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Budesonide in the first line treatment of patients with autoimmune hepatitis
Budesonida en primera línea de tratamiento de pacientes con hepatitis autoinmune
Ignasi Olivasa, Marina Cobrerosb, María-Carlota Londoñoa, Álvaro Díaz-Gonzálezb,
Corresponding author
alvaro.diaz@scsalud.es

Corresponding author.
a Liver Unit, Hospital Clínic of Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERehd, Universitat de Barcelona, Barcelona, Spain
b Digestive Diseases Department, Marqués de Valdecilla University Hospital, Instituto de investigación sanitaria Valdecilla (IDIVAL), Santander, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Autoimmune hepatitis &#40;AIH&#41; is a chronic inflammatory liver disease endowed with a progressive course&#46; This condition is characterized by hypertransaminasemia&#44; elevation of gammaglobulines and the presence of autoantibodies&#46; Histologically&#44; the typical findings are interface hepatitis and lymphoplasmacytic portal infiltrate&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">1</span></a> The exact pathogenesis of AIH is unknown&#46; Nevertheless&#44; different hypotheses point towards environmental agents that may trigger T cells-mediated immune response to liver antigens in a genetically predisposed host&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">2</span></a> Interestingly&#44; although AIH was the first liver disease with a targeted treatment in the early 60s&#44; it is still a challenging scenario where treatment options have not evolved significantly&#46; In fact&#44; this therapeutic armamentarium mainly consists of inducing remission with prednisone associated with a long-term use of steroid-sparing drugs&#44; usually azathioprine&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">1&#44;3</span></a> However&#44; international guidelines also recommend budesonide as an alternative first line agent in patients without cirrhosis or severe AIH<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">1&#44;3</span></a> &#40;defined as INR &#62;1&#46;5 and &#60;2 and&#47;or total bilirubin<span class="elsevierStyleHsp" style=""></span>&#62;&#61;<span class="elsevierStyleHsp" style=""></span>12<span class="elsevierStyleHsp" style=""></span>mg&#47;dL<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">4</span></a>&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The aim of this review is to deepen into the current knowledge and available evidence of budesonide as first-line option in the treatment of AIH&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">General pharmacologic characteristics of glucocorticoids</span><p id="par0015" class="elsevierStylePara elsevierViewall">Glucocorticoids are natural steroid hormones secreted by the adrenal gland&#44; whose production is regulated by the hypothalamic&#8211;anterior pituitary&#8211;adrenocortical axis&#44; being cortisol the most relevant glucocorticoid&#46; Briefly&#44; corticotrophin-releasing hormone induces the release of adrenocorticotrophic hormone &#40;ACTH&#41; in the anterior pituitary&#44; stimulating the delivery of cortisol from the adrenal gland&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a> Moreover&#44; cortisol production is characterized by a circadian pattern&#44; with the highest plasma concentrations in the morning and the lowest at night&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a> This hormone exhibits a plethora of effects involving almost every organ&#44; probably being the anti-inflammatory effects the most recognized ones&#46; Thus&#44; synthetic analogues of cortisol have been developed by means of structural modifications in the glucocorticoid nucleus&#44; enhancing the anti-inflammatory effect and decreasing the mineralocorticoid activity and being used for treating a wide range of inflammatory and immune-mediated diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a> These modifications confer an increased specificity for the glucocorticoid receptor&#44; with a longer efficacy and an increased lipophilicity&#46; The bioavailability of the drug after oral ingestion ranges from 60 to 100&#37;&#44; with a moderate protein binding to transcortin and albumin&#44; being the free fraction the responsible of both desired and undesired effects&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Prednisone</span><p id="par0020" class="elsevierStylePara elsevierViewall">Prednisone is a prodrug transformed by 11&#946;-hydroxysteroid dehydrogenase-1 into prednisolone&#44; the active drug&#46; After ingestion&#44; plasma concentrations reach its peak in 0&#46;5&#8211;3<span class="elsevierStyleHsp" style=""></span>h&#44; with a reported bioavailability of 84<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>13&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">6</span></a> Cortisol and prednisolone share a comparable biochemical structure&#44; although the latter presents a double bond C1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>C2&#44; contributing to its higher affinity to the glucocorticoid receptor and leading to a 4 times higher activity than cortisol&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">As mentioned before&#44; AIH was the first liver disease with a specific treatment&#44; being prednisone the drug of choice&#46; The evidence comes from the original clinical trials run in the 70s and 80s&#44; where untreated patients had a dismal evolution&#44; while those under corticosteroid therapy improved their liver tests and had longer survivals&#46; A summary of these trials is captured in<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Budesonide</span><p id="par0030" class="elsevierStylePara elsevierViewall">Under a structural point of view&#44; budesonide is a 17-&#945; substituted steroid obtained by modifying the 6-&#945;-hydroxy-prednisolone nucleus by adding a 16&#945; and 17&#945; acetyl group&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">8</span></a> The introduction of lipophilic constituents at the 17-&#945; and 16-&#945; positions increases tissue penetration and drug potency&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">8</span></a> In fact&#44; it is a potent topical anti-inflammatory agent<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">9</span></a> with an affinity for the glucocorticoid receptor 195 times greater than hydrocortisone and 15 times higher than prednisolone&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">10&#44;11</span></a> Mechanistically&#44; budesonide activates glucocorticoid receptors in the cytoplasm allowing its translocation to the nucleus&#44; preventing the transcription of inflammatory genes by binding to cortisol binding protein and decreasing cytokine production by activating HDCA2&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">12</span></a> When administered orally&#44; the systemic bioavailability of budesonide is around 10&#37;&#44; as the 90&#37; of the drug is cleared in the hepatic first-pass clearance&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">13&#44;14</span></a> The metabolism of budesonide is predominantly driven by CYP3A4&#44; obtaining the two most relevant metabolites&#58; 6&#946;-OH-budesonide and 16&#945;-OH-prednisolone&#44; both presenting a marginal glucocorticoid activity&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">15</span></a> Although budesonide is not characterized by presenting many drug-to-drug interactions&#44; some drugs should be used cautiously when administered concomitantly&#46; Hence&#44; cytochrome P450 inhibitors such as ketoconazole&#44; azithromycin or protease inhibitors&#44; among others&#44; may increase plasma exposure of budesonide&#44; and the combination should be avoided&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">16</span></a> On the other hand&#44; CYP3A4 inducers &#40;phenobarbital&#44; carbamazepine&#44; phenytoin&#41; reduce budesonide exposure&#44; decreasing its effectiveness&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Budesonide as first line drug for autoimmune hepatitis</span><p id="par0035" class="elsevierStylePara elsevierViewall">The usefulness of budesonide in the treatment of AIH was formerly evaluated in the seminal study carried out by Danielsson&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">17</span></a> in the early 1990s&#46; However&#44; it was not until 2005 where the first trial evaluating this drug in untreated patients was published&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">18</span></a> In this open one-arm multicenter phase IIa trial&#44; the authors evaluated the ability of budesonide in inducing response in these patients&#44; by measuring the drop of transaminases three months after starting the treatment&#46; The authors showed that budesonide was not only effective in reducing transaminase levels below twice the upper limit of normal&#44; but also reducing IgG and gammaglobulines&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">18</span></a> Furtherly&#44; Manns et al&#46; published the only currently available trial comparing prednisone and budesonide as first line therapies in the management of AIH&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">14</span></a> Budesonide was not only effective&#44; but also superior to prednisone&#46; In fact&#44; 47&#37; of patients treated with budesonide reached the primary endpoint&#44; while only 18&#46;4&#37; of those treated with prednisone did it&#46; These unexpected results may be explained by the unconventional definition of the primary endpoint&#44; as it was a composite one gathering biochemical remission with the absence of adverse events related to corticosteroids&#46; It is worth mentioning that this unusual endpoint was also used in a similar trial done in AIH pediatric patients&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a> However&#44; the results were remarkably different&#44; as the primary endpoint was only reached in 16&#37; and 15&#37; of patients treated with budesonide and prednisone&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Beyond these trials&#44; the evidence is limited&#46; Delgado et al&#46; published the results of a large retrospective multicenter cohort of AIH patients in Israel&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">20</span></a> Biochemical remission was achieved in 63&#37; of patients treated with budesonide plus azathioprine and 54&#46;9&#37; of patients treated with the combination of prednisone plus azathioprine&#46; However&#44; 15&#37; of these patients included were also diagnosed with overlap syndrome and&#44; notably&#44; budesonide &#40;or the combination of budesonide and azathioprine&#41; was used only in 21 patients&#46; In this regard&#44; a recent work from Turkey retrospectively evaluated this scenario&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">21</span></a> In their work&#44; they included 50 untreated AIH patients&#58; 25 treated with budesonide plus azathioprine and 25 with the combination of prednisone and azathioprine&#46; Although they did not identify differences in biochemical remission&#44; inflammatory activity&#44; indirectly measured by median transaminase levels&#44; was lower than in any other study -or in the real-life setting- and&#44; more importantly&#44; the definition they used did not consider the normalization of IgG &#40;or gammaglobulin&#41;&#44; potentially limiting the evaluation of the results&#46; These studies and others evaluating budesonide as first line alternative are summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Despite the good results obtained in phase II and phase III trials&#44; the use of budesonide in na&#239;ve AIH patients is rare&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">22&#44;23</span></a> Of note&#44; an international multicenter survey disclosing the current management of the disease in different worldwide centers with recognized expertise in the treatment of AIH patients&#44; evidenced that budesonide was not used in any center as first line option for the induction of disease remission&#46; The reason for this paucity of use is probably the consequence of the generalized perception of lower efficacy&#46; A recent multicenter Spanish work&#44; presented in the 2021s Spanish Association for the Study of the Liver annual meeting&#44; showed that budesonide use was marginal &#40;only 5&#46;4&#37; of the cohort&#41; and&#44; more importantly&#44; it was significantly inferior to prednisone&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">24</span></a> In terms of efficacy&#44; the authors compared the two cohorts through an Inverse Probability Treatment Weighting &#40;IPTW&#41; propensity score&#44; identifying that those patients treated with budesonide presented a lower probability of reaching biochemical response at 6 months &#40;OR 0&#46;44&#59; CI95&#37; 0&#46;24&#8211;0&#46;81&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;009&#41;&#44; at 12 months &#40;OR 0&#46;43&#59; CI95&#37; 0&#46;23&#8211;0&#46;8&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41; and during the follow-up &#40;OR 0&#46;29&#59; CI95&#37; 0&#46;14&#8211;0&#46;58&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Indications and regimen of budesonide as first line drug</span><p id="par0050" class="elsevierStylePara elsevierViewall">In untreated patients diagnosed of non-severe acute or chronic AIH&#44; budesonide is an adequate alternative treatment endorsed by international guidelines&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">1&#44;3</span></a> The recommended dose is budesonide 3<span class="elsevierStyleHsp" style=""></span>mg three times per day&#44; combined with weight-adjusted azathioprine&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">3</span></a> Once biochemical response is documented&#44; budesonide tapering during the upcoming 6 months is recommended&#44; until reaching a dose of 3<span class="elsevierStyleHsp" style=""></span>mg daily&#46; Once biochemical remission is consolidated&#44; budesonide withdrawal can be considered while maintaining AZA treatment&#46; However&#44; due to the short life of budesonide&#44; it is unclear whether this reduction scheme is reasonable&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">1</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">While budesonide is an alternative in the non-severe scenario&#44; it cannot be considered in the presence of acute liver failure or cirrhosis&#46; First&#44; because there is no evidence of its efficacy&#44; as these patients were not included in the former trial&#46; Second&#44; because the presence of portosystemic shunts in patients with cirrhosis may decrease budesonide efficacy and increase the risk of adverse events by bypassing the liver&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">25</span></a> Finally&#44; some reports have warned about the increased risk of portal thrombosis in cirrhotic patients treated with budesonide&#44; discouraging its use&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Budesonide safety profile</span><p id="par0060" class="elsevierStylePara elsevierViewall">Because of the marginal use of budesonide in untreated patients&#44; the extent of information about the safety profile in this specific scenario is scant&#46; In the original trial&#44; patients treated with budesonide presented a significant lower rate of adverse events &#40;AEs&#41; compared to patients on prednisone&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">14</span></a> Specifically&#44; 26&#37; of patients in the budesonide group presented at least one AE during the follow up&#44; being moon face&#44; acne and hirsutism the leading causes&#46; On the other hand&#44; up to 51&#46;5&#37; of patients treated with prednisone developed at least one AE&#44; reporting the same leading causes&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">14</span></a> Interestingly&#44; no patient treated with prednisone presented diabetes as side effect&#44; while 4 patients &#40;15&#46;4&#37;&#41; on budesonide presented this complication&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">A few years later&#44; a similar trial was carried out in the pediatric population&#46; The authors did not identify differences in the emergence of AEs in budesonide and prednisone cohorts either at 6 or 12 months after treatment initiation&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a> The data about AEs emergence in the different published studies is summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">A recent Dutch study specifically evaluated the risk of developing steroid related AEs in AIH patients &#8211; including overlap with Primary Biliary Cholangitis &#40;PBC&#41; or Primary Sclerosing Cholangiits &#40;PSC&#41; &#8211; treated with low doses of prednisone or budesonide&#46; There&#44; they reported that prednisone exposure increased the risk of AEs &#40;OR 1&#46;08&#44; CI95&#37; 1&#46;06&#8211;1&#46;11&#41;&#44; while budesonide&#44; although bordering the statistical significance&#44; did not &#40;OR 1&#46;09&#44; CI95&#37; 1&#46;00&#8211;1&#46;2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">22</span></a> Nevertheless&#44; the authors found that not only prednisone&#44; but also budesonide significantly increased the risk of cataracts and bone fracture&#46; In fact&#44; these latter AEs persisted after correcting for prior prednisone use&#44; suggesting that the use of budesonide does not avert the risk of them&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">A fearsome side effect of steroids is adrenal insufficiency&#44; as its consequences can be devastating&#46; On this subject&#44; a recent placebo-controlled trial of PBC patients treated with budesonide showed a slight reduction of serum cortisol in patients treated with the drug with respect to those on placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a> However&#44; besides some case reports describing anecdotal cases of this complication in the AIH setting&#44;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">27</span></a> the information is very limited and comes from studies ran in the inflammatory bowel disease &#40;IBD&#41; scenario&#46; There&#44; different studies agree with the results from the PBC study<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a>&#58; budesonide induces a mild reduction in plasma cortisol&#44; but it is not a clinical concern at the usual doses recommended in the treatment of AIH&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">11&#44;28</span></a> Moreover&#44; other studies analyzing long-term use of budesonide at 3&#8211;6<span class="elsevierStyleHsp" style=""></span>mg doses have shown an absence -or very limited- of effect on adrenal function&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">29&#8211;31</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Are calcium and vitamin D supplements necessary&#63;</span><p id="par0080" class="elsevierStylePara elsevierViewall">As per guidelines&#44; DEXA &#40;dual-energy X-ray absorptiometry&#41; scan of both vertebrae and hips should be done in patients at risk of osteoporosis at AIH diagnosis&#44; and every 2&#8211;3 years in patients with ongoing risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">3</span></a> In fact&#44; the most prevalent risk factor in AIH patients is the immunosuppressive treatment itself&#44; specifically the prolonged use of corticosteroids&#46; However&#44; the body of evidence mostly comes from the IBD setting<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">32</span></a> where a randomized trial comparing prednisone and budesonide in patients with active Crohn&#39;s disease showed a significantly higher bone loss in patients treated with prednisone&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a> However&#44; this was not confirmed on other studies&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">34</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Prospective long term studies evaluating impact of budesonide in the bone density of patients with AIH are lacking&#46; However&#44; Van den Brand et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">22</span></a> recently showed that budesonide exposure significantly increases the risk of bone fracture&#44; reporting an OR 1&#46;14 &#40;CI95&#37; 1&#46;03&#8211;1&#46;27&#41;&#46; Therefore&#44; considering the ease of use and its favorable profile&#44; as well as the need of prolonged therapy&#44; treatment with vitamin D and calcium is safe and probably a cost-effective approach&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">Budesonide is a potent synthetic corticosteroid with a lower systemic bioavailability because of the high first-hepatic pass clearance&#46; Although this drug is recommended as an effective alternative by the different international societies &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#44; its use in the real-life setting is low&#46; Recently&#44; a retrospective multicenter study developed in Spain showed that the probability of achieving biochemical remission in patients treated with budesonide is significantly lower than those treated by prednisone&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">24</span></a> However&#44; these results must be prospectively validated&#46; In terms of safety&#44; the former trial<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">14</span></a> showed a lower short-term rate of AEs in patients treated with budesonide&#46; However&#44; recent data show that budesonide also significantly increases the risk of bone fracture and cataract&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">22</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In conclusion&#44; budesonide is a safe and effective drug in the setting of AIH&#44; but further studies are needed in order to improve patient selection for its use as first line induction therapy&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflict of interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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          "identificador" => "xres1746451"
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              "identificador" => "abst0005"
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          "titulo" => "Keywords"
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          "titulo" => "Palabras clave"
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          "identificador" => "sec0005"
          "titulo" => "Background"
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        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "General pharmacologic characteristics of glucocorticoids"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Prednisone"
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        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Budesonide"
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        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Budesonide as first line drug for autoimmune hepatitis"
        ]
        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Indications and regimen of budesonide as first line drug"
        ]
        10 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Budesonide safety profile"
        ]
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          "identificador" => "sec0040"
          "titulo" => "Are calcium and vitamin D supplements necessary&#63;"
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        12 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Discussion"
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        13 => array:2 [
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          "titulo" => "Conflict of interest"
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        14 => array:1 [
          "titulo" => "References"
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    "fechaRecibido" => "2021-09-03"
    "fechaAceptado" => "2021-11-29"
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          "clase" => "keyword"
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          "palabras" => array:4 [
            0 => "Autoimmune hepatitis"
            1 => "Budesonide"
            2 => "Prednisone"
            3 => "Biochemical remission"
          ]
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
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          "palabras" => array:4 [
            0 => "Hepatitis autoinmune"
            1 => "Budesonida"
            2 => "Prednisona"
            3 => "Remisi&#243;n bioqu&#237;mica"
          ]
        ]
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Budesonide is a glucocorticoid characterized by its local action&#44; with a low systemic bioavailability&#46; Since the original trial comparing budesonide with prednisone in 2010&#44; it is recommended as an effective alternative for the treatment of non-severe acute or chronic autoimmune hepatitis&#46; In this document&#44; we review the general pharmacologic properties of glucocorticoids&#44; the available evidence for the use of budesonide as first line option for autoimmune hepatitis as well as the safety profile of the drug&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La budesonida es un glucocorticoide que se caracteriza por su acci&#243;n local&#44; con una baja biodisponibilidad sist&#233;mica&#46; Desde el ensayo original publicado en 2010&#44; en el que se compar&#243; la budesonida con prednisona&#44; se recomienda como una alternativa eficaz en el tratamiento de los pacientes con hepatitis autoinmune aguda o cr&#243;nica no grave&#46; En este documento&#44; revisamos las propiedades farmacol&#243;gicas generales de los glucocorticoides&#44; la evidencia disponible para el uso de budesonida como f&#225;rmaco de primera l&#237;nea en estos pacientes&#44; as&#237; como el perfil de seguridad del f&#225;rmaco&#46;</p></span>"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">TB&#58; total bilirubin&#59; AST&#58; aspartate aminotransferase&#59; PDN&#58; prednisone&#59; AZA&#58; azathioprine&#59; IgG&#58; immunoglobulin G&#59; ULN&#58; upper limit of normal&#59; CALD&#58; chronic active liver disease&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Adapted from Lammers et al&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">39</span></a></p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">End-point&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Side-effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cook et al&#46;&#44; 1971<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Unblinded&#44; randomized&#44; controlled trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Untreated patients diagnosed of active chronic hepatitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Corticosteroid group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>22&#41;&#58; PDN 15<span class="elsevierStyleHsp" style=""></span>mg&#47;day reduced whenever biochemical liver function test became normal or in the emergence of severe side-effectsControl group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mortality at 72 monthsTB&#44; AST&#44; albumin at 72 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mortality&#58; PDN 3&#47;22 &#40;13&#46;6&#37;&#41; untreated group 15&#47;27 &#40;55&#46;5&#37;&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;Albumin was significantly higher in the PDN group compared to the control group at 6&#44; 12&#44; 18 and 24 months&#46;TB was significantly lower in PDN group with respect to the control group at six and 24 months&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDN&#58; obesity 5&#47;22 &#40;23&#37;&#41;&#44; moon face 5&#47;22 &#40;23&#37;&#41;&#44; acne 4&#47;22 &#40;18&#37;&#41;&#44; Osteoporosis and vertebral collapse 2&#47;22 &#40;9&#37;&#41;&#44; Perforated duodenal ulcer 1&#47;22 &#40;5&#37;&#41;&#44; acute steroid psychosis 1&#47;22 &#40;5&#37;&#41;&#44; terminal bronchopneumonia 1&#47;22 &#40;5&#37;&#41;&#44; myositis 1&#47;22 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soloway et al&#46;&#44; 1972<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UK&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Randomized&#44; double-blinded&#44; controlled trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hepatic disease documented by clinical&#44; biochemical&#44; and histological abnormalities lasting at least 10 weeks and documented by biopsy&#44; jaundice&#44; or AST <span class="elsevierStyleUnderline">&#62;</span>10&#215;ULN or <span class="elsevierStyleUnderline">&#62;</span>5&#215;ULN plus IgG <span class="elsevierStyleUnderline">&#62;</span>2&#215;ULN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;a&#41; PDN &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>18&#41; 60<span class="elsevierStyleHsp" style=""></span>mg daily for one week&#44; 40<span class="elsevierStyleHsp" style=""></span>mg daily the following week&#44; 30<span class="elsevierStyleHsp" style=""></span>mg daily for two weeks and 20<span class="elsevierStyleHsp" style=""></span>mg daily as maintenance therapy&#46;&#40;b&#41; AZA &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41; 100<span class="elsevierStyleHsp" style=""></span>mg daily&#46;&#40;c&#41; PDN<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AZA &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41;&#58; 30<span class="elsevierStyleHsp" style=""></span>mg daily for 1 week&#44; 20<span class="elsevierStyleHsp" style=""></span>mg daily the following week&#44; 15<span class="elsevierStyleHsp" style=""></span>mg daily for 2 weeks&#44; and 10<span class="elsevierStyleHsp" style=""></span>mg daily as maintenance&#40;d&#41; Placebo &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#8211;38 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;1&#41; Remission defined as&#58;<span class="elsevierStyleHsp" style=""></span>&#40;a&#41; clinical normality&#44; return to all customary activitiesPLUS<span class="elsevierStyleHsp" style=""></span>&#40;b&#41; Disappearance of histological signs of disease activity normality or of minor changes indistinguishable from those in nonspecific or chronic persistent hepatitis&#40;2&#41; Mortality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDN group&#58; remission 8&#47;18 &#40;44&#37;&#41;&#44; mortality 1&#47;18 &#40;6&#37;&#41;&#44;PDN<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AZA group&#58; remission 3&#47;14 &#40;21&#37;&#41;&#44; mortality 1&#47;14 &#40;7&#37;&#41;&#46;AZA group&#58; remission 1&#47;14 &#40;7&#37;&#41;&#44; mortality 5&#47;14 &#40;36&#37;&#41;Placebo group&#58; mortality&#58; remission 0&#47;17 &#40;0&#37;&#41;&#44; mortality 7&#47;17 &#40;41&#37;&#41;Response rate in patients receiving PDN or combined treatment were superior to those receiving AZA or placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDN&#58; cushingoid appearance 13&#47;18 &#40;72&#37;&#41;&#44; serious side effects &#40;vertebral collapse&#44; aseptic necrosis of the femoral head&#44; or cataracts&#41; 3&#47;18 &#40;17&#37;&#41;&#44; diabetes requiring insulin 1&#47;18 &#40;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Murray-Lyon et al&#46;&#44; 1973<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">36</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Randomized&#44; double-blind&#44; controlled trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Active chronic hepatitis defined by hepatic disease lasting at least for 3 months with AST<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleUnderline">&#62;</span><span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>IU&#47;L and&#47;or IgG<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;100<span class="elsevierStyleHsp" style=""></span>mL&#46;Patients previously treated with AZA or corticosteroids were not excluded&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>47Cirrhosis &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDN group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>22&#41;&#58; 5<span class="elsevierStyleHsp" style=""></span>mg every 8<span class="elsevierStyleHsp" style=""></span>hAZA group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41;&#58; 75<span class="elsevierStyleHsp" style=""></span>mg dailyIn the absence of response or AST persistently <span class="elsevierStyleUnderline">&#62;</span>200<span class="elsevierStyleHsp" style=""></span>IU&#47;L&#44; PDN or AZA doses were increased to 20<span class="elsevierStyleHsp" style=""></span>mg or 112&#46;5<span class="elsevierStyleHsp" style=""></span>mg respectively&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Survival at 24 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDN group&#58; 95&#37; probability of survival at 24 monthsAZA group&#58; 72&#37; probability of survival at 24 monthsSignificant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41; decrease in bilirubin and globulin in both groupsHigher AST &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; and IgG &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; decrease in the first 6 months in patients treated with PDN&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PRD&#58; facial mooning 11&#47;22 &#40;50&#37;&#41;&#44; diabetes mellitus 3&#47;22 &#40;14&#37;&#41;&#59; hypertension 2&#47;22 &#40;9&#37;&#41;&#44; brush fracture of thoracic vertebrae 1&#47;22 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Summerskill et al&#46;&#44; 1975<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">37</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multicenter&#44; randomized&#44; double-blind&#44; controlled trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hepatic disease documented by clinical&#44; biochemical&#44; and histological abnormalities lasting at least 10 weeks and documented by biopsy&#44; jaundice&#44; or AST &#62;10&#215;ULN or &#62;5&#215;ULN plus IgG &#62;2&#215;ULN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>120&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;a&#41; Placebo &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41;&#40;b&#41; AZA 100<span class="elsevierStyleHsp" style=""></span>mg &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41;&#40;c&#41; PDN &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&#40;d&#41; PDN<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AZA &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&#40;e&#41; PDN at titrated doses attending to biochemical evolution &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>31&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;1&#41; Remission defined as&#58;<span class="elsevierStyleHsp" style=""></span>&#40;a&#41; Absence of symptoms and return of the patient to customary activitiesPLUS<span class="elsevierStyleHsp" style=""></span>&#40;b&#41; AST <span class="elsevierStyleUnderline">&#60;</span>2&#215;ULNPLUS<span class="elsevierStyleHsp" style=""></span>&#40;c&#41; Normalization of immunoserological tests&#40;2&#41; Mortality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDN&#58; 24&#47;30 &#40;80&#37;&#41; achieved remission&#46; Mortality 3&#47;30 &#40;10&#37;&#41;PDN<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AZA&#58; 24&#47;30 &#40;80&#37;&#41; achieved remission&#46; Mortality 2&#47;31 &#40;7&#37;&#41;Titrated PDN&#58; 23&#47;31 &#40;74&#37;&#41; achieved remission&#46; Mortality 2&#47;31 &#40;7&#37;&#41;Placebo or AZA&#58; 10&#47;29 &#40;34&#37;&#41; achieved remission&#46; Mortality 12&#47;29 &#40;41&#37;&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDN&#58; severe cosmetic changes 4&#47;30 &#40;13&#37;&#41;&#44; diabetes 4&#47;30&#47;13&#37;&#41;&#44; cataracts 2&#47;30 &#40;7&#37;&#41; vertebral collapse 1&#47;30 &#40;3&#37;&#41;PDN&#47;AZA&#58; diabetes 3&#47;30 &#40;10&#37;&#41;Titrated PDN&#58; diabetes 3&#47;31 &#40;10&#37;&#41;Pacebo or AZA&#58; gastrointestinal bleeding 5&#47;29 &#40;17&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tage-Jansen et al&#46;&#44; 1982<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">38</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Denmark&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multicenter&#44; randomized&#44; unblinded clinical trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patient with biopsy-proven chronic aggressive hepatitis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>99&#42; only information for 84 patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;a&#41; PDN 10 mg&#47;day if weight &#60;70<span class="elsevierStyleHsp" style=""></span>kg or 15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg if weight <span class="elsevierStyleUnderline">&#62;</span>70<span class="elsevierStyleHsp" style=""></span>kg&#46;&#40;b&#41; AZA 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;12&#8211;83 months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;1&#41; Remission defined as<span class="elsevierStyleHsp" style=""></span>&#40;a&#41; AST<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>UI&#47;L<span class="elsevierStyleHsp" style=""></span>&#40;b&#41; IgG<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>15&#46;1<span class="elsevierStyleHsp" style=""></span>g&#47;L&#40;2&#41; Mortality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PRD&#58; Remission&#58; 21&#47;47 &#40;45&#37;&#41;&#59; mortality&#58; 13&#47;27 &#40;28&#37;&#41;AZA&#58; Remission&#58; 6&#47;37 &#40;37&#37;&#41;&#44; mortality&#58; 10&#47;37 &#40;27&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not reported&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Clinical trials evaluating prednisone for treating autoimmune hepatitis&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">AST&#58; aspartate aminotransferase&#59; ALT&#58; alanine aminotransferase&#59; ULN&#58; upper limit of normal&#59; AIH&#58; autoimmune hepatitis&#59; BUD&#58; budesonide&#59; AZA&#58; azathioprine&#59; PDN&#58; prednisone&#59; pat&#58; patients&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Country&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Design&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Inclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Followup&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Primary endpoint&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Adverse EVENTS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Wiegand et al&#46;&#44; 2005<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Germany&#44; Netherlands&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multicenter Open label&#44; prospective clinical trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Untreated AIH patientsAST and ALT at least &#62;3&#215; ULN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#59; finally included <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Day 1&#58; 3<span class="elsevierStyleHsp" style=""></span>g twice daily from day 2&#58; 3<span class="elsevierStyleHsp" style=""></span>mg thrice daily&#46;Upon biochemical remission&#44; the dosage was individually reduced to 3<span class="elsevierStyleHsp" style=""></span>mg budesonideNo other immunosuppressive drugs allowed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Remission defined as drop of AST and ALT <span class="elsevierStyleUnderline">&#60;</span>2&#215;ULN&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete remission&#58; 7&#47;12Partial response 3&#47;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leukocytosis 5&#47;14 &#40;36&#37;&#41;Hypercholesterinaemia 4&#47;14 &#40;29&#37;&#41;Cushing-like symptoms 3&#47;14 &#40;21&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Csepregi et al&#46;&#44; 2006<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Germany&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multicenter Open label study&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Na&#239;ve or previously treated patients diagnosed of AIH or overlap&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>18First-line BUD in AIH&#58; <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BUD 3<span class="elsevierStyleHsp" style=""></span>mg thrice daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not defined&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Biochemical remission in AIH 4&#47;7No response in AIH&#58; 3&#47;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total incidence&#58; 6&#47;18 &#40;33&#37;&#41;Weight gain &#62;3<span class="elsevierStyleHsp" style=""></span>kg 3&#47;18 &#40;17&#37;&#41;&#44;Acne 2&#47;18 &#40;11&#37;&#41;Abdominal pain 1&#47;18 &#40;6&#37;&#41;Alopecia 1&#47;18 &#40;6&#37;&#41;Every AE emerged in patients with cirrhosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Manns et al&#46;&#44; 2010<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Germany&#44; Poland&#44; Ukraine&#44; Hungary&#44; Israel&#44; Sweden&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&#44; 6-month double-blind&#44; double-dummy&#44; controlled trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Untreated AIH patientsAST and ALT at least &#62;2&#215; ULN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>207 patientsBUD<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>102 patPDN<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>105 pat&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BUD&#58; 9<span class="elsevierStyleHsp" style=""></span>mg&#47;daily&#46;PDN group&#58; 40<span class="elsevierStyleHsp" style=""></span>mg&#47;daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Segment A 24 weeksSegment B 24 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Biochemical remission without corticosteroid-related adverse events&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary endpoint&#58;BUD&#58; 47&#47;100 &#40;47&#46;0&#37;&#41;PDN&#58; 19&#47;103 &#40;18&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BUD&#58; 26&#47;100 &#40;26&#37;&#41;Headache 11&#46;8&#37;Mood alterations 9&#46;8&#37;&#46;Weight gain 5&#46;9&#37;Muscular weakness 4&#46;9&#37;&#46;Hypertension 2&#46;9&#37;Insomnia 1&#37;&#46;PDN&#58; 53&#47;103 &#40;51&#46;5&#37;&#41;Weight gain 19&#37;&#46;Headache 7&#46;6&#37;&#46;Mood alterations 7&#46;6&#37;&#46;Muscular weakness 7&#46;6&#37;&#46;Hypertension 6&#46;7&#37;&#46;Insomnia 4&#46;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Efe et al&#46;&#44; 2012<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Turkey&#44; France&#44; Italy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multicenter&#44; retrospective study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Untreated definite or probable AIH defined by simplified AIH criteria &#40;IAIHG&#41;AIH&#47;PBC overlap syndrome according to Chazouilleres criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a>ALT or AST levels &#62;3&#215;ULN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BUD 9 mg&#47;day<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AZA 50<span class="elsevierStyleHsp" style=""></span>mg all patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;a&#41; Biochemical remission defined by AST and&#47;or ALT <span class="elsevierStyleUnderline">&#60;</span>2&#215;ULN&#40;b&#41; AST&#47;ALT drop &#62;50&#37; after 1 month on treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Biochemical remission&#58; 11&#47;18 &#40;61&#46;1&#37;&#41;No response&#58; 7&#47;18 &#40;38&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Incidence 11&#47;18 &#40;61&#37;&#41;Weight gain&#58; 6&#47;18 &#40;30&#37;&#41;&#59; acne 4&#47;18 &#40;20&#37;&#41;&#59; hirsutism&#58; 4&#47;18 &#40;20&#37;&#41;&#59; moon face&#58; 2&#47;18 &#40;10&#37;&#41;&#59; skin striae&#58; 2&#47;18 &#40;10&#37;&#41;&#59; buffalo hump&#58; 2&#47;18 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Woynarowski et al&#46;&#44; 2013<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Poland&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multicenter prospective&#44; double-blind&#44; randomized&#44; controlled trial in pediatric AIH patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pediatric AIH patients &#40;9&#8211;17 years&#41;AST and ALT at least &#62;2&#215; ULN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>46BUD<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19 patPDN<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27 pat&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3<span class="elsevierStyleHsp" style=""></span>mg 3 times daily or 3<span class="elsevierStyleHsp" style=""></span>mg twice daily after biochemical&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Segmentt A 24 weeksSegment B 24 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Biochemical remission without corticosteroid-related adverse events&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primary endpoint&#58;BUD&#58; 3&#47;19 &#40;16&#37;&#41;PDN&#58; 4&#47;27 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDN incidence 17&#47;27 &#40;63&#37;&#41;&#59; moon face&#58; 12&#47;27 &#40;44&#37;&#41;&#59; acne&#58; 7&#47;27 &#40;26&#37;&#41;&#59; skin striae&#58; 3&#47;27 &#40;11&#37;&#41;BUD incidence 9&#47;19 &#40;47&#37;&#41;&#44; acne 4&#47;19 &#40;21&#37;&#41;&#44; moon face 2&#47;19 &#40;11&#37;&#41;&#44; skin striae 1&#47;19 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Binicier et al&#46;&#44; 2019<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Turkey&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective unicenter study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Untreated AIH patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50PDN<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AZA<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25 patPDN<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BUD<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25 pat&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PRED&#47;AZA&#58; 30<span class="elsevierStyleHsp" style=""></span>mg&#47;day PRED and AZA&#46;BUD&#47;AZA&#58; 9 mg&#47;day BUD and AZA&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Biochemical remission defined by AST and ALT normalization&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Biochemical remission defined as transaminases normalization&#58;<span class="elsevierStyleHsp" style=""></span>-<span class="elsevierStyleHsp" style=""></span>PDN<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AZA&#58; 17&#47;25 &#40;68&#37;&#41;<span class="elsevierStyleHsp" style=""></span>-<span class="elsevierStyleHsp" style=""></span>BUD<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AZA&#58; 18&#47;25 &#40;72&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDN&#47;AZA incidence&#58; 9&#47;25 &#40;60&#37;&#41;&#44; acne 4&#47;25 &#40;16&#37;&#41;&#44; moon face 4&#47;24 &#40;16&#37;&#41;&#44; hirsutism 3&#47;25 &#40;12&#37;&#41;&#44; striae 2&#47;25 &#40;8&#37;&#41;&#44; myopathy 1&#47;25 &#40;4&#37;&#41;&#44; buffalo hump 1&#47;25 &#40;4&#37;&#41;&#46;BUD&#47;AZA Incidence 5&#47;25 &#40;20&#37;&#41; Acne 2&#47;25 &#40;8&#37;&#41;&#44; hirsutism 1&#47;25 &#40;4&#37;&#41;&#44; myopathy 1&#47;25 &#40;4&#37;&#41;&#44; moon face 1&#47;25 &#40;4&#37;&#41;&#44; buffalo hump 1&#47;25 &#40;4&#37;&#41;&#44; striae 2&#47;25 &#40;4&#37;&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Clinical trials &#38; retrospective studies evaluating budesonide for the treatment of autoimmune hepatitis&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Guideline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Induction dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tappering&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Azathioprine &#40;yes&#47;no&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Duration of treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AASLD 2020<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">3</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#8211;40<span class="elsevierStyleHsp" style=""></span>mg daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tapper to 5&#8211;10<span class="elsevierStyleHsp" style=""></span>mg daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">At least 2 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Budesonide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3<span class="elsevierStyleHsp" style=""></span>mg thrice daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tapper to 3<span class="elsevierStyleHsp" style=""></span>mg daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ESPGHAN 2019<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">41</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 mg&#47;kg daily &#40;maximum 60 mg&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tapper to 2&#46;5&#8211;5<span class="elsevierStyleHsp" style=""></span>mg daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">At least 2&#8211;3 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Budesonide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Undefined&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Undefined&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Undefined&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Undefined&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hellenic 2018<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">42</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisolone 0&#46;5&#8211;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Individualized according to response and side-effectsComplete PDN withdrawal after 6&#8211;8 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">At least 3 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Budesonide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9<span class="elsevierStyleHsp" style=""></span>mg daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not defined&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EASL 2015<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">1</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5&#8211;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;a&#41; From 60 to 20<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>-<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mg weekly&#40;b&#41; From 20<span class="elsevierStyleHsp" style=""></span>mg to 10<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>-<span class="elsevierStyleHsp" style=""></span>2&#46;5&#8211;5<span class="elsevierStyleHsp" style=""></span>mg biweekly&#40;c&#41; From 10<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>-<span class="elsevierStyleHsp" style=""></span>Individualized according to response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">At least three years and 24 months after biochemical remission&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Budesonide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9<span class="elsevierStyleHsp" style=""></span>mg daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not clearly defined&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BSG 2011<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">43</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30<span class="elsevierStyleHsp" style=""></span>mg daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5<span class="elsevierStyleHsp" style=""></span>mg weekly until 10<span class="elsevierStyleHsp" style=""></span>mg daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">At least 2 years and 12 months after biochemical remission&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Budesonide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9<span class="elsevierStyleHsp" style=""></span>mg daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not defined&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not defined&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">International guidelines recommendations for the treatment of autoimmune hepatitis&#46;</p>"
        ]
      ]
      3 => array:8 [
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        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">IQR&#58; interquartile range&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Centres&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">21 Spanish centers</th></tr><tr title="table-row"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Study period&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">2009&#8211;2020</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Budesonide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Prednisone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Number of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">151&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">218&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Women &#40;<span class="elsevierStyleItalic">n</span>&#44; &#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">107 &#40;70&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">154 &#40;70&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;years&#44; median&#44; IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#44;2 &#40;46&#46;3&#8211;71&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#44;4 &#40;50&#46;7&#8211;72&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cirrhosis &#40;<span class="elsevierStyleItalic">n</span>&#44; &#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;5&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;17&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Induction dose &#40;median&#44; IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;9&#8211;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;30&#8211;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Azathioprine &#40;<span class="elsevierStyleItalic">n</span>&#44; &#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">132 &#40;88&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">184 &#40;86&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of the patients included in the study by D&#237;az-Gonz&#225;lez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">24</span></a></p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:43 [
            0 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "EASL clinical practice guidelines&#58; autoimmune hepatitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;W&#46; Lohse"
                            1 => "O&#46; Chazouill&#232;res"
                            2 => "G&#46; Dalekos"
                            3 => "J&#46; Drenth"
                            4 => "M&#46; Heneghan"
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

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Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos