Anti-gp210-positive primary biliary cholangitis: The dilemma of clinical treatment and emerging mechanisms

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"apellidos" => "Cotrim" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268123002260?idApp=UINPBA00004N" "url" => "/16652681/0000002800000005/v1_202308301015/S1665268123002260/v1_202308301015/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Concise reviews" "titulo" => "Anti-gp210-positive primary biliary cholangitis: The dilemma of clinical treatment and emerging mechanisms" "tieneTextoCompleto" => true "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Xiaoyi Wang, Zhen Yang, Ying Ran, Long Li, Bangmao Wang, Lu Zhou" "autores" => array:6 [ 0 => array:3 [ "nombre" => "Xiaoyi" "apellidos" => "Wang" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "#" "identificador" => "fn1" ] ] ] 1 => array:3 [ "nombre" => "Zhen" "apellidos" => "Yang" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "#" "identificador" => "fn1" ] ] ] 2 => array:3 [ "nombre" => "Ying" "apellidos" => "Ran" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "#" "identificador" => "fn1" ] ] ] 3 => array:3 [ "nombre" => "Long" "apellidos" => "Li" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0002" ] ] ] 4 => array:3 [ "nombre" => "Bangmao" "apellidos" => "Wang" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] ] ] 5 => array:4 [ "nombre" => "Lu" "apellidos" => "Zhou" "email" => array:1 [ 0 => "lzhou01@tmu.edu.cn" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0003" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0001" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China" "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:3 [ "entidad" => "Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China" "etiqueta" => "b" "identificador" => "aff0002" ] 2 => array:3 [ "entidad" => "Department of Gastroenterology and Hepatology, People's Hospital of Hetian District, Xinjiang Uygur Autonomous Region, China" "etiqueta" => "c" "identificador" => "aff0003" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0001" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0001" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1756 "Ancho" => 3583 "Tamanyo" => 539706 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig 1&#58" "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "The structural diagram of nuclear pore membrane protein gp210." ] ] ] "textoCompleto" => "1IntroductionPrimary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease characterized by non-suppurative inflammation of small- and medium-sized bile ducts in the liver, which causes cirrhosis. Serum antimitochondrial antibody (AMA) is the major hallmark of PBC <a class="elsevierStyleCrossRef" href="#bib0001">[1]</a>. However, AMA is absent or present only in low titers in approximately 5%–10% of PBC patients <a class="elsevierStyleCrossRef" href="#bib0002">[2]</a>. More than 30% of AMA-negative PBC patients have PBC-specific anti-nuclear antibodies (ANA), including anti-gp210 and anti-sp100 antibodies <a class="elsevierStyleCrossRef" href="#bib0003">[3]</a>. Moreover, anti-gp210 can be detected in 13.8%–48.2% of PBC patients, with high specificity (>98%) for the diagnosis <a class="elsevierStyleCrossRefs" href="#bib0004">[4–17]</a>. Since 2017, anti-gp210 has become a diagnostic marker for the diagnosis of AMA-negative PBC, improving the diagnostic rate and thus avoiding unnecessary liver biopsy in some patients [<a class="elsevierStyleCrossRef" href="#bib0002">2</a>,<a class="elsevierStyleCrossRef" href="#bib0018">18</a>].Anti-gp210 is not only a highly specific antibody for the diagnosis of PBC but also a prognostic marker. Anti-gp210-positive PBC patients had worse responses to ursodeoxycholic acid (UDCA) (39.3% vs. 16.7%), higher levels of biochemical liver tests, more severe histopathological presentation, and worse prognosis as compared to anti-gp210-negative patients [<a class="elsevierStyleCrossRefs" href="#bib0004">4-6</a>,<a class="elsevierStyleCrossRef" href="#bib0019">19</a>]. The therapeutic effects of different drugs, including obeticholic acid (OCA), fibrates, glucocorticoids, and immunosuppressants in anti-gp210-positive and -negative PBC patients have been compared, and it has been found positivity remains a risk factor for poor treatment response [<a class="elsevierStyleCrossRef" href="#bib0008">8</a>,<a class="elsevierStyleCrossRef" href="#bib0019">19</a>]. Thus, anti-gp210 is a risk factor for poor response to UDCA and poor prognosis in PBC patients, and thus clarifying the production of anti-gp210 and its mechanism in PBC is very important for the development of effective therapeutic targets.Currently, studies on the molecular mechanisms of anti-gp210 in PBC are still limited. The antigen of anti-gp210 is gp210, one of the constitutive proteins of the nuclear pore complex <a class="elsevierStyleCrossRef" href="#bib0020">[20]</a>. Two antigenic epitopes of gp210 protein have been identified, which laid a theoretical basis for the detection of anti-gp210 and the exploration of antigen expression as well as antibody production [<a class="elsevierStyleCrossRef" href="#bib0021">21</a>,<a class="elsevierStyleCrossRef" href="#bib0022">22</a>]. Notably, Nickowitz et al. <a class="elsevierStyleCrossRef" href="#bib0006">[6]</a> found that the gp210 expression in biliary epithelial cells (BECs) in the liver of PBC patients was significantly increased compared to that in the patients of AIH and hepatitis C, however, it did not correlate with the production of anti-gp210 antibody. Thus, it is suggested that gp210 antigen may be involved in the bile duct injury of PBC. In addition, in terms of the potential mechanism for anti-gp210 production, molecular mimicry is the major hypothesis at present <a class="elsevierStyleCrossRef" href="#bib0021">[21]</a>. However, whether or not anti-gp210 is directly involved in the occurrence and development of PBC still requires more exploration or merely represents epiphenomenon. Collectively, the clinicopathological characteristics of anti-gp210-positive PBC patients, the production of anti-gp210 antibodies, and the possible pathogenic mechanism are reviewed to deeply understand the role of anti-gp210 in PBC.2Anti-gp210-positive PBC patients have poor treatment response and prognosisAnti-gp210-positive PBC patients have a lower UDCA response rate than their anti-gp210-negative counterparts. In a cohort of 499 PBC patients from the UK, Haldar et al. <a class="elsevierStyleCrossRef" href="#bib0004">[4]</a> reported that anti-gp210-positive patients treated with UDCA did not respond sufficiently to treatment as compared to anti-gp210-negative patients (39.3% vs. 16.7%). The study further confirmed that anti-gp210 could be used as an index to predict poor response to UDCA treatment, with sensitivity and specificity of 26.8% and 89.8%, respectively. Chen Q et al. <a class="elsevierStyleCrossRef" href="#bib0023">[23]</a> conducted a retrospective cohort study of 180 UDCA-treated Chinese PBC patients to assess the prognostic value of anti-gp210 and found that positivity for anti-gp210 was independently associated with a higher risk of liver-related death and transplantation. In summary, anti-gp210-positive PBC patients have low UDCA response rates and poor prognosis.Second-line therapeutic drugs, such as OCA, fibrates, and corticosteroids are available for UDCA-refractory PBC patients, however, the treatment efficacy remains unsatisfactory for anti-gp210-positive patients. Nakamura et al. <a class="elsevierStyleCrossRef" href="#bib0008">[8]</a> enrolled 50 and 114 anti-gp210-positive and -negative PBC patients, respectively, (115 PBC patients of UDCA monotherapy and 49 UDCA-refractory PBC patients of UDCA combined with prednisolone and/or bezafibrate) in a retrospective study. This study showed that the liver function of both groups had improved after 2 years of treatment, however, anti-gp210-positive patients presented with higher levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), and immunoglobulin M (IgM) after treatment than anti-gp210-negative patients. Then, Qian et al. <a class="elsevierStyleCrossRef" href="#bib0019">[19]</a> respectively compared the responses of 29 and 51 anti-gp210-positive and -negative PBC patients who received UDCA or UDCA, prednisolone, and immunosuppressant (AZA or MMF) triple therapy, and reported that the incidence of poor prognosis (such as increasing rate of PBC related complications, liver transplantation, and mortality) was higher in anti-gp210-positive PBC patients than in anti-gp210-negative patients.Anti-gp210 is closely associated with poor prognosis in PBC patients. In 1998, Itoh et al. <a class="elsevierStyleCrossRef" href="#bib0011">[11]</a> initially reported that anti-gp210-positive PBC patients had a three times higher mortality rate (40.0% vs. 13.6%), and 3.5 times higher probability of death from liver failure (32.0% vs. 9.1%) than anti-gp210-negative patients. The liver transplantation free survival time of anti-gp210-positive PBC patients was significantly shorter than their anti-gp210-negative PBC counterparts. Meanwhile, Yang F et al. <a class="elsevierStyleCrossRef" href="#bib0007">[7]</a> found that anti-gp210-positive patients had remarkably higher UK-PBC scores and poorer long-term prognoses than anti-gp210-negative patients. Previous investigators have reported that the presence of fatigue and pruritus during diagnosis is associated with poor responsiveness to UDCA treatment, and more inclined to evolve to cirrhosis and its complications in PBC <a class="elsevierStyleCrossRef" href="#bib0024">[24]</a>. Thus, anti-gp210 may help together with clinical features to identify the subgroup of PBC patients with more severe prognoses.Nakamura M et al. <a class="elsevierStyleCrossRef" href="#bib0025">[25]</a> further studied the relationship between the titer of anti-gp210 and disease severity and prognosis. They found that patients with reduced anti-gp210 titers showed milder disease and better prognosis than patients whose anti-gp210 titers were unchanged or elevated after UDCA treatment <a class="elsevierStyleCrossRef" href="#bib0005">[5]</a>. Furthermore, they concluded that the change of anti-gp210 titers in serum had great significance for the prognosis of the disease <a class="elsevierStyleCrossRef" href="#bib0005">[5]</a>. However, the issue of whether or not the titer of anti-gp210 is variable remains controversial because some studies have pointed out that anti-gp210 titers in PBC patients did not change over a long follow-up period of 3–10 years [<a class="elsevierStyleCrossRef" href="#bib0011">11</a>,<a class="elsevierStyleCrossRef" href="#bib0012">12</a>]. Therefore, we summarized the detection methods, substrates, and the changes of anti-gp210’s serum antibody titers in previous studies to figure out why those research results differ (<a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>) [<a class="elsevierStyleCrossRef" href="#bib0005">5</a>,<a class="elsevierStyleCrossRef" href="#bib0008">8</a>,<a class="elsevierStyleCrossRefs" href="#bib0011">11-13</a>]. We found that the change of antibody titer can be detected when the carboxy-terminal tail of gp210 was used as the detection substrate, whereas the studies reporting that the titer was unchanged did not indicate what detection substrate was used. Therefore, we speculated that the variability of anti-gp210 titers is related to different substrates in antibody detection. Currently, UDCA-refractory anti-gp210-positive PBC patients lack effective therapeutic strategies and have worse prognoses as compared to anti-gp210-negative patients. Thus, exploring new therapeutic targets is urgently needed.<elsevierMultimedia ident="tbl0001"></elsevierMultimedia>3Anti-gp210-positive PBC patients have severe biochemical liver tests and histological indexesIn biochemical liver tests, anti-gp210-positive PBC patients have higher levels of ALP, bilirubin, globulin and IgM than their anti-gp210-negative counterparts. In 1998, Itoh et al. <a class="elsevierStyleCrossRef" href="#bib0011">[11]</a> compared the biochemical liver tests in 25 and 88 anti-gp210-positive and -negative PBC patients at the first diagnosis, respectively, and found that the levels of ALT and total bilirubin were significantly higher in anti-gp210-positive PBC patients than that in anti-gp210-negative patients. Subsequently, anti-gp210-positive PBC patients had significantly higher liver biochemical and immunological indicators than their anti-gp210-negative counterparts (<a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a>) [<a class="elsevierStyleCrossRef" href="#bib0004">4</a>,<a class="elsevierStyleCrossRef" href="#bib0005">5</a>,<a class="elsevierStyleCrossRef" href="#bib0007">7</a>,<a class="elsevierStyleCrossRef" href="#bib0011">11</a>,<a class="elsevierStyleCrossRef" href="#bib0012">12</a>,<a class="elsevierStyleCrossRef" href="#bib0017">17</a>]. Therefore, anti-gp210-positive PBC patients had higher serum levels of bile duct injury-related indicators at the initial diagnosis as compared with anti-gp210-negative patients, thereby suggesting more severe bile duct injury at the early stage of the disease.<elsevierMultimedia ident="tbl0002"></elsevierMultimedia>Currently, the histological studies of anti-gp210 related are limited. Nakamura et al. <a class="elsevierStyleCrossRef" href="#bib0005">[5]</a> enrolled 23 anti-gp210-positive PBC patients and found that anti-gp210 titers were sustained at high levels in 10 patients after UDCA treatment, and showed more severe interface hepatitis and higher activity score than the patients with reduced titer. Subsequently, Nakamura et al. <a class="elsevierStyleCrossRef" href="#bib0006">[6]</a> had done immunohistochemical staining using gp210 monoclonal antibody in the liver tissue, and for the first time, they proposed that the expression of gp210 antigen was increased on the nuclear envelope of BECs of small bile ducts in PBC patients as compared to healthy controls. Furthermore, in this study, gp210 immunostained BECs were generally surrounded by inflammatory cells or fibrous tissues, and the degree of gp210 expression was positively correlated with portal inflammation, interface hepatitis, and lobular inflammation, thereby suggesting that the expression of gp210 antigen may be involved in the chemotactic process of lymphocytes infiltrating to BECs in PBC. However, there was no correlation between the high expression of gp210 antigen in the BECs and the positivity of anti-gp210 in the serum, thus further studies are needed to elucidate the relationship between the gp210 antigen production in BECs and anti-gp210 production in serum.4Molecular structures of anti-gp210 and gp210 antigen and the application in PBCAnti-gp210 is a reliable indicator for the diagnosis of PBC. The anti-gp210 positivity rates were 14.3%–48.2% and 15.4%–46.7% in PBC patients and AMA-negative PBC patients, with specificity of over 99% and sensitivity of approximately 25% [<a class="elsevierStyleCrossRefs" href="#bib0004">4–17</a>,<a class="elsevierStyleCrossRef" href="#bib0024">24</a>]. The study addressing the diagnostic accuracy of anti-gp210 for PBC diagnosis was performed in more than 4000 sera from patients suspected of having liver and non-liver autoimmune and non-autoimmune diseases, thereby demonstrating a very high specificity and positive predictive value for the diagnosis of PBC <a class="elsevierStyleCrossRef" href="#bib0026">[26]</a>. This suggests that anti-gp210 is highly correlated with the pathogenesis of PBC.In 1985, Ruffati et al. <a class="elsevierStyleCrossRef" href="#bib0020">[20]</a> discovered that anti-gp210 was an antinuclear membrane antibody that labeled the nucleus of Hep-2 cells with a rim-like pattern. The anti-gp210 antibody belonged to IgG, a specific antibody against the antigens including DNase I, RNase, and trypsin [<a class="elsevierStyleCrossRef" href="#bib0027">27</a>,<a class="elsevierStyleCrossRef" href="#bib0028">28</a>]. The sensitivity of anti-gp210 and the corresponding immunofluorescence pattern is higher when the detection of autoantibodies is performed at the level of IgG isotype (in particular IgG1 isotype) because it determines a wide gain in terms of sensitivity without a loss of specificity <a class="elsevierStyleCrossRef" href="#bib0029">[29]</a>. Anti-gp210 has high specificity but low sensitivity for the diagnosis of PBC. Therefore, other antinuclear antibodies in AMA -negative PBC cases are been investigated. Antibodies to hexokinase 1 (HK1) and kelch-like 12 (KLHL12) were described as additional biomarkers in these patients [<a class="elsevierStyleCrossRef" href="#bib0030">30</a>,<a class="elsevierStyleCrossRef" href="#bib0031">31</a>].Gp210 protein can be found in most nucleus cells, located on the nuclear membrane as one of the constituent proteins of the nuclear pore complex. Gp210 is a 210 kDa type I integral membrane protein that assembles nuclear pore protein after mitosis and fixes nuclear pore complex to the pore membrane. More importantly, gp210 protein mediates nuclear pore expansion and macromolecular transport between the nucleus and the cytoplasm <a class="elsevierStyleCrossRef" href="#bib0032">[32]</a>. In addition, gp210 consists of three domains, including a 1808 amino acid amino-terminal domain situated in the perinuclear space, a 20 amino acid transmembrane segment, and a 58 amino acid carboxy-terminal tail domain (<a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>) [<a class="elsevierStyleCrossRef" href="#bib0033">33</a>,<a class="elsevierStyleCrossRef" href="#bib0034">34</a>]. Collectively, these studies elucidated the localization, function, and structure of the gp210 antigen, thereby laying the foundation for the subsequent antibody detection and the production mechanism of anti-gp210.<elsevierMultimedia ident="fig0001"></elsevierMultimedia>Regarding the antigen-antibody interaction, two gp210 epitopes have been identified by serum anti-gp210 of PBC patients. One is the 15 amino acids located at the carboxy-terminal tail and the other one is in the glycosylation regions at the amino-terminal domain [<a class="elsevierStyleCrossRef" href="#bib0021">21</a>,<a class="elsevierStyleCrossRef" href="#bib0022">22</a>]. Thus, these two structural regions are important molecular regions to study gp210 and anti-gp210 as well as their roles in PBC. In 1993, Nickowitz et al. <a class="elsevierStyleCrossRef" href="#bib0021">[21]</a> detected serum antibodies of 25 anti-gp210-positive PBC patients using bacterial gp210 fusion proteins and demonstrated that 15 amino acids in the carboxy-terminal tail domain between 1869 and 1883 can bind to anti-gp210. Subsequently, Bandin O et al. <a class="elsevierStyleCrossRef" href="#bib0016">[16]</a> demonstrated that 97.2% (70/72) of the serum antibodies of anti-gp210-positive PBC patients identified the same carboxy-terminal epitope. Thus, the carboxy-terminal epitope of gp210 protein has been widely recognized in previous studies. Moreover, Wesierska-Gadek et al. <a class="elsevierStyleCrossRef" href="#bib0022">[22]</a> confirmed that the recognition epitopes to anti-gp210 existed in the glycosylation domain of the amino-terminal of gp210. In this study, 12 anti-gp210-positive PBC patients were enrolled, and antibodies against an epitope within the glycosylation domain of the amino-terminal and in the carboxy-terminal tail were detected in the sera of 8 and 4 patients, respectively. Howeve, the above studies suggest that the detection of antibodies with bacterial gp210 fusion proteins has certain limitations. Therefore, in the future, it is necessary to develop a detection kit for dual epitopes of anti-gp210 and explore additional detection sites to improve the sensitivity of antibody detection and avoid the delay of diagnosis and timely treatment in PBC patients.5Pathogenesis of anti-gp210-positive PBC patientsThe rate of anti-gp210 positivity among PBC patients in different studies varies in different countries and human species (<a class="elsevierStyleCrossRef" href="#tbl0003">Table 3</a>) <a class="elsevierStyleCrossRefs" href="#bib0004">[4–16]</a>. The detection rate of anti-gp210 in Chinese and German is higher than that in other countries, ranging from 35.7% to 48.2%. This difference suggests that genetic and environmental factors play an important role in the production of anti-gp210 in PBC.<elsevierMultimedia ident="tbl0003"></elsevierMultimedia>However, the mechanism of anti-gp210 in the development of PBC remains unclear. Regarding genetics, Wang et al. <a class="elsevierStyleCrossRef" href="#bib0014">[14]</a> conducted genome-wide association studies (GWAS) in 930 Chinese PBC patients based on their autoantibody status (anti-gp210 and anti-sp100), of which 350/912 (38.4%) were anti-gp210-positive patients, and no specific human leukocyte antigen (HLA) allele or single-nucleotide polymorphism (SNP) associated with anti-gp210 was found. In terms of environmental factors, Tang R et al. <a class="elsevierStyleCrossRef" href="#bib0035">[35]</a> analyzed the gut microbiome of 116 Chinese PBC patients and found that the gut microbiome of anti-gp210-positive patients showed relatively lower species richness and Faecalibacterium spp abundance than the anti-gp210-negative patients, thereby indicating that the gut microbiota may play a role in the pathogenesis of anti-gp210-positive PBC patients.Therefore, for the epitopes of anti-gp210 to be deeply investigated, some studies have found that molecular mimicry, induced by proteins with similar amino acid sequences to epitopes, may be one of the main mechanisms in anti-gp210 production. Molecular mimicry is the process by which exogenous antigens activate autoreactive T or B cells in susceptible individuals because of the similarity between exogenous peptides and self-peptides <a class="elsevierStyleCrossRef" href="#bib0036">[36]</a>. Before the 1990s, the transmembrane topology of gp210 closely resembled the envelope glycoproteins topology of various animal viruses <a class="elsevierStyleCrossRefs" href="#bib0037">[37–39]</a>. Subsequently, Nickowitz et al. <a class="elsevierStyleCrossRef" href="#bib0021">[21]</a> demonstrated that the cytoplasmic carboxy-terminal tail epitope of anti-gp210 had six consecutive amino acids which were homologous to the protein products of the Escherichia coli mutY and Salmonella typhimurium mutB genes. In addition, Haruta et al. <a class="elsevierStyleCrossRef" href="#bib0040">[40]</a> found that Streptococcus intermedius (S.i.) could induce the generation of anti-gp210 and cellular infiltration around the bile ducts in BALB/c mice. Moreover, the antibody against histone-like DNA-binding protein of Streptococcus intermedius (S.i.-HLP) could bind to synthetic gp210 peptide. Thus, these studies suggest that bacteria or viruses may induce the production of anti-gp210 through molecular mimicry (<a class="elsevierStyleCrossRef" href="#fig0002">Fig. 2</a>). Clinical studies also found that anti-gp210 could persist for more than 10 years after liver transplantation in some PBC patients <a class="elsevierStyleCrossRefs" href="#bib0009">[9–11]</a>, thereby further suggesting that the antigen inducing the generation of anti-gp210 might not be derived from the liver. Bacteria-induced molecular mimicry in the production of anti-gp210 may provide new insights into the pathogenesis of anti-gp210-positive PBC patients. In addition to exogenous peptides such as bacteria and viruses, molecular mimicry exists between endogenous peptides such as mitochondria and gp210 in PBC. Shimoda et al. <a class="elsevierStyleCrossRef" href="#bib0041">[41]</a> discovered that the selected specific T cell clones of a peptide corresponding to the mitochondrial pyruvate dehydrogenase complex E2 subunit could cross-react with the synthetic peptide of gp210, thereby indicating a possible cross pathway existed between AMA and the production process of anti-gp210. Furthermore, T cell clones selected by recombinant gp210 protein simultaneously reacted with the mimicry peptide of amino acid 188–201 in gp210, thereby indicating that the amino acid 188–201 in gp210 was one of the immunodominant T cell epitopes.<elsevierMultimedia ident="fig0002"></elsevierMultimedia>Current research on the relationship between anti-gp210 and the pathogenesis of PBC is very limited. Notably, anti-gp210 can be detected in the serum of the dominant-negative form of TGF-β receptor type II (dnTGF-βRII) mice, one of the main model mice of PBC. In addition, Yang CY et al. <a class="elsevierStyleCrossRef" href="#bib0042">[42]</a> found that the titer of anti-gp210 was significantly reduced by deleting specific cytokines (including IL-12p40, IL-23p19, IL-17, IL-6, and TNF-α) in dnTGF-βRII mice, thereby suggesting that these cytokines may be involved in the production of anti-gp210. In recent years, studies on immune cells and the pathogenesis of PBC are actively underway, and thus clarifying the pathogenesis of anti-gp210-positive PBC is essential to explore new therapeutic intervention targets for these patients. Collectively, current research on the pathogenesis of anti-gp210-positive PBC primarily focuses on aspects including genetic and environmental factors, molecular mimicry, and cytokines. Therefore, an in-depth investigation of the interrelationship among the above three aspects could provide direction for further study on anti-gp210-positive PBC.6Discussion and prospectAnti-gp210-positive PBC patients present with more severe biochemical indexes, severe bile duct injury and liver inflammation in histology, poorer response to treatment drugs, faster disease progression, and a worse prognosis than anti-gp210-negative patients. It is of clinical importance to identify the pathogenesis of anti-gp210-positive PBC and find preventive measures against the etiology to guide the diagnosis and treatment of the disease.7ConclusionsAnti-gp210 is an autoantibody against the nuclear membrane protein gp210, and thus the study of anti-gp210 and the antigen is essential for the pathogenesis of anti-gp210-positive PBC. Moreover, the species richness of gut microbiome in anti-gp210-positive PBC patients was lower than that in anti-gp210-negative patients, thereby suggesting that intestinal microecology may participate in disease development and progression. Molecular mimicry by bacteria is currently the main hypothesis for the pathogenesis, which still needs to be further explored. The study on the localization, structure, and epitope of gp210 antigen has laid a certain theoretical foundation for the study of anti-gp210-positive PBC pathogenesis. With the development of epidemiology, genetics, and animal models, further elucidation of the generation and molecular mechanism of anti-gp210 in PBC will be crucial for clinical prevention and treatment." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1955997" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abss0001" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1683527" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xpalclavsec1683528" "titulo" => "Abbreviations" ] 3 => array:2 [ "identificador" => "sec0001" "titulo" => "Introduction" ] 4 => array:2 [ "identificador" => "sec0002" "titulo" => "Anti-gp210-positive PBC patients have poor treatment response and prognosis" ] 5 => array:2 [ "identificador" => "sec0003" "titulo" => "Anti-gp210-positive PBC patients have severe biochemical liver tests and histological indexes" ] 6 => array:2 [ "identificador" => "sec0004" "titulo" => "Molecular structures of anti-gp210 and gp210 antigen and the application in PBC" ] 7 => array:2 [ "identificador" => "sec0005" "titulo" => "Pathogenesis of anti-gp210-positive PBC patients" ] 8 => array:2 [ "identificador" => "sec0006" "titulo" => "Discussion and prospect" ] 9 => array:2 [ "identificador" => "sec0007" "titulo" => "Conclusions" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-02-25" "fechaAceptado" => "2023-05-22" "PalabrasClave" => array:1 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1683527" "palabras" => array:4 [ 0 => "Anti-gp210" 1 => "Primary biliary cholangitis" 2 => "Treatment response" 3 => "Pathogenesis" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec1683528" "palabras" => array:12 [ 0 => "PBC" 1 => "AMA" 2 => "ANA" 3 => "UDCA" 4 => "OCA" 5 => "BECs" 6 => "AST" 7 => "ALP" 8 => "IgM" 9 => "GWAS" 10 => "HLA" 11 => "SNP" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Anti-gp210 is the disease-specific anti-nuclear antibody (ANA) of primary biliary cholangitis (PBC). Anti-gp210-positive PBC patients have worse responses to ursodeoxycholic acid (UDCA) as compared with anti-gp210-negative patients. Moreover, anti-gp210-positive patients always present with more severe histopathologic features including lobular inflammation, interfacial hepatitis, and bile duct injury, and have a worse prognosis than their anti-gp210-negative counterparts. Previous studies have identified two antigenic epitopes recognized by anti-gp210. Although the pathogenetic mechanism of anti-gp210 production remains unclear, evidence suggests that the autoimmune response to anti-gp210 production might be due to molecular mimicry induced by bacteria or endogenous peptides. T cells and related cytokines play a critical role in the pathogenesis of PBC, however, the mechanism hasn't been fully understood. Thus, this review focuses on the clinicopathological characteristics of anti-gp210-positive PBC patients, the fundamental research of gp210 antigen, and the possible mechanism of anti-gp210 production to clarify the mechanism of anti-gp210-positive PBC and provide potential molecular targets for disease prevention and treatment in the future." ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "#" "nota" => "Xiaoyi Wang, Zhen Yang, Ying Ran contributed equally to this work." "identificador" => "fn1" ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0001" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1756 "Ancho" => 3583 "Tamanyo" => 539706 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig 1&#58" "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "The structural diagram of nuclear pore membrane protein gp210." ] ] 1 => array:8 [ "identificador" => "fig0002" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2162 "Ancho" => 2917 "Tamanyo" => 477788 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0002" "detalle" => "Fig 2&#58" "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "The simulation diagram of bacterial induction of anti-gp210 through molecular mimicry." ] ] 2 => array:8 [ "identificador" => "tbl0001" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0003" "detalle" => "Table 1&#58" "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "IIF, indirect immunofluorescence; ELISA, enzyme-linked immunosorbent assay; IB, immunoblot." "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"><a name="en0001"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Methods of detection \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Time \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0003"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Country of cases \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Detection of substrate \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0005"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Variable titers (Follow up number) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0006"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Follow up time (month/year) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0007"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">IIF (Rim-like) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1998 <a class="elsevierStyleCrossRef" href="#bib0011">[11]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0009"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">HepG2 cells \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">NO (10) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">87.5 ± 56.0 m \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0013"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2003 <a class="elsevierStyleCrossRef" href="#bib0012">[12]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Italy \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">HEp-2 cell lines \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Not investigated \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0019"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">ELISA \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2003 <a class="elsevierStyleCrossRef" href="#bib0012">[12]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0021"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Italy \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Purified gp210 ELISA kits (IMTEC) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">NO (6) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">3–10 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0025"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2005 <a class="elsevierStyleCrossRef" href="#bib0005">[5]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">gp210 C-terminal peptide \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0029"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">YES (23) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">73.4 ± 54.3 m \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0031"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2007 <a class="elsevierStyleCrossRef" href="#bib0013">[13]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">gp210 C-terminal peptide (25 amino acids) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">YES (217) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1–292 m \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0037"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2014 <a class="elsevierStyleCrossRef" href="#bib0008">[8]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">gp210 C-terminal peptide (25 amino acids) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">YES (50) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">6–12 m \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3255935.png" ] ] ] ] "descripcion" => array:1 [ "en" => "The substrate used in detection anti-gp210 and the variability of anti-gp210." ] ] 3 => array:8 [ "identificador" => "tbl0002" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0004" "detalle" => "Table 2&#58" "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "TP, total protein; ALB, albumin; GLB, globulin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GGT, γ-glutamyl transferase; TBIL, total bilirubin; DBIL, direct bilirubin; TC, total cholesterol; Ig, immunoglobulin; Plt, platelet." "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"><a name="en0043"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Clinical research \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0044"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Time \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0045"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Country \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0046"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Number of patients% (gp210+/PBC) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0047"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Indicators with statistical difference \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0048"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Itoh S et al. <a class="elsevierStyleCrossRef" href="#bib0011">[11]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1998 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22.1 (25/113) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">ALP, TBIL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0053"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Paolo et al. <a class="elsevierStyleCrossRef" href="#bib0012">[12]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2003 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Italy \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">15.6 (15/96) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">ALP, GGT, TC, ALB, γ-GLB, IgA, IgM \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0058"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Minoru et al. <a class="elsevierStyleCrossRef" href="#bib0005">[5]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2005 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0061"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">32.4 (23/71) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">IgM \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0063"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Dimitrioa et al. <a class="elsevierStyleCrossRef" href="#bib0017">[17]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2007 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0065"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Spain and Greece \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10.5 (38/362) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">ALP, DBIL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0068"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Yang et al. <a class="elsevierStyleCrossRef" href="#bib0007">[7]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0069"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2017 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">China \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0071"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">48.2 (133/276) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">GGT, TBIL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0073"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Haldar et al. <a class="elsevierStyleCrossRef" href="#bib0004">[4]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2021 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">UK \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">16.7 (81/486) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">AST, ALT, TBIL \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3255937.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Biochemical liver Indicators of anti-gp210-positive PBC patients are higher than anti-gp210-negative PBC patients." ] ] 4 => array:8 [ "identificador" => "tbl0003" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0005" "detalle" => "Table 3&#58" "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "IIF, indirect immunofluorescence; ELISA, enzyme-linked immunosorbent assay; IB, immunoblot." "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"><a name="en0078"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Methods of detection \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0079"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Time \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0080"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Country of cases \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0081"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Positivity% (Anti-gp210+/PBC) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0082"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Positivity% (Anti-gp210+/AMA- PBC) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0083"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">IIF (Rim-like) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1996 <a class="elsevierStyleCrossRef" href="#bib0016">[16]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0085"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">France \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">30.5 (87/285) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">46.7 (7/15) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0088"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1998 <a class="elsevierStyleCrossRef" href="#bib0011">[11]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0091"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">27.4 (31/113) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">18.2 (2/11) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0093"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2003 <a class="elsevierStyleCrossRef" href="#bib0012">[12]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0095"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Italy \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10.0 (9/91) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">33.0 (5/19) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0098"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">ELISA \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0099"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1996 <a class="elsevierStyleCrossRef" href="#bib0016">[16]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">France \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0101"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25.5 (73/285) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0102"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">46.8 (7/15) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0103"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0104"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2003 <a class="elsevierStyleCrossRef" href="#bib0012">[12]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0105"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Italy \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0106"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">16.0 (15/96) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0107"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">15.4 (2/13) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0108"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0109"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2005 <a class="elsevierStyleCrossRef" href="#bib0005">[5]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0110"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0111"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">32.4 (23/71) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0112"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0113"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0114"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2006 <a class="elsevierStyleCrossRef" href="#bib0006">[6]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0115"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0116"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">38.5 (20/52) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0118"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0119"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2007 <a class="elsevierStyleCrossRef" href="#bib0013">[13]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0120"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0121"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">26.1 (72/276) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0123"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0124"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2014 <a class="elsevierStyleCrossRef" href="#bib0008">[8]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0125"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0126"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">30.5 (50/164) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0127"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0128"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0129"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2019 <a class="elsevierStyleCrossRef" href="#bib0014">[14]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0130"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">China \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0131"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">38.4 (350/912) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0132"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0133"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">IB \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0134"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1996 <a class="elsevierStyleCrossRef" href="#bib0016">[16]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0135"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">France \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0136"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25.3 (72/285) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0137"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0138"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0139"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1997 <a class="elsevierStyleCrossRef" href="#bib0010">[10]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0140"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">USA \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0141"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25.7 (9/35) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0142"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0143"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0144"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1998 <a class="elsevierStyleCrossRef" href="#bib0011">[11]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0145"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0146"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22.1 (25/113) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0147"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">20.0 (1/5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0148"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0149"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1998 <a class="elsevierStyleCrossRef" href="#bib0009">[9]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0150"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Germany \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0151"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">35.7 (15/42) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0152"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0153"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0154"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2003 <a class="elsevierStyleCrossRef" href="#bib0012">[12]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0155"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0156"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">26.3 (46/175) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0157"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">18.5 (10/54) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0158"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0159"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2003 <a class="elsevierStyleCrossRef" href="#bib0015">[15]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0160"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Japan \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0161"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">28.2 (46/163) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0162"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0163"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0164"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2017 <a class="elsevierStyleCrossRef" href="#bib0007">[7]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0165"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">China \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0166"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">48.2 (133/276) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0167"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">41.2 (7/17) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0168"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0169"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">2021 <a class="elsevierStyleCrossRef" href="#bib0004">[4]</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0170"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">UK \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0171"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">16.7 (81/486) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0172"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">16.9 (12/72) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3255936.png" ] ] ] ] "descripcion" => array:1 [ "en" => "The positive rate of anti-gp210 in PBC patients in different countries." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec1" "bibliografiaReferencia" => array:42 [ 0 => array:3 [ "identificador" => "bib0001" "etiqueta" => "[1]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.M. Kaplan" 1 => "M.E. Gershwin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMra043898" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2005" "volumen" => "353" "paginaInicial" => "1261" "paginaFinal" => "1273" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16177252" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0002" "etiqueta" => "[2]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K.D. Lindor" 1 => "C.L. Bowlus" 2 => "J. Boyer" 3 => "C. Levy" 4 => "M. Mayo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.30145" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2019" "volumen" => "69" "paginaInicial" => "394" "paginaFinal" => "419" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30070375" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0003" "etiqueta" => "[3]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Overcoming a “probable” diagnosis in antimitochondrial antibody negative primary biliary cirrhosis: study of 100 sera and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Bizzaro" 1 => "G. Covini" 2 => "F. Rosina" 3 => "P. Muratori" 4 => "E. Tonutti" 5 => "D. Villalta" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s12016-010-8234-y" "Revista" => array:5 [ "tituloSerie" => "Clin Rev Allergy Immunol" "fecha" => "2012" "volumen" => "42" "paginaInicial" => "288" "paginaFinal" => "297" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0004" "etiqueta" => "[4]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antibodies to gp210 and understanding risk in patients with primary biliary cholangitis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Haldar" 1 => "A. Janmohamed" 2 => "T. Plant" 3 => "M. Davidson" 4 => "H. Norman" 5 => "E. Russell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/liv.14688" "Revista" => array:6 [ "tituloSerie" => "Liver Int" "fecha" => "2021" "volumen" => "41" "paginaInicial" => "535" "paginaFinal" => "544" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33022821" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0005" "etiqueta" => "[5]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Nakamura" 1 => "Y. Shimizu-Yoshida" 2 => "Y. Takii" 3 => "A. Komori" 4 => "T. Yokoyama" 5 => "T. Ueki" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2004.11.016" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2005" "volumen" => "42" "paginaInicial" => "386" "paginaFinal" => "392" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15710222" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0006" "etiqueta" => "[6]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Nakamura" 1 => "Y. Takii" 2 => "M. Ito" 3 => "A. Komori" 4 => "T. Yokoyama" 5 => "Y. Shimizu-Yoshida" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaut.2005.10.007" "Revista" => array:6 [ "tituloSerie" => "J Autoimmun" "fecha" => "2006" "volumen" => "26" "paginaInicial" => "138" "paginaFinal" => "145" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16337775" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0007" "etiqueta" => "[7]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The risk predictive values of UK-PBC and GLOBE scoring system in Chinese patients with primary biliary cholangitis: the additional effect of anti-gp210" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Yang" 1 => "Y. Yang" 2 => "Q. Wang" 3 => "Z. Wang" 4 => "Q. Miao" 5 => "X. Xiao" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/apt.13927" "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther" "fecha" => "2017" "volumen" => "45" "paginaInicial" => "733" "paginaFinal" => "743" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28083929" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0008" "etiqueta" => "[8]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoantibody status and histological variables influence biochemical response to treatment and long-term outcomes in Japanese patients with primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Nakamura" 1 => "H. Kondo" 2 => "A. Tanaka" 3 => "A. Komori" 4 => "M. Ito" 5 => "K. Yamamoto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/hepr.12423" "Revista" => array:5 [ "tituloSerie" => "Hepatol Res" "fecha" => "2015" "volumen" => "45" "paginaInicial" => "846" "paginaFinal" => "855" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0009" "etiqueta" => "[9]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The antinuclear autoantibodies Sp100 and gp210 persist after orthotopic liver transplantation in patients with primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Luettig" 1 => "K.H. Boeker" 2 => "W. Schoessler" 3 => "H. Will" 4 => "S. Loges" 5 => "E. Schmidt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0168-8278(98)80233-x" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "1998" "volumen" => "28" "paginaInicial" => "824" "paginaFinal" => "828" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9625318" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0010" "etiqueta" => "[10]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Persistence of autoantibodies against recombinant mitochondrial and nuclear pore proteins after orthotopic liver transplantation for primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Mattalia" 1 => "B. Lüttig" 2 => "F. Rosina" 3 => "P.S. Leung" 4 => "J. Van de Water" 5 => "M. Bauducci" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1006/jaut.1997.0156" "Revista" => array:6 [ "tituloSerie" => "J Autoimmun" "fecha" => "1997" "volumen" => "10" "paginaInicial" => "491" "paginaFinal" => "497" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9376077" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0011" "etiqueta" => "[11]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoantibodies against a 210kDa glycoprotein of the nuclear pore complex as a prognostic marker in patients with primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Itoh" 1 => "T. Ichida" 2 => "T. Yoshida" 3 => "A. Hayakawa" 4 => "M. Uchida" 5 => "T. Tashiro-Itoh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1440-1746.1998.01553.x" "Revista" => array:6 [ "tituloSerie" => "J Gastroenterol Hepatol" "fecha" => "1998" "volumen" => "13" "paginaInicial" => "257" "paginaFinal" => "265" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9570238" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0012" "etiqueta" => "[12]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Muratori" 1 => "L. Muratori" 2 => "R. Ferrari" 3 => "F. Cassani" 4 => "G. Bianchi" 5 => "M. Lenzi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1572-0241.2003.07257.x" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol" "fecha" => "2003" "volumen" => "98" "paginaInicial" => "431" "paginaFinal" => "437" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12591064" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0013" "etiqueta" => "[13]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Nakamura" 1 => "H. Kondo" 2 => "T. Mori" 3 => "A. Komori" 4 => "M. Matsuyama" 5 => "M. Ito" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.21472" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2007" "volumen" => "45" "paginaInicial" => "118" "paginaFinal" => "127" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17187436" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0014" "etiqueta" => "[14]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genome-wide Association Studies of Specific Antinuclear Autoantibody Subphenotypes in Primary Biliary Cholangitis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Wang" 1 => "X. Zheng" 2 => "P. Jiang" 3 => "R. Tang" 4 => "Y. Gong" 5 => "Y. Dai" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.30604" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2019" "volumen" => "70" "paginaInicial" => "294" "paginaFinal" => "307" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30854688" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0015" "etiqueta" => "[15]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis: a multicenter study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Miyachi" 1 => "R.W. Hankins" 2 => "H. Matsushima" 3 => "F. Kikuchi" 4 => "T. Inomata" 5 => "T. Horigome" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0896-8411(03)00033-7" "Revista" => array:6 [ "tituloSerie" => "J Autoimmun" "fecha" => "2003" "volumen" => "20" "paginaInicial" => "247" "paginaFinal" => "254" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12753810" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0016" "etiqueta" => "[16]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Specificity and sensitivity of gp210 autoantibodies detected using an enzyme-linked immunosorbent assay and a synthetic polypeptide in the diagnosis of primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "O. Bandin" 1 => "J.C. Courvalin" 2 => "R. Poupon" 3 => "L. Dubel" 4 => "J.C. Homberg" 5 => "C. Johanet" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.510230512" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "1996" "volumen" => "23" "paginaInicial" => "1020" "paginaFinal" => "1024" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8621127" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0017" "etiqueta" => "[17]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anti-gp210 antibody mirrors disease severity in primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.P. Bogdanos" 1 => "C. Liaskos" 2 => "A. Pares" 3 => "G. Norman" 4 => "E.I. Rigopoulou" 5 => "L. Caballeria" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.21678" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2007" "volumen" => "45" "paginaInicial" => "1583" "paginaFinal" => "1584" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17538935" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0018" "etiqueta" => "[18]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chinese Medical Association" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Chinese Society of Hepatology" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3760/cma.j.cn112138-20211112-00794" "Revista" => array:6 [ "tituloSerie" => "Zhonghua Nei Ke Za Zhi" "fecha" => "2021" "volumen" => "60" "paginaInicial" => "1024" "paginaFinal" => "1037" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34856679" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0019" "etiqueta" => "[19]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of primary biliary cholangitis with ursodeoxycholic acid, prednisolone and immunosuppressants in patients not responding to ursodeoxycholic acid alone and the prognostic indicators" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.D. Qian" 1 => "T.T. Yao" 2 => "Y. Wang" 3 => "G.Q. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clinre.2020.03.026" "Revista" => array:6 [ "tituloSerie" => "Clin Res Hepatol Gastroenterol" "fecha" => "2020" "volumen" => "44" "paginaInicial" => "874" "paginaFinal" => "884" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32305248" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0020" "etiqueta" => "[20]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nuclear membrane-staining antinuclear antibody in patients with primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Ruffatti" 1 => "P. Arslan" 2 => "A. Floreani" 3 => "G. De Silvestro" 4 => "A. Calligaro" 5 => "R. Naccarato" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/BF00918255" "Revista" => array:6 [ "tituloSerie" => "J Clin Immunol" "fecha" => "1985" "volumen" => "5" "paginaInicial" => "357" "paginaFinal" => "361" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2414313" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0021" "etiqueta" => "[21]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoantibodies from patients with primary biliary cirrhosis recognize a restricted region within the cytoplasmic tail of nuclear pore membrane glycoprotein Gp210" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.E. Nickowitz" 1 => "H.J. Worman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1084/jem.178.6.2237" "Revista" => array:6 [ "tituloSerie" => "J Exp Med" "fecha" => "1993" "volumen" => "178" "paginaInicial" => "2237" "paginaFinal" => "2342" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7504063" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0022" "etiqueta" => "[22]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoantibodies from patients with primary biliary cirrhosis preferentially react with the amino-terminal domain of nuclear pore complex glycoprotein gp210" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Wesierska-Gadek" 1 => "H. Hohenauer" 2 => "E. Hitchman" 3 => "E. Penner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1084/jem.182.4.1159" "Revista" => array:6 [ "tituloSerie" => "J Exp Med" "fecha" => "1995" "volumen" => "182" "paginaInicial" => "1159" "paginaFinal" => "1162" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7561689" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0023" "etiqueta" => "[23]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The prognostic value of antibodies to gp210 among patients with primary biliary cholangitis in Northeast China" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Q. Chen" 1 => "R. Zhong" 2 => "K. Dong" 3 => "Y. Wang" 4 => "Y. Kui" 5 => "B. Ma" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.dld.2021.10.011" "Revista" => array:6 [ "tituloSerie" => "Dig Liver Dis" "fecha" => "2022" "volumen" => "54" "paginaInicial" => "1094" "paginaFinal" => "1100" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34789400" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0024" "etiqueta" => "[24]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fatigue and pruritus at onset identify a more aggressive subset of primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Quarneti" 1 => "P. Muratori" 2 => "C. Lalanne" 3 => "A. Fabbri" 4 => "R. Menichella" 5 => "A. Granito" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/liv.12560" "Revista" => array:6 [ "tituloSerie" => "Liver Int" "fecha" => "2015" "volumen" => "35" "paginaInicial" => "636" "paginaFinal" => "641" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24698666" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0025" "etiqueta" => "[25]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical significance of autoantibodies in primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M. Nakamura" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1055/s-0034-1383732" "Revista" => array:6 [ "tituloSerie" => "Semin Liver Dis" "fecha" => "2014" "volumen" => "34" "paginaInicial" => "334" "paginaFinal" => "340" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25057956" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0026" "etiqueta" => "[26]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns: diagnostic accuracy for primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Granito" 1 => "P. Muratori" 2 => "L. Muratori" 3 => "G. Pappas" 4 => "F. Cassani" 5 => "J. Worthington" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2036.2006.03172.x" "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther" "fecha" => "2006" "volumen" => "24" "paginaInicial" => "1575" "paginaFinal" => "1583" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17206945" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0027" "etiqueta" => "[27]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoantibodies against nuclear envelope-associated proteins in primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Lozano" 1 => "A. Parés" 2 => "L. Borche" 3 => "M. Plana" 4 => "T. Gallart" 5 => "J. Rodés" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.1840080438" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "1988" "volumen" => "8" "paginaInicial" => "930" "paginaFinal" => "938" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3292364" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0028" "etiqueta" => "[28]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The 210-kD nuclear envelope polypeptide recognized by human autoantibodies in primary biliary cirrhosis is the major glycoprotein of the nuclear pore" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.C. Courvalin" 1 => "K. Lassoued" 2 => "E. Bartnik" 3 => "G. Blobel" 4 => "R.W. Wozniak" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI114696" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "1990" "volumen" => "86" "paginaInicial" => "279" "paginaFinal" => "285" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2195063" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0029" "etiqueta" => "[29]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multiple nuclear dots and rim-like/membranous IgG isotypes in primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Muratori" 1 => "A. Granito" 2 => "S. Ferri" 3 => "G. Pappas" 4 => "U. Volta" 5 => "R. Menichella" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/08916930802709133" "Revista" => array:6 [ "tituloSerie" => "Autoimmunity" "fecha" => "2009" "volumen" => "42" "paginaInicial" => "224" "paginaFinal" => "227" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19301204" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0030" "etiqueta" => "[30]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antinuclear antibodies as ancillary markers in primary biliary cirrhosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Granito" 1 => "P. Muratori" 2 => "C. Quarneti" 3 => "G. Pappas" 4 => "R. Cicola" 5 => "L. Muratori" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1586/erm.11.82" "Revista" => array:6 [ "tituloSerie" => "Expert Rev Mol Diagn" "fecha" => "2012" "volumen" => "12" "paginaInicial" => "65" "paginaFinal" => "74" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22133120" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0031" "etiqueta" => "[31]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Surrogate Markers for Antimitochondrial Antibody-Negative Primary Biliary Cholangitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Granito" 1 => "L. Muratori" 2 => "F. Tovoli" 3 => "P. Muratori" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.14309/ajg.0000000000000928" "Revista" => array:6 [ "tituloSerie" => "Am J Gastroenterol" "fecha" => "2021" "volumen" => "116" "paginaInicial" => "215" "paginaFinal" => "217" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33009063" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0032" "etiqueta" => "[32]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The integral membrane nucleoporin pom121 functionally links nuclear pore complex assembly and nuclear envelope formation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "W. Antonin" 1 => "C. Franz" 2 => "U. Haselmann" 3 => "C. Antony" 4 => "I.W. Mattaj" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.molcel.2004.12.010" "Revista" => array:6 [ "tituloSerie" => "Mol Cell" "fecha" => "2005" "volumen" => "17" "paginaInicial" => "83" "paginaFinal" => "92" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15629719" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0033" "etiqueta" => "[33]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary structure analysis of an integral membrane glycoprotein of the nuclear pore" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.W. Wozniak" 1 => "E. Bartnik" 2 => "G. Blobel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1083/jcb.108.6.2083" "Revista" => array:5 [ "tituloSerie" => "J Cell Biol" "fecha" => "1989" "volumen" => "108" "paginaInicial" => "2083" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2738089" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0034" "etiqueta" => "[34]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A major glycoprotein of the nuclear pore complex is a membrane-spanning polypeptide with a large lumenal domain and a small cytoplasmic tail" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "U.F. Greber" 1 => "A. Senior" 2 => "L. Gerace" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/j.1460-2075.1990.tb08267.x" "Revista" => array:6 [ "tituloSerie" => "EMBO J" "fecha" => "1990" "volumen" => "9" "paginaInicial" => "1495" "paginaFinal" => "1502" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2184032" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0035" "etiqueta" => "[35]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Tang" 1 => "Y. Wei" 2 => "Y. Li" 3 => "W. Chen" 4 => "H. Chen" 5 => "Q. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gutjnl-2016-313332" "Revista" => array:6 [ "tituloSerie" => "Gut" "fecha" => "2018" "volumen" => "67" "paginaInicial" => "534" "paginaFinal" => "541" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28213609" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0036" "etiqueta" => "[36]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular mimicry and autoimmunity" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Rojas" 1 => "P. Restrepo-Jiménez" 2 => "D.M. Monsalve" 3 => "Y. Pacheco" 4 => "Y. Acosta-Ampudia" 5 => "C. Ramírez-Santana" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaut.2018.10.012" "Revista" => array:6 [ "tituloSerie" => "J Autoimmun" "fecha" => "2018" "volumen" => "95" "paginaInicial" => "100" "paginaFinal" => "123" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30509385" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0037" "etiqueta" => "[37]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vesicular stomatitis virus glycoprotein is anchored in the viral membrane by a hydrophobic domain near the COOH terminus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.K. Rose" 1 => "W.J. Welch" 2 => "B.M. Sefton" 3 => "F.S. Esch" 4 => "N.C. Ling" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.77.7.3884" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci U S A" "fecha" => "1980" "volumen" => "77" "paginaInicial" => "3884" "paginaFinal" => "3888" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6253998" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0038" "etiqueta" => "[38]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Location of the spike glycoproteins in the Semliki Forest virus membrane" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H. Garoff" 1 => "K. 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Xiaoyi Wanga,#, Zhen Yanga,#, Ying Rana,#, Long Lib, Bangmao Wanga, Lu Zhoua,c,

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lzhou01@tmu.edu.cn

Corresponding author.

a Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China

b Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China

c Department of Gastroenterology and Hepatology, People's Hospital of Hetian District, Xinjiang Uygur Autonomous Region, China

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The therapeutic effects of different drugs&#44; including obeticholic acid &#40;OCA&#41;&#44; fibrates&#44; glucocorticoids&#44; and immunosuppressants in anti-gp210-positive and -negative PBC patients have been compared&#44; and it has been found positivity remains a risk factor for poor treatment response &#91;<a class="elsevierStyleCrossRef" href="#bib0008">8</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0019">19</a>&#93;&#46; Thus&#44; anti-gp210 is a risk factor for poor response to UDCA and poor prognosis in PBC patients&#44; and thus clarifying the production of anti-gp210 and its mechanism in PBC is very important for the development of effective therapeutic targets&#46;</p><p id="para0004" class="elsevierStylePara elsevierViewall">Currently&#44; studies on the molecular mechanisms of anti-gp210 in PBC are still limited&#46; The antigen of anti-gp210 is gp210&#44; one of the constitutive proteins of the nuclear pore complex <a class="elsevierStyleCrossRef" href="#bib0020">&#91;20&#93;</a>&#46; Two antigenic epitopes of gp210 protein have been identified&#44; which laid a theoretical basis for the detection of anti-gp210 and the exploration of antigen expression as well as antibody production &#91;<a class="elsevierStyleCrossRef" href="#bib0021">21</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0022">22</a>&#93;&#46; Notably&#44; Nickowitz <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0006">&#91;6&#93;</a> found that the gp210 expression in biliary epithelial cells &#40;BECs&#41; in the liver of PBC patients was significantly increased compared to that in the patients of AIH and hepatitis C&#44; however&#44; it did not correlate with the production of anti-gp210 antibody&#46; Thus&#44; it is suggested that gp210 antigen may be involved in the bile duct injury of PBC&#46; In addition&#44; in terms of the potential mechanism for anti-gp210 production&#44; molecular mimicry is the major hypothesis at present <a class="elsevierStyleCrossRef" href="#bib0021">&#91;21&#93;</a>&#46; However&#44; whether or not anti-gp210 is directly involved in the occurrence and development of PBC still requires more exploration or merely represents epiphenomenon&#46; Collectively&#44; the clinicopathological characteristics of anti-gp210-positive PBC patients&#44; the production of anti-gp210 antibodies&#44; and the possible pathogenic mechanism are reviewed to deeply understand the role of anti-gp210 in PBC&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2</span><span class="elsevierStyleSectionTitle" id="cesectitle0005">Anti-gp210-positive PBC patients have poor treatment response and prognosis</span><p id="para0005" class="elsevierStylePara elsevierViewall">Anti-gp210-positive PBC patients have a lower UDCA response rate than their anti-gp210-negative counterparts&#46; In a cohort of 499 PBC patients from the UK&#44; Haldar et al&#46; <a class="elsevierStyleCrossRef" href="#bib0004">&#91;4&#93;</a> reported that anti-gp210-positive patients treated with UDCA did not respond sufficiently to treatment as compared to anti-gp210-negative patients &#40;39&#46;3&#37; vs&#46; 16&#46;7&#37;&#41;&#46; The study further confirmed that anti-gp210 could be used as an index to predict poor response to UDCA treatment&#44; with sensitivity and specificity of 26&#46;8&#37; and 89&#46;8&#37;&#44; respectively&#46; Chen Q <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0023">&#91;23&#93;</a> conducted a retrospective cohort study of 180 UDCA-treated Chinese PBC patients to assess the prognostic value of anti-gp210 and found that positivity for anti-gp210 was independently associated with a higher risk of liver-related death and transplantation&#46; In summary&#44; anti-gp210-positive PBC patients have low UDCA response rates and poor prognosis&#46;</p><p id="para0006" class="elsevierStylePara elsevierViewall">Second-line therapeutic drugs&#44; such as OCA&#44; fibrates&#44; and corticosteroids are available for UDCA-refractory PBC patients&#44; however&#44; the treatment efficacy remains unsatisfactory for anti-gp210-positive patients&#46; Nakamura <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0008">&#91;8&#93;</a> enrolled 50 and 114 anti-gp210-positive and -negative PBC patients&#44; respectively&#44; &#40;115 PBC patients of UDCA monotherapy and 49 UDCA-refractory PBC patients of UDCA combined with prednisolone and&#47;or bezafibrate&#41; in a retrospective study&#46; This study showed that the liver function of both groups had improved after 2 years of treatment&#44; however&#44; anti-gp210-positive patients presented with higher levels of aspartate aminotransferase &#40;AST&#41;&#44; alkaline phosphatase &#40;ALP&#41;&#44; and immunoglobulin M &#40;IgM&#41; after treatment than anti-gp210-negative patients&#46; Then&#44; Qian <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0019">&#91;19&#93;</a> respectively compared the responses of 29 and 51 anti-gp210-positive and -negative PBC patients who received UDCA or UDCA&#44; prednisolone&#44; and immunosuppressant &#40;AZA or MMF&#41; triple therapy&#44; and reported that the incidence of poor prognosis &#40;such as increasing rate of PBC related complications&#44; liver transplantation&#44; and mortality&#41; was higher in anti-gp210-positive PBC patients than in anti-gp210-negative patients&#46;</p><p id="para0007" class="elsevierStylePara elsevierViewall">Anti-gp210 is closely associated with poor prognosis in PBC patients&#46; In 1998&#44; Itoh <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0011">&#91;11&#93;</a> initially reported that anti-gp210-positive PBC patients had a three times higher mortality rate &#40;40&#46;0&#37; vs&#46; 13&#46;6&#37;&#41;&#44; and 3&#46;5 times higher probability of death from liver failure &#40;32&#46;0&#37; vs&#46; 9&#46;1&#37;&#41; than anti-gp210-negative patients&#46; The liver transplantation free survival time of anti-gp210-positive PBC patients was significantly shorter than their anti-gp210-negative PBC counterparts&#46; Meanwhile&#44; Yang F <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0007">&#91;7&#93;</a> found that anti-gp210-positive patients had remarkably higher UK-PBC scores and poorer long-term prognoses than anti-gp210-negative patients&#46; Previous investigators have reported that the presence of fatigue and pruritus during diagnosis is associated with poor responsiveness to UDCA treatment&#44; and more inclined to evolve to cirrhosis and its complications in PBC <a class="elsevierStyleCrossRef" href="#bib0024">&#91;24&#93;</a>&#46; Thus&#44; anti-gp210 may help together with clinical features to identify the subgroup of PBC patients with more severe prognoses&#46;</p><p id="para0008" class="elsevierStylePara elsevierViewall">Nakamura M <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0025">&#91;25&#93;</a> further studied the relationship between the titer of anti-gp210 and disease severity and prognosis&#46; They found that patients with reduced anti-gp210 titers showed milder disease and better prognosis than patients whose anti-gp210 titers were unchanged or elevated after UDCA treatment <a class="elsevierStyleCrossRef" href="#bib0005">&#91;5&#93;</a>&#46; Furthermore&#44; they concluded that the change of anti-gp210 titers in serum had great significance for the prognosis of the disease <a class="elsevierStyleCrossRef" href="#bib0005">&#91;5&#93;</a>&#46; However&#44; the issue of whether or not the titer of anti-gp210 is variable remains controversial because some studies have pointed out that anti-gp210 titers in PBC patients did not change over a long follow-up period of 3&#8211;10 years &#91;<a class="elsevierStyleCrossRef" href="#bib0011">11</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0012">12</a>&#93;&#46; Therefore&#44; we summarized the detection methods&#44; substrates&#44; and the changes of anti-gp210&#8217;s serum antibody titers in previous studies to figure out why those research results differ &#40;<a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#41; &#91;<a class="elsevierStyleCrossRef" href="#bib0005">5</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0008">8</a>&#44;<a class="elsevierStyleCrossRefs" href="#bib0011">11-13</a>&#93;&#46; We found that the change of antibody titer can be detected when the carboxy-terminal tail of gp210 was used as the detection substrate&#44; whereas the studies reporting that the titer was unchanged did not indicate what detection substrate was used&#46; Therefore&#44; we speculated that the variability of anti-gp210 titers is related to different substrates in antibody detection&#46; Currently&#44; UDCA-refractory anti-gp210-positive PBC patients lack effective therapeutic strategies and have worse prognoses as compared to anti-gp210-negative patients&#46; Thus&#44; exploring new therapeutic targets is urgently needed&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia></span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3</span><span class="elsevierStyleSectionTitle" id="cesectitle0006">Anti-gp210-positive PBC patients have severe biochemical liver tests and histological indexes</span><p id="para0009" class="elsevierStylePara elsevierViewall">In biochemical liver tests&#44; anti-gp210-positive PBC patients have higher levels of ALP&#44; bilirubin&#44; globulin and IgM than their anti-gp210-negative counterparts&#46; In 1998&#44; Itoh <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0011">&#91;11&#93;</a> compared the biochemical liver tests in 25 and 88 anti-gp210-positive and -negative PBC patients at the first diagnosis&#44; respectively&#44; and found that the levels of ALT and total bilirubin were significantly higher in anti-gp210-positive PBC patients than that in anti-gp210-negative patients&#46; Subsequently&#44; anti-gp210-positive PBC patients had significantly higher liver biochemical and immunological indicators than their anti-gp210-negative counterparts &#40;<a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a>&#41; &#91;<a class="elsevierStyleCrossRef" href="#bib0004">4</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0005">5</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0007">7</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0011">11</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0012">12</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0017">17</a>&#93;&#46; Therefore&#44; anti-gp210-positive PBC patients had higher serum levels of bile duct injury-related indicators at the initial diagnosis as compared with anti-gp210-negative patients&#44; thereby suggesting more severe bile duct injury at the early stage of the disease&#46;</p><elsevierMultimedia ident="tbl0002"></elsevierMultimedia><p id="para0010" class="elsevierStylePara elsevierViewall">Currently&#44; the histological studies of anti-gp210 related are limited&#46; Nakamura <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0005">&#91;5&#93;</a> enrolled 23 anti-gp210-positive PBC patients and found that anti-gp210 titers were sustained at high levels in 10 patients after UDCA treatment&#44; and showed more severe interface hepatitis and higher activity score than the patients with reduced titer&#46; Subsequently&#44; Nakamura <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0006">&#91;6&#93;</a> had done immunohistochemical staining using gp210 monoclonal antibody in the liver tissue&#44; and for the first time&#44; they proposed that the expression of gp210 antigen was increased on the nuclear envelope of BECs of small bile ducts in PBC patients as compared to healthy controls&#46; Furthermore&#44; in this study&#44; gp210 immunostained BECs were generally surrounded by inflammatory cells or fibrous tissues&#44; and the degree of gp210 expression was positively correlated with portal inflammation&#44; interface hepatitis&#44; and lobular inflammation&#44; thereby suggesting that the expression of gp210 antigen may be involved in the chemotactic process of lymphocytes infiltrating to BECs in PBC&#46; However&#44; there was no correlation between the high expression of gp210 antigen in the BECs and the positivity of anti-gp210 in the serum&#44; thus further studies are needed to elucidate the relationship between the gp210 antigen production in BECs and anti-gp210 production in serum&#46;</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">4</span><span class="elsevierStyleSectionTitle" id="cesectitle0007">Molecular structures of anti-gp210 and gp210 antigen and the application in PBC</span><p id="para0011" class="elsevierStylePara elsevierViewall">Anti-gp210 is a reliable indicator for the diagnosis of PBC&#46; The anti-gp210 positivity rates were 14&#46;3&#37;&#8211;48&#46;2&#37; and 15&#46;4&#37;&#8211;46&#46;7&#37; in PBC patients and AMA-negative PBC patients&#44; with specificity of over 99&#37; and sensitivity of approximately 25&#37; &#91;<a class="elsevierStyleCrossRefs" href="#bib0004">4&#8211;17</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0024">24</a>&#93;&#46; The study addressing the diagnostic accuracy of anti-gp210 for PBC diagnosis was performed in more than 4000 sera from patients suspected of having liver and non-liver autoimmune and non-autoimmune diseases&#44; thereby demonstrating a very high specificity and positive predictive value for the diagnosis of PBC <a class="elsevierStyleCrossRef" href="#bib0026">&#91;26&#93;</a>&#46; This suggests that anti-gp210 is highly correlated with the pathogenesis of PBC&#46;</p><p id="para0012" class="elsevierStylePara elsevierViewall">In 1985&#44; Ruffati <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0020">&#91;20&#93;</a> discovered that anti-gp210 was an antinuclear membrane antibody that labeled the nucleus of Hep-2 cells with a rim-like pattern&#46; The anti-gp210 antibody belonged to IgG&#44; a specific antibody against the antigens including DNase I&#44; RNase&#44; and trypsin &#91;<a class="elsevierStyleCrossRef" href="#bib0027">27</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0028">28</a>&#93;&#46; The sensitivity of anti-gp210 and the corresponding immunofluorescence pattern is higher when the detection of autoantibodies is performed at the level of IgG isotype &#40;in particular IgG1 isotype&#41; because it determines a wide gain in terms of sensitivity without a loss of specificity <a class="elsevierStyleCrossRef" href="#bib0029">&#91;29&#93;</a>&#46; Anti-gp210 has high specificity but low sensitivity for the diagnosis of PBC&#46; Therefore&#44; other antinuclear antibodies in AMA -negative PBC cases are been investigated&#46; Antibodies to hexokinase 1 &#40;HK1&#41; and kelch-like 12 &#40;KLHL12&#41; were described as additional biomarkers in these patients &#91;<a class="elsevierStyleCrossRef" href="#bib0030">30</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0031">31</a>&#93;&#46;</p><p id="para0013" class="elsevierStylePara elsevierViewall">Gp210 protein can be found in most nucleus cells&#44; located on the nuclear membrane as one of the constituent proteins of the nuclear pore complex&#46; Gp210 is a 210&#8239;kDa type I integral membrane protein that assembles nuclear pore protein after mitosis and fixes nuclear pore complex to the pore membrane&#46; More importantly&#44; gp210 protein mediates nuclear pore expansion and macromolecular transport between the nucleus and the cytoplasm <a class="elsevierStyleCrossRef" href="#bib0032">&#91;32&#93;</a>&#46; In addition&#44; gp210 consists of three domains&#44; including a 1808 amino acid amino-terminal domain situated in the perinuclear space&#44; a 20 amino acid transmembrane segment&#44; and a 58 amino acid carboxy-terminal tail domain &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>&#41; &#91;<a class="elsevierStyleCrossRef" href="#bib0033">33</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0034">34</a>&#93;&#46; Collectively&#44; these studies elucidated the localization&#44; function&#44; and structure of the gp210 antigen&#44; thereby laying the foundation for the subsequent antibody detection and the production mechanism of anti-gp210&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><p id="para0014" class="elsevierStylePara elsevierViewall">Regarding the antigen-antibody interaction&#44; two gp210 epitopes have been identified by serum anti-gp210 of PBC patients&#46; One is the 15 amino acids located at the carboxy-terminal tail and the other one is in the glycosylation regions at the amino-terminal domain &#91;<a class="elsevierStyleCrossRef" href="#bib0021">21</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0022">22</a>&#93;&#46; Thus&#44; these two structural regions are important molecular regions to study gp210 and anti-gp210 as well as their roles in PBC&#46; In 1993&#44; Nickowitz <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0021">&#91;21&#93;</a> detected serum antibodies of 25 anti-gp210-positive PBC patients using bacterial gp210 fusion proteins and demonstrated that 15 amino acids in the carboxy-terminal tail domain between 1869 and 1883 can bind to anti-gp210&#46; Subsequently&#44; Bandin O <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0016">&#91;16&#93;</a> demonstrated that 97&#46;2&#37; &#40;70&#47;72&#41; of the serum antibodies of anti-gp210-positive PBC patients identified the same carboxy-terminal epitope&#46; Thus&#44; the carboxy-terminal epitope of gp210 protein has been widely recognized in previous studies&#46; Moreover&#44; Wesierska-Gadek <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0022">&#91;22&#93;</a> confirmed that the recognition epitopes to anti-gp210 existed in the glycosylation domain of the amino-terminal of gp210&#46; In this study&#44; 12 anti-gp210-positive PBC patients were enrolled&#44; and antibodies against an epitope within the glycosylation domain of the amino-terminal and in the carboxy-terminal tail were detected in the sera of 8 and 4 patients&#44; respectively&#46; Howeve&#44; the above studies suggest that the detection of antibodies with bacterial gp210 fusion proteins has certain limitations&#46; Therefore&#44; in the future&#44; it is necessary to develop a detection kit for dual epitopes of anti-gp210 and explore additional detection sites to improve the sensitivity of antibody detection and avoid the delay of diagnosis and timely treatment in PBC patients&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">5</span><span class="elsevierStyleSectionTitle" id="cesectitle0008">Pathogenesis of anti-gp210-positive PBC patients</span><p id="para0015" class="elsevierStylePara elsevierViewall">The rate of anti-gp210 positivity among PBC patients in different studies varies in different countries and human species &#40;<a class="elsevierStyleCrossRef" href="#tbl0003">Table 3</a>&#41; <a class="elsevierStyleCrossRefs" href="#bib0004">&#91;4&#8211;16&#93;</a>&#46; The detection rate of anti-gp210 in Chinese and German is higher than that in other countries&#44; ranging from 35&#46;7&#37; to 48&#46;2&#37;&#46; This difference suggests that genetic and environmental factors play an important role in the production of anti-gp210 in PBC&#46;</p><elsevierMultimedia ident="tbl0003"></elsevierMultimedia><p id="para0016" class="elsevierStylePara elsevierViewall">However&#44; the mechanism of anti-gp210 in the development of PBC remains unclear&#46; Regarding genetics&#44; Wang <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0014">&#91;14&#93;</a> conducted genome-wide association studies &#40;GWAS&#41; in 930 Chinese PBC patients based on their autoantibody status &#40;anti-gp210 and anti-sp100&#41;&#44; of which 350&#47;912 &#40;38&#46;4&#37;&#41; were anti-gp210-positive patients&#44; and no specific human leukocyte antigen &#40;HLA&#41; allele or single-nucleotide polymorphism &#40;SNP&#41; associated with anti-gp210 was found&#46; In terms of environmental factors&#44; Tang R <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0035">&#91;35&#93;</a> analyzed the gut microbiome of 116 Chinese PBC patients and found that the gut microbiome of anti-gp210-positive patients showed relatively lower species richness and <span class="elsevierStyleItalic">Faecalibacterium spp</span> abundance than the anti-gp210-negative patients&#44; thereby indicating that the gut microbiota may play a role in the pathogenesis of anti-gp210-positive PBC patients&#46;</p><p id="para0017" class="elsevierStylePara elsevierViewall">Therefore&#44; for the epitopes of anti-gp210 to be deeply investigated&#44; some studies have found that molecular mimicry&#44; induced by proteins with similar amino acid sequences to epitopes&#44; may be one of the main mechanisms in anti-gp210 production&#46; Molecular mimicry is the process by which exogenous antigens activate autoreactive T or B cells in susceptible individuals because of the similarity between exogenous peptides and self-peptides <a class="elsevierStyleCrossRef" href="#bib0036">&#91;36&#93;</a>&#46; Before the 1990s&#44; the transmembrane topology of gp210 closely resembled the envelope glycoproteins topology of various animal viruses <a class="elsevierStyleCrossRefs" href="#bib0037">&#91;37&#8211;39&#93;</a>&#46; Subsequently&#44; Nickowitz <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0021">&#91;21&#93;</a> demonstrated that the cytoplasmic carboxy-terminal tail epitope of anti-gp210 had six consecutive amino acids which were homologous to the protein products of the <span class="elsevierStyleItalic">Escherichia coli mutY</span> and <span class="elsevierStyleItalic">Salmonella typhimurium mutB</span> genes&#46; In addition&#44; Haruta <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0040">&#91;40&#93;</a> found that <span class="elsevierStyleItalic">Streptococcus intermedius</span> &#40;<span class="elsevierStyleItalic">S&#46;i&#46;</span>&#41; could induce the generation of anti-gp210 and cellular infiltration around the bile ducts in BALB&#47;c mice&#46; Moreover&#44; the antibody against histone-like DNA-binding protein of <span class="elsevierStyleItalic">Streptococcus intermedius</span> &#40;<span class="elsevierStyleItalic">S&#46;i&#46;</span>-HLP&#41; could bind to synthetic gp210 peptide&#46; Thus&#44; these studies suggest that bacteria or viruses may induce the production of anti-gp210 through molecular mimicry &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>&#41;&#46; Clinical studies also found that anti-gp210 could persist for more than 10 years after liver transplantation in some PBC patients <a class="elsevierStyleCrossRefs" href="#bib0009">&#91;9&#8211;11&#93;</a>&#44; thereby further suggesting that the antigen inducing the generation of anti-gp210 might not be derived from the liver&#46; Bacteria-induced molecular mimicry in the production of anti-gp210 may provide new insights into the pathogenesis of anti-gp210-positive PBC patients&#46; In addition to exogenous peptides such as bacteria and viruses&#44; molecular mimicry exists between endogenous peptides such as mitochondria and gp210 in PBC&#46; Shimoda <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0041">&#91;41&#93;</a> discovered that the selected specific T cell clones of a peptide corresponding to the mitochondrial pyruvate dehydrogenase complex E2 subunit could cross-react with the synthetic peptide of gp210&#44; thereby indicating a possible cross pathway existed between AMA and the production process of anti-gp210&#46; Furthermore&#44; T cell clones selected by recombinant gp210 protein simultaneously reacted with the mimicry peptide of amino acid 188&#8211;201 in gp210&#44; thereby indicating that the amino acid 188&#8211;201 in gp210 was one of the immunodominant T cell epitopes&#46;</p><elsevierMultimedia ident="fig0002"></elsevierMultimedia><p id="para0018" class="elsevierStylePara elsevierViewall">Current research on the relationship between anti-gp210 and the pathogenesis of PBC is very limited&#46; Notably&#44; anti-gp210 can be detected in the serum of the dominant-negative form of TGF-&#946; receptor type II &#40;dnTGF-&#946;RII&#41; mice&#44; one of the main model mice of PBC&#46; In addition&#44; Yang CY <span class="elsevierStyleItalic">et al</span>&#46; <a class="elsevierStyleCrossRef" href="#bib0042">&#91;42&#93;</a> found that the titer of anti-gp210 was significantly reduced by deleting specific cytokines &#40;including IL-12p40&#44; IL-23p19&#44; IL-17&#44; IL-6&#44; and TNF-&#945;&#41; in dnTGF-&#946;RII mice&#44; thereby suggesting that these cytokines may be involved in the production of anti-gp210&#46; In recent years&#44; studies on immune cells and the pathogenesis of PBC are actively underway&#44; and thus clarifying the pathogenesis of anti-gp210-positive PBC is essential to explore new therapeutic intervention targets for these patients&#46; Collectively&#44; current research on the pathogenesis of anti-gp210-positive PBC primarily focuses on aspects including genetic and environmental factors&#44; molecular mimicry&#44; and cytokines&#46; Therefore&#44; an in-depth investigation of the interrelationship among the above three aspects could provide direction for further study on anti-gp210-positive PBC&#46;</p></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">6</span><span class="elsevierStyleSectionTitle" id="cesectitle0009">Discussion and prospect</span><p id="para0019" class="elsevierStylePara elsevierViewall">Anti-gp210-positive PBC patients present with more severe biochemical indexes&#44; severe bile duct injury and liver inflammation in histology&#44; poorer response to treatment drugs&#44; faster disease progression&#44; and a worse prognosis than anti-gp210-negative patients&#46; It is of clinical importance to identify the pathogenesis of anti-gp210-positive PBC and find preventive measures against the etiology to guide the diagnosis and treatment of the disease&#46;</p></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">7</span><span class="elsevierStyleSectionTitle" id="cesectitle0010">Conclusions</span><p id="para0020" class="elsevierStylePara elsevierViewall">Anti-gp210 is an autoantibody against the nuclear membrane protein gp210&#44; and thus the study of anti-gp210 and the antigen is essential for the pathogenesis of anti-gp210-positive PBC&#46; Moreover&#44; the species richness of gut microbiome in anti-gp210-positive PBC patients was lower than that in anti-gp210-negative patients&#44; thereby suggesting that intestinal microecology may participate in disease development and progression&#46; Molecular mimicry by bacteria is currently the main hypothesis for the pathogenesis&#44; which still needs to be further explored&#46; The study on the localization&#44; structure&#44; and epitope of gp210 antigen has laid a certain theoretical foundation for the study of anti-gp210-positive PBC pathogenesis&#46; With the development of epidemiology&#44; genetics&#44; and animal models&#44; further elucidation of the generation and molecular mechanism of anti-gp210 in PBC will be crucial for clinical prevention and treatment&#46;</p></span></span>"
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          "titulo" => "Anti-gp210-positive PBC patients have poor treatment response and prognosis"
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          "titulo" => "Anti-gp210-positive PBC patients have severe biochemical liver tests and histological indexes"
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          "titulo" => "Molecular structures of anti-gp210 and gp210 antigen and the application in PBC"
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          "titulo" => "Pathogenesis of anti-gp210-positive PBC patients"
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        1 => array:4 [
          "clase" => "abr"
          "titulo" => "Abbreviations"
          "identificador" => "xpalclavsec1683528"
          "palabras" => array:12 [
            0 => "PBC"
            1 => "AMA"
            2 => "ANA"
            3 => "UDCA"
            4 => "OCA"
            5 => "BECs"
            6 => "AST"
            7 => "ALP"
            8 => "IgM"
            9 => "GWAS"
            10 => "HLA"
            11 => "SNP"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><p id="spara009" class="elsevierStyleSimplePara elsevierViewall">Anti-gp210 is the disease-specific anti-nuclear antibody &#40;ANA&#41; of primary biliary cholangitis &#40;PBC&#41;&#46; Anti-gp210-positive PBC patients have worse responses to ursodeoxycholic acid &#40;UDCA&#41; as compared with anti-gp210-negative patients&#46; Moreover&#44; anti-gp210-positive patients always present with more severe histopathologic features including lobular inflammation&#44; interfacial hepatitis&#44; and bile duct injury&#44; and have a worse prognosis than their anti-gp210-negative counterparts&#46; Previous studies have identified two antigenic epitopes recognized by anti-gp210&#46; Although the pathogenetic mechanism of anti-gp210 production remains unclear&#44; evidence suggests that the autoimmune response to anti-gp210 production might be due to molecular mimicry induced by bacteria or endogenous peptides&#46; T cells and related cytokines play a critical role in the pathogenesis of PBC&#44; however&#44; the mechanism hasn&#39;t been fully understood&#46; Thus&#44; this review focuses on the clinicopathological characteristics of anti-gp210-positive PBC patients&#44; the fundamental research of gp210 antigen&#44; and the possible mechanism of anti-gp210 production to clarify the mechanism of anti-gp210-positive PBC and provide potential molecular targets for disease prevention and treatment in the future&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:3 [
        "etiqueta" => "&#35;"
        "nota" => "<p class="elsevierStyleNotepara" id="notep0001">Xiaoyi Wang&#44; Zhen Yang&#44; Ying Ran contributed equally to this work&#46;</p>"
        "identificador" => "fn1"
      ]
    ]
    "multimedia" => array:5 [
      0 => array:8 [
        "identificador" => "fig0001"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0001"
            "detalle" => "Fig 1&#58"
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">The structural diagram of nuclear pore membrane protein gp210&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "fig0002"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 2162
            "Ancho" => 2917
            "Tamanyo" => 477788
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        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0002"
            "detalle" => "Fig 2&#58"
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">The simulation diagram of bacterial induction of anti-gp210 through molecular mimicry&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0001"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0003"
            "detalle" => "Table 1&#58"
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spara004" class="elsevierStyleSimplePara elsevierViewall">IIF&#44; indirect immunofluorescence&#59; ELISA&#44; enzyme-linked immunosorbent assay&#59; IB&#44; immunoblot&#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"><a name="en0001"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Methods of detection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0003"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Country of cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Detection of substrate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0005"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Variable titers &#40;Follow up number&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0006"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Follow up time &#40;month&#47;year&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0007"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">IIF &#40;Rim-like&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1998 <a class="elsevierStyleCrossRef" href="#bib0011">&#91;11&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0009"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Japan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">HepG2 cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">NO &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">87&#46;5&#8239;&#177;&#8239;56&#46;0 m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0013"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2003 <a class="elsevierStyleCrossRef" href="#bib0012">&#91;12&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Italy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">HEp-2 cell lines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Not investigated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0019"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2003 <a class="elsevierStyleCrossRef" href="#bib0012">&#91;12&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0021"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Italy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Purified gp210 ELISA kits &#40;IMTEC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">NO &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3&#8211;10 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0025"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2005 <a class="elsevierStyleCrossRef" href="#bib0005">&#91;5&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Japan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">gp210 C-terminal peptide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0029"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">YES &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">73&#46;4&#8239;&#177;&#8239;54&#46;3 m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0031"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2007 <a class="elsevierStyleCrossRef" href="#bib0013">&#91;13&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Japan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">gp210 C-terminal peptide &#40;25 amino acids&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">YES &#40;217&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#8211;292 m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0037"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2014 <a class="elsevierStyleCrossRef" href="#bib0008">&#91;8&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Japan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">gp210 C-terminal peptide &#40;25 amino acids&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">YES &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6&#8211;12 m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">The substrate used in detection anti-gp210 and the variability of anti-gp210&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0002"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0004"
            "detalle" => "Table 2&#58"
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spara006" class="elsevierStyleSimplePara elsevierViewall">TP&#44; total protein&#59; ALB&#44; albumin&#59; GLB&#44; globulin&#59; ALT&#44; alanine aminotransferase&#59; AST&#44; aspartate aminotransferase&#59; ALP&#44; alkaline phosphatase&#59; GGT&#44; &#947;-glutamyl transferase&#59; TBIL&#44; total bilirubin&#59; DBIL&#44; direct bilirubin&#59; TC&#44; total cholesterol&#59; Ig&#44; immunoglobulin&#59; Plt&#44; platelet&#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"><a name="en0043"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Clinical research&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0044"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0045"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Country&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0046"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Number of patients&#37; &#40;gp210&#43;&#47;PBC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0047"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Indicators with statistical difference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Itoh S et al&#46; <a class="elsevierStyleCrossRef" href="#bib0011">&#91;11&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1998&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Japan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">22&#46;1 &#40;25&#47;113&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ALP&#44; TBIL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Paolo et al&#46; <a class="elsevierStyleCrossRef" href="#bib0012">&#91;12&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Italy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15&#46;6 &#40;15&#47;96&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ALP&#44; GGT&#44; TC&#44; ALB&#44; &#947;-GLB&#44; IgA&#44; IgM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Minoru et al&#46; <a class="elsevierStyleCrossRef" href="#bib0005">&#91;5&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Japan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0061"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">32&#46;4 &#40;23&#47;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">IgM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0063"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Dimitrioa et al&#46; <a class="elsevierStyleCrossRef" href="#bib0017">&#91;17&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0065"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Spain and Greece&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&#46;5 &#40;38&#47;362&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ALP&#44; DBIL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0068"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Yang et al&#46; <a class="elsevierStyleCrossRef" href="#bib0007">&#91;7&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0069"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0071"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">48&#46;2 &#40;133&#47;276&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">GGT&#44; TBIL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0073"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Haldar et al&#46; <a class="elsevierStyleCrossRef" href="#bib0004">&#91;4&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">UK&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16&#46;7 &#40;81&#47;486&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">AST&#44; ALT&#44; TBIL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3255937.png"
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          "en" => "<p id="spara005" class="elsevierStyleSimplePara elsevierViewall">Biochemical liver Indicators of anti-gp210-positive PBC patients are higher than anti-gp210-negative PBC patients&#46;</p>"
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        "identificador" => "tbl0003"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
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            "rol" => "short"
          ]
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        "tabla" => array:2 [
          "leyenda" => "<p id="spara008" class="elsevierStyleSimplePara elsevierViewall">IIF&#44; indirect immunofluorescence&#59; ELISA&#44; enzyme-linked immunosorbent assay&#59; IB&#44; immunoblot&#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"><a name="en0078"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Methods of detection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0079"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0080"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Country of cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0081"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Positivity&#37; &#40;Anti-gp210&#43;&#47;PBC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0082"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Positivity&#37; &#40;Anti-gp210&#43;&#47;AMA- PBC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0083"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">IIF &#40;Rim-like&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1996 <a class="elsevierStyleCrossRef" href="#bib0016">&#91;16&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0085"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">France&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">30&#46;5 &#40;87&#47;285&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">46&#46;7 &#40;7&#47;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0088"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1998 <a class="elsevierStyleCrossRef" href="#bib0011">&#91;11&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Japan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0091"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">27&#46;4 &#40;31&#47;113&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">18&#46;2 &#40;2&#47;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0093"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2003 <a class="elsevierStyleCrossRef" href="#bib0012">&#91;12&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0095"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Italy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&#46;0 &#40;9&#47;91&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">33&#46;0 &#40;5&#47;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0098"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ELISA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0099"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1996 <a class="elsevierStyleCrossRef" href="#bib0016">&#91;16&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">France&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0101"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">25&#46;5 &#40;73&#47;285&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0102"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">46&#46;8 &#40;7&#47;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0103"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0104"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2003 <a class="elsevierStyleCrossRef" href="#bib0012">&#91;12&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0105"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Italy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0106"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16&#46;0 &#40;15&#47;96&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0107"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15&#46;4 &#40;2&#47;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0108"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0109"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2005 <a class="elsevierStyleCrossRef" href="#bib0005">&#91;5&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0110"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Japan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0111"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">32&#46;4 &#40;23&#47;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0112"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0113"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0114"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2006 <a class="elsevierStyleCrossRef" href="#bib0006">&#91;6&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0115"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Japan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0116"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">38&#46;5 &#40;20&#47;52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0118"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0119"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2007 <a class="elsevierStyleCrossRef" href="#bib0013">&#91;13&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0120"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Japan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0121"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26&#46;1 &#40;72&#47;276&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0123"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0124"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2014 <a class="elsevierStyleCrossRef" href="#bib0008">&#91;8&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0125"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Japan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0126"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">30&#46;5 &#40;50&#47;164&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0127"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0128"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0129"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2019 <a class="elsevierStyleCrossRef" href="#bib0014">&#91;14&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0130"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0131"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">38&#46;4 &#40;350&#47;912&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0132"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0133"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">IB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0134"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1996 <a class="elsevierStyleCrossRef" href="#bib0016">&#91;16&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0135"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">France&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0136"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">25&#46;3 &#40;72&#47;285&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0137"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0138"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0139"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1997 <a class="elsevierStyleCrossRef" href="#bib0010">&#91;10&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0140"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0141"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">25&#46;7 &#40;9&#47;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0142"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0143"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0144"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">1998 <a class="elsevierStyleCrossRef" href="#bib0011">&#91;11&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0145"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Japan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0146"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">22&#46;1 &#40;25&#47;113&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0147"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">20&#46;0 &#40;1&#47;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0148"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0149"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1998 <a class="elsevierStyleCrossRef" href="#bib0009">&#91;9&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0150"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Germany&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0151"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">35&#46;7 &#40;15&#47;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0152"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0154"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2003 <a class="elsevierStyleCrossRef" href="#bib0012">&#91;12&#93;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0155"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Japan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0156"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26&#46;3 &#40;46&#47;175&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0157"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">18&#46;5 &#40;10&#47;54&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0159"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">2003 <a class="elsevierStyleCrossRef" href="#bib0015">&#91;15&#93;</a>&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="top">Japan&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">28&#46;2 &#40;46&#47;163&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">2017 <a class="elsevierStyleCrossRef" href="#bib0007">&#91;7&#93;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">China&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="top">48&#46;2 &#40;133&#47;276&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0167"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">41&#46;2 &#40;7&#47;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0168"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0169"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">2021 <a class="elsevierStyleCrossRef" href="#bib0004">&#91;4&#93;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">UK&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="top">16&#46;7 &#40;81&#47;486&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">16&#46;9 &#40;12&#47;72&#41;&nbsp;\t\t\t\t\t\t\n
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec1"
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            0 => array:3 [
              "identificador" => "bib0001"
              "etiqueta" => "&#91;1&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Primary biliary cirrhosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;M&#46; Kaplan"
                            1 => "M&#46;E&#46; Gershwin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMra043898"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2005"
                        "volumen" => "353"
                        "paginaInicial" => "1261"
                        "paginaFinal" => "1273"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16177252"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0002"
              "etiqueta" => "&#91;2&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Primary Biliary Cholangitis&#58; 2018 Practice Guidance from the American Association for the Study of Liver Diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "K&#46;D&#46; Lindor"
                            1 => "C&#46;L&#46; Bowlus"
                            2 => "J&#46; Boyer"
                            3 => "C&#46; Levy"
                            4 => "M&#46; Mayo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.30145"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2019"
                        "volumen" => "69"
                        "paginaInicial" => "394"
                        "paginaFinal" => "419"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30070375"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0003"
              "etiqueta" => "&#91;3&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Overcoming a &#8220;probable&#8221; diagnosis in antimitochondrial antibody negative primary biliary cirrhosis&#58; study of 100 sera and review of the literature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Bizzaro"
                            1 => "G&#46; Covini"
                            2 => "F&#46; Rosina"
                            3 => "P&#46; Muratori"
                            4 => "E&#46; Tonutti"
                            5 => "D&#46; Villalta"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12016-010-8234-y"
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Rev Allergy Immunol"
                        "fecha" => "2012"
                        "volumen" => "42"
                        "paginaInicial" => "288"
                        "paginaFinal" => "297"
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0004"
              "etiqueta" => "&#91;4&#93;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antibodies to gp210 and understanding risk in patients with primary biliary cholangitis"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Haldar"
                            1 => "A&#46; Janmohamed"
                            2 => "T&#46; Plant"
                            3 => "M&#46; Davidson"
                            4 => "H&#46; Norman"
                            5 => "E&#46; Russell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/liv.14688"
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                        "tituloSerie" => "Liver Int"
                        "fecha" => "2021"
                        "volumen" => "41"
                        "paginaInicial" => "535"
                        "paginaFinal" => "544"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33022821"
                            "web" => "Medline"
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              ]
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            4 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "&#91;5&#93;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
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                          "etal" => true
                          "autores" => array:6 [
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                            2 => "Y&#46; Takii"
                            3 => "A&#46; Komori"
                            4 => "T&#46; Yokoyama"
                            5 => "T&#46; Ueki"
                          ]
                        ]
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                    ]
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                    0 => array:2 [
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                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2005"
                        "volumen" => "42"
                        "paginaInicial" => "386"
                        "paginaFinal" => "392"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15710222"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
            ]
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                    0 => array:2 [
                      "titulo" => "Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Nakamura"
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                            2 => "M&#46; Ito"
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                            4 => "T&#46; Yokoyama"
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                        ]
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                    ]
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                    0 => array:2 [
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                        "tituloSerie" => "J Autoimmun"
                        "fecha" => "2006"
                        "volumen" => "26"
                        "paginaInicial" => "138"
                        "paginaFinal" => "145"
                        "link" => array:1 [
                          0 => array:2 [
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                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Yang"
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                            2 => "Q&#46; Wang"
                            3 => "Z&#46; Wang"
                            4 => "Q&#46; Miao"
                            5 => "X&#46; Xiao"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/apt.13927"
                      "Revista" => array:6 [
                        "tituloSerie" => "Aliment Pharmacol Ther"
                        "fecha" => "2017"
                        "volumen" => "45"
                        "paginaInicial" => "733"
                        "paginaFinal" => "743"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28083929"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0008"
              "etiqueta" => "&#91;8&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autoantibody status and histological variables influence biochemical response to treatment and long-term outcomes in Japanese patients with primary biliary cirrhosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            1 => "H&#46; Kondo"
                            2 => "A&#46; Tanaka"
                            3 => "A&#46; Komori"
                            4 => "M&#46; Ito"
                            5 => "K&#46; Yamamoto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/hepr.12423"
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                        "tituloSerie" => "Hepatol Res"
                        "fecha" => "2015"
                        "volumen" => "45"
                        "paginaInicial" => "846"
                        "paginaFinal" => "855"
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "etiqueta" => "&#91;9&#93;"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The antinuclear autoantibodies Sp100 and gp210 persist after orthotopic liver transplantation in patients with primary biliary cirrhosis"
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                          "etal" => true
                          "autores" => array:6 [
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                            1 => "K&#46;H&#46; Boeker"
                            2 => "W&#46; Schoessler"
                            3 => "H&#46; Will"
                            4 => "S&#46; Loges"
                            5 => "E&#46; Schmidt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0168-8278(98)80233-x"
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                        "tituloSerie" => "J Hepatol"
                        "fecha" => "1998"
                        "volumen" => "28"
                        "paginaInicial" => "824"
                        "paginaFinal" => "828"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9625318"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "&#91;10&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Persistence of autoantibodies against recombinant mitochondrial and nuclear pore proteins after orthotopic liver transplantation for primary biliary cirrhosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Mattalia"
                            1 => "B&#46; L&#252;ttig"
                            2 => "F&#46; Rosina"
                            3 => "P&#46;S&#46; Leung"
                            4 => "J&#46; Van de Water"
                            5 => "M&#46; Bauducci"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1006/jaut.1997.0156"
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                        "tituloSerie" => "J Autoimmun"
                        "fecha" => "1997"
                        "volumen" => "10"
                        "paginaInicial" => "491"
                        "paginaFinal" => "497"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9376077"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0011"
              "etiqueta" => "&#91;11&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autoantibodies against a 210kDa glycoprotein of the nuclear pore complex as a prognostic marker in patients with primary biliary cirrhosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Itoh"
                            1 => "T&#46; Ichida"
                            2 => "T&#46; Yoshida"
                            3 => "A&#46; Hayakawa"
                            4 => "M&#46; Uchida"
                            5 => "T&#46; Tashiro-Itoh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1440-1746.1998.01553.x"
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                        "tituloSerie" => "J Gastroenterol Hepatol"
                        "fecha" => "1998"
                        "volumen" => "13"
                        "paginaInicial" => "257"
                        "paginaFinal" => "265"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9570238"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
              ]
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            11 => array:3 [
              "identificador" => "bib0012"
              "etiqueta" => "&#91;12&#93;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Muratori"
                            1 => "L&#46; Muratori"
                            2 => "R&#46; Ferrari"
                            3 => "F&#46; Cassani"
                            4 => "G&#46; Bianchi"
                            5 => "M&#46; Lenzi"
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                      ]
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                    0 => array:2 [
                      "doi" => "10.1111/j.1572-0241.2003.07257.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Gastroenterol"
                        "fecha" => "2003"
                        "volumen" => "98"
                        "paginaInicial" => "431"
                        "paginaFinal" => "437"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12591064"
                            "web" => "Medline"
                          ]
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                      ]
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                  ]
                ]
              ]
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            12 => array:3 [
              "identificador" => "bib0013"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Nakamura"
                            1 => "H&#46; Kondo"
                            2 => "T&#46; Mori"
                            3 => "A&#46; Komori"
                            4 => "M&#46; Matsuyama"
                            5 => "M&#46; Ito"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.21472"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2007"
                        "volumen" => "45"
                        "paginaInicial" => "118"
                        "paginaFinal" => "127"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17187436"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            13 => array:3 [
              "identificador" => "bib0014"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genome-wide Association Studies of Specific Antinuclear Autoantibody Subphenotypes in Primary Biliary Cholangitis"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Wang"
                            1 => "X&#46; Zheng"
                            2 => "P&#46; Jiang"
                            3 => "R&#46; Tang"
                            4 => "Y&#46; Gong"
                            5 => "Y&#46; Dai"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.30604"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2019"
                        "volumen" => "70"
                        "paginaInicial" => "294"
                        "paginaFinal" => "307"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30854688"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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            14 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "&#91;15&#93;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis&#58; a multicenter study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Miyachi"
                            1 => "R&#46;W&#46; Hankins"
                            2 => "H&#46; Matsushima"
                            3 => "F&#46; Kikuchi"
                            4 => "T&#46; Inomata"
                            5 => "T&#46; Horigome"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0896-8411(03)00033-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Autoimmun"
                        "fecha" => "2003"
                        "volumen" => "20"
                        "paginaInicial" => "247"
                        "paginaFinal" => "254"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12753810"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0016"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Specificity and sensitivity of gp210 autoantibodies detected using an enzyme-linked immunosorbent assay and a synthetic polypeptide in the diagnosis of primary biliary cirrhosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "O&#46; Bandin"
                            1 => "J&#46;C&#46; Courvalin"
                            2 => "R&#46; Poupon"
                            3 => "L&#46; Dubel"
                            4 => "J&#46;C&#46; Homberg"
                            5 => "C&#46; Johanet"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.510230512"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "1996"
                        "volumen" => "23"
                        "paginaInicial" => "1020"
                        "paginaFinal" => "1024"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8621127"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            16 => array:3 [
              "identificador" => "bib0017"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anti-gp210 antibody mirrors disease severity in primary biliary cirrhosis"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;P&#46; Bogdanos"
                            1 => "C&#46; Liaskos"
                            2 => "A&#46; Pares"
                            3 => "G&#46; Norman"
                            4 => "E&#46;I&#46; Rigopoulou"
                            5 => "L&#46; Caballeria"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.21678"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2007"
                        "volumen" => "45"
                        "paginaInicial" => "1583"
                        "paginaFinal" => "1584"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17538935"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0018"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chinese Medical Association"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "Chinese Society of Hepatology"
                          "etal" => false
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3760/cma.j.cn112138-20211112-00794"
                      "Revista" => array:6 [
                        "tituloSerie" => "Zhonghua Nei Ke Za Zhi"
                        "fecha" => "2021"
                        "volumen" => "60"
                        "paginaInicial" => "1024"
                        "paginaFinal" => "1037"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34856679"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            18 => array:3 [
              "identificador" => "bib0019"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of primary biliary cholangitis with ursodeoxycholic acid&#44; prednisolone and immunosuppressants in patients not responding to ursodeoxycholic acid alone and the prognostic indicators"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
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                            1 => "T&#46;T&#46; Yao"
                            2 => "Y&#46; Wang"
                            3 => "G&#46;Q&#46; Wang"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clinre.2020.03.026"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Res Hepatol Gastroenterol"
                        "fecha" => "2020"
                        "volumen" => "44"
                        "paginaInicial" => "874"
                        "paginaFinal" => "884"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32305248"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            19 => array:3 [
              "identificador" => "bib0020"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nuclear membrane-staining antinuclear antibody in patients with primary biliary cirrhosis"
                      "autores" => array:1 [
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Ruffatti"
                            1 => "P&#46; Arslan"
                            2 => "A&#46; Floreani"
                            3 => "G&#46; De Silvestro"
                            4 => "A&#46; Calligaro"
                            5 => "R&#46; Naccarato"
                          ]
                        ]
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/BF00918255"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Immunol"
                        "fecha" => "1985"
                        "volumen" => "5"
                        "paginaInicial" => "357"
                        "paginaFinal" => "361"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2414313"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autoantibodies from patients with primary biliary cirrhosis recognize a restricted region within the cytoplasmic tail of nuclear pore membrane glycoprotein Gp210"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46;E&#46; Nickowitz"
                            1 => "H&#46;J&#46; Worman"
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1084/jem.178.6.2237"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Exp Med"
                        "fecha" => "1993"
                        "volumen" => "178"
                        "paginaInicial" => "2237"
                        "paginaFinal" => "2342"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7504063"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0022"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Autoantibodies from patients with primary biliary cirrhosis preferentially react with the amino-terminal domain of nuclear pore complex glycoprotein gp210"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46; Wesierska-Gadek"
                            1 => "H&#46; Hohenauer"
                            2 => "E&#46; Hitchman"
                            3 => "E&#46; Penner"
                          ]
                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1084/jem.182.4.1159"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Exp Med"
                        "fecha" => "1995"
                        "volumen" => "182"
                        "paginaInicial" => "1159"
                        "paginaFinal" => "1162"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7561689"
                            "web" => "Medline"
                          ]
                        ]
                      ]
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                ]
              ]
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            22 => array:3 [
              "identificador" => "bib0023"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The prognostic value of antibodies to gp210 among patients with primary biliary cholangitis in Northeast China"
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                          "etal" => true
                          "autores" => array:6 [
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                            1 => "R&#46; Zhong"
                            2 => "K&#46; Dong"
                            3 => "Y&#46; Wang"
                            4 => "Y&#46; Kui"
                            5 => "B&#46; Ma"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "Dig Liver Dis"
                        "fecha" => "2022"
                        "volumen" => "54"
                        "paginaInicial" => "1094"
                        "paginaFinal" => "1100"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34789400"
                            "web" => "Medline"
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            23 => array:3 [
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Fatigue and pruritus at onset identify a more aggressive subset of primary biliary cirrhosis"
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "Liver Int"
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                        "volumen" => "35"
                        "paginaInicial" => "636"
                        "paginaFinal" => "641"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24698666"
                            "web" => "Medline"
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                0 => array:2 [
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                          "etal" => false
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                            0 => "M&#46; Nakamura"
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                        "tituloSerie" => "Semin Liver Dis"
                        "fecha" => "2014"
                        "volumen" => "34"
                        "paginaInicial" => "334"
                        "paginaFinal" => "340"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25057956"
                            "web" => "Medline"
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            25 => array:3 [
              "identificador" => "bib0026"
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                0 => array:2 [
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                      ]
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                    0 => array:2 [
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                        "tituloSerie" => "Aliment Pharmacol Ther"
                        "fecha" => "2006"
                        "volumen" => "24"
                        "paginaInicial" => "1575"
                        "paginaFinal" => "1583"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17206945"
                            "web" => "Medline"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Autoantibodies against nuclear envelope-associated proteins in primary biliary cirrhosis"
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                    0 => array:2 [
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                        "tituloSerie" => "Hepatology"
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                        "volumen" => "8"
                        "paginaInicial" => "930"
                        "paginaFinal" => "938"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3292364"
                            "web" => "Medline"
                          ]
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                0 => array:2 [
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                    0 => array:2 [
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                        0 => array:2 [
                          "etal" => false
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                            4 => "R&#46;W&#46; Wozniak"
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "1990"
                        "volumen" => "86"
                        "paginaInicial" => "279"
                        "paginaFinal" => "285"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2195063"
                            "web" => "Medline"
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                ]
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            28 => array:3 [
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                0 => array:2 [
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                    0 => array:2 [
                      "doi" => "10.1080/08916930802709133"
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                        "tituloSerie" => "Autoimmunity"
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                        "volumen" => "42"
                        "paginaInicial" => "224"
                        "paginaFinal" => "227"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19301204"
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            29 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "&#91;30&#93;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antinuclear antibodies as ancillary markers in primary biliary cirrhosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Granito"
                            1 => "P&#46; Muratori"
                            2 => "C&#46; Quarneti"
                            3 => "G&#46; Pappas"
                            4 => "R&#46; Cicola"
                            5 => "L&#46; Muratori"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1586/erm.11.82"
                      "Revista" => array:6 [
                        "tituloSerie" => "Expert Rev Mol Diagn"
                        "fecha" => "2012"
                        "volumen" => "12"
                        "paginaInicial" => "65"
                        "paginaFinal" => "74"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22133120"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0031"
              "etiqueta" => "&#91;31&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Surrogate Markers for Antimitochondrial Antibody-Negative Primary Biliary Cholangitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Granito"
                            1 => "L&#46; Muratori"
                            2 => "F&#46; Tovoli"
                            3 => "P&#46; Muratori"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.14309/ajg.0000000000000928"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Gastroenterol"
                        "fecha" => "2021"
                        "volumen" => "116"
                        "paginaInicial" => "215"
                        "paginaFinal" => "217"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33009063"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0032"
              "etiqueta" => "&#91;32&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The integral membrane nucleoporin pom121 functionally links nuclear pore complex assembly and nuclear envelope formation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "W&#46; Antonin"
                            1 => "C&#46; Franz"
                            2 => "U&#46; Haselmann"
                            3 => "C&#46; Antony"
                            4 => "I&#46;W&#46; Mattaj"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.molcel.2004.12.010"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Cell"
                        "fecha" => "2005"
                        "volumen" => "17"
                        "paginaInicial" => "83"
                        "paginaFinal" => "92"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15629719"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0033"
              "etiqueta" => "&#91;33&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Primary structure analysis of an integral membrane glycoprotein of the nuclear pore"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46;W&#46; Wozniak"
                            1 => "E&#46; Bartnik"
                            2 => "G&#46; Blobel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1083/jcb.108.6.2083"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Cell Biol"
                        "fecha" => "1989"
                        "volumen" => "108"
                        "paginaInicial" => "2083"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2738089"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0034"
              "etiqueta" => "&#91;34&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A major glycoprotein of the nuclear pore complex is a membrane-spanning polypeptide with a large lumenal domain and a small cytoplasmic tail"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "U&#46;F&#46; Greber"
                            1 => "A&#46; Senior"
                            2 => "L&#46; Gerace"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/j.1460-2075.1990.tb08267.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "EMBO J"
                        "fecha" => "1990"
                        "volumen" => "9"
                        "paginaInicial" => "1495"
                        "paginaFinal" => "1502"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2184032"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "&#91;35&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Tang"
                            1 => "Y&#46; Wei"
                            2 => "Y&#46; Li"
                            3 => "W&#46; Chen"
                            4 => "H&#46; Chen"
                            5 => "Q&#46; Wang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gutjnl-2016-313332"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gut"
                        "fecha" => "2018"
                        "volumen" => "67"
                        "paginaInicial" => "534"
                        "paginaFinal" => "541"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28213609"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0036"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Molecular mimicry and autoimmunity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Rojas"
                            1 => "P&#46; Restrepo-Jim&#233;nez"
                            2 => "D&#46;M&#46; Monsalve"
                            3 => "Y&#46; Pacheco"
                            4 => "Y&#46; Acosta-Ampudia"
                            5 => "C&#46; Ram&#237;rez-Santana"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaut.2018.10.012"
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                        "tituloSerie" => "J Autoimmun"
                        "fecha" => "2018"
                        "volumen" => "95"
                        "paginaInicial" => "100"
                        "paginaFinal" => "123"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30509385"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0037"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vesicular stomatitis virus glycoprotein is anchored in the viral membrane by a hydrophobic domain near the COOH terminus"
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                          "etal" => false
                          "autores" => array:5 [
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                            1 => "W&#46;J&#46; Welch"
                            2 => "B&#46;M&#46; Sefton"
                            3 => "F&#46;S&#46; Esch"
                            4 => "N&#46;C&#46; Ling"
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                    ]
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                    0 => array:2 [
                      "doi" => "10.1073/pnas.77.7.3884"
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci U S A"
                        "fecha" => "1980"
                        "volumen" => "77"
                        "paginaInicial" => "3884"
                        "paginaFinal" => "3888"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6253998"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0038"
              "etiqueta" => "&#91;38&#93;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Location of the spike glycoproteins in the Semliki Forest virus membrane"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "H&#46; Garoff"
                            1 => "K&#46; Simons"
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                    ]
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                    0 => array:2 [
                      "doi" => "10.1073/pnas.71.10.3988"
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                        "tituloSerie" => "Proc Natl Acad Sci U S A"
                        "fecha" => "1974"
                        "volumen" => "71"
                        "paginaInicial" => "3988"
                        "paginaFinal" => "3992"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4530279"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0039"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Structural domains and organizational conformation involved in the sorting and transport of influenza virus transmembrane proteins"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46;P&#46; Nayak"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1146/annurev.mi.43.100189.002341"
                      "Revista" => array:6 [
                        "tituloSerie" => "Annu Rev Microbiol"
                        "fecha" => "1989"
                        "volumen" => "43"
                        "paginaInicial" => "465"
                        "paginaFinal" => "501"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2679361"
                            "web" => "Medline"
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                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0040"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation"
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                          "etal" => true
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                            3 => "M&#46; Nakamura"
                            4 => "H&#46; Miyakawa"
                            5 => "K&#46; Hirota"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/labinvest.2010.40"
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                        "tituloSerie" => "Lab Invest"
                        "fecha" => "2010"
                        "volumen" => "90"
                        "paginaInicial" => "577"
                        "paginaFinal" => "588"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20142809"
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                      "titulo" => "Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis"
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                            0 => "S&#46; Shimoda"
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                            2 => "H&#46; Ishibashi"
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                            4 => "T&#46; Kamihira"
                            5 => "N&#46; Sakamoto"
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                        "tituloSerie" => "Gastroenterology"
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                        "volumen" => "124"
                        "paginaInicial" => "1915"
                        "paginaFinal" => "1925"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12806624"
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                        "tituloSerie" => "Clin Exp Immunol"
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                        "link" => array:1 [
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Article information

ISSN: 16652681
Original language: English

DOI:10.1016/j.aohep.2023.101121

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