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In this review&#44; we will refer to this disease using the new term agreed on by the Spanish Association for the Study of the Liver &#40;AEEH&#41; following a Delphi process&#58; <span class="elsevierStyleItalic">metabolic-associated fatty liver disease</span>&#44; or MAFLD&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">4</span></a> MAFLD comprises a spectrum of hepatic lesions ranging from fat accumulation in the liver&#44; which is a metabolic disorder considered to have a low risk of progression&#44; to steatohepatitis&#44; an inflammatory disorder that can progress to cirrhosis and its complications&#46; MAFLD is generally asymptomatic and occurs in association with metabolic syndrome &#40;MetS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">5</span></a> It is in fact recognized as the hepatic manifestation of this syndrome and can precede other manifestations&#46;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">6&#44;7</span></a> MetS is a group of metabolic disorders among which hepatic disorders are considered particularly significant&#46;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">6&#44;7</span></a> MALFD has a wide clinical spectrum &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; with a dynamic course characterized by periods of progression&#44; regression&#44; and stability&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">8&#44;9</span></a> This variability can in part be explained by genetics and lifestyle changes&#44; but factors such as age&#44; sex&#44; race&#44; alcohol consumption&#44; and gut microbiota also influence clinical presentation and responses to treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The prevalence of MALFD is rising progressively&#44; in line with that of MetS&#44; obesity&#44; and type 2 diabetes&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">8&#44;10</span></a> MALFD is estimated to affect 25&#37; of the population and 55&#46;5&#37; of people with type 2 diabetes&#46; Although the percentage of patients with MALFD who develop nonalcoholic steatohepatitis &#40;NASH&#41; is unknown&#44; it is in excess of 10&#37;&#46; The prevalence of biopsy-proven NASH in patients with MAFLD appears to have increased in recent years from 29&#46;9&#37; to 59&#46;1&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">NASH progresses to fibrosis in 40&#46;76&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">8</span></a> The estimated prevalence of MAFLD in Spain is 25&#46;8&#37;&#44; while that of significant fibrosis estimated by sequential combination of transition elastography &#40;TE&#41; and liver biopsy is 2&#46;8&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Prognosis in MALFD is influenced by progression to NASH&#44; fibrosis&#44; and comorbidities&#46; Advanced fibrosis increases the risk of liver-related morbidity and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">10&#44;11</span></a> MALFD thus constitutes a significant health problem and a major reason for liver transplantation&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">9&#44;12</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The evidence supporting the relationship between psoriasis and MAFLD is substantial&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">15</span></a> In general&#44; MAFLD is more common in patients with more severe psoriasis&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">16&#44;17</span></a> Phan et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">15</span></a> corroborating previous findings&#44;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">18</span></a> showed that patients with psoriasis were twice as likely to have MAFLD as those without psoriasis&#46; In Spain&#44; the percentage of patients with psoriasis and MAFLD is 42&#46;3&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">19</span></a> A direct correlation has also been observed between psoriasis severity and liver disease severity&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">20</span></a> One cross-sectional study found that advanced fibrosis was more common in patients with psoriasis than in healthy controls&#44; and that psoriasis was a significant predictor of advanced liver fibrosis independently of age&#44; sex&#44; body mass index&#44; hypertension&#44; and diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">21</span></a> Psoriasis is currently recognized as an independent risk factor for MAFLD&#46;<a class="elsevierStyleCrossRefs" href="#bib0580"><span class="elsevierStyleSup">22&#44;23</span></a> Likewise&#44; hypertension&#44; hyperglycemia&#44; and obesity are the main risk factors for MAFLD in patients with psoriasis&#46; The association between psoriasis and MAFLD is independent of confounders&#44; confirming a shared pathophysiology involving inflammatory pathways and genetic predisposition&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">15</span></a> Psoriasis and MAFLD have a common etiology of low-intensity chronic inflammation involving adipokines that participate in energy balance and inflammatory cytokines &#40;interleukin &#91;IL&#93; 17&#44; tumor necrosis factor-&#945;&#44; and IL-6&#93;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0485"><span class="elsevierStyleSup">3&#44;24&#44;25</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The above findings suggest that early screening for MAFLD is necessary in patients with psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">26</span></a> The AEEH recently published a consensus statement on the detection of prevalent occult liver diseases and referral criteria&#46; Among its conclusions with clinical implications were <span class="elsevierStyleItalic">1</span>&#41; chronic liver disease should be screened for and monitored in patients with immune-mediated skin disorders and <span class="elsevierStyleItalic">2</span>&#41; chronic liver disease is more common in this setting due to immunological and inflammatory mechanisms and hepatotoxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">26</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">To encourage multidisciplinary management and update current recommendations on screening&#44; diagnosis&#44; monitoring&#44; and referral for MAFLD in patients with psoriasis&#44; we formed an expert panel to design a set of consensus-based recommendations based on current evidence and real-world experience&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Methodology</span><p id="par0045" class="elsevierStylePara elsevierViewall">A working group of 12 experts with experience in the management of psoriasis and MAFLD&#8212;7 dermatologists and 5 hepatologists&#8212;was formed to prepare this document&#46; The methodology was based on the so-called <span class="elsevierStyleItalic">formal method</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0605"><span class="elsevierStyleSup">27&#44;28</span></a> The group began by reviewing the current evidence and completing several purpose-designed questionnaires on psoriasis and risk of liver disease to identify key points related to detection&#44; screening&#44; diagnosis&#44; and management&#46; Over the course of 3 meetings&#44; the group analyzed clinical aspects related to the definition and management of at-risk patients&#46; At a final meeting&#44; they agreed on an algorithm for managing these patients&#44; which included practical diagnostic and monitoring recommendations based on the main clinical practice guidelines &#40;CPGs&#41; and the clinical experience of the members of the panel&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Identifying Risk Factors for Liver Disease in Patients With Psoriasis</span><p id="par0050" class="elsevierStylePara elsevierViewall">The expert panel recommends screening for liver disease in patients with psoriasis according to current Spanish CPGs&#44;<a class="elsevierStyleCrossRefs" href="#bib0615"><span class="elsevierStyleSup">29&#44;30</span></a> regardless of treatment or time since diagnosis&#44; if at least 1 of the criteria accompanying steatosis in a diagnosis of MAFLD is present<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">31</span></a>&#58; overweight or obesity&#44; T2D&#44; and&#47;or evidence of metabolic dysregulation&#46; These criteria are as follows&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Waist circumference<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>102<span class="elsevierStyleHsp" style=""></span>cm in men and &#8805;<span class="elsevierStyleHsp" style=""></span>88<span class="elsevierStyleHsp" style=""></span>cm in women</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Blood pressure<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>130&#47;85<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>Hg or specific drug treatment</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Plasma triglycerides<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>150<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>1&#46;70<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41; or specific drug treatment</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Plasma HDL cholesterol<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;&#60;<span class="elsevierStyleHsp" style=""></span>1&#46;0<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41; for men and &#60;<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;&#60;<span class="elsevierStyleHsp" style=""></span>1&#46;3<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41; for women&#44; or specific drug treatment</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Prediabetes &#40;fasting glucose levels 100&#8211;125<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#91;5&#46;6&#8211;6&#46;9<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#93; or 2-h postload glucose levels 140&#8211;199<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#91;7&#46;8&#8211;11&#46;0<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#93; or HbA1c 5&#46;7&#37;&#8211;6&#46;4&#37; &#91;39&#8211;47<span class="elsevierStyleHsp" style=""></span>mmol&#47;mol&#93;&#41;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0080" class="elsevierStylePara elsevierViewall">HOMA-IR &#40;homeostatic model of assessment for insulin resistance&#41; score<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2&#46;5</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Plasma high-sensitivity C-reactive protein level<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mg&#47;L</p></li></ul></p><p id="par0090" class="elsevierStylePara elsevierViewall">Patients with psoriasis and at least 1 risk factor for MetS should be screened for the risk or presence of liver disease&#46; As MAFLD is a silent disease&#44; national and international CPGs recommend using noninvasive methods such as the Fibrosis-4 Index for Liver Fibrosis &#40;FIB-4&#41; for the early detection of risk factors for the different stages of MALFD &#40;from steatosis to advanced stages such as fibrosis&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">10&#44;30&#44;31</span></a> Transaminases should not be explored in isolation for the early diagnosis of MAFLD&#44; as levels can be normal&#44; even in patients with advanced fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">32</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Screening Recommendations for MetS</span><p id="par0095" class="elsevierStylePara elsevierViewall">Once an at-risk patient is identified&#44; the first step in the proposed screening and follow-up algorithm &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; should be applied&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Consensus is lacking on which noninvasive diagnostic tools&#44; or cutoffs &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; should be used instead of liver biopsy to screen for MAFLD&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">10&#44;22&#44;31</span></a> Liver biopsy is the current gold standard&#44;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">33</span></a> but it is not without complications&#46; The CPGs recommend combining serum-based testing and TE&#44; as this reduces the need for biopsy by approximately 50&#37; to 60&#37; and secures an accurate diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">34</span></a> Serum-based fibrosis tests are the first-choice option for screening purposes&#44; with TE to be used in patients considered at high risk&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> lists a number of noninvasive liver fibrosis screening tests&#46; The expert panel considers FIB-4 to be most suitable test for initial screening in dermatology units&#58; it has been externally validated for fibrosis screening in patients with fatty liver disease&#44; is readily available and easy to process&#44; and is recommended by CPGs&#46;<a class="elsevierStyleCrossRefs" href="#bib0520"><span class="elsevierStyleSup">10&#44;22&#44;31</span></a> FIB-4 takes account of platelet count&#44; age&#44; and aspartate aminotransferase and alanine aminotransferase values&#46; It has high negative predictive value &#40;NPV&#41; for the diagnosis of advanced fibrosis &#40;stage F3-F4&#41;&#44; meaning that liver biopsy can be avoided&#46;<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">35&#44;36</span></a> A score of less than 1&#46;30 rules out advanced fibrosis with an NPV of 85&#37;&#46; Scores of more than 2&#46;67 indicate advanced fibrosis with a positive predictive value &#40;PPV&#41; of 79&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">37</span></a> A number of factors&#44; however&#44; must be considered&#44; including the risk of false positives from PPVs&#44; a relatively high probability &#40;1 in 3&#41; of intermediate scores &#40;1&#46;30&#8211;2&#46;67&#41;&#44; and the influence of age on the accuracy of predictions &#40;a threshold score of 2 is recommended for people aged over 65 years&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">38</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The accuracy of FIB-4 depends on age&#58; the index is not suitable for people younger than 35 years&#44; and more tailored cutoffs are needed to improve its specificity in those older than 65 years&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">39</span></a> Another serum-based tool&#44; the HEPAMET Fibrosis Score &#40;HFS&#41;&#44; offers greater specificity &#40;higher predictive values than FIB-4&#41; and accuracy&#44; resulting in less diagnostic uncertainty&#46; Its only limitation is that it includes HOMA-IR&#44; which is generally not a routinely ordered test&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">40</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">When serum-based testing indicates a low risk&#44; twice-yearly dermatologic follow-up with reassessment of risk is recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">31</span></a> TE is recommended in patients with a medium to high risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0625"><span class="elsevierStyleSup">31&#44;38&#44;48</span></a> It has proven effective for monitoring disease severity&#44; has high diagnostic accuracy for advanced stages of fibrosis &#40;F3-F4&#41;&#44; correlates with clinical findings&#44;<a class="elsevierStyleCrossRefs" href="#bib0715"><span class="elsevierStyleSup">49&#44;50</span></a> and&#44; as a noninvasive test&#44; does not increase risk&#46; It should be noted that a high FIB-4 score indicates increased risk&#44; regardless of TE results&#46; Decisions to refer a patient for TE should therefore be based on availability and expected usefulness &#40;whether or not it will influence outcomes&#41;&#46; Patients with an intermediate FIB-4 score should be referred for TE due to the high level of uncertainty&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Wong et al&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">51</span></a> showed that a TE cutoff of 7&#46;9<span class="elsevierStyleHsp" style=""></span>kPa had the highest accuracy &#40;sensitivity&#44; 91&#37;&#59; specificity&#44; 75&#37;&#59; and positive predictive power&#44; 97&#37;&#41; for the diagnosis of advanced fibrosis and cirrhosis in patients with MAFLD&#46; The recommended cutoff for high-risk patients is therefore 8<span class="elsevierStyleHsp" style=""></span>kPa&#46; Patients with a high FIB-4 score and a TE value of 8<span class="elsevierStyleHsp" style=""></span>kPa or lower should be reassessed annually using FIB-4 and&#47;or a repeat TE if available&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Patients with a TE value of more than 8<span class="elsevierStyleHsp" style=""></span>kPa and a risk of advanced fibrosis &#40;F3-F4&#41; should be referred to the gastroenterology department for evaluation of the most appropriate management strategy &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; If TE is not available&#44; patients with a high FIB-4 score should be referred to a gastroenterologist&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Current Treatments for Psoriasis and Their Impact on MAFLD</span><p id="par0130" class="elsevierStylePara elsevierViewall">The expert panel recommendations are general guidelines for common clinical situations that should be applied according to the criteria of each specialist&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">CPG diet and exercise recommendations are the mainstay treatment for MAFLD&#46;<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">31</span></a> Weight reductions of 10&#37; or more can resolve NASH and reduce fibrosis severity by at least 1 stage&#46; Minor weight loss &#40;5&#37;&#8211;10&#37;&#41; can improve certain components of MAFLD&#46; A Mediterranean diet&#44; even without weight loss&#44; reduces liver fat content&#46;<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">52</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">A number of drugs are currently under development for MAFLD&#46; Details of clinical trials evaluating their efficacy and safety are summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">MetS factors should be evaluated in patients without severe liver disease who have a TE value of 6 to 8<span class="elsevierStyleHsp" style=""></span>kPa&#44; regardless of FIB-4 score&#46; Determining the degree of metabolic disease is important for estimating the risk of progression to advanced fibrosis or cirrhosis&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">7</span></a> The results of this assessment will determine the need for follow-up and further tests in accordance with the respective recommendations &#40;annual follow-up and repeat FIB-4&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Patients with psoriasis and liver disease have an increased risk of drug-induced hepatotoxicity &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0810"><span class="elsevierStyleSup">68</span></a> Methotrexate is the most widely used conventional systemic drug in moderate to severe psoriasis due to its cost-effectiveness and the extensive experience with its use&#46; It is&#44; however&#44; hepatotoxic and can cause fibrosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0815"><span class="elsevierStyleSup">69&#8211;71</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">A recent study of patients with moderate to severe psoriasis treated with methotrexate in Spain showed a correlation between treatment duration and risk of liver fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">72</span></a> The percentage of patients with a high risk &#40;FIB-4<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1&#46;3&#41; increased from 18&#46;2&#37; when patients received methotrexate for 16 to 24 weeks to 27&#46;3&#37; when they were treated for 52 to 104 weeks and 32&#46;3&#37; when they were treated for longer&#46;<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">72</span></a> Shetty et al&#46;<a class="elsevierStyleCrossRef" href="#bib0825"><span class="elsevierStyleSup">71</span></a> suggested that the intensity and frequency of monitoring should be tailored to individual risk factors and emphasized the increased risk of methotrexate-induced liver damage in patients with NASH or NASH-fibrosis&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Patients under treatment with steatogenic drugs should also be monitored for liver damage&#46;<a class="elsevierStyleCrossRef" href="#bib0810"><span class="elsevierStyleSup">68</span></a> According to a recent CPG&#44; amiodarone&#44; methotrexate&#44; tamoxifen&#44; and the chemotherapeutic agents 5-fluorouracil and irinotecan are risk factors for MAFLD and should be maintained or withdrawn based on their potential to protect against progression to liver disease &#40;grade B recommendation based on extrapolation from level 1 evidence studies&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">89</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">TE is recommended in patients with a low FIB-4 score under hepatotoxic treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0820"><span class="elsevierStyleSup">70&#44;89&#44;90</span></a> The decision whether to continue treatment with a hepatotoxic drug in patients with moderate to severe psoriasis and a TE value of 8<span class="elsevierStyleHsp" style=""></span>kPa or lower &#40;tested because of a high FIB-4 score or reevaluated with a low FIB-4 score due to treatment&#41; should be based on an individual risk-benefit analysis and the recommendations of the hepatologist&#46; Hepatotoxic drugs are not recommended in patients with a high FIB-4 score and&#47;or a TE of more than 8<span class="elsevierStyleHsp" style=""></span>kPa due to the risk of advanced fibrosis &#40;F3-F4&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Discussion</span><p id="par0170" class="elsevierStylePara elsevierViewall">Agreement among dermatologists and hepatologists on simple&#44; evidence-based&#44; criteria to identify&#44; diagnose&#44; and monitor at-risk individuals is essential for the efficient management of MAFLD&#46; General recommendations should be tailored to the specific characteristics&#44; needs&#44; and organizational and care delivery set-ups of different hospital and health care providers&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Potential interactions between psoriasis treatments and MAFLD must be taken into account&#44; with consideration of both the prevalence of liver disease and the potential and diverse impacts of these treatments&#46; Decisions on whether to continue with a potentially hepatotoxic treatment in patients with a risk of liver fibrosis should be taken after weighing up the risks and benefits&#46; Individual evaluation and follow-up is necessary&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Of all the treatments investigated&#44; methotrexate is the only one associated with an increased risk of new-onset or worsening MAFLD&#46; There is no evidence that phototherapy or certain new-generation conventional treatments cause hepatotoxicity in patients with hepatic steatosis&#46; Although most biologic therapies have a favorable risk-benefit profile in patients with steatosis and varying degrees of fibrosis&#44; their hepatotoxic potential is diverse &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0930"><span class="elsevierStyleSup">92</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusions</span><p id="par0185" class="elsevierStylePara elsevierViewall">Considering the prevalence of MAFLD in patients with psoriasis and the interconnections between these diseases&#44; we recommend screening for liver disease and certain components of MAFLD in patients with psoriasis&#44; regardless of the presence or extent of liver biochemistry abnormalities&#46; This screening should be a routine part of psoriasis care in dermatology departments and clinics&#46; The first-choice strategy is to use a combination of FIB-4 and TE and to refer patients to the hepatology department when a significant risk of advanced fibrosis is detected&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Funding</span><p id="par0190" class="elsevierStylePara elsevierViewall">The expert panel meetings were funded by <span class="elsevierStyleGrantSponsor" id="gs1">Novartis Farmac&#233;utica S&#46;A&#46;</span></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflicts of Interest</span><p id="par0195" class="elsevierStylePara elsevierViewall">The expert panel meetings were funded by Novartis&#44; but none of the employees at this company participated in the design or production of the scientific material&#44; any of the discussions&#44; or the resulting manuscript&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Antonio Olveira has participated as a researcher&#44; speaker&#44; or consultant in projects sponsored by Abbvie&#44; Alexion&#44; BMS&#44; Janssen&#44; MSD&#44; Gilead&#44; and Novartis&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Isabel Belinch&#243;n has served as a consultant and&#47;or speaker and&#47;or participated in clinical trials sponsored by companies that make drugs used to treat psoriasis&#44; including Janssen Pharmaceuticals Inc&#46;&#44; Almirall SA&#44; Lilly&#44; Abbvie&#44; Novartis&#44; Celgene&#44; Biogen&#44; Amgen&#44; LEO Pharma&#44; Pfizer-Wyeth&#44; MSD&#44; and UCB&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Pedro Herranz has participated as a researcher&#44; speaker&#44; or consultant in projects sponsored by Abbvie&#44; Almirall&#44; Amgen&#44; Celgene&#44; LEO Pharma&#44; Lilly&#44; Novartis&#44; Pfizer&#44; Sandoz&#44; Sanofi&#44; and UCB&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Javier Crespo has participated as a researcher&#44; speaker&#44; or consultant in projects sponsored by Abbvie&#44; Alexion&#44; BMS&#44; Amgen&#44; Celgene&#44; Gilead&#44; Janssen&#44; and MSD&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Eva Vilarrasa has received consultancy&#47;speakers&#8217; fees from and&#47;or participated in clinical trials sponsored by Abbvie&#44; Almirall&#44; Amgen&#44; Bayer&#44; Boehringer Ingelheim&#44; Celgene&#44; Gebro&#44; Isdin&#44; Janssen&#44; LEO Pharma&#44; Lilly&#44; Merck-Serono&#44; MSD&#44; Novartis&#44; Pfizer&#44; Roche&#44; Sandoz&#44; Sanofi&#44; and UCB&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Salvador Benlloch P&#233;rez has participated as a researcher&#44; speaker&#44; or consultant in projects and clinical trials sponsored by Novartis&#44; Novo Nordisk&#44; and Gilead&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Jorge Alonso Su&#225;rez P&#233;rez has served on a steering committee and&#47;or participated as a guest speaker for Novartis&#44; LEO Pharma&#44; Abbvie&#44; Lilly&#44; Janssen&#44; UCB&#44; Amgen&#44; and Almirall&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Jos&#233; Manuel Carrascosa has served as a principal investigator&#47;co-investigator and&#47;or was a guest speaker for Novartis&#44; LEO Pharma&#44; Abbvie&#44; Lilly&#44; Janssen&#44; UCB&#44; Sandoz&#44; Mylan&#44; Amgen&#44; Almirall&#44; Bristol-Myers-Squibb&#44; and Boehringer Ingelheim&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Javier Ampuero declares that he has no conflicts of interest&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Francisco Guimer&#224; declares that he has no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
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          "titulo" => "Introduction"
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          "titulo" => "Methodology"
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            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Identifying Risk Factors for Liver Disease in Patients With Psoriasis"
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              "identificador" => "sec0020"
              "titulo" => "Screening Recommendations for MetS"
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            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Current Treatments for Psoriasis and Their Impact on MAFLD"
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          "titulo" => "Discussion"
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          "titulo" => "References"
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    "fechaRecibido" => "2022-11-10"
    "fechaAceptado" => "2023-01-17"
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            1 => "Metabolic-associated fatty liver disease"
            2 => "MAFLD"
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            0 => "Psoriasis"
            1 => "Esteatosis hep&#225;tica metab&#243;lica"
            2 => "EHmet"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Recent years have seen concerted efforts to understand the relation between psoriasis and metabolic-associated fatty liver disease &#40;MAFLD&#41;&#46; Not only is MALFD diagnosed more often in patients with psoriasis&#44; but its clinical course is also more aggressive&#46; A common approach is therefore needed to enable early detection of liver disease coincident with psoriasis&#46; Especially important is an analysis of risks and benefits of potentially hepatotoxic treatments&#46; This consensus paper presents the recommendations of a group of experts in dermatology and hepatology regarding screening for MALFD as well as criteria for monitoring patients and referring them to hepatologists when liver disease is suspected&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">En los &#250;ltimos a&#241;os se est&#225;n haciendo notables esfuerzos para entender la relaci&#243;n existente entre la psoriasis y la esteatosis hep&#225;tica metab&#243;lica &#40;EHmet&#41;&#46; Este trastorno no solo se presenta con una mayor prevalencia en pacientes psori&#225;sicos&#44; sino que adem&#225;s se acompa&#241;a de una mayor gravedad&#46; Con este precedente se evidencia la necesidad de establecer un protocolo de abordaje precoz de la enfermedad hep&#225;tica en los pacientes con psoriasis&#46; Asimismo&#44; es de especial relevancia la evaluaci&#243;n del riesgo y del beneficio en referencia al uso de tratamientos con potencial hepatot&#243;xico&#46; En el presente manuscrito se exponen las recomendaciones de un panel de expertos en dermatolog&#237;a y hepatolog&#237;a para el cribado&#44; el diagn&#243;stico&#44; la monitorizaci&#243;n y los criterios de derivaci&#243;n en pacientes con psoriasis&#44; en caso de sospecha de esteatosis hep&#225;tica metab&#243;lica&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">All the members of the Working Group for the Common Approach to Psoriasis and MALFD &#40;GACPE&#41; are listed in the Appendix&#46;</p>"
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            "apendice" => "<p id="par0250" class="elsevierStylePara elsevierViewall">GACPE&#44; the Working Group for a Common Approach to Psoriasis and MAFLD&#44; is composed of 7 dermatologists and 5 hepatologists with experience in managing psoriasis and MAFLD&#46; The respective experts are listed below&#46;</p>"
            "etiqueta" => "Appendix"
            "titulo" => "Working Group for a Common Approach to Psoriasis and MAFLD &#40;GACPE&#41;"
            "identificador" => "sec0050"
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                "apendice" => "<p id="par0260" class="elsevierStylePara elsevierViewall">Jorge Alonso Su&#225;rez-P&#233;rez&#46; Departamento de Dermatolog&#237;a&#44; Hospital Universitario Virgen de la Victoria&#44; M&#225;laga&#44; Spain&#46;</p> <p id="par0265" class="elsevierStylePara elsevierViewall">Susana Armesto Alonso&#46; Departamento de Dermatolog&#237;a&#44; Hospital Universitario Marqu&#233;s de Valdecilla&#44; Santander&#44; Spain&#46;</p> <p id="par0270" class="elsevierStylePara elsevierViewall">Isabel Belinch&#243;n Romero&#46; Departamento de Dermatolog&#237;a&#44; Hospital General Universitario de Alicante&#44; Instituto de Investigaci&#243;n Sanitaria y Biom&#233;dica &#40;ISABIAL&#41;&#44; Universidad Miguel Hern&#225;ndez de Elche&#44; Alicante&#44; Spain&#46;</p> <p id="par0275" class="elsevierStylePara elsevierViewall">Jos&#233; Manuel Carrascosa Carrillo&#46; Departamento de Dermatolog&#237;a&#46; Hospital Universitario Germans Trias i Pujol&#46; Universitat Aut&#242;noma de Barcelona&#46; IGTP Badalona&#44; Spain&#46;</p> <p id="par0280" class="elsevierStylePara elsevierViewall">Francisco Guimer&#225; Mart&#237;n-Neda&#46; Servicio de Dermatolog&#237;a y Patolog&#237;a&#44; Hospital Universitario de Canarias&#44; La Laguna&#44; Spain&#46;</p> <p id="par0285" class="elsevierStylePara elsevierViewall">Pedro Herranz Pinto&#46; Departamento de Dermatolog&#237;a&#44; Hospital Universitario La Paz&#44; Madrid&#44; Spain&#46;</p> <p id="par0290" class="elsevierStylePara elsevierViewall">Eva Vilarrasa Rull&#46; Departamento de Dermatolog&#237;a&#44; Hospital Santa Creu i Sant Pau&#44; Universitat Aut&#242;noma de Barcelona&#44; Barcelona&#44; Spain&#46;</p>"
                "titulo" => "Dermatologists"
                "identificador" => "sec0055"
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                "apendice" => "<p id="par0295" class="elsevierStylePara elsevierViewall">Javier Ampuero Herrojo&#46; Departamento de Enfermedades Digestivas&#44; Hospital Universitario Virgen del Roc&#237;o&#46; Laboratorio 213&#44; Instituto de Biomedicina de Sevilla &#40;IBIS&#41;&#46; Departamento de Medicina&#44; Universidad de Sevilla&#46; Centro Biom&#233;dico en Red de Enfermedades Hep&#225;ticas y Digestivas &#40;CIBERehd&#41;&#46; Sevilla&#44; Spain&#46;</p> <p id="par0300" class="elsevierStylePara elsevierViewall">Salvador Benlloch P&#233;rez&#46; Servicio de Enfermedades Digestivas&#44; Hospital Arnau de Vilanova&#46; Valencia&#46; Centro Biom&#233;dico en Red de Enfermedades Hep&#225;ticas y Digestivas &#40;CIBERehd&#41;&#46; Valencia&#44; Spain&#46;</p> <p id="par0305" class="elsevierStylePara elsevierViewall">Javier Crespo Garc&#237;a&#46; Servicio de Gastroenterolog&#237;a y Hepatolog&#237;a&#46; Hospital Universitario Marqu&#233;s de Valdecilla&#46; IDIVAL&#46; Escuela de Medicina&#46; Universidad de Cantabria&#46; Santander&#44; Spain&#46;</p> <p id="par0310" class="elsevierStylePara elsevierViewall">Antonio Olveira Mart&#237;n&#46; Servicio de Aparato Digestivo&#44; Hospital Universitario La Paz&#44; Madrid&#44; Spain&#46;</p>"
                "titulo" => "Hepatologists"
                "identificador" => "sec0060"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Progression of metabolic-associated fatty liver disease&#46; From steatosis &#40;stable&#44; with little risk of progression&#44; characterized by the accumulation of intracellular fat in the hepatocyte&#41; to nonalcoholic steatohepatitis &#40;NASH&#41; &#40;fat accumulation accompanied by inflammatory changes and cell damage&#41; and hepatic fibrosis &#40;collagen deposition in the form of fibrous septa that cause architectural remodeling and progressive hepatocyte dysfunction&#41;&#46; Fibrosis predisposes to the development of cirrhosis &#40;fibrotic septa and regeneration nodules&#41; and hepatocelular carcinoma and&#47;or liver failure&#46;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">6&#44;8&#44;10&#44;12&#8211;14</span></a></p>"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Screening algorithm for patients at risk of MAFLD&#46; Depending on the situation of each hospital and test availability&#44; the dermatology department can order TE or refer the patient to the gastroenterology department&#46; MAFLD indicates metabolic-associated fatty liver disease&#59; FIB-4&#44; Fibrosis-4 Index for Liver Fibrosis&#59; HFS&#44; Hepamet Fibrosis Score&#59; TE&#44; transient elastography&#46; <span class="elsevierStyleSup">a</span>TE should be performed to evaluate the risk of fibrosis in patients with a low FIB-4 score and under a potentially hepatotoxic treatment&#46;</p>"
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; ALT&#44; alanine aminotransferase&#59; APRI&#44; AST to platelet ratio index&#59; AST&#44; aspartate aminotransferase&#59; BMI&#44; body mass index&#59; ELF&#44; enhanced liver fibrosis test&#59; GGT&#44; gamma-glutamyl transferase&#59; HFS&#44; Hepamet Fibrosis Score&#59; HOMA&#44; homeostatic model assessment for insulin resistance&#59; HSI&#44; hepatic steatosis index&#59; NAFLD-FS&#44; nonalcoholic fatty liver disease fibrosis score&#59; PIIINP&#44; procollagen III amino-terminal peptide&#59; TIMP-1&#44; tissue inhibitor of matrix metalloproteinase 1&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameters&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Risk of advanced fibrosis according to cutoff values</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HSI<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Steatosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ALT&#47;AST&#44; BMI&#44; sex&#44; diabetes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>30&#58; low&#62;<span class="elsevierStyleHsp" style=""></span>36&#58; high</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FLI<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">42</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Steatosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Waist circumference&#44; BMI&#44; triglycerides&#44; GGT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>30&#58; low30&#8211;59&#58; intermediate&#8805;<span class="elsevierStyleHsp" style=""></span>60&#58; high</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NAFLD-FS<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">43</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">Fasting blood glucose or diabetes mellitus&#44; age&#44; BMI&#44; ALT&#44; AST&#44; platelets&#44; albumin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>&#8722;1&#46;455&#58; F0-F2&#44; low&#8722;1&#46;455&#8211;0&#46;675&#58; indeterminate&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;675&#58; F3-F4&#44; high</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">FIB-4<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">44</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Fibrosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Age&#44; ALT&#44; AST&#44; platelets&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>1&#46;30&#58; F0-F2&#44; low&#62;<span class="elsevierStyleHsp" style=""></span>2&#46;67&#58; F3-F4&#44; high</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HFS<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sex&#44; age&#44; diabetes&#44; glucose&#44; insulin&#44; HOMA-IR &#40;no diabetes&#41;&#44; AST&#44; albumin&#44; platelets&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HFS score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F2-F4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F3-F4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;12&#8211;0&#46;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#46;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">86&#46;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">APRI<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AST&#44; platelets&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F0-F2&#58; &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#59; 72&#46;7&#37;F3-F4&#58; &#62;<span class="elsevierStyleHsp" style=""></span>1&#46;5&#59; 54&#46;2&#37;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BARD score<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">46</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ALT&#44; AST&#44; diabetes&#44; BMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#8211;1&#58; low2&#8211;4&#58; high</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ELF<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">47</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HA&#44; PIIINP&#44; TIMP-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>7&#46;7&#58; zero or low&#8805;<span class="elsevierStyleHsp" style=""></span>7&#46;7&#8211;9&#46;7&#58; moderate&#8805;<span class="elsevierStyleHsp" style=""></span>9&#46;8 high</td></tr></tbody></table>
                  """
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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        "fuente" => "Adapted from&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">53</span></a>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; ACC&#44; acetyl-coenzyme A carboxylase&#59; ASK1&#58; apoptosis signal-regulatory kinase 1&#59; CCR2&#47;5&#44; chemokine coreceptor type 2&#47;5&#59; FGF21&#44; fibroblast growth factor 21&#59; FXR&#44; farnesoid X receptor&#59; GLP1&#44; glucagon-like peptide 1&#59; HSP47 siRNA&#58; heat shock protein 47 small interfering ribonucleic acid&#59; PPAR&#945;&#47;&#948;&#44; peroxisome proliferator&#8211;activated receptor&#945;&#47;&#948;&#59; SCD&#44; stearoyl-coenzyme A desaturase&#59; SGLT2&#44; sodium-glucose cotransporter type 2&#59; TLR4&#44; toll-like receptor 4&#59; TR&#946;&#44; thyroid hormone receptor &#946;&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Target&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Action&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Phase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ref&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diabetes&#44; insulin resistance</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Semaglutide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GLP-1 receptor analog&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">54</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Canagliflozin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SGLT2 inhibitor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pilot&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">55</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BMS-986036&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recombinant FGF21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">56</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dyslipidemia</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aramcol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SCD inhibitor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">57</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Firsocostat &#40;GS-0976&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ACC inhibitor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">58</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nuclear receptor</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Obeticholic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FXR agonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">59</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Elafibranor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PPAR&#945;&#47;&#948; agonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">60</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resmetirom &#40;MGL-3196&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TR&#946; agonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0775"><span class="elsevierStyleSup">61</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Apoptosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Emricasan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Capsase inhibitor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">62</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inflammation&#44; fibrosis</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Selonsertib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ASK1 inhibitor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">63</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cenicriviroc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CCR2&#47;5 antagonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">64</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GR-MD-02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Galectina-3 inhibitor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">65</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JKB-121&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TLR4 antagonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">66</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ND-LO2-s0201&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HSP47 siRNA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><a class="elsevierStyleCrossRef" href="#bib0805"><span class="elsevierStyleSup">67</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Clinical trials evaluating treatments for metabolic-associated fatty liver disease&#46;</p>"
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        "etiqueta" => "Table 3"
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        "fuente" => "Adapted from&#46;<a class="elsevierStyleCrossRefs" href="#bib0595"><span class="elsevierStyleSup">25&#44;69&#8211;88</span></a>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; IL&#44; interleukin&#59; NA&#44; not applicable &#40;no studies&#41;&#59; TBIL&#44; total bilirubin&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">The group of TNF inhibitors includes etanercept&#44; adalimumab&#44; and infliximab&#46; The group of IL-17A inhibitors includes brodalumab&#44; ixekizumab&#44; and secukinumab&#46; The group of IL-23 inhibitors includes tildrakizumab&#44; guselkumab&#44; and risankizumab&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Toxicity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of damage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Liver failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Increased risk of liver damage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Methotrexate<a class="elsevierStyleCrossRefs" href="#bib0815"><span class="elsevierStyleSup">69&#8211;73</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oxidative damage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Use with precautionContraindicated if TBIL<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MAFLD&#47;obesity&#44; leflunomide&#44; alcohol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acitretin<a class="elsevierStyleCrossRefs" href="#bib0840"><span class="elsevierStyleSup">74&#44;75</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mitochondrial dysfunction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Contraindicated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Elevated transaminases 15&#37;-30&#37;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">75</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TNF inhibitors<a class="elsevierStyleCrossRefs" href="#bib0850"><span class="elsevierStyleSup">76&#8211;78</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liver failure&#44; noninfectious hepatitis&#44; hepatic insufficiency&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased risk of liver damage with adalimumab<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">79</span></a> and autoimmune hepatitis with infliximab<a class="elsevierStyleCrossRef" href="#bib0860"><span class="elsevierStyleSup">78</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-12&#47;23 antibodies<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">79</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#47;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-23 antibodies<a class="elsevierStyleCrossRefs" href="#bib0870"><span class="elsevierStyleSup">80&#8211;82</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Elevated transaminases<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-17 antibodies<a class="elsevierStyleCrossRefs" href="#bib0885"><span class="elsevierStyleSup">83&#8211;85</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Possible protective effect against inhibition of IL-17A in animal models<a class="elsevierStyleCrossRef" href="#bib0900"><span class="elsevierStyleSup">86</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Apremilast<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cyclosporine<a class="elsevierStyleCrossRef" href="#bib0910"><span class="elsevierStyleSup">88</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rare&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oxidative damage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SafeDose reduction required&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Obesity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Drugs Used to Treat Psoriasis and Their Impact on the Liver&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Psoriasis severity scores&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">BSA<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> 10&#37; or PASI<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10 or DLQI<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">c</span></a><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Location&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Visible areas &#40;face and dorsum of hands&#41;&#44; palms&#44; soles&#44; genitals&#44; scalp&#44; nails&#44; and also recalcitrant plaques with a functional or psychological impact&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Previous treatment failure&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Not controlled by topical therapy or phototherapy&nbsp;\t\t\t\t\t\t\n
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">The Psoriasis Area Severity Index &#40;PASI&#41; is the most widely used measurement scale for assessing the extent and severity of psoriasis and guiding treatment decisions&#46; This index combines a severity score ranging from 0 to 4 assigned to each psoriasis lesion &#40;0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>none&#44; 1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>mild&#44; 2<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>moderate&#44; 3<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>marked&#44; 4<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>very marked&#41; in 4 parts of the body &#40;head&#44; trunk&#44; upper limbs&#44; and lower limbs&#41;&#46; The score is based on 3 parameters&#58; erythema&#44; induration&#44; and desquamation&#46;<a class="elsevierStyleCrossRefs" href="#bib0930"><span class="elsevierStyleSup">92&#44;93</span></a></p>"
            ]
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">The Dermatology Life Quality Index &#40;DLQI&#41; is composed of 10 questions on the extent to which a person&#39;s skin problem has affected their life over the past week&#46; Each question has 4 possible answers&#58; not at all &#40;0&#41;&#44; a little &#40;1&#41;&#44; a lot &#40;2&#41;&#44; very much &#40;3&#41;&#46; The scores &#40;0&#8211;3&#41; are added to obtain a total score&#46; A higher score indicates worse quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">94</span></a></p>"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Characteristics of Moderate to Severe Psoriasis in Candidates for Systemic Treatment According to the Definitions of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology &#40;AEDV&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">29</span></a></p>"
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                      "titulo" => "Prevalence of ten immune-mediated inflammatory diseases &#40;IMID&#41; in Spain"
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                          "autores" => array:6 [ …6]
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                        "tituloSerie" => "Rev Esp Salud Publica"
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                      "titulo" => "Psoriasis and comorbid diseases"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
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                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "2017"
                        "volumen" => "76"
                        "paginaInicial" => "377"
                        "paginaFinal" => "390"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relationship between non-alcoholic fatty liver disease and psoriasis&#58; a novel Hepato-Dermal axis&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
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                    0 => array:2 [
                      "doi" => "10.3390/ijms17020217"
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Mol Sci"
                        "fecha" => "2016"
                        "volumen" => "17"
                        "paginaInicial" => "217"
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                          0 => array:2 [ …2]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Looking for a new name for non-alcoholic fatty liver disease in Spanish&#58; esteatosis hep&#225;tica metab&#243;lica &#40;EHmet&#41;"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
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                        "tituloSerie" => "Rev Esp Enferm Dig"
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                        "volumen" => "113"
                        "paginaInicial" => "161"
                        "paginaFinal" => "163"
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                          0 => array:2 [ …2]
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                      "titulo" => "Non-alcoholic fatty liver disease&#58; metabolic&#44; genetic&#44; epigenetic and environmental risk factors"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
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                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Environ Res Public Health"
                        "fecha" => "2021"
                        "volumen" => "18"
                        "paginaInicial" => "5227"
                        "link" => array:1 [
                          0 => array:2 [ …2]
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            5 => array:3 [
              "identificador" => "bib0500"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Non-alcoholic fatty liver disease&#58; a sign of systemic disease"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
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                        "tituloSerie" => "Metabolism"
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                        "paginaInicial" => "94"
                        "paginaFinal" => "108"
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            6 => array:3 [
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                0 => array:2 [
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                      "titulo" => "The metabolic syndrome and its influence on nonalcoholic steatohepatitis"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
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                      "doi" => "10.1016/j.cld.2015.10.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Liver Dis"
                        "fecha" => "2016"
                        "volumen" => "20"
                        "paginaInicial" => "225"
                        "paginaFinal" => "243"
                        "link" => array:1 [
                          0 => array:2 [ …2]
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            7 => array:3 [
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              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
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