Psoriasis and Nonalcoholic Fatty Liver Disease | Actas Dermo-Sifiliográficas

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Carrascosa, C. Bonanad, E. Dauden, R. Botella, A. Olveira-Martín" "autores" => array:6 [ 0 => array:4 [ "nombre" => "J.M." "apellidos" => "Carrascosa" "email" => array:1 [ 0 => "jmcarrascosac@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "C." "apellidos" => "Bonanad" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "E." "apellidos" => "Dauden" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "R." "apellidos" => "Botella" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "A." "apellidos" => "Olveira-Martín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] 5 => array:1 [ "colaborador" => "on behalf of the Systemic Inflammation in Psoriasis Working Group" ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Servicio de Dermatologia, Hospital Universitari Germans Trias i Pujol. Universitat Autònoma de Barcelona, Badadalona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Cardiología, Hospital Clínico Universitario, Valencia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital La Princesa, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitario La Fe, Valencia, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Aparato Digestivo, Hospital la Paz, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Psoriasis e hígado graso no alcohólico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1899 "Ancho" => 2543 "Tamanyo" => 220759 ] ] "descripcion" => array:1 [ "en" => "Nonalcoholic fatty liver disease (NAFLD) in patients with psoriasis. Adapted from clinical guidelines.<a class="elsevierStyleCrossRef" href="#bib0385">17</a> a Aspartate transaminase (ASP), alanine transaminase (ALT), and γ-glutamyltransferase (GGT). bAny increase in ASP, ALT, and/or GGT." ] ] ] "textoCompleto" => "Nonalcoholic Fatty Liver Disease: The ConceptNonalcoholic fatty liver disease (NAFLD) is a process in which fat is deposited in the liver in the absence of significant alcohol consumption or the use of drugs—such as steroids, methotrexate (MTX), tamoxifen, or amiodarone—that facilitate steatosis.<a class="elsevierStyleCrossRef" href="#bib0305">1</a> Certain hereditary conditions such as Wilson disease, abetalipoproteinemia, Wolman disease, and cholesteryl ester storage disease are also incompatible with a diagnosis of NAFLD.<a class="elsevierStyleCrossRef" href="#bib0305">1</a> Once these conditions are excluded, nearly all patients diagnosed with NAFLD share the characteristics associated with metabolic risk, such as obesity, type 2 diabetes mellitus, hypertension, and dyslipidemia. NAFLD and metabolic syndrome share the pathophysiologic mechanism of insulin resistance.<a class="elsevierStyleCrossRef" href="#bib0310">2</a>Two histologic forms of the disease can be distinguished: one is steatosis, in which fat has been deposited but liver cells are not yet damaged, and the other is steatohepatitis, which is characterized by liver inflammation that can eventually lead to fibrosis. Mortality is higher in patients with NAFLD than in the general population, regardless of which of these histologic variants is present; the cause of death is usually cardiovascular disease.<a class="elsevierStyleCrossRef" href="#bib0315">3</a> Because steatohepatitis is an inflammatory condition, the liver is threatened, and 15% to 25% of patients will have progressed to cirrhosis within 10 years. Once cirrhosis develops, complications (liver failure, esophageal varices, and liver cancer) will lead to death in 25% of affected patients within 5 years.<a class="elsevierStyleCrossRef" href="#bib0320">4</a> Why fat deposition causes inflammation and fibrosis in some patients but not others is poorly understood, although genetic and environmental factors are probably both relevant.<a class="elsevierStyleCrossRef" href="#bib0325">5</a>NAFLD is important in the West because it is currently the most prevalent liver disorder. Approximately 20% of adults in the general population have NAFLD, and among them about 20% have the aggressive form, steatohepatitis.<a class="elsevierStyleCrossRef" href="#bib0330">6</a> The prevalence is much higher among adults with metabolic syndrome, where 38% of overweight persons (with a body mass index [BMI] between 25 and 30) have NAFLD. The prevalence rates in obese (BMI, 30–40) and severely obese (BMI, 40–45) persons are 46% and 65%, respectively. Finally, some 90% of morbidly obese patients (BMI>45) have this condition, and 5% of them have cirrhosis. Among diabetics, the prevalence is 69%, and among patients with elevated triglyceride levels, 50%.<a class="elsevierStyleCrossRef" href="#bib0335">7</a> A sign of the seriousness of this situation is that nonalcoholic steatohepatitis is currently the second most common cause of liver transplantation in the United States, and it is expected to become the first cause in the coming years.<a class="elsevierStyleCrossRef" href="#bib0340">8</a>In spite of these statistics, NAFLD is clearly underdiagnosed because there are no signs or symptoms that arouse suspicion except when the disease becomes advanced and also because serum biochemical markers show only slight, nonspecific changes; results may even stay within the normal limits in 15% to 39% of patients.<a class="elsevierStyleCrossRefs" href="#bib0345">9,10</a>A diagnosis of NAFLD requires evidence of steatosis by liver biopsy or imaging and the exclusion of alcohol consumption or other general causes of liver disease or conditions that lead to steatosis.<a class="elsevierStyleCrossRef" href="#bib0305">1</a> The first criterion—evidence of steatosis—is critical. The list of causes of liver disease are well established<a class="elsevierStyleCrossRef" href="#bib0355">11</a> while the alternative causes of steatosis are very rare and, in principle, relatively easy to identify. A liver biopsy is the gold standard, but it is invasive, has associated risk of complications and death, and is costly.<a class="elsevierStyleCrossRef" href="#bib0360">12</a> Furthermore, it is not reasonable or even feasible to biopsy 20% of the population. Interest in finding a noninvasive approach to diagnosis is therefore growing. A fatty liver is usually detected through imaging (ultrasound, computed tomography scans, or nuclear magnetic resonance); the sensitivity and specificity of images are 60% and 94%, respectively.<a class="elsevierStyleCrossRefs" href="#bib0365">13,14</a> Ultrasound is usually chosen because it is innocuous and widely available.<a class="elsevierStyleCrossRef" href="#bib0305">1</a> However, neither liver enzymes nor images can distinguish between steatosis and steatohepatitis. Nor can they establish or rule out the presence of fibrosis. Various scoring systems using the results of serum tests have therefore been developed. The most widely accepted is the NAFLD fibrosis score,<a class="elsevierStyleCrossRef" href="#bib0375">15</a> which is calculated according to a formula (<a href="http://nafldscore.com/">http://nafldscore.com</a>) based on easy-to-obtain measurements: BMI; age; platelet count; and serum albumin, aspartate transaminase (AST), and alanine transaminase (ALT) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Moreover, this score is highly sensitive (67%) and specific (60%) for excluding (67%) or detecting (97%) the presence of advanced fibrosis using an area under the receiver operating characteristic curve of 0.85 as the cutoff. The severity of liver damage can also potentially be assessed by measuring liver stiffness indirectly with elastography. The usefulness of this approach would mainly be to identify patients at low risk of advanced fibrosis or cirrhosis given the test's lack of precision when disease is advanced.<a class="elsevierStyleCrossRef" href="#bib0380">16</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The European Association for the Study of the Liver, the European Association for the Study of Diabetes, and the European Association for the Study of Obesity have recently published new joint guidelines for managing NAFLD.<a class="elsevierStyleCrossRef" href="#bib0385">17</a> They recommend that all patients with insulin resistance or risk factors for metabolic syndrome be screened for NAFLD by ultrasound and liver biochemistry. Any increase in AST, ALT, and/or γ-glutamyltransferase are relevant, regardless of magnitude. The screening algorithm is shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.<a class="elsevierStyleCrossRef" href="#bib0385">17</a><elsevierMultimedia ident="fig0005"></elsevierMultimedia>Therapeutic Management of NAFLDAt this time there is no specific treatment for NAFLD available. Weight loss of at least 7% to 10% and exercise are associated with histologic improvement,<a class="elsevierStyleCrossRef" href="#bib0390">18</a> but they are difficult to achieve and particularly difficult to maintain long-term. Alcohol, saturated fats, and fructose-sweetened beverages should be avoided.<a class="elsevierStyleCrossRef" href="#bib0395">19</a> Coffee consumption, on the other hand, can be recommended.<a class="elsevierStyleCrossRef" href="#bib0400">20</a> Several drugs (metformin, pioglitazone, eicosapentenoic acid, statins, and vitamin E) have been tried, but there is a lack of sufficient evidence on which to base a strong recommendation.<a class="elsevierStyleCrossRefs" href="#bib0305">1,6,21–24</a>NAFLD and PsoriasisThe first observational studies showing an association between NAFLD and psoriasis began to appear during the last 10 years,<a class="elsevierStyleCrossRefs" href="#bib0425">25,26</a> and the association has since been confirmed.<a class="elsevierStyleCrossRefs" href="#bib0435">27,28</a> Gisondietal.<a class="elsevierStyleCrossRef" href="#bib0425">25</a> saw a higher rate of ultrasound-diagnosed NAFLD (47%) in a series of 130 consecutive patients with psoriasis than in 260 healthy controls (28%) matched for age, sex, and BMI. The psoriasis patients were also more likely to have metabolic syndrome and higher C-reactive protein levels; those who also had NAFLD had higher interleukin (IL) 6 and lower adiponectin levels than those without the disease. Abedinietal.<a class="elsevierStyleCrossRef" href="#bib0440">28</a> reported finding NAFLD in 65.6% of patients with psoriasis (vs 35% of healthy controls), and vanderVoortetal.<a class="elsevierStyleCrossRef" href="#bib0435">27</a> found that 46.2% of psoriatic patients and 33.3% of controls had NAFLD in a population-based series of 2292 persons over the age of 55 years in Rotterdam. These findings may be attributable to the association between psoriasis and metabolic syndrome, given that the conditions defining the latter are those that lead to NAFLD.<a class="elsevierStyleCrossRef" href="#bib0445">29</a> Mieleetal.<a class="elsevierStyleCrossRef" href="#bib0430">26</a> studied a cohort of psoriasis patients with and without NAFLD, finding that NAFLD was also associated with psoriatic arthritis. Robertsetal.<a class="elsevierStyleCrossRef" href="#bib0450">30</a> reported finding a relationship between greater severity of psoriasis and NAFLD. Specifically, they saw steatohepatitis in 22% of the patients with both psoriasis and NAFLD who underwent liver biopsy. The NAFLD patients with steatohepatitis were also more likely to be obese and have higher insulin and transaminase levels; they also found marked differences in risk for NAFLD according to ethnic origin. Similarly, vanderVoortetal.<a class="elsevierStyleCrossRef" href="#bib0435">27</a> found that patients of Latin American origin carried greater risk (83%), followed by Caucasians (39%), and finally African Americans (33%).Clinical Suspicion and Screening for NAFLD in DermatologyA high index of suspicion concerning NAFLD is needed in dermatology because most cases encountered will be asymptomatic. The dermatologist should above all be aware of the high prevalence in patients with psoriasis. It is also important to note signs of the components of metabolic syndrome: diabetes mellitus, obesity, dyslipidemia, and hypertension. Abnormal liver enzymes may be difficult to discern because elevations are usually slight, at less than 2- to 3-fold the normal values and with an ALT/AST ratio greater than 1; alkaline phosphatase and γ-glutamyltransferase are occasionally elevated.<a class="elsevierStyleCrossRef" href="#bib0455">31</a> Liver enzymes can be normal in 15% to 30% or more of patients with NAFLD,<a class="elsevierStyleCrossRef" href="#bib0350">10</a> even though 35% of such patients have advanced fibrosis or cirrhosis. Given this situation, in the presence of the most prevalent indicator of risk for NAFLD—namely components of metabolic syndrome—ultrasound imaging to rule out liver disease is indicated even when biochemistry is normal.<a class="elsevierStyleCrossRef" href="#bib0385">17</a> At this time, however, the clinical algorithm recommended by most medical associations specializing in NAFLD (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), does not recognize the need for imaging to evaluate patients with psoriasis in the absence of liver enzyme abnormalities.Once NAFLD has been confirmed, the dermatologist must cooperate in prescribing the necessary dietary measures and adjusting drug dosages if transaminase levels are elevated.The absence of liver damage according to the initial assessment does not exclude its development over the coming years. Therefore, patients will have to be reassessed if analyses reveal signs of damage or if metabolic syndrome develops.<a class="elsevierStyleCrossRef" href="#bib0385">17</a>Pathogenesis of NAFLD in PsoriasisThis review does not attempt to delve deeply into the pathogenesis of NAFLD, but it is useful to be aware of the two-hit hypothesis.<a class="elsevierStyleCrossRef" href="#bib0460">32</a> In this theory, the first phase would be marked by the abnormal accumulation of triglycerides in liver cells, a development in which insulin resistance plays a large role. In the second phase, the steatotic liver appears to become susceptible to injury induced by several players and events involving various adipokines and oxidative stress in the endoplasmic reticulum, as well as mitochondrial dysfunction and liver apoptosis. These events favor the transition from simple steatosis to steatohepatitis. Besides the involvement of insulin resistance in both these phases of progression toward NAFLD—as well as in the induction and activation of profibrotic cytokines—other chronic inflammatory processes that might be present, such as psoriasis, can contribute proinflammatory cytokines.<a class="elsevierStyleCrossRef" href="#bib0465">33</a> Thus, the pathogenic relationship between NAFLD and psoriasis is complex and probably multifactorial, although it is presumably related to a state of chronic underlying inflammation.NAFLD and psoriasis are probably linked partly because some of the conditions that often accompany psoriasis are also the ones that cause NAFLD. Among them, obesity stands out. The epidemiologic association between obesity and psoriasis is clear, particularly in severe psoriasis, and the influences probably operate in both directions, such that obesity favors psoriasis and vice versa.<a class="elsevierStyleCrossRef" href="#bib0470">34</a> The prevalence of NAFLD is also clearly higher in obese patients, especially those with excess abdominal fat, which is more metabolically active than subcutaneous fat.<a class="elsevierStyleCrossRef" href="#bib0475">35</a> Obesity is associated with risk for developing insulin resistance, the main factor in the development of NAFLD.<a class="elsevierStyleCrossRef" href="#bib0480">36</a> Excessive fat deposition leads to an imbalance between pro- and anti-inflammatory cytokines, favoring the progression of liver disease. When adipose tissue secretes an abundance of adipokines—tumor necrosis factor (TNF), IL-6, leptin, visfatin, or resistin—a proinflammatory state may develop in psoriatic skin as the result of the proliferation of keratinocytes, angiogenesis, the response of type 1T cells, or the expression of adhesion molecules. This state may also be expressed in NAFLD, contributing to insulin resistance or liver fibrosis. In addition, there is also a decrease in the concentration of adipokines that protect against inflammation—such as adiponectin, a promotor of skin anti-inflammatory cytokines that enhances insulin sensitivity.<a class="elsevierStyleCrossRef" href="#bib0485">37</a>The involvement of IL-17 in both psoriasis and NAFLD is interesting. T cells in adipose tissue synthesize IL-17, which is able to regulate adipogenesis and glucose metabolism. Type 17T helper cells and IL-17 could facilitate the progression from simple steatosis to steatohepatitis.<a class="elsevierStyleCrossRef" href="#bib0490">38</a>Implications for the Management of Conventional Systemic TreatmentsThe high prevalence of NAFLD in psoriasis leads to therapeutic concerns because this chronic skin disease must be treated over decades.The incidence of MTX-induced liver damage is known to be higher in psoriasis<a class="elsevierStyleCrossRef" href="#bib0495">39</a> than in other chronic inflammatory diseases. A recent retrospective study saw, for example, that 58% of 710 patients on MTX for psoriasis had elevated transaminase levels.<a class="elsevierStyleCrossRef" href="#bib0500">40</a> In the light of our current understanding, this finding may be relevant to the known association between NAFLD and psoriasis. Given the high rates of both NAFLD and steatohepatitis in this setting, we should rule out significant steatosis before starting MTX, at least in patients with signs of metabolic syndrome. In addition to ultrasound screening, two new tools, the FibroTest and the FibroScan (liver elastography) may be useful for assessing liver fibrosis.<a class="elsevierStyleCrossRef" href="#bib0505">41</a>MTX toxicity presents with histologic findings and may therefore reflect pathogenic mechanisms that are different from those associated with NAFLD. However, the shared risk factors that aggravate both MTX toxicity and NAFLD—such as obesity, diabetes, or hyperlipidemia—are observed often in patients with severe psoriasis.<a class="elsevierStyleCrossRef" href="#bib0510">42</a>Liver toxicity is also among the potential adverse effects of ciclosporin. The effect may be direct or it may be a byproduct of a deteriorating lipid profile.<a class="elsevierStyleCrossRef" href="#bib0515">43</a> Acitretin can also raise triglyceride levels and has been associated with transaminase elevations in 1 out of 4 patients, although tissue damage following intermittent use of the drug has not been reported.<a class="elsevierStyleCrossRef" href="#bib0520">44</a>Biologic Agents in Patients With Psoriasis and NAFLDTNF plays a central role in the inflammatory process in NAFLD, as in other chronic inflammatory diseases.<a class="elsevierStyleCrossRef" href="#bib0525">45</a> In fact, TNF has been studied for its potential use as a diagnostic and prognostic tool in NAFLD.<a class="elsevierStyleCrossRef" href="#bib0530">46</a> Given the pathogenic role of this cytokine, anti-TNF agents such as infliximab and adalimumab have also been tried in this setting<a class="elsevierStyleCrossRefs" href="#bib0535">47,48</a> because of improvements observed in liver and metabolic biomarkers after biologic therapy for other inflammatory diseases.<a class="elsevierStyleCrossRefs" href="#bib0545">49,50</a>Biologics have a better safety profile than the conventional treatments for NAFLD mentioned earlier. For example, when adalimumab was used for an average of 5 years in 32 patients with liver disease and psoriasis, no cases of liver disease progression or development of liver toxicity were observed.<a class="elsevierStyleCrossRef" href="#bib0555">51</a>Biologic therapy could exercise regulatory effects on some adipocytokines. Shibataetal.<a class="elsevierStyleCrossRef" href="#bib0560">52</a> reported an increase in adiponectin and IL-6 levels during treatment with infliximab, and adalimumab and etanercept may inhibit proinflammatory adipocytokines.<a class="elsevierStyleCrossRef" href="#bib0565">53</a>Studies of the impact of anti-TNF agents on the lipid profile, a risk factor for NAFLD, have yielded inconsistent results. While some authors have not been able to demonstrate a significant effect, others have reported elevated triglycerides and lower high-density lipoprotein (HDL) cholesterol levels in patients with infliximab-treated psoriatic arthritis.<a class="elsevierStyleCrossRef" href="#bib0570">54</a> Etanercept therapy, on the other hand, has favorably modulated the antioxident and anti-inflammatory properties of HDL cholesterol as well as modulated adipolipoprotein A1 and B levels, reducing lipid peroxidation.<a class="elsevierStyleCrossRef" href="#bib0575">55</a>Marra et al.<a class="elsevierStyleCrossRef" href="#bib0580">56</a> showed improved insulin sensitivity in patients treated with etanercept for psoriasis, an effect that could potentially have a favorable influence on the course of NAFLD.It must be borne in mind that anti-TNF agents can occasionally induce autoimmune or drug-related hepatitis.<a class="elsevierStyleCrossRef" href="#bib0585">57</a> The risk is very low, however. Only 20 cases of autoimmune hepatitis have ever been reported; most were mild cases associated with infliximab and responded quickly to steroid treatment.<a class="elsevierStyleCrossRef" href="#bib0505">41</a> Anti-TNF agents have also been linked to weight gain in psoriasis patients, although the gains have generally been modest. However, long-term use has led to considerable gain in some patients, and this adverse effect potentially aggravates the obesity associated with severe psoriasis and NAFLD.<a class="elsevierStyleCrossRef" href="#bib0590">58</a>High transaminase levels were detected in 6 patients in a series of 44 treated with ustekinumab for an average of 46.7 months.<a class="elsevierStyleCrossRef" href="#bib0595">59</a> Five of the 6 patients developed hepatotoxicity related to other drugs, 3 developed fatty liver, and 3 were receiving other hepatotoxic drugs while taking ustekinumab. The authors concluded that ustekinumab-related toxicity was mild and uncommon. Hepatotoxicity is not described as a side effect detected in clinical trials of secukinumab<a class="elsevierStyleCrossRef" href="#bib0600">60</a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>ConclusionsNAFLD is the most frequent liver disorder in the West (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Patients with psoriasis have a higher prevalence of NAFLD, a higher rate of severe disease, and a worse prognosis. Dermatologists should routinely evaluate psoriasis patients for NAFLD. The pathogenic links between psoriasis and NAFLD are chronic inflammation and peripheral insulin resistance, which is a common finding in diseases associated with psoriasis. The dermatologist should be aware not only of the high prevalence of NAFLD in psoriasis but also of the possibility of steatohepatitis, especially when psoriasis is severe or when there are signs of metabolic syndrome. Psoriasis patients with insulin resistance or risk factors for metabolic syndrome should be specifically evaluated for fatty liver by abdominal ultrasound and liver biochemistry. Concurrent psoriasis and NAFLD, and the likely synergy between them, affect the general recommendations we can make and the treatment strategies we can adopt. Some drugs carry risk of hepatotoxicity. On the other hand, there is a possibility that achieving good control of inflammation and pathogenic factors associated with NAFLD will improve the prognosis.<elsevierMultimedia ident="tb0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Ethical DisclosuresProtection of human and animal subjectsThe authors declare that no experiments were performed on humans or animals for this investigation.Data confidentialityThe authors declare that no private patient data are disclosed in this article.Right to privacy and informed consentThe authors declare that no private patient data are disclosed in this article.Conflicts of InterestAbbvie sponsored the meetings of the working group, but no employees of the laboratory participated in the research, interpretation, discussion, or drafting of the text.J. M. Carrascosa has served as a consultant, given invited talks, and/or participated in clinical trials sponsored by the following laboratories: Abbvie, Janssen, Lilly, Pfizer, Novartis, Pfizer, and Celgene." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres858564" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec852686" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres858565" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec852685" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Nonalcoholic Fatty Liver Disease: The Concept" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Therapeutic Management of NAFLD" ] ] ] 5 => array:3 [ "identificador" => "sec0015" "titulo" => "NAFLD and Psoriasis" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Clinical Suspicion and Screening for NAFLD in Dermatology" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Pathogenesis of NAFLD in Psoriasis" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Implications for the Management of Conventional Systemic Treatments" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Biologic Agents in Patients With Psoriasis and NAFLD" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Conclusions" ] 8 => array:3 [ "identificador" => "sec0050" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Data confidentiality" ] 2 => array:2 [ "identificador" => "sec0065" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflicts of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-07-21" "fechaAceptado" => "2016-12-31" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec852686" "palabras" => array:6 [ 0 => "Psoriasis" 1 => "Nonalcoholic fatty liver disease" 2 => "Steatosis" 3 => "Treatment" 4 => "Biologic agents" 5 => "Methotrexate" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec852685" "palabras" => array:6 [ 0 => "Psoriasis" 1 => "Hígado graso no alcohólico" 2 => "Esteatosis" 3 => "Tratamiento" 4 => "Biológicos" 5 => "Metotrexato" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the West. The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis. The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance, a common finding in diseases associated with psoriasis. NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis, in particular if they show signs of metabolic syndrome and require systemic treatment. Concomitant psoriasis and NAFLD and the likelihood of synergy between them place limitations on general recommendations and treatment for these patients given the potential for liver toxicity. As hepatotoxic risk is associated with some of the conventional drugs used in this setting (e.g., acitretin, methotrexate, and ciclosporin), patients prescribed these treatments should be monitored as appropriate. Anti-tumor necrosis factor agents hold the promise of potential benefits based on their effects on the inflammatory process and improving peripheral insulin resistance. However, cases of liver toxicity have also been reported in relation to these biologics. No evidence has emerged to suggest that anti-p40 or anti-interleukin 17 agents provide benefits or have adverse effects." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El hígado graso no alcohólico es la principal causa de enfermedad hepática en nuestro medio. Los pacientes con psoriasis presentan mayor prevalencia y gravedad y peor pronóstico de esta hepatopatía. El vínculo patogénico entre ambas es el estado de inflamación crónica y la resistencia periférica a la insulina, habitual en las comorbilidades asociadas a la psoriasis. Por este motivo, en la evaluación de los pacientes con psoriasis, en particular si existen componentes del síndrome metabólico y se requiere tratamiento sistémico, se recomienda descartar esta posibilidad. La coexistencia de psoriasis e hígado graso no alcohólico, con probable sinergia entre ambos, condiciona las medidas generales que deben recomendarse en estos pacientes y también la estrategia terapéutica, por la potencial hepatotoxicidad de algunos de ellos. En este sentido, algunos de los fármacos convencionales habituales como acitretino, metotrexato o ciclosporina presentan potenciales efectos hepatotóxicos cuya repercusión en cada paciente debe evaluarse de forma individualizada. Los fármacos anti-TNF podrían tener efectos beneficiosos fundamentados en el buen control del proceso inflamatorio y de una mejoría de la resistencia periférica a la insulina. Sin embargo, se han descrito casos de hepatotoxicidad en algunos pacientes. No existe evidencia de efectos beneficiosos o perjudiciales de los fármacos anti p40 o anti IL-17." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Carrascosa JM, Bonanad C, Dauden E, Botella R, Olveira-Martín A, en nombre del Grupo de Trabajo en Inflamación Sistémica en Psoriasis. Psoriasis e hígado graso no alcohólico. Actas Dermosifiliogr. 2017;108:506–514." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1899 "Ancho" => 2543 "Tamanyo" => 220759 ] ] "descripcion" => array:1 [ "en" => "Nonalcoholic fatty liver disease (NAFLD) in patients with psoriasis. Adapted from clinical guidelines.<a class="elsevierStyleCrossRef" href="#bib0385">17</a> a Aspartate transaminase (ASP), alanine transaminase (ALT), and γ-glutamyltransferase (GGT). bAny increase in ASP, ALT, and/or GGT." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; BMI, body mass index; NAFLD, nonalcoholic fatty liver disease." "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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NAFLD Fibrosis Score=–1.675+0.037×age in y+0.094×BMI (kg/m2)+1.13×glucose intolerance or diabetes (yes=1, no=0)+0.99×AST/ALT ratio–0.013×platelet count (×109/L)–0.66×albumin (g/dL) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Calculator available from: http://nafldscore.com \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A score <–1.455 predicts low risk for advanced fibrosis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A score >0.676 predicts advanced fibrosis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Risk is indeterminate if the score falls between –1.455 and 0.676. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1450819.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Adapted from Angulo et al.<a class="elsevierStyleCrossRef" href="#bib0375">15</a>" ] ] ] "descripcion" => array:1 [ "en" => "Formula for the NAFLD Fibrosis Score and Risk Interpretation <a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>" ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; CRP, C-reactive protein; NAFLD, nonalcoholic fatty liver disease; OR, odds ratio; PASI, Psoriasis Area and Severity Index." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Authors \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study Population \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Psoriasis, n \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No Psoriasis, n \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Findings \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Ethnicity \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Roberts et al.<a class="elsevierStyleCrossRef" href="#bib0450">30</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Patients with psoriasis or psoriatic arthritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">103 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NAFLD prevalence, 47%. Steatohepatitis in 22% of patients with NAFLD. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Caucasians, Latin Americans, African Americans, Asians \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gisondi et al.<a class="elsevierStyleCrossRef" href="#bib0425">25</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hospitalized dermatology patients; controls, hospital staff \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">130 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">260 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NAFLD prevalence higher in psoriasis patients (47%) than controls (28%) (P<.0001). Metabolic syndrome and elevated CRP levels more prevalent in patients with psoriasis and NAFLD (n=61), who also had higher mean (SD) PASI levels: 14.2 (12.6) vs 9.6 (7.4) for patients without NAFLD (n=69) (P<.01). \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not reported (Caucasians?) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Miele et al.<a class="elsevierStyleCrossRef" href="#bib0430">26</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Patients with psoriasis; patients with NAFLD without psoriasis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">142 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">125 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">59.2% were diagnosed with NAFLD. Metabolic syndrome, obesity, dyslipidemia, elevated AST/ALT ratio, and psoriatic arthritis frequencies were higher in patients with both psoriasis and NAFLD. NAFLD patients with psoriasis had more severe liver disease than patients without psoriasis. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not reported (Caucasians?) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Abedini et al.<a class="elsevierStyleCrossRef" href="#bib0440">28</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Patients with psoriasis vs healthy controls \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">123 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">123 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prevalence of NAFLD was higher in psoriasis patients (65.6% vs 35% in controls) (P<.01, OR=3.53). Moderately severe NAFLD (grade 2) was more common than mild NAFLD (grade 1) (P<.01) in psoriasis patients. Higher rates of hypertension (16.5%), altered liver function (16.4%), and metabolic syndrome (46.6%) also found in patients with psoriasis and NAFLD. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not reported (Caucasians?) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">van der Voort et al.<a class="elsevierStyleCrossRef" href="#bib0435">27</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Patients >55 years with NAFLD and psoriasis vs NAFLD patients without psoriasis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">118 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2174 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46.2% had NAFLD and psoriasis; 33%, only NAFLD. Psoriasis continued to be a predictor of NAFLD after controlling for alcohol consumption, ALT level, and presence of metabolic syndrome. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">95% Caucasian \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1450821.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main Findings of Studies on the Prevalence and Features of NAFLD in Psoriasis." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Abbreviation: HDL, high-density lipoprotein." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Waist circumference ≥94cm (♂),≥80cm (♀) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Blood pressure≥130/85mmHg or on antihypertensive treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fasting glucose≥100mg/dL or in treatment for type 2 diabetes mellitus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Triglycerides≥150mg/dL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HDL cholesterol<40mg/dL (♂) or<50mg/dL (♀) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1450820.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "Source, joint guidelines of the European Association for the Study of the Liver, the European Association for the Study of Diabetes, and the European Association for the Study of Obesity.<a class="elsevierStyleCrossRef" href="#bib0385">17</a>" ] ] ] "descripcion" => array:1 [ "en" => "Risk Factors for Metabolic Syndrome <a class="elsevierStyleCrossRef" href="#tblfn0010">a</a>" ] ] 4 => array:5 [ "identificador" => "tb0005" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "Key Points<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">-The incidence of NAFLD is 1.5- to 3-fold higher in psoriasis patients than in the nonpsoriatic population, meaning we can expect to find NAFLD in roughly half of our patients with psoriasis. The prevalence of steatohepatitis is also higher in psoriasis.</li><li class="elsevierStyleListItem" id="lsti0010">-Prognosis in NAFLD is affected by the presence and severity of steatohepatitis and liver fibrosis.</li><li class="elsevierStyleListItem" id="lsti0015">-Abdominal ultrasound screening is recommended in patients with insulin resistance or signs of metabolic syndrome and moderate to severe psoriasis, even in the absence of abnormal liver enzymes.</li><li class="elsevierStyleListItem" id="lsti0020">-Patients with NAFLD should be referred to a specialist for evaluation and follow-up.</li><li class="elsevierStyleListItem" id="lsti0025">-A fatty liver limits therapeutic options and makes it advisable to tailor monitoring in patients taking potentially hepatotoxic drugs.</li><li class="elsevierStyleListItem" id="lsti0030">-Anti-TNF biologics offer theoretical benefits for patients with NAFLD as a result of better control of the inflammatory process and peripheral insulin resistance. 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Psoriasis and Nonalcoholic Fatty Liver Disease

Psoriasis e hígado graso no alcohólico

J.M. Carrascosaa,

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jmcarrascosac@hotmail.com

Corresponding author.

, C. Bonanadb, E. Daudenc, R. Botellad, A. Olveira-Martíne, on behalf of the Systemic Inflammation in Psoriasis Working Group

a Servicio de Dermatologia, Hospital Universitari Germans Trias i Pujol. Universitat Autònoma de Barcelona, Badadalona, Spain

b Servicio de Cardiología, Hospital Clínico Universitario, Valencia, Spain

c Servicio de Dermatología, Hospital La Princesa, Madrid, Spain

d Servicio de Dermatología, Hospital Universitario La Fe, Valencia, Spain

e Servicio de Aparato Digestivo, Hospital la Paz, Madrid, Spain

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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Nonalcoholic fatty liver disease &#40;NAFLD&#41; in patients with psoriasis&#46; Adapted from clinical guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">17</span></a></p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span> Aspartate transaminase &#40;ASP&#41;&#44; alanine transaminase &#40;ALT&#41;&#44; and &#947;-glutamyltransferase &#40;GGT&#41;&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">b</span>Any increase in ASP&#44; ALT&#44; and&#47;or GGT&#46;</p>"
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nearly all patients diagnosed with NAFLD share the characteristics associated with metabolic risk&#44; such as obesity&#44; type 2 diabetes mellitus&#44; hypertension&#44; and dyslipidemia&#46; NAFLD and metabolic syndrome share the pathophysiologic mechanism of insulin resistance&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Two histologic forms of the disease can be distinguished&#58; one is steatosis&#44; in which fat has been deposited but liver cells are not yet damaged&#44; and the other is steatohepatitis&#44; which is characterized by liver inflammation that can eventually lead to fibrosis&#46; Mortality is higher in patients with NAFLD than in the general population&#44; regardless of which of these histologic variants is present&#59; the cause of death is usually cardiovascular disease&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">3</span></a> Because steatohepatitis is an inflammatory condition&#44; the liver is threatened&#44; and 15&#37; to 25&#37; of patients will have progressed to cirrhosis within 10 years&#46; Once cirrhosis develops&#44; complications &#40;liver failure&#44; esophageal varices&#44; and liver cancer&#41; will lead to death in 25&#37; of affected patients within 5 years&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">4</span></a> Why fat deposition causes inflammation and fibrosis in some patients but not others is poorly understood&#44; although genetic and environmental factors are probably both relevant&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">NAFLD is important in the West because it is currently the most prevalent liver disorder&#46; Approximately 20&#37; of adults in the general population have NAFLD&#44; and among them about 20&#37; have the aggressive form&#44; steatohepatitis&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">6</span></a> The prevalence is much higher among adults with metabolic syndrome&#44; where 38&#37; of overweight persons &#40;with a body mass index &#91;BMI&#93; between 25 and 30&#41; have NAFLD&#46; The prevalence rates in obese &#40;BMI&#44; 30&#8211;40&#41; and severely obese &#40;BMI&#44; 40&#8211;45&#41; persons are 46&#37; and 65&#37;&#44; respectively&#46; Finally&#44; some 90&#37; of morbidly obese patients &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>45&#41; have this condition&#44; and 5&#37; of them have cirrhosis&#46; Among diabetics&#44; the prevalence is 69&#37;&#44; and among patients with elevated triglyceride levels&#44; 50&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">7</span></a> A sign of the seriousness of this situation is that nonalcoholic steatohepatitis is currently the second most common cause of liver transplantation in the United States&#44; and it is expected to become the first cause in the coming years&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In spite of these statistics&#44; NAFLD is clearly underdiagnosed because there are no signs or symptoms that arouse suspicion except when the disease becomes advanced and also because serum biochemical markers show only slight&#44; nonspecific changes&#59; results may even stay within the normal limits in 15&#37; to 39&#37; of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">A diagnosis of NAFLD requires evidence of steatosis by liver biopsy or imaging and the exclusion of alcohol consumption or other general causes of liver disease or conditions that lead to steatosis&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">1</span></a> The first criterion&#8212;evidence of steatosis&#8212;is critical&#46; The list of causes of liver disease are well established<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">11</span></a> while the alternative causes of steatosis are very rare and&#44; in principle&#44; relatively easy to identify&#46; A liver biopsy is the gold standard&#44; but it is invasive&#44; has associated risk of complications and death&#44; and is costly&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">12</span></a> Furthermore&#44; it is not reasonable or even feasible to biopsy 20&#37; of the population&#46; Interest in finding a noninvasive approach to diagnosis is therefore growing&#46; A fatty liver is usually detected through imaging &#40;ultrasound&#44; computed tomography scans&#44; or nuclear magnetic resonance&#41;&#59; the sensitivity and specificity of images are 60&#37; and 94&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">13&#44;14</span></a> Ultrasound is usually chosen because it is innocuous and widely available&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">1</span></a> However&#44; neither liver enzymes nor images can distinguish between steatosis and steatohepatitis&#46; Nor can they establish or rule out the presence of fibrosis&#46; Various scoring systems using the results of serum tests have therefore been developed&#46; The most widely accepted is the NAFLD fibrosis score&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">15</span></a> which is calculated according to a formula &#40;<a href="http://nafldscore.com/">http&#58;&#47;&#47;nafldscore&#46;com</a>&#41; based on easy-to-obtain measurements&#58; BMI&#59; age&#59; platelet count&#59; and serum albumin&#44; aspartate transaminase &#40;AST&#41;&#44; and alanine transaminase &#40;ALT&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Moreover&#44; this score is highly sensitive &#40;67&#37;&#41; and specific &#40;60&#37;&#41; for excluding &#40;67&#37;&#41; or detecting &#40;97&#37;&#41; the presence of advanced fibrosis using an area under the receiver operating characteristic curve of 0&#46;85 as the cutoff&#46; The severity of liver damage can also potentially be assessed by measuring liver stiffness indirectly with elastography&#46; The usefulness of this approach would mainly be to identify patients at low risk of advanced fibrosis or cirrhosis given the test&#39;s lack of precision when disease is advanced&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">16</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The European Association for the Study of the Liver&#44; the European Association for the Study of Diabetes&#44; and the European Association for the Study of Obesity have recently published new joint guidelines for managing NAFLD&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">17</span></a> They recommend that all patients with insulin resistance or risk factors for metabolic syndrome be screened for NAFLD by ultrasound and liver biochemistry&#46; Any increase in AST&#44; ALT&#44; and&#47;or &#947;-glutamyltransferase are relevant&#44; regardless of magnitude&#46; The screening algorithm is shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">17</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Therapeutic Management of NAFLD</span><p id="par0035" class="elsevierStylePara elsevierViewall">At this time there is no specific treatment for NAFLD available&#46; Weight loss of at least 7&#37; to 10&#37; and exercise are associated with histologic improvement&#44;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">18</span></a> but they are difficult to achieve and particularly difficult to maintain long-term&#46; Alcohol&#44; saturated fats&#44; and fructose-sweetened beverages should be avoided&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">19</span></a> Coffee consumption&#44; on the other hand&#44; can be recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">20</span></a> Several drugs &#40;metformin&#44; pioglitazone&#44; eicosapentenoic acid&#44; statins&#44; and vitamin E&#41; have been tried&#44; but there is a lack of sufficient evidence on which to base a strong recommendation&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">1&#44;6&#44;21&#8211;24</span></a></p></span></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">NAFLD and Psoriasis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The first observational studies showing an association between NAFLD and psoriasis began to appear during the last 10 years&#44;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">25&#44;26</span></a> and the association has since been confirmed&#46;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">27&#44;28</span></a> Gisondi<span class="elsevierStyleHsp" style=""></span>et<span class="elsevierStyleHsp" style=""></span>al&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">25</span></a> saw a higher rate of ultrasound-diagnosed NAFLD &#40;47&#37;&#41; in a series of 130 consecutive patients with psoriasis than in 260 healthy controls &#40;28&#37;&#41; matched for age&#44; sex&#44; and BMI&#46; The psoriasis patients were also more likely to have metabolic syndrome and higher C-reactive protein levels&#59; those who also had NAFLD had higher interleukin &#40;IL&#41; 6 and lower adiponectin levels than those without the disease&#46; Abedini<span class="elsevierStyleHsp" style=""></span>et<span class="elsevierStyleHsp" style=""></span>al&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">28</span></a> reported finding NAFLD in 65&#46;6&#37; of patients with psoriasis &#40;vs 35&#37; of healthy controls&#41;&#44; and van<span class="elsevierStyleHsp" style=""></span>der<span class="elsevierStyleHsp" style=""></span>Voort<span class="elsevierStyleHsp" style=""></span>et<span class="elsevierStyleHsp" style=""></span>al&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">27</span></a> found that 46&#46;2&#37; of psoriatic patients and 33&#46;3&#37; of controls had NAFLD in a population-based series of 2292 persons over the age of 55 years in Rotterdam&#46; These findings may be attributable to the association between psoriasis and metabolic syndrome&#44; given that the conditions defining the latter are those that lead to NAFLD&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">29</span></a> Miele<span class="elsevierStyleHsp" style=""></span>et<span class="elsevierStyleHsp" style=""></span>al&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">26</span></a> studied a cohort of psoriasis patients with and without NAFLD&#44; finding that NAFLD was also associated with psoriatic arthritis&#46; Roberts<span class="elsevierStyleHsp" style=""></span>et<span class="elsevierStyleHsp" style=""></span>al&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">30</span></a> reported finding a relationship between greater severity of psoriasis and NAFLD&#46; Specifically&#44; they saw steatohepatitis in 22&#37; of the patients with both psoriasis and NAFLD who underwent liver biopsy&#46; The NAFLD patients with steatohepatitis were also more likely to be obese and have higher insulin and transaminase levels&#59; they also found marked differences in risk for NAFLD according to ethnic origin&#46; Similarly&#44; van<span class="elsevierStyleHsp" style=""></span>der<span class="elsevierStyleHsp" style=""></span>Voort<span class="elsevierStyleHsp" style=""></span>et<span class="elsevierStyleHsp" style=""></span>al&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">27</span></a> found that patients of Latin American origin carried greater risk &#40;83&#37;&#41;&#44; followed by Caucasians &#40;39&#37;&#41;&#44; and finally African Americans &#40;33&#37;&#41;&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Clinical Suspicion and Screening for NAFLD in Dermatology</span><p id="par0045" class="elsevierStylePara elsevierViewall">A high index of suspicion concerning NAFLD is needed in dermatology because most cases encountered will be asymptomatic&#46; The dermatologist should above all be aware of the high prevalence in patients with psoriasis&#46; It is also important to note signs of the components of metabolic syndrome&#58; diabetes mellitus&#44; obesity&#44; dyslipidemia&#44; and hypertension&#46; Abnormal liver enzymes may be difficult to discern because elevations are usually slight&#44; at less than 2- to 3-fold the normal values and with an ALT&#47;AST ratio greater than 1&#59; alkaline phosphatase and &#947;-glutamyltransferase are occasionally elevated&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">31</span></a> Liver enzymes can be normal in 15&#37; to 30&#37; or more of patients with NAFLD&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">10</span></a> even though 35&#37; of such patients have advanced fibrosis or cirrhosis&#46; Given this situation&#44; in the presence of the most prevalent indicator of risk for NAFLD&#8212;namely components of metabolic syndrome&#8212;ultrasound imaging to rule out liver disease is indicated even when biochemistry is normal&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">17</span></a> At this time&#44; however&#44; the clinical algorithm recommended by most medical associations specializing in NAFLD &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; does not recognize the need for imaging to evaluate patients with psoriasis in the absence of liver enzyme abnormalities&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Once NAFLD has been confirmed&#44; the dermatologist must cooperate in prescribing the necessary dietary measures and adjusting drug dosages if transaminase levels are elevated&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The absence of liver damage according to the initial assessment does not exclude its development over the coming years&#46; Therefore&#44; patients will have to be reassessed if analyses reveal signs of damage or if metabolic syndrome develops&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Pathogenesis of NAFLD in Psoriasis</span><p id="par0060" class="elsevierStylePara elsevierViewall">This review does not attempt to delve deeply into the pathogenesis of NAFLD&#44; but it is useful to be aware of the two-hit hypothesis&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">32</span></a> In this theory&#44; the first phase would be marked by the abnormal accumulation of triglycerides in liver cells&#44; a development in which insulin resistance plays a large role&#46; In the second phase&#44; the steatotic liver appears to become susceptible to injury induced by several players and events involving various adipokines and oxidative stress in the endoplasmic reticulum&#44; as well as mitochondrial dysfunction and liver apoptosis&#46; These events favor the transition from simple steatosis to steatohepatitis&#46; Besides the involvement of insulin resistance in both these phases of progression toward NAFLD&#8212;as well as in the induction and activation of profibrotic cytokines&#8212;other chronic inflammatory processes that might be present&#44; such as psoriasis&#44; can contribute proinflammatory cytokines&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">33</span></a> Thus&#44; the pathogenic relationship between NAFLD and psoriasis is complex and probably multifactorial&#44; although it is presumably related to a state of chronic underlying inflammation&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">NAFLD and psoriasis are probably linked partly because some of the conditions that often accompany psoriasis are also the ones that cause NAFLD&#46; Among them&#44; obesity stands out&#46; The epidemiologic association between obesity and psoriasis is clear&#44; particularly in severe psoriasis&#44; and the influences probably operate in both directions&#44; such that obesity favors psoriasis and vice versa&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">34</span></a> The prevalence of NAFLD is also clearly higher in obese patients&#44; especially those with excess abdominal fat&#44; which is more metabolically active than subcutaneous fat&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">35</span></a> Obesity is associated with risk for developing insulin resistance&#44; the main factor in the development of NAFLD&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">36</span></a> Excessive fat deposition leads to an imbalance between pro- and anti-inflammatory cytokines&#44; favoring the progression of liver disease&#46; When adipose tissue secretes an abundance of adipokines&#8212;tumor necrosis factor &#40;TNF&#41;&#44; IL-6&#44; leptin&#44; visfatin&#44; or resistin&#8212;a proinflammatory state may develop in psoriatic skin as the result of the proliferation of keratinocytes&#44; angiogenesis&#44; the response of type 1<span class="elsevierStyleHsp" style=""></span>T cells&#44; or the expression of adhesion molecules&#46; This state may also be expressed in NAFLD&#44; contributing to insulin resistance or liver fibrosis&#46; In addition&#44; there is also a decrease in the concentration of adipokines that protect against inflammation&#8212;such as adiponectin&#44; a promotor of skin anti-inflammatory cytokines that enhances insulin sensitivity&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">37</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The involvement of IL-17 in both psoriasis and NAFLD is interesting&#46; T cells in adipose tissue synthesize IL-17&#44; which is able to regulate adipogenesis and glucose metabolism&#46; Type 17<span class="elsevierStyleHsp" style=""></span>T helper cells and IL-17 could facilitate the progression from simple steatosis to steatohepatitis&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">38</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Implications for the Management of Conventional Systemic Treatments</span><p id="par0075" class="elsevierStylePara elsevierViewall">The high prevalence of NAFLD in psoriasis leads to therapeutic concerns because this chronic skin disease must be treated over decades&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The incidence of MTX-induced liver damage is known to be higher in psoriasis<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">39</span></a> than in other chronic inflammatory diseases&#46; A recent retrospective study saw&#44; for example&#44; that 58&#37; of 710 patients on MTX for psoriasis had elevated transaminase levels&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">40</span></a> In the light of our current understanding&#44; this finding may be relevant to the known association between NAFLD and psoriasis&#46; Given the high rates of both NAFLD and steatohepatitis in this setting&#44; we should rule out significant steatosis before starting MTX&#44; at least in patients with signs of metabolic syndrome&#46; In addition to ultrasound screening&#44; two new tools&#44; the FibroTest and the FibroScan &#40;liver elastography&#41; may be useful for assessing liver fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">41</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">MTX toxicity presents with histologic findings and may therefore reflect pathogenic mechanisms that are different from those associated with NAFLD&#46; However&#44; the shared risk factors that aggravate both MTX toxicity and NAFLD&#8212;such as obesity&#44; diabetes&#44; or hyperlipidemia&#8212;are observed often in patients with severe psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">42</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Liver toxicity is also among the potential adverse effects of ciclosporin&#46; The effect may be direct or it may be a byproduct of a deteriorating lipid profile&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">43</span></a> Acitretin can also raise triglyceride levels and has been associated with transaminase elevations in 1 out of 4 patients&#44; although tissue damage following intermittent use of the drug has not been reported&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">44</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Biologic Agents in Patients With Psoriasis and NAFLD</span><p id="par0095" class="elsevierStylePara elsevierViewall">TNF plays a central role in the inflammatory process in NAFLD&#44; as in other chronic inflammatory diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">45</span></a> In fact&#44; TNF has been studied for its potential use as a diagnostic and prognostic tool in NAFLD&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">46</span></a> Given the pathogenic role of this cytokine&#44; anti-TNF agents such as infliximab and adalimumab have also been tried in this setting<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">47&#44;48</span></a> because of improvements observed in liver and metabolic biomarkers after biologic therapy for other inflammatory diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0545"><span class="elsevierStyleSup">49&#44;50</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Biologics have a better safety profile than the conventional treatments for NAFLD mentioned earlier&#46; For example&#44; when adalimumab was used for an average of 5 years in 32 patients with liver disease and psoriasis&#44; no cases of liver disease progression or development of liver toxicity were observed&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">51</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Biologic therapy could exercise regulatory effects on some adipocytokines&#46; Shibata<span class="elsevierStyleHsp" style=""></span>et<span class="elsevierStyleHsp" style=""></span>al&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">52</span></a> reported an increase in adiponectin and IL-6 levels during treatment with infliximab&#44; and adalimumab and etanercept may inhibit proinflammatory adipocytokines&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">53</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Studies of the impact of anti-TNF agents on the lipid profile&#44; a risk factor for NAFLD&#44; have yielded inconsistent results&#46; While some authors have not been able to demonstrate a significant effect&#44; others have reported elevated triglycerides and lower high-density lipoprotein &#40;HDL&#41; cholesterol levels in patients with infliximab-treated psoriatic arthritis&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">54</span></a> Etanercept therapy&#44; on the other hand&#44; has favorably modulated the antioxident and anti-inflammatory properties of HDL cholesterol as well as modulated adipolipoprotein A1 and B levels&#44; reducing lipid peroxidation&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">55</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Marra et al&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">56</span></a> showed improved insulin sensitivity in patients treated with etanercept for psoriasis&#44; an effect that could potentially have a favorable influence on the course of NAFLD&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">It must be borne in mind that anti-TNF agents can occasionally induce autoimmune or drug-related hepatitis&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">57</span></a> The risk is very low&#44; however&#46; Only 20 cases of autoimmune hepatitis have ever been reported&#59; most were mild cases associated with infliximab and responded quickly to steroid treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">41</span></a> Anti-TNF agents have also been linked to weight gain in psoriasis patients&#44; although the gains have generally been modest&#46; However&#44; long-term use has led to considerable gain in some patients&#44; and this adverse effect potentially aggravates the obesity associated with severe psoriasis and NAFLD&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">58</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">High transaminase levels were detected in 6 patients in a series of 44 treated with ustekinumab for an average of 46&#46;7 months&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">59</span></a> Five of the 6 patients developed hepatotoxicity related to other drugs&#44; 3 developed fatty liver&#44; and 3 were receiving other hepatotoxic drugs while taking ustekinumab&#46; The authors concluded that ustekinumab-related toxicity was mild and uncommon&#46; Hepatotoxicity is not described as a side effect detected in clinical trials of secukinumab<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">60</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusions</span><p id="par0130" class="elsevierStylePara elsevierViewall">NAFLD is the most frequent liver disorder in the West &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Patients with psoriasis have a higher prevalence of NAFLD&#44; a higher rate of severe disease&#44; and a worse prognosis&#46; Dermatologists should routinely evaluate psoriasis patients for NAFLD&#46; The pathogenic links between psoriasis and NAFLD are chronic inflammation and peripheral insulin resistance&#44; which is a common finding in diseases associated with psoriasis&#46; The dermatologist should be aware not only of the high prevalence of NAFLD in psoriasis but also of the possibility of steatohepatitis&#44; especially when psoriasis is severe or when there are signs of metabolic syndrome&#46; Psoriasis patients with insulin resistance or risk factors for metabolic syndrome should be specifically evaluated for fatty liver by abdominal ultrasound and liver biochemistry&#46; Concurrent psoriasis and NAFLD&#44; and the likely synergy between them&#44; affect the general recommendations we can make and the treatment strategies we can adopt&#46; Some drugs carry risk of hepatotoxicity&#46; On the other hand&#44; there is a possibility that achieving good control of inflammation and pathogenic factors associated with NAFLD will improve the prognosis&#46;<elsevierMultimedia ident="tb0005"></elsevierMultimedia></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Ethical Disclosures</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Protection of human and animal subjects</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Data confidentiality</span><p id="par0175" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data are disclosed in this article&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Right to privacy and informed consent</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data are disclosed in this article&#46;</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflicts of Interest</span><p id="par0185" class="elsevierStylePara elsevierViewall">Abbvie sponsored the meetings of the working group&#44; but no employees of the laboratory participated in the research&#44; interpretation&#44; discussion&#44; or drafting of the text&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">J&#46; M&#46; Carrascosa has served as a consultant&#44; given invited talks&#44; and&#47;or participated in clinical trials sponsored by the following laboratories&#58; Abbvie&#44; Janssen&#44; Lilly&#44; Pfizer&#44; Novartis&#44; Pfizer&#44; and Celgene&#46;</p></span></span>"
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          "titulo" => "Nonalcoholic Fatty Liver Disease&#58; The Concept"
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              "titulo" => "Therapeutic Management of NAFLD"
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          "titulo" => "NAFLD and Psoriasis"
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          "titulo" => "Biologic Agents in Patients With Psoriasis and NAFLD"
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            0 => "Psoriasis"
            1 => "Nonalcoholic fatty liver disease"
            2 => "Steatosis"
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            4 => "Biologic agents"
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            0 => "Psoriasis"
            1 => "H&#237;gado graso no alcoh&#243;lico"
            2 => "Esteatosis"
            3 => "Tratamiento"
            4 => "Biol&#243;gicos"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Nonalcoholic fatty liver disease &#40;NAFLD&#41; is the most prevalent liver condition in the West&#46; The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis&#46; The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance&#44; a common finding in diseases associated with psoriasis&#46; NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis&#44; in particular if they show signs of metabolic syndrome and require systemic treatment&#46; Concomitant psoriasis and NAFLD and the likelihood of synergy between them place limitations on general recommendations and treatment for these patients given the potential for liver toxicity&#46; As hepatotoxic risk is associated with some of the conventional drugs used in this setting &#40;e&#46;g&#46;&#44; acitretin&#44; methotrexate&#44; and ciclosporin&#41;&#44; patients prescribed these treatments should be monitored as appropriate&#46; Anti-tumor necrosis factor agents hold the promise of potential benefits based on their effects on the inflammatory process and improving peripheral insulin resistance&#46; However&#44; cases of liver toxicity have also been reported in relation to these biologics&#46; No evidence has emerged to suggest that anti-p40 or anti-interleukin 17 agents provide benefits or have adverse effects&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El h&#237;gado graso no alcoh&#243;lico es la principal causa de enfermedad hep&#225;tica en nuestro medio&#46; Los pacientes con psoriasis presentan mayor prevalencia y gravedad y peor pron&#243;stico de esta hepatopat&#237;a&#46; El v&#237;nculo patog&#233;nico entre ambas es el estado de inflamaci&#243;n cr&#243;nica y la resistencia perif&#233;rica a la insulina&#44; habitual en las comorbilidades asociadas a la psoriasis&#46; Por este motivo&#44; en la evaluaci&#243;n de los pacientes con psoriasis&#44; en particular si existen componentes del s&#237;ndrome metab&#243;lico y se requiere tratamiento sist&#233;mico&#44; se recomienda descartar esta posibilidad&#46; La coexistencia de psoriasis e h&#237;gado graso no alcoh&#243;lico&#44; con probable sinergia entre ambos&#44; condiciona las medidas generales que deben recomendarse en estos pacientes y tambi&#233;n la estrategia terap&#233;utica&#44; por la potencial hepatotoxicidad de algunos de ellos&#46; En este sentido&#44; algunos de los f&#225;rmacos convencionales habituales como acitretino&#44; metotrexato o ciclosporina presentan potenciales efectos hepatot&#243;xicos cuya repercusi&#243;n en cada paciente debe evaluarse de forma individualizada&#46; Los f&#225;rmacos anti-TNF podr&#237;an tener efectos beneficiosos fundamentados en el buen control del proceso inflamatorio y de una mejor&#237;a de la resistencia perif&#233;rica a la insulina&#46; Sin embargo&#44; se han descrito casos de hepatotoxicidad en algunos pacientes&#46; No existe evidencia de efectos beneficiosos o perjudiciales de los f&#225;rmacos anti p40 o anti IL-17&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as&#58; Carrascosa JM&#44; Bonanad C&#44; Dauden E&#44; Botella R&#44; Olveira-Mart&#237;n A&#44; en nombre del Grupo de Trabajo en Inflamaci&#243;n Sist&#233;mica en Psoriasis&#46; Psoriasis e h&#237;gado graso no alcoh&#243;lico&#46; Actas Dermosifiliogr&#46; 2017&#59;108&#58;506&#8211;514&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Nonalcoholic fatty liver disease &#40;NAFLD&#41; in patients with psoriasis&#46; Adapted from clinical guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">17</span></a></p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span> Aspartate transaminase &#40;ASP&#41;&#44; alanine transaminase &#40;ALT&#41;&#44; and &#947;-glutamyltransferase &#40;GGT&#41;&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">b</span>Any increase in ASP&#44; ALT&#44; and&#47;or GGT&#46;</p>"
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; ALT&#44; alanine transaminase&#59; AST&#44; aspartate transaminase&#59; BMI&#44; body mass index&#59; NAFLD&#44; nonalcoholic fatty liver disease&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NAFLD Fibrosis Score<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8211;1&#46;675<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>0&#46;037<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>age in y<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>0&#46;094<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>BMI &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1&#46;13<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>glucose intolerance or diabetes &#40;yes<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44; no<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#41;<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>0&#46;99<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>AST&#47;ALT ratio&#8211;0&#46;013<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>platelet count &#40;&#215;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>&#47;L&#41;&#8211;0&#46;66<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>albumin &#40;g&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Calculator available from&#58; http&#58;&#47;&#47;nafldscore&#46;com&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>A score &#60;<span class="elsevierStyleHsp" style=""></span>&#8211;1&#46;455 predicts low risk for advanced fibrosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>A score &#62;<span class="elsevierStyleHsp" style=""></span>0&#46;676 predicts advanced fibrosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Risk is indeterminate if the score falls between &#8211;1&#46;455 and 0&#46;676&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Adapted from Angulo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">15</span></a></p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Formula for the NAFLD Fibrosis Score and Risk Interpretation <a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; ALT&#44; alanine transaminase&#59; AST&#44; aspartate transaminase&#59; CRP&#44; C-reactive protein&#59; NAFLD&#44; nonalcoholic fatty liver disease&#59; OR&#44; odds ratio&#59; PASI&#44; Psoriasis Area and Severity Index&#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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Authors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study Population&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Psoriasis&#44; n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No Psoriasis&#44; n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Findings&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Ethnicity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Roberts et al&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">30</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patients with psoriasis or psoriatic arthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">103&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NAFLD prevalence&#44; 47&#37;&#46; Steatohepatitis in 22&#37; of patients with NAFLD&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Caucasians&#44; Latin Americans&#44; African Americans&#44; Asians&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gisondi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hospitalized dermatology patients&#59;<br>controls&#44; hospital staff&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">260&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NAFLD prevalence higher in psoriasis patients &#40;47&#37;&#41; than controls &#40;28&#37;&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46; Metabolic syndrome and elevated CRP levels more prevalent in patients with psoriasis and NAFLD &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>61&#41;&#44; who also had higher mean &#40;SD&#41; PASI levels&#58; 14&#46;2 &#40;12&#46;6&#41; vs 9&#46;6 &#40;7&#46;4&#41; for patients without NAFLD &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>69&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;&#46;01&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not reported<br>&#40;Caucasians&#63;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Miele et al&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patients with psoriasis&#59; patients with NAFLD without psoriasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">142&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">125&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59&#46;2&#37; were diagnosed with NAFLD&#46; Metabolic syndrome&#44; obesity&#44; dyslipidemia&#44; elevated AST&#47;ALT ratio&#44; and psoriatic arthritis frequencies were higher in patients with both psoriasis and NAFLD&#46; NAFLD patients with psoriasis had more severe liver disease than patients without psoriasis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not reported<br>&#40;Caucasians&#63;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Abedini et al&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">28</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patients with psoriasis vs healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">123&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">123&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Prevalence of NAFLD was higher in psoriasis patients &#40;65&#46;6&#37; vs 35&#37; in controls&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;&#46;01&#44; OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#46;53&#41;&#46;<br>Moderately severe NAFLD &#40;grade 2&#41; was more common than mild NAFLD &#40;grade 1&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;&#46;01&#41; in psoriasis patients&#46; Higher rates of hypertension &#40;16&#46;5&#37;&#41;&#44; altered liver function &#40;16&#46;4&#37;&#41;&#44; and metabolic syndrome &#40;46&#46;6&#37;&#41; also found in patients with psoriasis and NAFLD&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not reported<br>&#40;Caucasians&#63;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">van der Voort et al&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Patients &#62;55 years with NAFLD and psoriasis vs NAFLD patients without psoriasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">118&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2174&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">46&#46;2&#37; had NAFLD and psoriasis&#59; 33&#37;&#44; only NAFLD&#46; Psoriasis continued to be a predictor of NAFLD after controlling for alcohol consumption&#44; ALT level&#44; and presence of metabolic syndrome&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&#37; Caucasian&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Main Findings of Studies on the Prevalence and Features of NAFLD in Psoriasis&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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            "identificador" => "at3"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Abbreviation&#58; HDL&#44; high-density lipoprotein&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Waist circumference <span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>94<span class="elsevierStyleHsp" style=""></span>cm &#40;&#9794;&#41;&#44;<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>80<span class="elsevierStyleHsp" style=""></span>cm &#40;&#9792;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">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 on antihypertensive treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fasting glucose<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>mg&#47;dL or in treatment for type 2 diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Triglycerides<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>150<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HDL cholesterol<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;&#9794;&#41; or<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;&#9792;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            0 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Source&#44; joint guidelines of the European Association for the Study of the Liver&#44; the European Association for the Study of Diabetes&#44; and the European Association for the Study of Obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">17</span></a></p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Risk Factors for Metabolic Syndrome&#160;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a></p>"
        ]
      ]
      4 => array:5 [
        "identificador" => "tb0005"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Key Points</span><p id="par0135" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0140" class="elsevierStylePara elsevierViewall">The incidence of NAFLD is 1&#46;5- to 3-fold higher in psoriasis patients than in the nonpsoriatic population&#44; meaning we can expect to find NAFLD in roughly half of our patients with psoriasis&#46; The prevalence of steatohepatitis is also higher in psoriasis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0145" class="elsevierStylePara elsevierViewall">Prognosis in NAFLD is affected by the presence and severity of steatohepatitis and liver fibrosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0150" class="elsevierStylePara elsevierViewall">Abdominal ultrasound screening is recommended in patients with insulin resistance or signs of metabolic syndrome and moderate to severe psoriasis&#44; even in the absence of abnormal liver enzymes&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0155" class="elsevierStylePara elsevierViewall">Patients with NAFLD should be referred to a specialist for evaluation and follow-up&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0160" class="elsevierStylePara elsevierViewall">A fatty liver limits therapeutic options and makes it advisable to tailor monitoring in patients taking potentially hepatotoxic drugs&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0165" class="elsevierStylePara elsevierViewall">Anti-TNF biologics offer theoretical benefits for patients with NAFLD as a result of better control of the inflammatory process and peripheral insulin resistance&#46; Ustekinumab and secukinumab do not seem to affect NAFLD adversely&#46;</p></li></ul></p></span></span>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:60 [
            0 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The diagnosis and management of non-alcoholic fatty liver disease&#58; Practice guideline by the American Association for the Study of Liver Diseases&#44; American College of Gastroenterology&#44; and the American Gastroenterological Association"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Chalasani"
                            1 => "Z&#46; Younossi"
                            2 => "J&#46;E&#46; Lavine"
                            3 => "A&#46;M&#46; Diehl"
                            4 => "E&#46;M&#46; Brunt"
                            5 => "K&#46; Cusi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.25762"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2012"
                        "volumen" => "55"
                        "paginaInicial" => "2005"
                        "paginaFinal" => "2023"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22488764"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nonalcoholic fatty liver disease&#58; A precursor of the metabolic syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46; Lonardo"
                            1 => "S&#46; Ballestri"
                            2 => "G&#46; Marchesini"
                            3 => "P&#46; Angulo"
                            4 => "P&#46; Loria"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.dld.2014.09.020"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dig Liver Dis"
                        "fecha" => "2015"
                        "volumen" => "47"
                        "paginaInicial" => "181"
                        "paginaFinal" => "190"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25739820"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "NAFLD&#58; A multisystem disease"
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Article information

ISSN: 15782190
Original language: English

DOI:10.1016/j.adengl.2017.05.017

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	24	7	31
2024 October	145	40	185
2024 September	170	28	198
2024 August	196	53	249
2024 July	167	36	203
2024 June	153	32	185
2024 May	146	41	187
2024 April	206	36	242
2024 March	175	38	213
2024 February	133	42	175
2024 January	123	32	155
2023 December	103	32	135
2023 November	124	42	166
2023 October	123	58	181
2023 September	98	50	148
2023 August	81	21	102
2023 July	92	45	137
2023 June	77	32	109
2023 May	84	30	114
2023 April	73	32	105
2023 March	117	42	159
2023 February	101	36	137
2023 January	90	46	136
2022 December	103	49	152
2022 November	55	40	95
2022 October	88	29	117
2022 September	39	47	86
2022 August	30	27	57
2022 July	37	59	96
2022 June	39	30	69
2022 May	81	55	136
2022 April	141	47	188
2022 March	117	61	178
2022 February	94	44	138
2022 January	80	48	128
2021 December	75	48	123
2021 November	55	65	120
2021 October	80	78	158
2021 September	363	60	423
2021 August	151	71	222
2021 July	70	50	120
2021 June	97	41	138
2021 May	101	79	180
2021 April	181	187	368
2021 March	112	71	183
2021 February	95	93	188
2021 January	83	52	135
2020 December	139	37	176
2020 November	80	53	133
2020 October	84	37	121
2020 September	69	20	89
2020 August	53	43	96
2020 July	70	38	108
2020 June	51	51	102
2020 May	42	31	73
2020 April	37	35	72
2020 March	38	28	66
2020 February	4	0	4
2020 January	3	0	3
2019 December	4	0	4
2019 November	4	0	4
2019 September	4	0	4
2019 August	4	0	4
2019 July	4	0	4
2019 June	4	0	4
2019 May	3	0	3
2019 April	2	0	2
2019 March	1	0	1
2019 February	2	0	2
2019 January	5	0	5
2018 December	12	0	12
2018 November	2	0	2
2018 October	9	0	9
2018 September	4	0	4
2018 May	2	0	2
2018 February	54	11	65
2018 January	63	9	72
2017 December	80	19	99
2017 November	57	15	72
2017 October	65	17	82
2017 September	64	18	82
2017 August	56	42	98
2017 July	156	34	190
2017 June	22	30	52

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