serum levelsVitamin D levels were higher in patients enrolled in Summer/Autumn than in Winter/Fall [31.2ng/mL (IQR 19.8-35.0) vs. 18.4ng/mL (IQR 12.8-24.1); P < 0.001] (<a class="elsevierStyleCrossRef" href="#f0010">Figure 1</a>). Median 25(OH)D levels was 18.0 ng/mL (12.7 - 23.2) for females and 24.0 ng/mL (17.2 - 31.8) for males (P = 0.002). Vitamin D did not differ between näive and PEG-INF treated patients (P = 0.921). When 25(OH)D serum levels were stratified among rs7041 and rs4588 genotypes and haplotypes, there was no statistical significance (P > 0.05), however a trend is graphically observed for AA genotype of rs7041 and TT genotype of rs4588, as well as for AT/AT and AG/AT haplotypes (<a class="elsevierStyleCrossRef" href="#f0015">Figure 2</a>). Transforming the mentioned genotypes and haplo-types into dichotomous variables, it is observed that 25(OH)D levels are lower for AA genotype of rs7041, TT genotype of rs4588 and AT/AT + AG/AT haplotypes when compared to their counterparts (<a class="elsevierStyleCrossRef" href="#t0020">Table 3</a>). In multiple linear regression the variables associated with diminished 25(OH)D circulating levels were blood withdrawn in Winter/Spring, the risk haplotypes AT/AT + AG/AT and female sex (<a class="elsevierStyleCrossRef" href="#t0025">Table 4</a>).<elsevierMultimedia ident="f0010"></elsevierMultimedia><elsevierMultimedia ident="f0015"></elsevierMultimedia><elsevierMultimedia ident="t0020"></elsevierMultimedia><elsevierMultimedia ident="t0025"></elsevierMultimedia>Variables related to liver fibrosisIn <a class="elsevierStyleCrossRef" href="#t0030">table 5</a> are presented the association of studied variables with severity of liver fibrosis. Older age; higher BMI, ALT, GGT and glucose; lower platelets and 25(OH)D; diabetes and severe vitamin D deficiency were related to severe liver fibrosis in bivariate analysis. None of the evaluated genotypes and haplotypes of rs7041 and rs4588 were associated with fibrosis severity. In the logistic regression analysis were included sex, age, 25(OH)D > 10 ng/mL, season of blood withdrawn (Summer/Autumn vs. Winter/Spring), diabetes mellitus, BMI, ALT, AST, GGT, cholesterol, glucose, platelets, rs4588 and rs7041 haplo-types (AT/AT + AG/AT vs. others). The variables that remained in the model were age, 25(OH)D < 10 ng/mL, glucose levels, BMI and platelets count. When 25(OH)D is included as a continuous variable it loses statistical significance in the model.<elsevierMultimedia ident="t0030"></elsevierMultimedia>DiscussionIn recent years, the influence of vitamin D in liver diseases has been broadly discussed since it undergoes hepatic metabolism. Herein we evaluated the association of vitamin D serum levels and of rs7041 and rs4588 polymorphisms from GC gene in severe liver fibrosis in a sample of 132 chronic hepatitis C genotype 1 patients.In this sample, vitamin D median levels were 19.9 ng/ mL and deficiency prevalence was 50%. In a study with 496 CHC patients from Swiss hospitals, median 25(OH)D was 13.4 ng/mL, and 74% presented levels below 20.0 ng/ mL.<a class="elsevierStyleCrossRef" href="#bib0080">15</a> It has been described that the prevalence of vitamin D insufficiency and deficiency in patients with chronic liver disease ranges between 64 and 92%.<a class="elsevierStyleCrossRef" href="#bib0085">16</a>Serum levels of 25 (OH)D fluctuate strongly as a result of variations in sunlight exposure during the season, type of food, presence of comorbidities, vitamin D supplementation and others. It is important to also evaluate the different genetic variants of vitamin D metabolism, which could provide an assessment of long term vitamin D status. In multiple regression analysis, 25(OH)D levels were influenced by season, sex and genetic factors. Polymorphisms in genes involved in synthesis, transport and vitamin D metabolism are known to affect its circulating levels, especially in GC, DHCR7 and CYP2R1 loci.<a class="elsevierStyleCrossRefs" href="#bib0040">7,8,17</a> The GC gene codifies the protein responsible for carrying vitamin D and its metabolites in the circulation and in our study the haplotypes AT/AT and AG/AT were responsible for the lower levels of vitamin D, showing that the T allele of rs4588 has the biggest influence in vitamin D levels. Our findings are similar to Santos, et al., which found the same results in healthy Brazilian girls.<a class="elsevierStyleCrossRef" href="#bib0095">18</a> The Gc-2 isoform is described to have the lowest affinity for its ligand, which is in accordance confirming the lowest levels of vitamin D described in both studies.<a class="elsevierStyleCrossRef" href="#bib0055">10</a>Vitamin D deficiency seems to be associated with a poorer prognosis of the liver disease. In this sample, a difference in 25(OH)D serum levels was observed in none/ mild and severe fibrosis (21.1 vs. 18.1 ng/mL; P = 0.014). Baur, et al. reported that individuals with CHC METAVIR 2 presented 15.5 ng/mL 25(OH)D levels compared to 22.2 ng/mL of individuals METAVIR 0/1.<a class="elsevierStyleCrossRef" href="#bib0100">19</a> Meanwhile, Petta described that CHC G1 with Scheuer scoring 0-2 presented 25.5ng/mL vs. 21.9 ng/mL from patients Scheuer scoring of 3-4.<a class="elsevierStyleCrossRef" href="#bib0105">20</a> In our sample the overall prevalence of severe deficiency was 13.6% (18/132), in patients with none/mild fibrosis was 5.6% (4/72) and in patients with severe fibro-sis was 23.3% (14/60). In a cohort of German CHC patients, severe deficiency prevalence was 25%.<a class="elsevierStyleCrossRef" href="#bib0110">21</a> In logistic regression, severe vitamin D deficiency was associated with severe fibrosis along with age, BMI and platelets count. Although the studied polymorphisms have presented association with vitamin D circulating levels, they were not related to liver fibrosis. There are studies that have shown that polymorphisms of vitamin D metabolism relate to the stages of liver disease. Studies from Petta and Grünhage identified the polymorphism rs12785878 in the gene of cholesterol reductase (DHCR7) associated with a greater degree of liver fibrosis.<a class="elsevierStyleCrossRefs" href="#bib0115">22,23</a> This polymorphism was not evaluated in the present sample. Another gene that is important in liver fibrosis is VDR, since it can down-regulate the activation of hepatic stellate cells by competing for several genomic sites related to fibrosis, which are activated by SMAD3, an effector of the transforming growth factor beta 1 (TGFβ1).<a class="elsevierStyleCrossRef" href="#bib0125">24</a> The rs1544410, rs7975232 and rs731236 polymorphisms have been associated with the rate of progression of fibrosis and cirrhosis.<a class="elsevierStyleCrossRef" href="#bib0100">19</a>As limitation of this study we could cite that some co-founding factors were not analyzed, such as smoking, intravenous drug use, duration of HCV infection. Also, it was a cross-sectional study that analyzed only two polymorphisms. Although the sample size is relatively small, we considered as a main strength the use of a well-defined cohort of HCV genotype 1 patients that represent the real-world experience. Our results corroborate the literature findings, whereas lower vitamin D levels are found among patients with higher liver fibrosis. Identifying those patients is important since oral supplementation of vitamin D is a very simple therapeutic measure. Several studied have demonstrated that vitamin D deficiency I is likely to be related to lower odds of sustained virological response (SVR) to treatment with pegylated interferon plus ribavi-rin.<a class="elsevierStyleCrossRef" href="#bib0130">25</a> and recently, in a Japanese trial, vitamin D3 supplementation increased SVR rates on refractory CHC patients on treatment with simeprevir, pegylated interferon plus ribavirin.<a class="elsevierStyleCrossRef" href="#bib0135">26</a>In summary, vitamin D levels were associated with severity of liver fibrosis in chronic hepatitis C genotype 1 patients. Although the rs7041 and rs4588 GC gene polymorphisms are strong predictors of vitamin D levels, they do not play a direct role in liver fibrosis.Abbreviations<ul class="elsevierStyleList" id="l0010"><li class="elsevierStyleListItem" id="u0010">•1,25(OH)D: 1,25-dihydroxyvitamin D.</li><li class="elsevierStyleListItem" id="u0015">•25(OH)D: 25-hydroxyvitamin D.</li><li class="elsevierStyleListItem" id="u0020">•ALT: alanine aminotransferase.</li><li class="elsevierStyleListItem" id="u0025">•AST: aspartate aminotransferase.</li><li class="elsevierStyleListItem" id="u0030">•BMI: body mass index.</li><li class="elsevierStyleListItem" id="u0035">•CHC: chronic hepatitis C.</li><li class="elsevierStyleListItem" id="u0040">•DHCR7: 7-dehydrocholesterol redutase.</li><li class="elsevierStyleListItem" id="u0045">•ECM: extracellular matrix.</li><li class="elsevierStyleListItem" id="u0050">•GGT: gamma-glutamyl-transferase.</li><li class="elsevierStyleListItem" id="u0055">•SVR: sustained virological response.</li><li class="elsevierStyleListItem" id="u0060">•VDR: vitamin D receptor.</li></ul>Financial SupportThe authors would like to thank Fundo de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre (FIPE-HCPA), Programa de Apoio à Pós-Graduação da Coorde-nação de Aperfeiçoamento de Pessoal de Nível Superior (PROAP-CAPES) and Conselho Nacional de Desen-volvimento Científico e Tecnológico (CNPq).Authors ContributionStudy conception and design: LAA; UM; TRS; MRAS. Performed the experiments: LAA; JWB; JPB. Analyzed the data: LAA. Wrote the paper: LAA; UM; TRS; JPB; JWB; MRAS. Critical revision: UM; TRS; MRAS." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1197553" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abs0010" "titulo" => "Introduction and aim" ] 1 => array:2 [ "identificador" => "abs0015" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abs0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abs0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1116239" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "s0010" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "s0015" "titulo" => "Material and Methods" ] 4 => array:3 [ "identificador" => "s0020" "titulo" => "Genotypic analysis" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "s0025" "titulo" => "Statistical analysis" ] ] ] 5 => array:3 [ "identificador" => "s0030" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "s0035" "titulo" => "Patient features" ] 1 => array:2 [ "identificador" => "s0040" "titulo" => "Predictors of 25(OH)D serum levels" ] 2 => array:2 [ "identificador" => "s0045" "titulo" => "Variables related to liver fibrosis" ] ] ] 6 => array:2 [ "identificador" => "s0050" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "s0055" "titulo" => "Abbreviations" ] 8 => array:2 [ "identificador" => "s0060" "titulo" => "Financial Support" ] 9 => array:2 [ "identificador" => "s0065" "titulo" => "Authors Contribution" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-10-22" "fechaAceptado" => "2017-04-02" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1116239" "palabras" => array:4 [ 0 => "Liver disease" 1 => "25-hydroxyvitamin D" 2 => "Gc-globulin" 3 => "Genetics" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Introduction and aimVitamin D has been associated with chronic liver diseases and low vitamin levels may contribute to progression of chronic hepatitis C. The aim of this study was to evaluate the influence of vitamin D serum levels and GC gene polymorphisms in the severity of liver fibrosis in patients with chronic hepatitis C genotype 1. Material and methodsCross-sectional study that enrolled 132 adult patients with chronic hepatitis C genotype 1 attended at the outpatient Clinic of Gastroenterology Division at Hospital de Clínicas de Porto Alegre. At the time of enrollment patients had a blood withdraw for serum 25(OH)D determination and genotypic analysis of rs7041 and rs4588 polymorphisms in GC gene. None/mild fibrosis was considered as METAVIR F0, F1 and F2 and severe fibrosis as METAVIR F3 and F4. ResultsMedian 25(OH)D levels in the sample were 19.9 ng/mL (P25-P75: 14.0-29.4). Fifty percent of patients presented vitamin D deficiency (< 20 ng/mL). In stepwise multiple linear regression the variables associated with 25(OH)D levels were blood withdrawn in Winter/spring season, the haplotypes AT/AT + AG/AT of rs7041 and rs4588 and female sex. For evaluation of severe fibrosis, variables associated in logistic regression were age, vitamin D severe deficiency (< 10 ng/mL), glucose levels, BMI and platelets count. ConclusionsVitamin D levels are associated with severity of liver fibrosis in chronic hepatitis C genotype 1 patients. Although the rs7041 and rs4588 GC polymorphisms are strong predictors of vitamin D levels, they do not play a direct role in liver fibrosis." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abs0010" "titulo" => "Introduction and aim" ] 1 => array:2 [ "identificador" => "abs0015" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abs0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abs0025" "titulo" => "Conclusions" ] ] ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 785 "Ancho" => 999 "Tamanyo" => 91809 ] ] "descripcion" => array:1 [ "en" => "Median 25(OH)D serum levels of the enrolled patients according to investigation month." ] ] 1 => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 607 "Ancho" => 2071 "Tamanyo" => 87410 ] ] "descripcion" => array:1 [ "en" => "Box plots showing the distribution of 25(OH) D serum levels stratified according to (A) rs7041 genotypes, (B) rs4588 genotypes and (C) rs7041 and rs4588 haplotypes. Upper horizontal line of box, 75th percentile; lower horizontal line of box, 25th percentile; horizontal bar within box, median; upper horizontal bar outside box, 90th percentile; lower horizontal bar outside box, 10th percentile. * Circles represent outliers. P values for Kruskal-Wallis test." ] ] 2 => array:7 [ "identificador" => "t0010" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "DM: diabetes mellitus. a Percentage (n). b Mean (standard deviation). c Median (IQR P25-P75). Total sample for: BMI = 125; platelets = 131." "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">Variable \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">Chronic hepatitis C genotype 1 (n = 132) \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" 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">Sex (male)a \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">53.8% (71) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Age (years)b \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">53 (± 9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Body mass index (kg/m<a class="elsevierStyleCrossRef" href="#bib0015">2</a>)b \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">28.5 (± 5.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">ALT (IU/L)c \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">64 (42-100) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">AST(IU/L)c \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">53 (36-84) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">GGT(IU/L)c \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">90 (43-156) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Platelets (103/μL)b \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">186 (± 51) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Cholesterol (mg/dL)c \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">164 (147-185) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Glucose (mg/dL) c \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">100 (91-111) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">DM presence (yes)a \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">21.2% (28) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">METAVIRa \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">F0 \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">12.9% (17) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">F1 \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">22.7% (30) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">F2 \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">18.9% (25) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">F3 \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">12.1% (16) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">F4 \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">33.3% (44) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Näivea \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">56.8% (75) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">25OH vitamin D (ng/mL)c \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">19.9 (14.0-29.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Vitamin D statusa \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Severe deficiency \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">13.6% (18) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Deficiency \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">36.4% (48) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Insufficiency \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">27.3% (36) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Sufficiency \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">22.7% (30) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Season of blood withdrawn \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Summer/Autumn \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">25% (33) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2045101.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Demographic, clinical and biochemical features of chronic hepatitis C genotype 1 patients." ] ] 3 => array:7 [ "identificador" => "t0015" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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">Chronic hepatitis C genotype 1 (n = 129) \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" 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">rs7041<a class="elsevierStyleCrossRef" href="#tbl2fn1">a</a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">C \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">46.1% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">CC \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">19.4% (25) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">AC \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">53.5% (69) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">AA \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">27.1% (35) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">rs4588<a class="elsevierStyleCrossRef" href="#tbl2fn1">a</a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">T \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">21.3% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">TT \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">6.2% (8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">GT \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">30.2% (39) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">GG \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">63.6% (82) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Haplotypes<a class="elsevierStyleCrossRef" href="#tbl2fn1">a</a> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">AT/AT \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">6.2% (8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">AG/AT \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">9.3% (12) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">AG/AG \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">11.6% (15) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">CG/AT \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">20.9% (27) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">CG/CG \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">19.4% (25) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">AG/CG \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">32.6% (42) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2045103.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tbl2fn1" "etiqueta" => "a" "nota" => "Percentage (n)." ] ] ] "descripcion" => array:1 [ "en" => "Allelic, genotypic and haplotypic data of rs7041 and rs4588 polymorphisms in chronic hepatitis C genotype 1 patients." ] ] 4 => array:7 [ "identificador" => "t0020" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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">25(OH) D (ng/mL)<a class="elsevierStyleCrossRef" href="#tbl3fn1">*</a> \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">P 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" 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">rs7041 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">0.026 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">CC + CA \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">22.8 (16.2-30.1) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">AA \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">17.0 (8.9-26.6) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">rs4588 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">0.023 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">GG + GT \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">20.2 (15.8-29.8) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">TT \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">9.6 (8.1-20.9) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Haplotypes \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">AT/AT + AG/AT \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">12.3 (8.1-19.2) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">AG/AG + CG/AT +CG/CG +AG/CG \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">21.2 (16.2-30.1) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2045104.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tbl3fn1" "etiqueta" => "*" "nota" => "Median (IQR P25-P75) Mann-Whitney" ] ] ] "descripcion" => array:1 [ "en" => "Median 25 (OH)D stratified according to risky genotypes and haplotypes of rs7041 and rs4588." ] ] 5 => array:7 [ "identificador" => "t0025" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Variables included in the model: sex, age, fibrosis (none/mild or severe), diabetes mellitus, BMI, ALT, AST, GGT, cholesterol, glucose, platelets, rs4588 and rs7041 haplotypes (AT/AT + AG/AT vs. others), season of blood withdrawn (Summer/Autumn vs. Winter/Spring). β: standardized coefficient beta. SE: standard error." "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">Variables \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">β \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">SE \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">P 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" 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">Winter/Spring vs. Summer/Autumn \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">-0.375 \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">2.003 \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">< 0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Female sex \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">-0.261 \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">1.740 \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">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Haplotypes AT/AT + AG/AT vs. others \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">-0.259 \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">1.254 \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">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2045102.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Stepwise forward multiple linear regression analysis for variables associated with 25(OH)D serum levels." ] ] 6 => array:7 [ "identificador" => "t0030" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Bivariate analysis: a Percentage (n) Fisher's Exact Test. b Mean (standard deviation) T test. c Median (IQR P25-P75) Mann-Whitney. Variables included in the stepwise logistic regression model with forward approach: sex, age, 25(OH)D > 10 ng/mL, season of blood withdrawn (summer/autumn vs. winter/spring), diabetes mellitus, BMI, ALT, AST, GGT, cholesterol, glucose, platelets, rs4588 and rs7041 haplotypes (AT/AT + AG/AT vs. others). OR: odds ratio. CI: confidence interval." "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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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">None/mild fibrosis n = 72 \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">Severe fibrosis n = 60 \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">Bivariate analysis P value \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">Logistic reg OR (CI 95%) \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">ression P 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" 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">Sex (male)a \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">54.2% (39) \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">53.3% (32) \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">1.000 \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">- \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">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Age (years)b \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">50.9 (±8.2) \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">55.6 (±8.6) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002 \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">1.058 (1.001-1.117) \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">0.045 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Body mass index (kg/m<a class="elsevierStyleCrossRef" href="#bib0015">2</a>)c \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">27.6 (±4.3) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29.6 (±6.1) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.042 \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">1.142 (1.037-1.258) \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">0.007 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">ALT (IU/L)c \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">58 (41-92) \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">71 (47-105) \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">0.001 \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">- \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">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">AST(IU/L)c \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">45 (34-76) \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">66 (48-98) \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">0.131 \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">- \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">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">GGT(IU/L)c \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">64 (31-125) \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">117 (70-187) \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">0.001 \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">- \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">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Cholesterol (mg/dL)c \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">163 (147-186) \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">166 (147-177) \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">0.922 \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">- \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">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Glucose (mg/dL)c \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">96 (87-106) \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">102 (93-133) \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"><0.001 \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">1.011 (0.999-1.023) \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">0.072 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Platelets (103/μL)b \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">213 (±62) \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">155 (±68) \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"><0.001 \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">0.985 (0.977-0.993) \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"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">DM presence (yes)a \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">12.5% (9) \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">31.7% (19) \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">0.010 \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">- \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">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">25OH vitamin D (ng/mL)c \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">21.1 (17.5-30.0) \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">18.1 (10.5-25.5) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.014 \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">- \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">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">25OH vitamin D < 10 ng/mLa \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">5.6% (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23.3% (14) \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">0.004 \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">4.558 (1.184-17.543) \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">0.027 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">25OH vitamin D < 20 ng/mLa \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">43.1% (31) \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">58.3% (35) \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">0.115 \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">- \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">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">25OH vitamin D < 30 ng/mLa \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">75.0% (54) \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">80.0% (48) \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">0.537 \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">- \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">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">rs7041a \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">0.242 \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">- \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">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">CC + CA \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">77.1% (54) \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">67.8% (40) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">AA \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">22.9% (16) \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">32.2% (19) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">rs4588a \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">0.468 \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">- \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">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">GG + GT \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">95.7% (67) \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">91.5% (54) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">TT \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">4.3% (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.5% (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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Haplotypesa \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">0.465 \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">- \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">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">AT/AT + AG/AT \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">12.9% (9) \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">18.6% (11) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">AG/AG + CG/AT +CG/CG +AG/CG \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">87.1% (61) \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">81.4% (48) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2045105.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Bivariate and logistic regression analysis of risk factors associated with severe fibrosis in chronic hepatitis C genotypes 1 patients." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0010" "bibliografiaReferencia" => array:26 [ 0 => array:3 [ "identificador" => "bib0010" "etiqueta" => "1." 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Laura A. Azevedo

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laura.alencastro@ufrgs.br

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, Ursula Matte**,***, Themis R. Silveira*,***, Jacqueline W. Bonfanti****, Juliana P. Bruch*, Mário R. Álvares-da-Silva*,****

* Graduate Program in Gastroenterology and Hepatology Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

** Department of Genetics; Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

*** Graduate Program in Child and Adolescence Health, Universidade Federal do Rio Grande do Sul; Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

**** Department of Internal Medicine, Universidade Federal do Rio Grande do Sul; Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Introduction</span><p id="p0010" class="elsevierStylePara elsevierViewall">Liver fibrosis is defined by extracellular matrix &#40;ECM&#41; accumulation with consequent loss of liver function&#44; due to acute or chronic damage&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">1</span></a> Chronic hepatitis C &#40;CHC&#41; leads to liver fibrosis and 20-30&#37; of patients progress to cirrhosis after 25-30 years of infection&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">2</span></a> Several factors influence the evolution of CHC and formation of liver fi-brosis&#44; such as age&#44; obesity&#44; virus C genotype&#44; alcohol consumption&#44; duration of infection&#44; presence of viral co-infections and metabolic disorders&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">2</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">Vitamin D has been associated with chronic liver diseases and low vitamin levels may contribute to progression of CHC&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">3</span></a> Vitamin D is mainly synthesized in the skin by 7-dehydrocholesterol redutase &#40;DHCR7&#41; in pre-vitamin D&#44; which is converted into vitamin D by isomeri-zation&#46; Vitamin D and its metabolites circulate bounded to vitamin D-binding protein &#40;GC-globulin&#41;&#46; Vitamin D goes under hydroxylation in the liver by cytochrome P450 enzymes forming 25-hydroxyvitamin D &#40;25&#40;OH&#41;D&#41; and is used to evaluate vitamin D status&#46; The metabolite 25&#40;OH&#41;D is hydroxylated by CYP27B1 in the kidney&#44; producing 1&#44;25-dihydroxyvitamin D &#40;1&#44;25&#40;OH&#41;D&#41;&#44; the active form that binds to vitamin D receptor &#40;VDR&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">4</span></a> Vitamin D deficiency is a risk factor for all-cause mortality in the general population<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">5</span></a> as well as for cirrhotic patients&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">6</span></a></p><p id="p0020" class="elsevierStylePara elsevierViewall">GC-globulin is coded by <span class="elsevierStyleItalic">GC</span> gene&#46; The three protein isoforms are coded by different alleles&#44; which are formed by single nucleotide polymorphisms &#40;SNPs&#41;&#46; Polymorphism rs7041 has two alternative alleles&#44; containing either A or C&#44; and polymorphism rs4588 has either G or T&#46; Each person carries two copies of the <span class="elsevierStyleItalic">GC</span> gene&#59; therefore possible genotypes for rs7041 are AA&#44; AC or CC&#44; for example&#46; Different SNPs at the same gene are inherited together forming a haplotype&#46; For rs7041 and rs4588 possible haplo-types are CT&#44; CG or AT&#46; These two SNPs are responsible for the three major circulating isoforms of GC-globulin Gc1F &#40;CT&#41;&#44; Gc1S &#40;CG&#41; and Gc2rs &#40;AT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">7</span></a> The Gc-2 iso-form is described to have the lowest affinity for its ligand&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">8</span></a> The three common haplotype variants combined form CT-CT&#44; CT-CG&#44; CG-CG&#44; CG-AT&#44; CT-AT and AT-AT&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">It is known that several polymorphisms involved in the vitamin D metabolism are associated with its serum con-centrations&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">9&#44;10</span></a> The aim of this study was to evaluate the influence of vitamin D serum levels and <span class="elsevierStyleItalic">GC</span> polymorphisms in the severity of liver fibrosis in patients with chronic hepatitis C genotype 1&#46;</p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Material and Methods</span><p id="p0030" class="elsevierStylePara elsevierViewall">This was a cross-sectional study that enrolled 132 adult patients with chronic hepatitis C genotype 1 attended at the outpatient Clinic of Gastroenterology Division at Hospital de Cl&#237;nicas de Porto Alegre&#44; Brazil&#44; from June 2013 to February 2015&#46; Hepatitis C virus infection was confirmed by anti-HCV ELISA 3 and by detection of viral RNA by polymerase chain reaction &#40;HCV RNA PCR&#41;&#46; Patients infected by the human immunodeficiency virus &#40;HIV&#41; or hepatitis B virus &#40;HBV&#41;&#44; alcohol abusers &#40;&#62; 40g&#47; day&#41;&#44; chronic renal injured&#44; liver transplanted&#44; decompen-sated cirrhotic and those with hepatocellular carcinoma &#40;HCC&#41; or in immunosuppressive or antiviral treatment were excluded&#46; Both na&#239;ve and previously PEG-INF treated patients were included&#46;</p><p id="p0035" class="elsevierStylePara elsevierViewall">At the time of the enrollment patients had a blood withdraw for vitamin D serum levels determination and geno-typic analysis&#46; Alanine aminotransferase &#40;ALT&#41;&#44; aspartate aminotransferase &#40;AST&#41;&#44; gamma-glutamyl-transferase &#40;GGT&#41;&#44; platelets&#44; glucose&#44; cholesterol and body mass index &#40;BMI&#41; were extracted from patient&#39;s chart from the previous 6 months&#46; Severity of fibrosis was evaluated by the last liver biopsy done by the outpatients Clinic routine&#46; Liver biopsies were evaluated by the same pathologist and scored with METAVIR system&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">11</span></a> Serum 25&#40;OH&#41;D levels were determined using a chemoluminescent immunoassay on a Liaison automatic analyzer &#40;Dia-Sorin&#41;&#46; Vitamin D levels below 10 ng&#47;mL were considered severe deficiency&#59; 10 to 20 ng&#47;mL deficiency&#59; 20 to 30 ng&#47; mL insufficiency&#59; and above 30 ng&#47;mL sufficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">12</span></a> Date of sample collection was categorized into two seasons&#44; Summer&#47;autumn &#40;December-May&#41; and Winter&#47;spring &#40;June-November&#41;&#46; The study was conducted according to the principles of the Declaration of Helsinki and was approved by the hospital Ethical Committee&#46; All patients gave written informed consent to participate in the study&#46;</p></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Genotypic analysis</span><p id="p0040" class="elsevierStylePara elsevierViewall">The genomic DNA was extracted from whole blood EDTA using Wizard&#174; Genomic DNA Purification Kit &#40;Promega&#41; according to manufacturer&#39;s instructions&#46; The polymorphisms rs7041 and rs4588 from the <span class="elsevierStyleItalic">GC</span> gene were identified using hydrolysis probes &#40;TaqMan Assays&#59; ABI&#41;&#44; IDs&#58; C&#95;3133594&#95;30 and C&#95;8278879&#95;10&#44; respectively&#46; A total of 10 ng of DNA was used in a final reaction volume of 12&#46;5 &#956;L for real-time PCR on StepOne&#8482; System &#40;Thermo Fisher&#41;&#46;</p><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055">Statistical analysis</span><p id="p0045" class="elsevierStylePara elsevierViewall">Categorical variables are presented as frequencies&#46; Continuous variables with normal distribution are presented as mean and standard deviation and variables with non-normal distribution as median and interquartile range &#40;P25-P75&#41;&#46; To check the normal distribution of the variables&#44; a Sha-piro-Wilk test was applied&#46; Associations between continuous variables were carried out with T test&#44; Mann-Whitney or Kruskall-Wallis as appropriated and associations between categorical variables were evaluated with Fisher&#39;s exact test&#46; Stepwise multiple linear regression analysis with a forward approach using a cutoff value of 0&#46;05 was performed to identify independent predictors of 25&#40;OH&#41;D levels&#46; Step-wise logistic regression analysis with a forward approach using a cutoff value of 0&#46;05 was performed to identify independent predictors of liver fibrosis&#46; Variables included in the model were sex&#44; age&#44; fibrosis &#40;none&#47;mild or severe&#41;&#44; diabetes mellitus&#44; BMI&#44; ALT&#44; AST&#44; GGT&#44; cholesterol&#44; glucose&#44; platelets&#44; rs4588 and rs7041 haplotypes &#40;AT&#47;AT &#43; AG&#47; AT <span class="elsevierStyleItalic">vs&#46;</span> others&#41;&#44; season of blood withdrawn &#40;Summer&#47;Autumn <span class="elsevierStyleItalic">vs&#46;</span> Winter&#47;Spring&#41;&#46; For analysis purposes none&#47;mild fibrosis was considered as METAVIR F0&#44; F1 and F2 and severe fibrosis as METAVIR F3 and F4 &#40;cirrhosis&#41;&#46; A &#967;<span class="elsevierStyleSup">2</span> test was employed to verify whether the proportions of the two polymorphisms were distributed in accordance with the Hardy-Weinberg Equilibrium&#46; Haplotypes for rs7041 and rs4588 were statistically reconstructed using the PHASE program&#44; version 2&#46;1&#44; which implements a Bayesian statistical method for haplotyping reconstructing from genotype data&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">13&#44;14</span></a> Statistical analysis was performed using SPSS 20&#46;0 &#40;SPSS Inc&#44; Chicago&#44; Il&#44; USA&#41;&#46; Significance level was set at &#945;&#60; 0&#46;05&#46;</p></span></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060">Results</span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Patient features</span><p id="p0050" class="elsevierStylePara elsevierViewall">Demographical&#44; clinical&#44; biochemical and genotypic features of enrolled patients are described in <a class="elsevierStyleCrossRef" href="#t0010">table 1</a>&#46; Patients&#8217; age varied from 26 to 74 years&#46; The majority of patients were cirrhotic &#40;33&#46;3&#37;&#41;&#46; Median 25&#40;OH&#41;D levels were 19&#46;9 ng&#47;mL &#40;14&#46;0 - 29&#46;4&#41;&#46; Fifty percent of patients presented deficiency or severe deficiency of vitamin D&#46;</p><elsevierMultimedia ident="t0010"></elsevierMultimedia><p id="p0055" class="elsevierStylePara elsevierViewall">Genotypes and alleles frequencies of rs7041 and rs4588 were in Hardy Weinberg Equilibrium&#46; The most frequent genotypes were AC for rs7041 and GG for rs4588 &#40;<a class="elsevierStyleCrossRef" href="#t0015">Table 2</a>&#41;&#46; Finally&#44; for haplotypes&#44; GC&#47;TA&#44; GC&#47;GC and GC&#47;GC were the most common ones&#46;</p><elsevierMultimedia ident="t0015"></elsevierMultimedia></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Predictors of 25&#40;OH&#41;D serum levels</span><p id="p0060" class="elsevierStylePara elsevierViewall">Vitamin D levels were higher in patients enrolled in Summer&#47;Autumn than in Winter&#47;Fall &#91;31&#46;2ng&#47;mL &#40;IQR 19&#46;8-35&#46;0&#41; <span class="elsevierStyleItalic">vs</span>&#46; 18&#46;4ng&#47;mL &#40;IQR 12&#46;8-24&#46;1&#41;&#59; P &#60; 0&#46;001&#93; &#40;<a class="elsevierStyleCrossRef" href="#f0010">Figure 1</a>&#41;&#46; Median 25&#40;OH&#41;D levels was 18&#46;0 ng&#47;mL &#40;12&#46;7 - 23&#46;2&#41; for females and 24&#46;0 ng&#47;mL &#40;17&#46;2 - 31&#46;8&#41; for males &#40;P &#61; 0&#46;002&#41;&#46; Vitamin D did not differ between n&#228;ive and PEG-INF treated patients &#40;P &#61; 0&#46;921&#41;&#46; When 25&#40;OH&#41;D serum levels were stratified among rs7041 and rs4588 genotypes and haplotypes&#44; there was no statistical significance &#40;P &#62; 0&#46;05&#41;&#44; however a trend is graphically observed for AA genotype of rs7041 and TT genotype of rs4588&#44; as well as for AT&#47;AT and AG&#47;AT haplotypes &#40;<a class="elsevierStyleCrossRef" href="#f0015">Figure 2</a>&#41;&#46; Transforming the mentioned genotypes and haplo-types into dichotomous variables&#44; it is observed that 25&#40;OH&#41;D levels are lower for AA genotype of rs7041&#44; TT genotype of rs4588 and AT&#47;AT &#43; AG&#47;AT haplotypes when compared to their counterparts &#40;<a class="elsevierStyleCrossRef" href="#t0020">Table 3</a>&#41;&#46; In multiple linear regression the variables associated with diminished 25&#40;OH&#41;D circulating levels were blood withdrawn in Winter&#47;Spring&#44; the risk haplotypes AT&#47;AT &#43; AG&#47;AT and female sex &#40;<a class="elsevierStyleCrossRef" href="#t0025">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="f0010"></elsevierMultimedia><elsevierMultimedia ident="f0015"></elsevierMultimedia><elsevierMultimedia ident="t0020"></elsevierMultimedia><elsevierMultimedia ident="t0025"></elsevierMultimedia></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Variables related to liver fibrosis</span><p id="p0065" class="elsevierStylePara elsevierViewall">In <a class="elsevierStyleCrossRef" href="#t0030">table 5</a> are presented the association of studied variables with severity of liver fibrosis&#46; Older age&#59; higher BMI&#44; ALT&#44; GGT and glucose&#59; lower platelets and 25&#40;OH&#41;D&#59; diabetes and severe vitamin D deficiency were related to severe liver fibrosis in bivariate analysis&#46; None of the evaluated genotypes and haplotypes of rs7041 and rs4588 were associated with fibrosis severity&#46; In the logistic regression analysis were included sex&#44; age&#44; 25&#40;OH&#41;D &#62; 10 ng&#47;mL&#44; season of blood withdrawn &#40;Summer&#47;Autumn <span class="elsevierStyleItalic">vs&#46;</span> Winter&#47;Spring&#41;&#44; diabetes mellitus&#44; BMI&#44; ALT&#44; AST&#44; GGT&#44; cholesterol&#44; glucose&#44; platelets&#44; rs4588 and rs7041 haplo-types &#40;AT&#47;AT &#43; AG&#47;AT <span class="elsevierStyleItalic">vs&#46;</span> others&#41;&#46; The variables that remained in the model were age&#44; 25&#40;OH&#41;D &#60; 10 ng&#47;mL&#44; glucose levels&#44; BMI and platelets count&#46; When 25&#40;OH&#41;D is included as a continuous variable it loses statistical significance in the model&#46;</p><elsevierMultimedia ident="t0030"></elsevierMultimedia></span></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Discussion</span><p id="p0070" class="elsevierStylePara elsevierViewall">In recent years&#44; the influence of vitamin D in liver diseases has been broadly discussed since it undergoes hepatic metabolism&#46; Herein we evaluated the association of vitamin D serum levels and of rs7041 and rs4588 polymorphisms from <span class="elsevierStyleItalic">GC</span> gene in severe liver fibrosis in a sample of 132 chronic hepatitis C genotype 1 patients&#46;</p><p id="p0075" class="elsevierStylePara elsevierViewall">In this sample&#44; vitamin D median levels were 19&#46;9 ng&#47; mL and deficiency prevalence was 50&#37;&#46; In a study with 496 CHC patients from Swiss hospitals&#44; median 25&#40;OH&#41;D was 13&#46;4 ng&#47;mL&#44; and 74&#37; presented levels below 20&#46;0 ng&#47; mL&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">15</span></a> It has been described that the prevalence of vitamin D insufficiency and deficiency in patients with chronic liver disease ranges between 64 and 92&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">16</span></a></p><p id="p0080" class="elsevierStylePara elsevierViewall">Serum levels of 25 &#40;OH&#41;D fluctuate strongly as a result of variations in sunlight exposure during the season&#44; type of food&#44; presence of comorbidities&#44; vitamin D supplementation and others&#46; It is important to also evaluate the different genetic variants of vitamin D metabolism&#44; which could provide an assessment of long term vitamin D status&#46; In multiple regression analysis&#44; 25&#40;OH&#41;D levels were influenced by season&#44; sex and genetic factors&#46; Polymorphisms in genes involved in synthesis&#44; transport and vitamin D metabolism are known to affect its circulating levels&#44; especially in <span class="elsevierStyleItalic">GC</span>&#44; <span class="elsevierStyleItalic">DHCR7</span> and <span class="elsevierStyleItalic">CYP2R1</span> loci&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">7&#44;8&#44;17</span></a> The <span class="elsevierStyleItalic">GC</span> gene codifies the protein responsible for carrying vitamin D and its metabolites in the circulation and in our study the haplotypes AT&#47;AT and AG&#47;AT were responsible for the lower levels of vitamin D&#44; showing that the T allele of rs4588 has the biggest influence in vitamin D levels&#46; Our findings are similar to Santos&#44; <span class="elsevierStyleItalic">et al&#46;</span>&#44; which found the same results in healthy Brazilian girls&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">18</span></a> The Gc-2 isoform is described to have the lowest affinity for its ligand&#44; which is in accordance confirming the lowest levels of vitamin D described in both studies&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">10</span></a></p><p id="p0085" class="elsevierStylePara elsevierViewall">Vitamin D deficiency seems to be associated with a poorer prognosis of the liver disease&#46; In this sample&#44; a difference in 25&#40;OH&#41;D serum levels was observed in none&#47; mild and severe fibrosis &#40;21&#46;1 <span class="elsevierStyleItalic">vs&#46;</span> 18&#46;1 ng&#47;mL&#59; P &#61; 0&#46;014&#41;&#46; Baur&#44; <span class="elsevierStyleItalic">et al&#46;</span> reported that individuals with CHC METAVIR 2 presented 15&#46;5 ng&#47;mL 25&#40;OH&#41;D levels compared to 22&#46;2 ng&#47;mL of individuals METAVIR 0&#47;1&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">19</span></a> Meanwhile&#44; Petta described that CHC G1 with Scheuer scoring 0-2 presented 25&#46;5ng&#47;mL <span class="elsevierStyleItalic">vs&#46;</span> 21&#46;9 ng&#47;mL from patients Scheuer scoring of 3-4&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">20</span></a> In our sample the overall prevalence of severe deficiency was 13&#46;6&#37; &#40;18&#47;132&#41;&#44; in patients with none&#47;mild fibrosis was 5&#46;6&#37; &#40;4&#47;72&#41; and in patients with severe fibro-sis was 23&#46;3&#37; &#40;14&#47;60&#41;&#46; In a cohort of German CHC patients&#44; severe deficiency prevalence was 25&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">21</span></a> In logistic regression&#44; severe vitamin D deficiency was associated with severe fibrosis along with age&#44; BMI and platelets count&#46; Although the studied polymorphisms have presented association with vitamin D circulating levels&#44; they were not related to liver fibrosis&#46; There are studies that have shown that polymorphisms of vitamin D metabolism relate to the stages of liver disease&#46; Studies from Petta and Gr&#252;nhage identified the polymorphism rs12785878 in the gene of cholesterol reductase &#40;<span class="elsevierStyleItalic">DHCR7</span>&#41; associated with a greater degree of liver fibrosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">22&#44;23</span></a> This polymorphism was not evaluated in the present sample&#46; Another gene that is important in liver fibrosis is <span class="elsevierStyleItalic">VDR</span>&#44; since it can down-regulate the activation of hepatic stellate cells by competing for several genomic sites related to fibrosis&#44; which are activated by <span class="elsevierStyleItalic">SMAD3</span>&#44; an effector of the transforming growth factor beta 1 &#40;TGF&#946;1&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">24</span></a> The rs1544410&#44; rs7975232 and rs731236 polymorphisms have been associated with the rate of progression of fibrosis and cirrhosis&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">19</span></a></p><p id="p0090" class="elsevierStylePara elsevierViewall">As limitation of this study we could cite that some co-founding factors were not analyzed&#44; such as smoking&#44; intravenous drug use&#44; duration of HCV infection&#46; Also&#44; it was a cross-sectional study that analyzed only two polymorphisms&#46; Although the sample size is relatively small&#44; we considered as a main strength the use of a well-defined cohort of HCV genotype 1 patients that represent the real-world experience&#46; Our results corroborate the literature findings&#44; whereas lower vitamin D levels are found among patients with higher liver fibrosis&#46; Identifying those patients is important since oral supplementation of vitamin D is a very simple therapeutic measure&#46; Several studied have demonstrated that vitamin D deficiency I is likely to be related to lower odds of sustained virological response &#40;SVR&#41; to treatment with pegylated interferon plus ribavi-rin&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">25</span></a> and recently&#44; in a Japanese trial&#44; vitamin D3 supplementation increased SVR rates on refractory CHC patients on treatment with simeprevir&#44; pegylated interferon plus ribavirin&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">26</span></a></p><p id="p0095" class="elsevierStylePara elsevierViewall">In summary&#44; vitamin D levels were associated with severity of liver fibrosis in chronic hepatitis C genotype 1 patients&#46; Although the rs7041 and rs4588 <span class="elsevierStyleItalic">GC</span> gene polymorphisms are strong predictors of vitamin D levels&#44; they do not play a direct role in liver fibrosis&#46;</p></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Abbreviations</span><p id="p0100" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="l0010"><li class="elsevierStyleListItem" id="u0010"><span class="elsevierStyleLabel">&#8226;</span><p id="p0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">1&#44;25&#40;OH&#41;D&#58;</span> 1&#44;25-dihydroxyvitamin D&#46;</p></li><li class="elsevierStyleListItem" id="u0015"><span class="elsevierStyleLabel">&#8226;</span><p id="p0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">25&#40;OH&#41;D&#58;</span> 25-hydroxyvitamin D&#46;</p></li><li class="elsevierStyleListItem" id="u0020"><span class="elsevierStyleLabel">&#8226;</span><p id="p0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">ALT&#58;</span> alanine aminotransferase&#46;</p></li><li class="elsevierStyleListItem" id="u0025"><span class="elsevierStyleLabel">&#8226;</span><p id="p0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">AST&#58;</span> aspartate aminotransferase&#46;</p></li><li class="elsevierStyleListItem" id="u0030"><span class="elsevierStyleLabel">&#8226;</span><p id="p0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">BMI&#58;</span> body mass index&#46;</p></li><li class="elsevierStyleListItem" id="u0035"><span class="elsevierStyleLabel">&#8226;</span><p id="p0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">CHC&#58;</span> chronic hepatitis C&#46;</p></li><li class="elsevierStyleListItem" id="u0040"><span class="elsevierStyleLabel">&#8226;</span><p id="p0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">DHCR7&#58;</span> 7-dehydrocholesterol redutase&#46;</p></li><li class="elsevierStyleListItem" id="u0045"><span class="elsevierStyleLabel">&#8226;</span><p id="p0140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">ECM&#58;</span> extracellular matrix&#46;</p></li><li class="elsevierStyleListItem" id="u0050"><span class="elsevierStyleLabel">&#8226;</span><p id="p0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">GGT&#58;</span> gamma-glutamyl-transferase&#46;</p></li><li class="elsevierStyleListItem" id="u0055"><span class="elsevierStyleLabel">&#8226;</span><p id="p0150" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">SVR&#58;</span> sustained virological response&#46;</p></li><li class="elsevierStyleListItem" id="u0060"><span class="elsevierStyleLabel">&#8226;</span><p id="p0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">VDR&#58;</span> vitamin D receptor&#46;</p></li></ul></p></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">Financial Support</span><p id="p0160" class="elsevierStylePara elsevierViewall">The authors would like to thank Fundo de Incentivo &#224; Pesquisa do Hospital de Cl&#237;nicas de Porto Alegre &#40;FIPE-HCPA&#41;&#44; Programa de Apoio &#224; P&#243;s-Gradua&#231;&#227;o da Coorde-na&#231;&#227;o de Aperfei&#231;oamento de Pessoal de N&#237;vel Superior &#40;PROAP-CAPES&#41; and Conselho Nacional de Desen-volvimento Cient&#237;fico e Tecnol&#243;gico &#40;CNPq&#41;&#46;</p></span><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Authors Contribution</span><p id="p0165" class="elsevierStylePara elsevierViewall">Study conception and design&#58; LAA&#59; UM&#59; TRS&#59; MRAS&#46; Performed the experiments&#58; LAA&#59; JWB&#59; JPB&#46; Analyzed the data&#58; LAA&#46; Wrote the paper&#58; LAA&#59; UM&#59; TRS&#59; JPB&#59; JWB&#59; MRAS&#46; Critical revision&#58; UM&#59; TRS&#59; MRAS&#46;</p></span></span>"
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              "titulo" => "Predictors of 25&#40;OH&#41;D serum levels"
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              "titulo" => "Variables related to liver fibrosis"
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        "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015"><span class="elsevierStyleBold">Introduction and aim</span></span><p id="sp0060" class="elsevierStyleSimplePara elsevierViewall">Vitamin D has been associated with chronic liver diseases and low vitamin levels may contribute to progression of chronic hepatitis C&#46; The aim of this study was to evaluate the influence of vitamin D serum levels and <span class="elsevierStyleItalic">GC</span> gene polymorphisms in the severity of liver fibrosis in patients with chronic hepatitis C genotype 1&#46;</p></span> <span id="abs0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020"><span class="elsevierStyleBold">Material and methods</span></span><p id="sp0065" class="elsevierStyleSimplePara elsevierViewall">Cross-sectional study that enrolled 132 adult patients with chronic hepatitis C genotype 1 attended at the outpatient Clinic of Gastroenterology Division at Hospital de Cl&#237;nicas de Porto Alegre&#46; At the time of enrollment patients had a blood withdraw for serum 25&#40;OH&#41;D determination and genotypic analysis of rs7041 and rs4588 polymorphisms in <span class="elsevierStyleItalic">GC</span> gene&#46; None&#47;mild fibrosis was considered as METAVIR F0&#44; F1 and F2 and severe fibrosis as METAVIR F3 and F4&#46;</p></span> <span id="abs0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025"><span class="elsevierStyleBold">Results</span></span><p id="sp0070" class="elsevierStyleSimplePara elsevierViewall">Median 25&#40;OH&#41;D levels in the sample were 19&#46;9 ng&#47;mL &#40;P25-P75&#58; 14&#46;0-29&#46;4&#41;&#46; Fifty percent of patients presented vitamin D deficiency &#40;&#60; 20 ng&#47;mL&#41;&#46; In stepwise multiple linear regression the variables associated with 25&#40;OH&#41;D levels were blood withdrawn in Winter&#47;spring season&#44; the haplotypes AT&#47;AT &#43; AG&#47;AT of rs7041 and rs4588 and female sex&#46; For evaluation of severe fibrosis&#44; variables associated in logistic regression were age&#44; vitamin D severe deficiency &#40;&#60; 10 ng&#47;mL&#41;&#44; glucose levels&#44; BMI and platelets count&#46;</p></span> <span id="abs0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030"><span class="elsevierStyleBold">Conclusions</span></span><p id="sp0075" class="elsevierStyleSimplePara elsevierViewall">Vitamin D levels are associated with severity of liver fibrosis in chronic hepatitis C genotype 1 patients&#46; Although the rs7041 and rs4588 <span class="elsevierStyleItalic">GC</span> polymorphisms are strong predictors of vitamin D levels&#44; they do not play a direct role in liver fibrosis&#46;</p></span>"
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          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Box plots showing the distribution of 25&#40;OH&#41; D serum levels stratified according to &#40;<span class="elsevierStyleBold">A</span>&#41; rs7041 genotypes&#44; &#40;<span class="elsevierStyleBold">B</span>&#41; rs4588 genotypes and &#40;<span class="elsevierStyleBold">C&#41;</span> rs7041 and rs4588 haplotypes&#46; Upper horizontal line of box&#44; 75th percentile&#59; lower horizontal line of box&#44; 25th percentile&#59; horizontal bar within box&#44; median&#59; upper horizontal bar outside box&#44; 90th percentile&#59; lower horizontal bar outside box&#44; 10th percentile&#46; &#42; Circles represent outliers&#46; P values for Kruskal-Wallis test&#46;</p>"
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          "leyenda" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">DM&#58; diabetes mellitus&#46; <span class="elsevierStyleSup">a</span> Percentage &#40;n&#41;&#46; <span class="elsevierStyleSup">b</span> Mean &#40;standard deviation&#41;&#46; <span class="elsevierStyleSup">c</span> Median &#40;IQR P25-P75&#41;&#46; Total sample for&#58; BMI &#61; 125&#59; platelets &#61; 131&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Chronic hepatitis C genotype 1 &#40;n &#61; 132&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Sex &#40;male&#41;<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">53&#46;8&#37; &#40;71&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Age &#40;years&#41;<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">53 &#40;&#177; 9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Body mass index &#40;kg&#47;m<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">2</span></a>&#41;<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">28&#46;5 &#40;&#177; 5&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ALT &#40;IU&#47;L&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">64 &#40;42-100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">AST&#40;IU&#47;L&#41;<span class="elsevierStyleSup">c</span>&nbsp;\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">53 &#40;36-84&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">GGT&#40;IU&#47;L&#41;<span class="elsevierStyleSup">c</span>&nbsp;\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">90 &#40;43-156&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Platelets &#40;103&#47;&#956;L&#41;<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">186 &#40;&#177; 51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">Cholesterol &#40;mg&#47;dL&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glucose &#40;mg&#47;dL&#41; c&nbsp;\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
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                  \t\t\t\t">100 &#40;91-111&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">21&#46;2&#37; &#40;28&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">F0&nbsp;\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
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                  \t\t\t\t">12&#46;9&#37; &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">33&#46;3&#37; &#40;44&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">25OH vitamin D &#40;ng&#47;mL&#41;<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Sufficiency&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">22&#46;7&#37; &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Season of blood withdrawn&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Summer&#47;Autumn&nbsp;\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">25&#37; &#40;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2045101.png"
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          "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Demographic&#44; clinical and biochemical features of chronic hepatitis C genotype 1 patients&#46;</p>"
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        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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            0 => array:2 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Chronic hepatitis C genotype 1 &#40;n &#61; 129&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">CC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">19&#46;4&#37; &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">AC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">53&#46;5&#37; &#40;69&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">27&#46;1&#37; &#40;35&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">rs4588<a class="elsevierStyleCrossRef" href="#tbl2fn1"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">T&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  """
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">AT&#47;AT &#43; AG&#47;AT&nbsp;\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
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                  \t\t\t\t">12&#46;3 &#40;8&#46;1-19&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">AG&#47;AG &#43; CG&#47;AT &#43;CG&#47;CG &#43;AG&#47;CG&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2045104.png"
              ]
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          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tbl3fn1"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="np0015">Median &#40;IQR P25-P75&#41; Mann-Whitney</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">Median 25 &#40;OH&#41;D stratified according to risky genotypes and haplotypes of rs7041 and rs4588&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "t0025"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="sp0045" class="elsevierStyleSimplePara elsevierViewall">Variables included in the model&#58; sex&#44; age&#44; fibrosis &#40;none&#47;mild or severe&#41;&#44; diabetes mellitus&#44; BMI&#44; ALT&#44; AST&#44; GGT&#44; cholesterol&#44; glucose&#44; platelets&#44; rs4588 and rs7041 haplotypes &#40;AT&#47;AT &#43; AG&#47;AT vs&#46; others&#41;&#44; season of blood withdrawn &#40;Summer&#47;Autumn vs&#46; Winter&#47;Spring&#41;&#46; &#946;&#58; standardized coefficient beta&#46; SE&#58; standard error&#46;</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">Variables&nbsp;\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">&#946;&nbsp;\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">SE&nbsp;\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">P value&nbsp;\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" 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">Winter&#47;Spring <span class="elsevierStyleItalic">vs</span>&#46; Summer&#47;Autumn&nbsp;\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">-0&#46;375&nbsp;\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">2&#46;003&nbsp;\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">&#60; 0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">Female sex&nbsp;\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">-0&#46;261&nbsp;\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">1&#46;740&nbsp;\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">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">Haplotypes AT&#47;AT &#43; AG&#47;AT <span class="elsevierStyleItalic">vs&#46;</span> others&nbsp;\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">-0&#46;259&nbsp;\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">1&#46;254&nbsp;\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">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2045102.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">Stepwise forward multiple linear regression analysis for variables associated with 25&#40;OH&#41;D serum levels&#46;</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "t0030"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="sp0055" class="elsevierStyleSimplePara elsevierViewall">Bivariate analysis&#58; <span class="elsevierStyleSup">a</span> Percentage &#40;n&#41; Fisher&#39;s Exact Test&#46; <span class="elsevierStyleSup">b</span> Mean &#40;standard deviation&#41; T test&#46; <span class="elsevierStyleSup">c</span> Median &#40;IQR P25-P75&#41; Mann-Whitney&#46; Variables included in the stepwise logistic regression model with forward approach&#58; sex&#44; age&#44; 25&#40;OH&#41;D &#62; 10 ng&#47;mL&#44; season of blood withdrawn &#40;summer&#47;autumn vs&#46; winter&#47;spring&#41;&#44; diabetes mellitus&#44; BMI&#44; ALT&#44; AST&#44; GGT&#44; cholesterol&#44; glucose&#44; platelets&#44; rs4588 and rs7041 haplotypes &#40;AT&#47;AT &#43; AG&#47;AT vs&#46; others&#41;&#46; OR&#58; odds ratio&#46; CI&#58; confidence interval&#46;</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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\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">None&#47;mild fibrosis n &#61; 72&nbsp;\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">Severe fibrosis n &#61; 60&nbsp;\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">Bivariate analysis P value&nbsp;\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">Logistic reg OR &#40;CI 95&#37;&#41;&nbsp;\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">ression P value&nbsp;\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" 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">Sex &#40;male&#41;<span class="elsevierStyleSup">a</span>&nbsp;\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">54&#46;2&#37; &#40;39&#41;&nbsp;\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">53&#46;3&#37; &#40;32&#41;&nbsp;\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">1&#46;000&nbsp;\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">-&nbsp;\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">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">Age &#40;years&#41;<span class="elsevierStyleSup">b</span>&nbsp;\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">50&#46;9 &#40;&#177;8&#46;2&#41;&nbsp;\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">55&#46;6 &#40;&#177;8&#46;6&#41;&nbsp;\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">0&#46;002&nbsp;\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">1&#46;058 &#40;1&#46;001-1&#46;117&#41;&nbsp;\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">0&#46;045&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">Body mass index &#40;kg&#47;m<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">2</span></a>&#41;<span class="elsevierStyleSup">c</span>&nbsp;\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">27&#46;6 &#40;&#177;4&#46;3&#41;&nbsp;\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">29&#46;6 &#40;&#177;6&#46;1&#41;&nbsp;\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">0&#46;042&nbsp;\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">1&#46;142 &#40;1&#46;037-1&#46;258&#41;&nbsp;\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">0&#46;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">ALT &#40;IU&#47;L&#41;<span class="elsevierStyleSup">c</span>&nbsp;\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">58 &#40;41-92&#41;&nbsp;\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">71 &#40;47-105&#41;&nbsp;\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">0&#46;001&nbsp;\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">-&nbsp;\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">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">AST&#40;IU&#47;L&#41;<span class="elsevierStyleSup">c</span>&nbsp;\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">45 &#40;34-76&#41;&nbsp;\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">66 &#40;48-98&#41;&nbsp;\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">0&#46;131&nbsp;\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">-&nbsp;\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">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">GGT&#40;IU&#47;L&#41;<span class="elsevierStyleSup">c</span>&nbsp;\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">64 &#40;31-125&#41;&nbsp;\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">117 &#40;70-187&#41;&nbsp;\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">0&#46;001&nbsp;\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">-&nbsp;\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">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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Article information

ISSN: 16652681
Original language: English

DOI:10.5604/01.3001.0010.2748

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2024 November	9	5	14
2024 October	23	1	24
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2024 August	20	1	21
2024 July	61	3	64
2024 June	35	2	37
2024 May	38	3	41
2024 April	18	4	22
2024 March	40	2	42
2024 February	28	4	32
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2023 October	7	5	12
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2023 March	60	1	61
2023 February	22	6	28
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2022 November	19	5	24
2022 October	18	9	27
2022 September	74	16	90
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2022 July	39	8	47
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2022 April	11	10	21
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2022 February	8	6	14
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2021 December	12	12	24
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2021 July	9	8	17
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2021 May	11	6	17
2021 April	11	9	20
2021 March	16	5	21
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2020 December	7	5	12
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2020 September	10	6	16
2020 August	7	6	13
2020 July	10	7	17
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2020 May	9	3	12
2020 April	3	3	6
2020 March	5	1	6
2020 February	9	4	13
2020 January	13	2	15
2019 December	6	4	10
2019 November	4	2	6
2019 October	4	1	5
2019 September	8	3	11
2019 August	3	2	5
2019 July	1	3	4
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