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Liver Injury in Psoriasis Patients Receiving Ustekinumab: A Retrospective Study of 44 Patients Treated in the Clinical Practice Setting
Análisis de la hepatotoxicidad en psoriasis tratada con ustekinumab. Estudio retrospectivo de 44 pacientes en práctica clínica habitual
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"apellidos" => "Daudén" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital Universitario de la Princesa, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Análisis de la hepatotoxicidad en psoriasis tratada con ustekinumab. Estudio retrospectivo de 44 pacientes en práctica clínica habitual" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The greater frequency of adverse effects with classic systemic treatments limits available therapeutic options in patients with psoriasis and liver disease.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">1</span></a> In the case of viral hepatitis, some drugs (interferon and ribavirin) can trigger or worsen pre-existing psoriasis,<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">2</span></a> and immunosuppressive and hepatotoxic drugs are relatively contraindicated.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">2</span></a> Anti–tumor necrosis factor alfa (anti-TNF-α) agents are considered a safer option.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a> Anti-TNF-α agents, especially etanercept, have generally proven successful in patients with hepatitis C virus infection.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">2,4,5</span></a> In contrast, viral replication has been reported in patients with hepatitis B virus infection and psoriasis who are taking anti-TNF-α agents,<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a> even in cases where the infection has resolved.<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">6–8</span></a> Therefore, even though these patients are HBsAg-negative, they should be closely monitored.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">9</span></a> Furthermore, anti-TNF-α agents have exceptionally been associated with severe liver damage (liver failure, cholestasis, and autoimmune hepatitis).</p><p id="par0010" class="elsevierStylePara elsevierViewall">Little is known about the effects on the liver of ustekinumab (UTK), an anti-p40 agent that has proven efficacious in patients with psoriasis. Normal transaminase values were recorded in the PHOENIX 1 study.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">10</span></a> In the PHOENIX 2 study, a patient from the placebo group developed hepatocellular carcinoma, and no significant differences were found between patients treated with placebo and patients treated with UTK.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">11</span></a> Similarly, in the ACCEPT study,<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">12</span></a> no differences in transaminase values were recorded between UTK and etanercept. With respect to clinical practice, several recent series of patients treated with UTK did not reveal adverse liver effects,<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">13–15</span></a> and only 1 study found elevated transaminases (44% of patients), although neither the levels nor the duration were specified.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">16</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The primary objective of our study was to estimate the frequency of liver toxicity in patients with psoriasis treated with UTK according to habitual clinical practice; the secondary objective was to assess the affect of UTK on liver involvement in patients with liver disease or elevated transaminases before initiation of treatment.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">We performed an observational, retrospective study of consecutive patients with moderate to severe psoriasis who started treatment with UTK between March 1, 2009 and June 30, 2011 at the Psoriasis Unit of Hospital de la Princesa, Madrid, Spain. The study was approved by the Ethics Committee of the Biomedical Research Foundation of Hospital la Princesa. Patients aged <18 years or whose clinical history lacked valid data were excluded. Clinical histories and additional test results were reviewed. The data recorded included height, weight, type of psoriasis, age at diagnosis, disease duration, nail involvement, psoriatic arthritis, Psoriasis Areas and Severity Index (PASI), body surface area (BSA), Dermatology Life Quality Index (DLQI), alcohol consumption, smoking, previous liver disease, previous biologic and systemic drugs, and concomitant medication (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The analytical data reviewed included a complete blood count, biochemistry with liver profile (aspartate aminotransferase [AST, reference range, 7-35<span class="elsevierStyleHsp" style=""></span>U/L; alanine aminotransferase [ALT], reference range, 8-40<span class="elsevierStyleHsp" style=""></span>U/L; and gamma glutamyl transpeptidase [GGT], reference range, 6-50<span class="elsevierStyleHsp" style=""></span>U/L), lipid profile, serology (hepatitis B and C virus, human immunodeficiency virus [HIV]), result of a Mantoux test with booster, and chest radiograph. All patients received subcutaneous UTK (45<span class="elsevierStyleHsp" style=""></span>mg) at weeks 0, 4, and every 12 weeks thereafter. Liver function was determined in all patients at 4 and 16 weeks and at most follow-up visits. Ultrasound examination of the liver was performed in patients with a previous history of liver disease or elevated transaminases and, during follow-up, in all those patients who presented altered transaminase levels or signs or symptoms suggestive of or compatible with liver disease.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Patients with a positive Mantoux result were treated with isoniazid (300<span class="elsevierStyleHsp" style=""></span>mg/d) for 9 months; prophylaxis was started 1 month before initiation of UTK.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Elevated transaminases were classified according to severity as follows: grade 1 (up to 3 times the upper reference value); grade 2 (3-5 times the upper reference value); and grade 3 (5-10 times the upper reference value and acute hepatitis).<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">17</span></a> Ultrasound examination of the liver enabled patients to be classed as healthy or ill (fatty liver disease, fibrosis, or cirrhosis).</p><p id="par0035" class="elsevierStylePara elsevierViewall">The statistical analysis was performed using SPSS version 19 for Windows (SPSS Inc). Quantitative variables were analyzed using the <span class="elsevierStyleItalic">t</span> test. Binomial variables were analyzed using the chi-square test and a Fisher exact test when necessary.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">The study population comprised 44 patients, of whom 59% were men and the majority nonsmokers (57.5%). The mean follow-up time with UTK was 46.2 months (range, 25.3-63.4).</p><p id="par0045" class="elsevierStylePara elsevierViewall">Most patients treated with UTK had plaque psoriasis; nail involvement was recorded in 58.8%. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows baseline population data, previous biologic and systemic drugs used to treat psoriasis, and the percentage of patients with relevant comorbid conditions. Three patients had received a cumulative dose of methotrexate greater than 2<span class="elsevierStyleHsp" style=""></span>g, although none had reached 3<span class="elsevierStyleHsp" style=""></span>g. The mean cumulative dose was 190<span class="elsevierStyleHsp" style=""></span>mg. Some patients simultaneously received hepatotoxic drugs such as statins (5 patients), methotrexate (2 patients), hypoglycemic agents (2 patients), and angiotensin II antagonists (1 patient).</p><p id="par0050" class="elsevierStylePara elsevierViewall">Confounding factors for liver toxicity were analyzed. Only 4 patients had previously had hepatitis B infection; no patients had hepatitis C infection, HIV infection, or active hepatitis B infection. Mean ferritin was 108.92<span class="elsevierStyleHsp" style=""></span>mg/L (range, 15-366<span class="elsevierStyleHsp" style=""></span>mg/L) in the 24 patients studied (local reference value, 15-150<span class="elsevierStyleHsp" style=""></span>mg/mL). Only 1 patient had elevated ferritin (366<span class="elsevierStyleHsp" style=""></span>mg/L), although hemochromatosis was ruled out. Two patients were obese (body mass index [BMI] >30). Ultrasound examination of the liver revealed fatty liver in 9 patients. No patients had fibrosis or cirrhosis at baseline.</p><p id="par0055" class="elsevierStylePara elsevierViewall">As for previous liver disease, 41.9% of patients had had elevated transaminases associated with other drugs such as infliximab (5 cases), etanercept (3 cases), adalimumab (2 cases), and isoniazid (2 cases).</p><p id="par0060" class="elsevierStylePara elsevierViewall">Two patients started UTK with increased baseline transaminases (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The first was a 45-year-old man with a 15-year history of moderate to severe psoriasis and a clinical history that was unremarkable except for chronic alcoholism and obesity (BMI, 31.5). When the patient started UTK, the values for severity of psoriasis were as follows: baseline PASI, 9.6; BSA, 7.1%; and DLQI, 13. At 16 weeks of treatment these values were as follows: PASI, 3; BSA, 3%; and DLQI, 1. Levels of AST and ALT remained stable during treatment, with a slight upward trend. The second patient was a 43-year-old man with fatty liver disease and a BMI of 26.2. He did not consume alcohol, had elevated transaminases, and had been treated with ciclosporin, retinoids, narrowband UV-B therapy, and methotrexate. His transaminase levels had fallen gradually but returned to normal after 19 months of treatment with UTK.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">During treatment, 6 patients had grade 1 elevated transaminases (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Five had had liver toxicity associated with other drugs used to treat psoriasis, 3 had fatty liver disease, and 3 were receiving hepatotoxic agents concomitantly with UTK. The increase in transaminase levels occurred between 1 and 17 months after starting treatment (mean [SD], 3 [1.4]). Increased GGT was recorded in another patient. No patients showed signs or symptoms of liver disease or had to suspend or modify treatment because of liver toxicity. No severe adverse liver effects or cases of viral reactivation were detected during treatment with UTK.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The statistical analysis did not reveal statistically significant differences between patients with or without altered transaminase levels in terms of age (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">=</span><span class="elsevierStyleHsp" style=""></span>.592), alcohol consumption (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">=</span><span class="elsevierStyleHsp" style=""></span>.541), or BMI (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">=</span><span class="elsevierStyleHsp" style=""></span>.116). Similarly, no differences were detected for the percentage of patients who reached PASI 75 at 16 weeks (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">=</span><span class="elsevierStyleHsp" style=""></span>.597).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">Given the mechanism of action of UTK,<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">18,19</span></a> some liver effects are to be expected during treatment. In hepatitis B infection, the increase in interleukin (IL) 12 levels is correlated with hepatolysis, viral clearance,<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">18</span></a> and sustained control of viremia in patients with chronic disease.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">19</span></a> The exact mechanism is unknown, because the activity of the IL-23/IL-17 proinflammatory pathway is also overexpressed in hepatitis B virus infection and could facilitate the chronic nature of the process.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">20</span></a> Type 17 helper T-cell (T<span class="elsevierStyleInf">H</span>17) counts are increased in chronic hepatitis B virus infection, and the increase in the T<span class="elsevierStyleInf">H</span>17/regulatory T-cell ratio can indicate poor prognosis.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">21</span></a> In hepatitis C virus infection, virus-induced activation of T<span class="elsevierStyleInf">H</span>17 cells can contribute to viral clearance, because IL12p40 levels are higher in patients who respond to interferon alfa,<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">22</span></a> although Zhang et al.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">23</span></a> did not confirm this observation. Polymorphisms in IL12p40 can modulate hepatitis C virus infection<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">24</span></a> and account for the inconsistencies in published results. In the light of basic research data, UTK should be used with caution in patients with viral hepatitis, and although some series indicate that it is safe in clinical practice,<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">25</span></a> reactivation of hepatitis B and C virus has been reported.<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">26,27</span></a> We found no cases of reactivation of previous hepatitis B virus.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Increased IL17 levels have been detected in the liver of patients with nonalcoholic fatty liver disease and can facilitate the transition to steatohepatitis.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">28</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">IL-12 is also involved in other liver diseases and played a key role in the development of autoimmune cholangitis in a murine primary biliary cirrhosis model.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">29</span></a> Finally, T<span class="elsevierStyleInf">H</span>17 cells are involved in rejection of liver allografts in rats.<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">30</span></a> Therefore, modulation of T<span class="elsevierStyleInf">H</span>17 could lead to improvement in many liver diseases. We did not observe any worsening of liver disease that was present at the start of treatment with UTK.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Comorbid conditions in patients with psoriasis have been widely studied.<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">31,32</span></a> In our series, 42% of the patients were smokers, as reported elsewhere.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a> Mean alcohol consumption was 6.36 g/d, which is lower than usually reported by other studies showing higher consumption in patients with psoriasis.<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">34</span></a> In addition to being cytotoxic in the liver and in bone marrow, alcohol has an immunosuppressive effect. In fact, consuming more than 2-3 alcoholic drinks per week significantly increases the risk of psoriasis,<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">34,35</span></a> and more than 100 g/d in men is a risk factor for increased activity of psoriasis.<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">36</span></a> Other authors found no association between alcohol consumption and severity of psoriasis. The fact that we took a clinical history could have influenced the levels of alcohol consumption reported by the patients.</p><p id="par0095" class="elsevierStylePara elsevierViewall">The prevalence of obesity has been reported to be double in patients with psoriasis, as has an association between BMI and PASI, namely, poorer disease control in patients with a high BMI.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a> In our study, 20.5% of patients were obese (the prevalence of obesity in the general population in Spain was 13.3% during the same period<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">37</span></a>). These data agree with those reported by Kim et al.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Nonalcoholic fatty liver disease is a chronic metabolic disease associated with both metabolic syndrome and with insulin resistance. It is the main cause of elevated transaminases in Europe.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">33</span></a> Of the 8 patients with nonalcoholic fatty liver disease in our study, only the eldest (62 years) had developed diabetes and dyslipidemia. Gisondi et al.<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">38</span></a> reported that up to 50% of cases of nonalcoholic fatty liver disease are not diagnosed. This finding is consistent with ours and suggests that psoriasis could be a risk factor for onset, although other authors would require patients with high alcohol consumption to be ruled out.<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">39</span></a> None of the patients with nonalcoholic fatty liver disease in our study consumed high amounts of alcohol, although 5 were obese. This finding is consistent with those of Gisondi et al.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Drug-induced liver toxicity is defined as a >3-fold increase in normal transaminase levels or twice the normal levels of bilirubin.<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">40</span></a> We detected no cases of drug-induced liver toxicity. Elevated transaminases have been observed during treatment with anti-TNF-α agents,<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">41</span></a> especially with infliximab,<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">3</span></a> but also with etanercept and adalimumab.<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">42</span></a> In our series, elevated transaminases were observed in 14.3% of patients during treatment with UTK. Despite reports of anti-TNF-α–induced liver toxicity in patients treated with a drug from the same family without recurrences,<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">41,43–45</span></a> using drugs with a different mechanism of action seems safer.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Lastly, 5 of the patients in the present study were treated with statins, which induce liver toxicity and cause liver damage in 1% of cases. Grade 1 elevated transaminase levels were observed in a single analysis in only 1 patient, although this abnormality resolved without sequelae. Therefore, statins do not appear to be contraindicated in our series or in the literature reviewed.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">21</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Our study is limited by sample size, short follow-up, and absence of data on the dose of previously prescribed hepatotoxic agents.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Our findings show that liver toxicity associated with UTK is mild and uncommon. Similarly, UTK seems to be a safe alternative in patients with previous liver disease or in those who have experienced liver alterations during treatment with antipsoriatic drugs, including anti-TNF-α agents.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Ethical Disclosures</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Protection of Persons and Animals</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that this research did not involve experiments performed on humans or animals.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Confidentiality of Data</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors declare that they have followed their hospital's protocol on the publication of data concerning patients.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Right to privacy and informed consent</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data are disclosed in this article.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of Interest</span><p id="par0140" class="elsevierStylePara elsevierViewall">M Llamas-Velasco has participated in clinical trials and advisory boards for AbbVie, Janssen-Cilag, and Novartis.</p><p id="par0145" class="elsevierStylePara elsevierViewall">E Daudén has participated in advisory boards and clinical trials, acted as a consultant, and received grant support, research support, and fees for talks from the following companies: AbbVie Astellas, Biogen, Centocor Ortho Biotech Inc., Galderma, Glaxo, Janssen-Cilag, Leo Pharma, Merck-Serono, Novartis, Pfizer, Schering-Plough, Stiefel, Wyeth Pharmaceuticals, 3M, and Celgene.</p><p id="par0150" class="elsevierStylePara elsevierViewall">A García-Diez has retired and has no conflicts of interest.</p><p id="par0155" class="elsevierStylePara elsevierViewall">María José Concha-Garzón declares that she has no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres527242" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec547556" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres527243" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec547555" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0025" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Protection of Persons and Animals" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Confidentiality of Data" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflicts of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-10-05" "fechaAceptado" => "2015-02-08" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec547556" "palabras" => array:3 [ 0 => "Ustekinumab" 1 => "Liver disease" 2 => "Drug toxicity" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec547555" "palabras" => array:3 [ 0 => "Ustekinumab" 1 => "Hepatopatía" 2 => "Toxicidad farmacológica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The therapy of patients with psoriasis and liver disease can be a challenge due to the increased risk of adverse effects from traditional systemic treatments; in addition, although the anti-tumor necrosis factor agents are considered safer, they have also been associated with drug-induced liver injury and reactivation of viral hepatitis. Ustekinumab has a different mechanism of action and the little that is known of its effects on the liver comes from pivotal studies. The objectives of this study were to estimate the incidence of drug-induced liver injury in patients treated with ustekinumab in daily clinical practice and to analyze liver alterations in those patients with pre-existing liver disease.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">All patients treated with the standard regimen of ustekinumab were included in the study. Variables gathered included age, sex, type of psoriasis, nail involvement, arthritis, previous treatments, history of liver disease, viral serology, Psoriasis Area Severity Index (at baseline and at 12, 16, and 52 weeks), transaminase levels, manifestations of liver disease, liver ultrasound, and factors such as body mass index, alcohol consumption, and ferritin levels.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Grade 1 elevation of the transaminases was only observed in 6 patients; no cases of severe hypertransaminasemia were observed. None of the patients with elevation of the transaminases at baseline developed problems during treatment.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Ustekinumab-related liver injury is uncommon and mild. From a hepatic point of view, the drug appears safe, even in patients with pre-existing liver disease and those who have developed altered liver function previously with other drugs.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con psoriasis y hepatopatías son un reto terapéutico dado el mayor riesgo de efectos adversos que presentan con el tratamiento sistémico clásico y a que, aunque los fármacos anti-TNF-α son considerados más seguros, también se han descrito reactivaciones de hepatitis vírica y hepatitis tóxica en relación con los mismos. El ustekinumab (UTK) tiene un mecanismo de acción diferente y se sabe poco de sus efectos en el hígado, sobre todo a partir de los estudios pivotales. Nuestro objetivo ha sido estimar la incidencia de toxicidad hepática en los pacientes tratados con UTK en la práctica clínica habitual, y examinar los cambios hepáticos en aquellos pacientes tratados que tenían hepatopatía de base.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Método</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron todos los pacientes tratados con UTK según pauta habitual. Se analizaron la edad, el género, el tipo de psoriasis, la afectación ungueal, la artritis, los tratamientos previos, la hepatopatía previa, las serologías virales y el PASI (basal y a las 12, 16 y 52 semanas). Se analizaron también las transaminasas, los signos y síntomas de hepatopatía y los factores como el índice de masa corporal, el hábito enólico, la ferritina y la ecografía hepática.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se observaron hipertransaminasemias de grado 1 en solo 6 pacientes. Ninguno presentó hipertransaminasemias graves. Ninguno de los pacientes con hipertransaminasemia basal tuvo problemas durante el tratamiento.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La hepatotoxicidad asociada a UTK es poco frecuente y grave, y parece seguro a nivel hepático, incluso en pacientes con hepatopatía basal o que habían presentado con anterioridad alteraciones hepáticas con otros fármacos.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as: Llamas-Velasco M, Concha-Garzón MJ, García-Diez A, Daudén E. Análisis de la hepatotoxicidad en psoriasis tratada con ustekinumab. Estudio retrospectivo de 44 pacientes en práctica clínica habitual. Actas Dermosifiliogr. 2015;106:470–476.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; PASI, Psoriasis Area Severity Index; PUVA, psoralen-UV-A.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Result (N<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>44) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age, y, mean (SD) [range], sex (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47.76 (17.99) [18-87], men 59.1%, women 40.9% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Duration of psoriasis, y, mean (SD) [range] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25.58 (15.94) [4-74] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Type of psoriasis, %</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Plaque \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">84.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Guttate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Erythrodermic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Total psoriatic arthropathy, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Axial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Peripheral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">57.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Axial and peripheral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Baseline PASI, mean (SD) [range] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23.4 (14.09) [2.4-56.8] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">PASI 12 weeks median (SD) [range] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.5 (6.1) [0-35] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">PASI 16 weeks median (SD) [range] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.22 (2.4) [0-22.5] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Weight, kg, mean (SD) [range] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">75.3 (13.82) [47-100] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Body mass index, mean (SD) [range] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26.62 (4.43) [18.12-37] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Diabetes mellitus, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hypertension, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Dyslipidemia, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Previous treatment, drug name (total number of patients) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Methotrexate (22) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ciclosporin (22) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Etanercept (18) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PUVA (14) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Acitretin (14) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Adalimumab (14) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Infliximab (9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Efalizumab (8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Etretinate (5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Onercept (1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hydroxyurea (1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Previous hepatitis B, No. (%)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 (9.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Alcohol consumption, g/d Mean (SD) [range] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.4 (19.72) [0-82] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Baseline liver enzymes (U/L), mean (SD)</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>AST \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.9 (8.99) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ALT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22.8 (16.22) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Liver ultrasound, %<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fatty liver \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fibrosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cirrhosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab849456.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Previous hepatitis B, HbsAg (neg), antiHBc antibodies</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Baseline liver ultrasound in 18 patients.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Baseline Data of a Cohort of 44 Patients Treated With Ustekinumab.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: AC, acitretin; ADA, adalimumab; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; Csa, ciclosporin; DM, diabetes mellitus; EF, efalizumab; ET, etretinate; ETN, etanercept; FL, fatty liver; HT, hypertension; HU, hydroxyurea; IFX, infliximab; MTX, methotrexate; N, normal, no abnormalities; NBUVB, narrowband UV-B therapy; ND, not done; ON, onercept; PUVA, psoralen-UV-A.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="11" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age/sex \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PASIBaseline \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Previous Treatment for Psoriasis in Order of Use \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Past History of HepatotoxicityGrade (Drug) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">BMI/Alcohol Consumption, g/d \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Liver Ultrasound, % \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Increase in Transaminase Levels \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Maximum AST/ALT Value<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Concomitant Hepatotoxic Liver Drug \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HTA/DM/DL \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Follow-up, Mo \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top">Baseline Liver Disease</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>45M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Grade 1 (unknown) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31/12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In >2 tests \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">101/74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No/Yes/No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.97 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>43M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MTX, Csa, NBUVB, HU, AC, ADA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Grade 1 (ADA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In >2 tests \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30/66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No/No/No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top">Liver Disease During Treatment With Ustekinumab</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>57M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ET, PUVA, Csa, MTX, ETN, IFX, EF, ADA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In a single test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">71/44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Simvastatin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No/No/Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36.57 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>30M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ETN, UV-A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Grade 1 (unknown) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In a single test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">111/58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No/No/No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28.07 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>51M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PUVA, Csa, AC, ETN<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>MTX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Grade 1 (ETN) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In a single test \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40/60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Candesartan \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/Yes/No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>51M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MTX, Csa, AC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Grade 1 (isoniazid) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND/12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In >2 tests \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18/45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Isoniazid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/No/Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15.50 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>38M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PUVA, Csa, NT, IFX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Grade 1 (isoniazid) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">33/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In >2 tests \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">67/39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No/No/Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.33 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>41W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Csa, EF, ON, IFX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Grade 1 (Csa, IFX, ETN) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">In >2 tests \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23/41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No/No/Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.90 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab849455.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Reference values: AST, 7-35<span class="elsevierStyleHsp" style=""></span>U/L; ALT, 8-40<span class="elsevierStyleHsp" style=""></span>U/L.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Relevant Demographic Data and Data on Previous Liver Toxicity, BMI, and Other Comorbidities. Maximum Transaminase Values in Patients Treated With Ustekinumab Who Presented Liver Disease at Baseline or Who Developed Liver Disease During Treatment.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:45 [ 0 => array:3 [ "identificador" => "bib0230" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Afectación hepática y terapia biológica en el tratamiento de la psoriasis. Consideraciones prácticas" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Llamas-Velasco" 1 => "R. Navarro" 2 => "M. Concha Garzón" 3 => "E. Daudén-Tello" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Piel" "fecha" => "2011" "volumen" => "26" "paginaInicial" => "80" "paginaFinal" => "85" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0235" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Psoriasis and hepatitis C treated with anti-TNF alpha therapy (etanercept)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R. Cecchi" 1 => "L. Bartoli" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Dermatol Online J" "fecha" => "2006" "volumen" => "12" "paginaInicial" => "4" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17459290" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0240" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A series of critically challenging case scenarios in moderate to severe psoriasis: A Delphi consensus approach" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Strober" 1 => "E. Berger" 2 => "J. Cather" 3 => "D. Cohen" 4 => "J.J. Crowley" 5 => "K.B. Gordon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2009.03.017" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2009" "volumen" => "61" "paginaInicial" => "S1" "paginaFinal" => "S46" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19527820" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0245" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Etanercept treatment for three months is safe in patients with rheumatological manifestations associated with hepatitis C virus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H. Marotte" 1 => "E. Fontanges" 2 => "F. Bailly" 3 => "F. Zoulim" 4 => "C. Trepo" 5 => "P. Miossec" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rheumatology (Oxford)" "fecha" => "2007" "volumen" => "46" "paginaInicial" => "97" "paginaFinal" => "99" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0250" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Etanercept monotherapy for a patient with psoriasis, psoriatic arthritis, and concomitant hepatitis C infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. Rokhsar" 1 => "N. Rabhan" 2 => "S.R. Cohen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2005.05.043" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2006" "volumen" => "54" "paginaInicial" => "361" "paginaFinal" => "362" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16443079" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0255" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Occult hepatitis B and infliximab-induced HBV reactivation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Madonia" 1 => "A. Orlando" 2 => "D. Scimeca" 3 => "M. Olivo" 4 => "F. Rossi" 5 => "M. Cottone" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ibd.20035" "Revista" => array:6 [ "tituloSerie" => "Inflamm Bowel Dis" "fecha" => "2007" "volumen" => "13" "paginaInicial" => "508" "paginaFinal" => "509" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17206687" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0260" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B virus reactivation during therapy with etanercept in an HBsAg-negative and anti-HBs-positive patient" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P.M. Montiel" 1 => "J.A. Solis" 2 => "J.A. Chirinos" 3 => "B. Casis" 4 => "F. Sanchez" 5 => "S. Rodriguez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1478-3231.2007.01665.x" "Revista" => array:6 [ "tituloSerie" => "Liver Int" "fecha" => "2008" "volumen" => "28" "paginaInicial" => "718" "paginaFinal" => "720" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18433400" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0265" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adalimumab-induced lethal hepatitis B virus reactivation in an HBsAg-negative patient with clinically resolved hepatitis B virus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "T. Matsumoto" 1 => "H. Marusawa" 2 => "M. Dogaki" 3 => "Y. Suginoshita" 4 => "T. Inokuma" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1478-3231.2010.02238.x" "Revista" => array:6 [ "tituloSerie" => "Liver Int" "fecha" => "2010" "volumen" => "30" "paginaInicial" => "1241" "paginaFinal" => "1242" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20345703" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0270" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Awareness about possible reactivation of HBsAg-negative patients when prescribing biological therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R. Navarro" 1 => "S. Ibanes" 2 => "M. Llamas" 3 => "E. Sotomayor" 4 => "E. Garcia-Martin" 5 => "E. Dauden" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1468-3083.2010.03833.x" "Revista" => array:6 [ "tituloSerie" => "J Eur Acad Dermatol Venereol" "fecha" => "2011" "volumen" => "25" "paginaInicial" => "1232" "paginaFinal" => "1233" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20726937" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0275" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.L. Leonardi" 1 => "A.B. Kimball" 2 => "K.A. Papp" 3 => "N. Yeilding" 4 => "C. Guzzo" 5 => "Y. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(08)60725-4" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2008" "volumen" => "371" "paginaInicial" => "1665" "paginaFinal" => "1674" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18486739" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0280" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.A. Papp" 1 => "R.G. Langley" 2 => "M. Lebwohl" 3 => "G.G. Krueger" 4 => "P. Szapary" 5 => "N. Yeilding" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(08)60726-6" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2008" "volumen" => "371" "paginaInicial" => "1675" "paginaFinal" => "1684" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18486740" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0285" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.E. Griffiths" 1 => "B.E. Strober" 2 => "P. van de Kerkhof" 3 => "V. Ho" 4 => "R. Fidelus-Gort" 5 => "N. Yeilding" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0810652" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2010" "volumen" => "362" "paginaInicial" => "118" "paginaFinal" => "128" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20071701" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0290" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ustekinumab in clinical practice: Response depends on dose and previous treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "V. Ruiz Salas" 1 => "L. Puig" 2 => "A. Alomar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1468-3083.2011.04325.x" "Revista" => array:6 [ "tituloSerie" => "J Eur Acad Dermatol Venereol" "fecha" => "2012" "volumen" => "26" "paginaInicial" => "508" "paginaFinal" => "513" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22077903" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0295" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Practical experience of ustekinumab in the treatment of psoriasis: Experience from a multicentre, retrospective case cohort study across the U.K. and Ireland" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.M. Laws" 1 => "A.M. Downs" 2 => "R. Parslew" 3 => "B. Dever" 4 => "C.H. Smith" 5 => "J.N. Barker" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2133.2011.10638.x" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2012" "volumen" => "166" "paginaInicial" => "189" "paginaFinal" => "195" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21929536" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0300" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety and effectiveness of ustekinumab for treatment of moderate to severe psoriasis: A prospective study in a clinical setting" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Molina-Leyva" 1 => "H. Husein-Elahmed" 2 => "R. Naranjo-Sintes" 3 => "J.C. Ruiz-Carrascosa" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Drugs Dermatol" "fecha" => "2014" "volumen" => "13" "paginaInicial" => "971" "paginaFinal" => "974" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25116977" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0305" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ustekinumab treatment for psoriasis in 119 patients maintained on therapy for a minimum of one year: A review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E.G. Wilder" 1 => "M. Patel" 2 => "K. Hebeler" 3 => "A. Menter" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Drugs Dermatol" "fecha" => "2014" "volumen" => "13" "paginaInicial" => "905" "paginaFinal" => "910" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25116966" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0310" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Liver enzyme alteration: A guide for clinicians" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E.G. Giannini" 1 => "R. Testa" 2 => "V. Savarino" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1503/cmaj.1040752" "Revista" => array:6 [ "tituloSerie" => "CMAJ" "fecha" => "2005" "volumen" => "172" "paginaInicial" => "367" "paginaFinal" => "379" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15684121" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0315" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interleukin-12 induction of Th1 cytokines is important for viral clearance in chronic hepatitis B" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Rossol" 1 => "G. Marinos" 2 => "P. Carucci" 3 => "M.V. Singer" 4 => "R. Williams" 5 => "N.V. Naoumov" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI119498" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "1997" "volumen" => "99" "paginaInicial" => "3025" "paginaFinal" => "3033" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9185527" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0320" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increase of plasma IL-12/p40 ratio induced by the combined therapy of DNA vaccine and lamivudine correlates with sustained viremia control in CHB carriers" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S.J. Im" 1 => "S.H. Yang" 2 => "S.K. Yoon" 3 => "Y.C. Sung" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4110/in.2009.9.1.20" "Revista" => array:6 [ "tituloSerie" => "Immune Netw" "fecha" => "2009" "volumen" => "9" "paginaInicial" => "20" "paginaFinal" => "26" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20107534" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0325" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Activated IL-23/IL-17 pathway closely correlates with increased Foxp3 expression in livers of chronic hepatitis B patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Q. Wang" 1 => "Y. Zheng" 2 => "Z. Huang" 3 => "Y. Tian" 4 => "J. Zhou" 5 => "Q. Mao" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2172-12-25" "Revista" => array:5 [ "tituloSerie" => "BMC Immunol" "fecha" => "2011" "volumen" => "12" "paginaInicial" => "25" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21489307" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0330" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The ratio of Th-17 to Treg cells is associated with survival of patients with acute-on-chronic hepatitis B liver failure" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Zhai" 1 => "L. Zhang" 2 => "S. Dang" 3 => "Y. Yu" 4 => "Z. Zhao" 5 => "W. Zhao" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/vim.2010.0135" "Revista" => array:6 [ "tituloSerie" => "Viral Immunol" "fecha" => "2011" "volumen" => "24" "paginaInicial" => "303" "paginaFinal" => "310" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21721931" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0335" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interleukin-12 p40/p70 ratio and in vivo responsiveness to IFN-alpha treatment in chronic hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G. Piazzolla" 1 => "C. Tortorella" 2 => "G. Fiore" 3 => "M. Fanelli" 4 => "M. Pisconti" 5 => "S. Antonaci" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/10799900152434303" "Revista" => array:6 [ "tituloSerie" => "J Interferon Cytokine Res" "fecha" => "2001" "volumen" => "21" "paginaInicial" => "453" "paginaFinal" => "461" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11506737" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0340" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cytokine levels in serum of patients with chronic hepatitis C and its significance" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "L. Zhang" 1 => "L. Miao" 2 => "F. Han" 3 => "X.G. Dou" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi" "fecha" => "2011" "volumen" => "27" "paginaInicial" => "301" "paginaFinal" => "303" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21419051" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0345" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association of interleukin-12 p40 gene 3’-untranslated region polymorphism and outcome of HCV infection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.M. Yin" 1 => "W.F. Zhu" 2 => "L. Wei" 3 => "X.Y. Xu" 4 => "D.G. Sun" 5 => "Y.B. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "World J Gastroenterol" "fecha" => "2004" "volumen" => "10" "paginaInicial" => "2330" "paginaFinal" => "2333" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15285014" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0350" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and chronic viral hepatitis B or C: A retrospective, multicentre study in a clinical setting" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Navarro" 1 => "E. Vilarrasa" 2 => "P. Herranz" 3 => "L. Puig" 4 => "X. Bordas" 5 => "J.M. Carrascosa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bjd.12045" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2013" "volumen" => "168" "paginaInicial" => "609" "paginaFinal" => "616" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22985451" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0355" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis B virus reactivation during therapy with ustekinumab for psoriasis in a hepatitis B surface-antigen-negative anti-HBs-positive patient" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Koskinas" 1 => "M. Tampaki" 2 => "P.P. Doumba" 3 => "E. Rallis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bjd.12120" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2013" "volumen" => "168" "paginaInicial" => "679" "paginaFinal" => "680" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23121260" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0360" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The safety profile of ustekinumab in the treatment of patients with psoriasis and concurrent hepatitis B or C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "H.Y. Chiu" 1 => "C.H. Chen" 2 => "M.S. Wu" 3 => "Y.P. Cheng" 4 => "T.F. Tsai" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bjd.12461" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2013" "volumen" => "169" "paginaInicial" => "1295" "paginaFinal" => "1303" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23746170" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0365" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Tang" 1 => "Z. Bian" 2 => "L. Zhao" 3 => "Y. Liu" 4 => "S. Liang" 5 => "Q. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2249.2011.04471.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Immunol" "fecha" => "2011" "volumen" => "166" "paginaInicial" => "281" "paginaFinal" => "290" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21985374" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0370" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Deletion of interleukin-12p40 suppresses autoimmune cholangitis in dominant negative transforming growth factor beta receptor type II mice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Yoshida" 1 => "G.X. Yang" 2 => "W. Zhang" 3 => "M. Tsuda" 4 => "K. Tsuneyama" 5 => "Y. Moritoki" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.23132" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2009" "volumen" => "50" "paginaInicial" => "1494" "paginaFinal" => "1500" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19676134" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0375" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Th17 promotes acute rejection following liver transplantation in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "X.J. Xie" 1 => "Y.F. Ye" 2 => "L. Zhou" 3 => "H.Y. Xie" 4 => "G.P. Jiang" 5 => "X.W. Feng" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1631/jzus.B1000030" "Revista" => array:6 [ "tituloSerie" => "J Zhejiang Univ Sci B" "fecha" => "2010" "volumen" => "11" "paginaInicial" => "819" "paginaFinal" => "827" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21043049" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0380" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Integrated approach to comorbidity in patients with psoriasis" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "Working group on psoriasis-associated comorbidities" "etal" => true "autores" => array:6 [ 0 => "E. Dauden" 1 => "S. Castaneda" 2 => "C. Suarez" 3 => "J. Garcia-Campayo" 4 => "A.J. Blasco" 5 => "M.D. Aguilar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0001-7310(12)70001-7" "Revista" => array:7 [ "tituloSerie" => "Actas Dermosifiliogr" "fecha" => "2012" "volumen" => "103" "numero" => "Suppl 1" "paginaInicial" => "1" "paginaFinal" => "64" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22364603" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0385" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical practice guideline for an integrated approach to comorbidity in patients with psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Dauden" 1 => "S. Castaneda" 2 => "C. Suarez" 3 => "J. Garcia-Campayo" 4 => "A.J. Blasco" 5 => "M.D. Aguilar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jdv.12024" "Revista" => array:6 [ "tituloSerie" => "J Eur Acad Dermatol Venereol" "fecha" => "2013" "volumen" => "27" "paginaInicial" => "1387" "paginaFinal" => "1404" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23134338" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0390" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comorbidities in psoriasis patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "N. Kim" 1 => "B. Thrash" 2 => "A. Menter" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Semin Cutans Med Surg" "fecha" => "2010" "volumen" => "29" "paginaInicial" => "10" "paginaFinal" => "15" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0395" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Excess mortality related to alcohol and smoking among hospital-treated patients with psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K. Poikolainen" 1 => "J. Karvonen" 2 => "E. Pukkala" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol" "fecha" => "1999" "volumen" => "135" "paginaInicial" => "1490" "paginaFinal" => "1493" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10606054" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0400" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alcohol and skin disorders: with a focus on psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. Kazakevich" 1 => "M.N. Moody" 2 => "J.M. Landau" 3 => "L.H. Goldberg" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Skin therapy Lett" "fecha" => "2011" "volumen" => "16" "paginaInicial" => "5" "paginaFinal" => "6" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21833462" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0405" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alcohol intake and risk of incident psoriasis in US women: A prospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.A. Qureshi" 1 => "P.L. Dominguez" 2 => "H.K. Choi" 3 => "J. Han" 4 => "G. Curhan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archdermatol.2010.204" "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol" "fecha" => "2010" "volumen" => "146" "paginaInicial" => "1364" "paginaFinal" => "1369" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20713772" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0410" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalencia de sobrepeso y obesidad en adultos españoles" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E. Rodríguez-Rodríguez" 1 => "A. López-Plata" 2 => "R. López-Sobaler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1590/S0212-16112011000200017" "Revista" => array:6 [ "tituloSerie" => "Nutr Hosp" "fecha" => "2011" "volumen" => "26" "paginaInicial" => "355" "paginaFinal" => "363" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21666974" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0415" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non-alcoholic fatty liver disease in patients with chronic plaque psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P. Gisondi" 1 => "G. Targher" 2 => "G. Zoppini" 3 => "G. Girolomoni" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2009.04.020" "Revista" => array:6 [ "tituloSerie" => "J Hepatol" "fecha" => "2009" "volumen" => "51" "paginaInicial" => "758" "paginaFinal" => "764" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19560226" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0420" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non-alcoholic fatty liver disease, alcohol intake and psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Bordignon" 1 => "G. Viel" 2 => "A. Peserico" 3 => "M. Alaibac" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jhep.2010.04.012" "Revista" => array:5 [ "tituloSerie" => "J Hepatol" "fecha" => "2010" "volumen" => "53" "paginaInicial" => "587" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20561701" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0425" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Infliximab single administration followed by acute liver injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "E. Ierardi" 1 => "N. Della Valle" 2 => "M.C. Nacchiero" 3 => "V. De Francesco" 4 => "G. Stoppino" 5 => "C. Panella" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.mib.0000246783.75753.9f" "Revista" => array:6 [ "tituloSerie" => "Inflamm Bowel Dis" "fecha" => "2006" "volumen" => "12" "paginaInicial" => "1089" "paginaFinal" => "1091" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17075352" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0430" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Occurrence of hepatoxicicty and elevated liver enzymes in a Crohn's disease patient treated with infliximab" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "B. Moum" 1 => "Z. Konopski" 2 => "K.F. Tufteland" 3 => "J. Jahnsen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ibd.20230" "Revista" => array:6 [ "tituloSerie" => "Inflamm Bowel Dis" "fecha" => "2007" "volumen" => "13" "paginaInicial" => "1584" "paginaFinal" => "1586" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17663423" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0435" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome concomitant with systemic sclerosis, immune thrombocytopenic purpura" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Toyoda" 1 => "H. Yokomori" 2 => "F. Kaneko" 3 => "H. Yoshida" 4 => "K. Hoshi" 5 => "H. Takeuchi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Intern Med" "fecha" => "2009" "volumen" => "48" "paginaInicial" => "2019" "paginaFinal" => "2023" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19952485" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0440" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment with etanercept in a patient with hepatotoxicity closely related to infliximab" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.M. Garcia Aparicio" 1 => "J.R. Rey" 2 => "A.H. Sanz" 3 => "J.S. Alvarez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-006-0253-y" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2007" "volumen" => "26" "paginaInicial" => "811" "paginaFinal" => "813" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16550301" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0445" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficiency and safety of etanercept after acute hepatitis induced by infliximab for psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. Kluger" 1 => "C. Girard" 2 => "B. Guillot" 3 => "D. Bessis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2340/00015555-0619" "Revista" => array:6 [ "tituloSerie" => "Acta Derm Venereol" "fecha" => "2009" "volumen" => "89" "paginaInicial" => "332" "paginaFinal" => "334" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19479148" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0450" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis: A rare, but important, complication of infliximab therapy for psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Wahie" 1 => "A. Alexandroff" 2 => "N.J. Reynolds" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2230.2006.02086.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Dermatol" "fecha" => "2006" "volumen" => "31" "paginaInicial" => "460" "paginaFinal" => "461" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16681606" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010600000006/v1_201506260207/S1578219015001523/v1_201506260207/en/main.assets" "Apartado" => array:4 [ "identificador" => "6155" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010600000006/v1_201506260207/S1578219015001523/v1_201506260207/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219015001523?idApp=UINPBA000044" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 8 | 4 | 12 |
| 2024 Octubre | 117 | 59 | 176 |
| 2024 Septiembre | 105 | 86 | 191 |
| 2024 Agosto | 121 | 85 | 206 |
| 2024 Julio | 115 | 37 | 152 |
| 2024 Junio | 124 | 56 | 180 |
| 2024 Mayo | 98 | 48 | 146 |
| 2024 Abril | 91 | 29 | 120 |
| 2024 Marzo | 107 | 45 | 152 |
| 2024 Febrero | 93 | 35 | 128 |
| 2024 Enero | 93 | 43 | 136 |
| 2023 Diciembre | 98 | 25 | 123 |
| 2023 Noviembre | 91 | 37 | 128 |
| 2023 Octubre | 81 | 41 | 122 |
| 2023 Septiembre | 96 | 51 | 147 |
| 2023 Agosto | 81 | 28 | 109 |
| 2023 Julio | 106 | 62 | 168 |
| 2023 Junio | 88 | 50 | 138 |
| 2023 Mayo | 83 | 62 | 145 |
| 2023 Abril | 64 | 40 | 104 |
| 2023 Marzo | 90 | 49 | 139 |
| 2023 Febrero | 57 | 34 | 91 |
| 2023 Enero | 67 | 42 | 109 |
| 2022 Diciembre | 79 | 55 | 134 |
| 2022 Noviembre | 41 | 41 | 82 |
| 2022 Octubre | 37 | 24 | 61 |
| 2022 Septiembre | 31 | 41 | 72 |
| 2022 Agosto | 24 | 18 | 42 |
| 2022 Julio | 23 | 33 | 56 |
| 2022 Junio | 22 | 30 | 52 |
| 2022 Mayo | 56 | 72 | 128 |
| 2022 Abril | 70 | 61 | 131 |
| 2022 Marzo | 56 | 60 | 116 |
| 2022 Febrero | 61 | 42 | 103 |
| 2022 Enero | 85 | 40 | 125 |
| 2021 Diciembre | 36 | 53 | 89 |
| 2021 Noviembre | 55 | 46 | 101 |
| 2021 Octubre | 68 | 63 | 131 |
| 2021 Septiembre | 46 | 34 | 80 |
| 2021 Agosto | 97 | 29 | 126 |
| 2021 Julio | 55 | 28 | 83 |
| 2021 Junio | 74 | 22 | 96 |
| 2021 Mayo | 50 | 24 | 74 |
| 2021 Abril | 100 | 50 | 150 |
| 2021 Marzo | 93 | 24 | 117 |
| 2021 Febrero | 70 | 37 | 107 |
| 2021 Enero | 60 | 20 | 80 |
| 2020 Diciembre | 60 | 26 | 86 |
| 2020 Noviembre | 39 | 25 | 64 |
| 2020 Octubre | 41 | 19 | 60 |
| 2020 Septiembre | 34 | 17 | 51 |
| 2020 Agosto | 35 | 19 | 54 |
| 2020 Julio | 31 | 23 | 54 |
| 2020 Junio | 35 | 37 | 72 |
| 2020 Mayo | 31 | 31 | 62 |
| 2020 Abril | 40 | 26 | 66 |
| 2020 Marzo | 64 | 21 | 85 |
| 2020 Febrero | 4 | 3 | 7 |
| 2019 Diciembre | 4 | 4 | 8 |
| 2019 Noviembre | 0 | 2 | 2 |
| 2019 Octubre | 0 | 11 | 11 |
| 2019 Septiembre | 6 | 2 | 8 |
| 2019 Agosto | 0 | 1 | 1 |
| 2019 Julio | 0 | 22 | 22 |
| 2019 Junio | 0 | 33 | 33 |
| 2019 Mayo | 2 | 88 | 90 |
| 2019 Abril | 0 | 61 | 61 |
| 2019 Marzo | 0 | 14 | 14 |
| 2019 Febrero | 2 | 15 | 17 |
| 2019 Enero | 0 | 8 | 8 |
| 2018 Diciembre | 1 | 1 | 2 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 2 | 0 | 2 |
| 2018 Septiembre | 8 | 14 | 22 |
| 2018 Agosto | 0 | 21 | 21 |
| 2018 Julio | 0 | 20 | 20 |
| 2018 Junio | 0 | 14 | 14 |
| 2018 Mayo | 0 | 14 | 14 |
| 2018 Abril | 0 | 21 | 21 |
| 2018 Marzo | 0 | 24 | 24 |
| 2018 Febrero | 38 | 58 | 96 |
| 2018 Enero | 34 | 243 | 277 |
| 2017 Diciembre | 39 | 57 | 96 |
| 2017 Noviembre | 45 | 49 | 94 |
| 2017 Octubre | 28 | 38 | 66 |
| 2017 Septiembre | 36 | 38 | 74 |
| 2017 Agosto | 34 | 40 | 74 |
| 2017 Julio | 30 | 42 | 72 |
| 2017 Junio | 27 | 50 | 77 |
| 2017 Mayo | 27 | 57 | 84 |
| 2017 Abril | 46 | 35 | 81 |
| 2017 Marzo | 14 | 60 | 74 |
| 2017 Febrero | 22 | 62 | 84 |
| 2017 Enero | 29 | 28 | 57 |
| 2016 Diciembre | 32 | 22 | 54 |
| 2016 Noviembre | 42 | 11 | 53 |
| 2016 Octubre | 29 | 41 | 70 |
| 2016 Septiembre | 0 | 31 | 31 |
| 2016 Agosto | 0 | 32 | 32 |
| 2016 Julio | 4 | 19 | 23 |
| 2016 Junio | 5 | 4 | 9 |
| 2016 Mayo | 3 | 15 | 18 |
| 2016 Abril | 1 | 5 | 6 |
| 2016 Marzo | 1 | 15 | 16 |
| 2016 Febrero | 13 | 37 | 50 |
| 2016 Enero | 1 | 5 | 6 |
| 2015 Diciembre | 0 | 7 | 7 |
| 2015 Noviembre | 0 | 23 | 23 |
| 2015 Octubre | 0 | 7 | 7 |
| 2015 Septiembre | 0 | 19 | 19 |
| 2015 Agosto | 0 | 24 | 24 |
| 2015 Julio | 3 | 6 | 9 |
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