MASLD biomarkers: Are we facing a new era?

Maya-Miles, Douglas; Ampuero, Javier; Martí-Aguado, David; Conthe, Andrés; Gallego-Durán, Rocío
doi:10.1016/j.gastrohep.2024.02.004
 array:23 [
  "pii" => "S0210570524000530"
  "issn" => "02105705"
  "doi" => "10.1016/j.gastrohep.2024.02.004"
  "estado" => "S300"
  "fechaPublicacion" => "2024-04-01"
  "aid" => "2173"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;. All rights reserved"
  "copyrightAnyo" => "2024"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "sco"
  "cita" => "Gastroenterol Hepatol. 2024;47:393-6"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemSiguiente" => array:17 [
    "pii" => "S021057052300393X"
    "issn" => "02105705"
    "doi" => "10.1016/j.gastrohep.2023.08.006"
    "estado" => "S300"
    "fechaPublicacion" => "2024-04-01"
    "aid" => "2111"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "ssu"
    "cita" => "Gastroenterol Hepatol. 2024;47:397-400"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>"
      "titulo" => "<span class="elsevierStyleItalic">MSH3</span>-related adenomatous polyposis in a patient with the negative family history of colorectal polyps"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "397"
          "paginaFinal" => "400"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Poliposis adenomatosa relacionada con MSH3 en un paciente con antecedentes familiares negativos de p&#243;lipos colorrectales"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0015"
          "etiqueta" => "Figure 3"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr3.jpeg"
              "Alto" => 841
              "Ancho" => 2508
              "Tamanyo" => 116500
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A retrospective chronological phenotypic description of our patient&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Aleksandar Gavric, Mateja Krajc, Luka Strnisa, Ana Ursula Gavric, Samo Plut"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "Aleksandar"
              "apellidos" => "Gavric"
            ]
            1 => array:2 [
              "nombre" => "Mateja"
              "apellidos" => "Krajc"
            ]
            2 => array:2 [
              "nombre" => "Luka"
              "apellidos" => "Strnisa"
            ]
            3 => array:2 [
              "nombre" => "Ana Ursula"
              "apellidos" => "Gavric"
            ]
            4 => array:2 [
              "nombre" => "Samo"
              "apellidos" => "Plut"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S021057052300393X?idApp=UINPBA00004N"
    "url" => "/02105705/0000004700000004/v2_202406091228/S021057052300393X/v2_202406091228/en/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S0210570523004752"
    "issn" => "02105705"
    "doi" => "10.1016/j.gastrohep.2023.11.005"
    "estado" => "S300"
    "fechaPublicacion" => "2024-04-01"
    "aid" => "2142"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;"
    "documento" => "simple-article"
    "crossmark" => 1
    "subdocumento" => "cor"
    "cita" => "Gastroenterol Hepatol. 2024;47:391-2"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>"
      "titulo" => "Ischemic colitis due to Kayexalate crystals"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "391"
          "paginaFinal" => "392"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Colitis isqu&#233;mica por cristales de kayexalato"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "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" => 1862
              "Ancho" => 2417
              "Tamanyo" => 748598
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Cecum and ascending colon wall thickening in CT scan&#46; &#40;b&#41; Endoscopic ulcers at cecum&#44; ileocecal valve&#46; &#40;c&#41; Ulcerated areas&#44; observing fibrinoleukocyte material and granulation tissue with Kayexalate crystals&#46; &#40;d&#41; Kayexalate crystals amplified in size&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Berta Lopez-Saez, Alex Casalots, Eva Ballesteros, Eduard Brunet-Mas"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Berta"
              "apellidos" => "Lopez-Saez"
            ]
            1 => array:2 [
              "nombre" => "Alex"
              "apellidos" => "Casalots"
            ]
            2 => array:2 [
              "nombre" => "Eva"
              "apellidos" => "Ballesteros"
            ]
            3 => array:2 [
              "nombre" => "Eduard"
              "apellidos" => "Brunet-Mas"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570523004752?idApp=UINPBA00004N"
    "url" => "/02105705/0000004700000004/v2_202406091228/S0210570523004752/v2_202406091228/en/main.assets"
  ]
  "en" => array:15 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Young corner</span>"
    "titulo" => "MASLD biomarkers&#58; Are we facing a new era&#63;"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "393"
        "paginaFinal" => "396"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Douglas Maya-Miles, Javier Ampuero, David Mart&#237;-Aguado, Andr&#233;s Conthe, Roc&#237;o Gallego-Dur&#225;n"
        "autores" => array:5 [
          0 => array:3 [
            "nombre" => "Douglas"
            "apellidos" => "Maya-Miles"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Javier"
            "apellidos" => "Ampuero"
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "David"
            "apellidos" => "Mart&#237;-Aguado"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Andr&#233;s"
            "apellidos" => "Conthe"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
            ]
          ]
          4 => array:4 [
            "nombre" => "Roc&#237;o"
            "apellidos" => "Gallego-Dur&#225;n"
            "email" => array:1 [
              0 => "rgallego-ibis@us.es"
            ]
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:5 [
          0 => array:3 [
            "entidad" => "SeLiver Group&#44; Instituto de Biomedicina de Sevilla&#47;CSIC&#47;Universidad de Sevilla&#44; Sevilla&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Hepatic and Digestive Diseases Networking Biomedical Research Centre &#40;CIBERehd&#41;&#44; Madrid&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Digestive Diseases Unit&#44; Hospital Universitario Virgen del Roc&#237;o&#44; Sevilla&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Servicio de Aparato Digestivo&#44; Hospital Cl&#237;nico Universitario de Valencia&#44; INCLIVA Instituto de Investigaci&#243;n Sanitaria&#44; Valencia&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Secci&#243;n de Hepatolog&#237;a&#44; Servicio de Aparato Digestivo&#44; Hospital General Universitario Gregorio Mara&#241;&#243;n&#44; Madrid&#44; Spain"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Biomarcadores en MASLD&#44; &#191;estamos ante una nueva era&#63;"
      ]
    ]
    "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" => 2439
            "Ancho" => 2925
            "Tamanyo" => 500218
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Facing a new era in MASLD biomarkers&#46; Progressive forms of liver disease require the use of targeted therapies adapted to stratified groups of patients&#44; considering the main drivers of the disease to define patients&#8217; subphenotypes&#46; Biomarkers have proven diagnostic accuracy in targeted populations &#40;higher prevalence&#41;&#44; but require further validation in primary care settings &#40;lower prevalence&#41; for screening purposes&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">During the past decades&#44; dramatic changes in lifestyle have paralleled the worldwide epidemic of obesity&#44; metabolic disease and chronic liver disorders&#46; This is currently considered a major health concern&#44; in which aberrant metabolism is the root cause for a number of severe health conditions that are currently placing a heavy burden on individuals&#44; families&#44; governments&#44; and healthcare systems&#46; In this context&#44; metabolic dysfunction-associated steatotic liver disease &#40;MASLD&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">1</span></a> formerly known as NAFLD&#41;&#44; has emerged as the most predominant chronic liver disorder worldwide&#46; The global prevalence among adults is currently estimated to be 25&#37; in the general population&#44; and is expected to become the leading cause of end-stages liver diseases worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">2</span></a> MASLD is considered the hepatic manifestation of metabolic syndrome and is linked to extrahepatic complications including malignancies&#44; chronic kidney disease&#44; endocrinopathies&#44; brain ageing and cognitive impairment&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">3&#8211;5</span></a> MASLD encompasses a large spectrum of clinical and metabolic phenotypes&#46; Patients can suffer from steatosis&#44; characterized by the accumulation of lipids in the hepatocytes&#44; or a progressive form of the disease so-called metabolic dysfunction associated steatohepatitis &#40;MASH&#41;&#44; identified by steatosis&#44; inflammation and ballooning&#44; a form of liver degeneration with cell swelling&#46; MASH is associated with liver fibrosis and progression of liver disease to cirrhosis and hepatocellular carcinoma in &#8764;3&#8211;9&#37; of patients&#44; and consequently has become one of the most prevalent indications for liver transplantation worldwide&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a> Further&#44; hepatic fibrosis strongly correlates with morbidity and has been reported as the best predictor of mortality in MASLD patients&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">7</span></a> Despite its global burden&#44; there are no effective drugs approved for MASLD treatment other than changes in lifestyle that lead to weight loss&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a> Finally&#44; histological evaluation of the liver is the reference method for diagnosis and disease activity&#44; but requires an invasive liver biopsy that has associated risks and limitations&#44; and therefore&#44; is not adequate for follow-up studies or to monitor disease progression&#46; Hence&#44; improving diagnosis and therapeutic approaches for MASLD is a key health objective&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">MASLD&#44; a multi-layered disease</span><p id="par0010" class="elsevierStylePara elsevierViewall">Currently&#44; in order to conceive new therapies&#44; there is an urgent need to better understand the pathophysiology behind this disease&#46; Since the term MASLD groups a heterogenous population of patients&#44; it is essential to stratify them following the main driver&#47;drivers of the disease&#44; creating patients&#8217; sub-phenotypes based on personalized medicine strategies&#46; MASLD is the result from a complex and dynamic interaction of several modifiable and non-modifiable factors&#44; including sex&#44; ethnicity&#44; diet patterns and physical activity&#44; comorbidities&#44; genetic polymorphisms&#44; alcohol intake&#44; microbiota and socioeconomic status&#44; and this heterogeneity will lead to different natural history&#44; prognosis and eventually&#44; response to therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a> Thus&#44; it has been suggested that the main factors that shape heterogeneity in MASLD need to be considered when devising and applying risk-stratification scores and algorithms to diagnose MASLD&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">10</span></a> Further&#44; availability and cost of the techniques are equally important&#44; since the pragmatic utilization is key to avoid ineffective referrals&#44; long waiting lists and the collapse of health resources&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">MASLD&#44; the search for non-invasive approaches</span><p id="par0015" class="elsevierStylePara elsevierViewall">Current available non-invasive tools and scores are quite efficient in detecting patients with advanced liver fibrosis&#44; which is a good indicator of disease severity&#44; as it will not only increase the odds of promoting liver-related complications &#40;i&#46;e&#46; cirrhosis&#44; hepatocellular carcinoma and liver failure&#41;&#44; but also the chances of deaths that cannot be directly attributed to liver dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">11</span></a> These tools&#44; however&#44; leave a large proportion of individuals with moderate disease undetected&#44; because no simple and efficient strategy is available for early screen in the general population&#46; These patients in turn only get diagnosed when advanced liver disease is present and complications are more likely to take place&#44; limiting the potential benefits of treatment and lifestyle advice&#44; so early detection tools are necessary&#46; The identification of significant fibrosis and MASH &#40;&#8805;F2 fibrosis&#44; NAFLD activity score &#91;NAS&#93;<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>4&#41; in high-risk patients is also of utmost importance for given prognosis&#44; correlation with progression to cirrhosis and major adverse liver outcomes&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">12&#44;13</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Comparative study of the new horizons</span><p id="par0020" class="elsevierStylePara elsevierViewall">Two of the biggest Consortia aiming to find new biomarkers for MASLD diagnosis and progression&#44; the Liver Investigation&#58; Testing Marker Utility in Steatohepatitis &#40;LITMUS&#41; and the Non-Invasive Biomarkers of Metabolic Liver Disease &#40;NIMBLE&#41;&#44; have recently published their primary project results&#46; LITMUS has evaluated in approximately 1000 patients coming from 13 European countries&#44; a panel of 17 non-invasive biomarkers&#44; including serological and imaging approaches&#44; together with multimarker scores chosen based on their performance in identifying either fibrosis or MASH&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">14</span></a> On the other hand&#44; the NIMBLE study tested the efficacy of five serological biomarker panels&#8217; diagnostic performance &#40;NIS4&#44; OWLiver&#44; PROC3&#44; ELF and FibroMeter VCTE&#41; for the diagnosis of MASH&#44; high NAS Score rates and severity of liver fibrosis in MASLD patients in USA &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;073&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">15</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Analyses in these large multinational cohorts indicated that <span class="elsevierStyleBold">NIS4&#44;</span><span class="elsevierStyleBold">SomaSignal</span> and the <span class="elsevierStyleBold">FAST algorithm</span> are good tools to discriminate patients with at-risk MASH&#44; which is logical if we consider that all of them were specifically designed with this purpose&#46; <span class="elsevierStyleBold">NIS4</span> is a proprietary technology that utilizes a panel of four independent biomarkers &#40;miR-34a-5p&#44; alpha-2 macroglobulin &#91;A2M&#93;&#44; glycated haemoglobin &#91;HbA1c&#93;&#44; and chitinase-3-like protein 1 &#91;CHI3L1&#59; also known as YKL-40&#93;&#41; specifically designed for detecting at-risk MASH in patients with metabolic risk factors&#46; NIS4 value lower than 0&#46;36 ruled out at-risk MASH with 81&#46;5&#37; sensitivity and 63&#46;0&#37; specificity and a negative predictive value &#40;NPV&#41; of 77&#46;9&#37;&#46; On the other hand&#44; NIS4 values higher than 0&#46;63 ruled-in at-risk MASH patients with 87&#46;1&#37; specificity&#44; and 50&#46;7&#37; sensitivity&#44; and a positive predictive value &#40;PPV&#41; of 79&#46;2&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">16</span></a> NIS4 ability to detect at-risk MASH has been recently validated in an additional cohort from the RESOLVE-IT trial &#40;0&#46;792 &#91;0&#46;772&#8211;0&#46;811&#93;&#44; <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;035&#41; in which a simpler where A2M and HbA1c are no longer required&#44; and sex was incorporated into the equation&#46; This NIS2&#43;&#44; demonstrated a similar ability to discriminate at-risk NASH &#40;0&#46;813 &#91;0&#46;795&#44; 0&#46;832&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">17</span></a> In NIMBLE report&#44; NIS4 was the only panel with an intended use to diagnose the underlying composite phenotype of at-risk MASH &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>539 within the full cohort&#41;&#46; The sensitivity and specificity of NIS4 were 78&#46;1&#37; and 73&#46;6&#37;&#44; respectively&#44; with an AUROC of 0&#46;815&#44; which was superior to other two scores&#44; ALT &#40;AUROC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;726&#41; and FIB-4 &#40;AUROC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;704&#41;&#46; NIS4 also obtained the best ability to detect significant fibrosis &#91;0&#46;874 &#40;0&#46;848&#44; 0&#46;899&#41;&#93; but not advanced fibrosis or cirrhosis&#44; in which Fibrometer VCTE achieved the highest performance &#91;F3&#58; AUC 0&#46;858 &#40;0&#46;814&#8211;0&#46;902&#41; and F4 AUC 0&#46;897 &#40;0&#46;843&#8211;0&#46;951&#41;&#93; followed by ELF &#91;F3&#58; AUC&#58; 0&#46;835 &#40;0&#46;807&#8211;0&#46;863&#41; and F4&#58; AUC 0&#46;855 &#40;0&#46;818&#8211;0&#46;892&#41;&#93;&#46; In this cohort&#44; and since OWLiver provides the results in categorical format&#44; not permitting the generation of an AUROC&#59; it was reported a sensitivity of 77&#46;3&#37; and a specificity of 66&#46;8&#37; for at-risk MASH&#46; The AUROCs of the ELF test&#44; PROC3 and FibroMeterVCTE for significant fibrosis&#44; advanced fibrosis or cirrhosis were all &#8805;0&#46;8&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">SomaSignal</span> is a proprietary test that relies on chemically modified nucleotides able to bind to proteins for the &#8220;identification&#8221; and the amplification of reporter sequences by quantitative real-time PCR&#46; Proteins included for at-risk MASH detection have been identified through a training and validation of whole arrays of proteins against biopsy results for each component &#40;steatosis &#91;12 protein analytes&#93;&#44; lobular inflammation &#91;14 protein analytes&#93;&#44; hepatocellular ballooning &#91;five protein analytes&#93;&#44; and fibrosis &#91;eight protein analysts&#93;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">18&#44;19</span></a> LITMUS identified SomaSignal as the best method to diagnose MASH &#91;AUC 0&#46;81 &#91;0&#46;75&#8211;0&#46;86&#41;&#93; and advanced fibrosis &#91;AUC 0&#46;90 &#91;0&#46;86&#8211;0&#46;94&#41;&#93;&#44; but this was analyzed in a relatively small subset of patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>264&#41;&#46; This test&#44; however&#44; achieved better results during its original training and validation for at-risk MASH detection &#40;training AUC&#58; 0&#46;86&#59; validation AUC&#58; 0&#46;91&#41; in a larger population &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>636&#41;&#46; ADAPT also reached a good accuracy for advanced fibrosis detection &#91;AUC 0&#46;85 &#40;0&#46;81&#8211;0&#46;89&#41;&#93; together with FibroScan &#91;AUC 0&#46;83 &#40;0&#46;80&#8211;0&#46;86&#41;&#93;&#46; <span class="elsevierStyleBold">FibroScan-AST &#40;FAST</span>&#41; algorithm is a combination of VCTE with AST which originally obtained a first <span class="elsevierStyleItalic">C</span>-statistic of 0&#46;80 &#91;0&#46;76&#8211;0&#46;85&#41; for at-risk MASH detection&#44; quite consistent across the validation cohorts&#44; in which it was assessed &#40;<span class="elsevierStyleItalic">C</span>-statistic range 0&#46;74&#8211;0&#46;95&#44; 0&#46;85&#59; 95&#37; CI 0&#46;83&#8211;0&#46;87&#44; <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1026&#41;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a> and when was validated in the NASH-CRN cohort in an independent study &#40;AUC&#58; 0&#46;81 &#91;0&#46;77&#8211;0&#46;84&#93;&#41;&#46; Usual cutoffs include 0&#46;35 for high sensitivity and 0&#46;67 for high specificity&#46; A recent comprehensive analysis of screening data from seven non-cirrhotic phase 2 trials for MASH including 2173 individuals with centrally assessed liver biopsies revealed as AST levels&#44; FAST-score&#44; FIB-4 and HbA1c levels key independent predictors&#46; This study recommended the use of the FAST-score&#44; with a suggested cutoff point of 0&#46;5 for patients with HbA1c<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>6&#46;5&#37; and 0&#46;67 for patients with HbA1c<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>6&#46;5&#37;&#44; as a simple and effective tool for stratifying at-risk MASH patients&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Other promising new biomarkers for at-risk MASH including the promising MRI-aspartate aminotransferase score &#40;MAST&#41;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a>&#40;AUC&#58; 0&#46;93 &#91;0&#46;88&#8211;0&#46;97&#93;&#41;&#44; or alternative combinations of routine analytics obtained with circulating proteins<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">22&#44;23</span></a> or metabolites<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">24</span></a> are emerging&#46; Although still none of the markers achieved AUCs to be considered as alternative of biopsy&#44; these biomarkers could be used for pre-screening strategies in randomized clinical trials recruitment&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Concluding remarks</span><p id="par0040" class="elsevierStylePara elsevierViewall">In MASLD&#44; early disease detection has arisen as a cornerstone in personalized medicine&#46; Understanding disease prevalence&#44; addressing NAFLD heterogeneity and contributing factors is essential for effective resource allocation in healthcare&#46; The heterogeneity in MASLD sub-phenotypes has presumably hampered the progress towards effective non-invasive tools&#46; On one hand&#44; efficient referral pathways are needed at detecting fibrosis from primary care or targeted groups&#44; without resulting in futile referrals and preferably at low costs&#46; The current strategies are quite efficient in detecting advanced stages of the disease&#44; but offer modest sensitivity in patients with intermediate risk &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Further&#44; current recruitment for clinical trials is based on liver biopsy&#46; Screening failure rates could be reduced in trials if only those patients positive for the proposed biomarkers underwent a biopsy for eligibility&#46; Thus&#44; a pre-selection would be performed to substantially reduce the number of liver biopsies&#46; Although great progress has been recently made&#44; some gaps need to be filled for qualification&#44; so further studies will be required to validate their diagnostic accuracy and utility&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:7 [
        0 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        1 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "MASLD&#44; a multi-layered disease"
        ]
        2 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "MASLD&#44; the search for non-invasive approaches"
        ]
        3 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Comparative study of the new horizons"
        ]
        4 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Concluding remarks"
        ]
        5 => array:2 [
          "identificador" => "xack750365"
          "titulo" => "Acknowledgements"
        ]
        6 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "multimedia" => array:1 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2439
            "Ancho" => 2925
            "Tamanyo" => 500218
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Facing a new era in MASLD biomarkers&#46; Progressive forms of liver disease require the use of targeted therapies adapted to stratified groups of patients&#44; considering the main drivers of the disease to define patients&#8217; subphenotypes&#46; Biomarkers have proven diagnostic accuracy in targeted populations &#40;higher prevalence&#41;&#44; but require further validation in primary care settings &#40;lower prevalence&#41; for screening purposes&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:24 [
            0 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A multisociety Delphi consensus statement on new fatty liver disease nomenclature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;E&#46; Rinella"
                            1 => "J&#46;V&#46; Lazarus"
                            2 => "V&#46; Ratziu"
                            3 => "S&#46;M&#46; Francque"
                            4 => "A&#46;J&#46; Sanyal"
                            5 => "F&#46; Kanwal"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/HEP.0000000000000520"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2023"
                        "volumen" => "78"
                        "paginaInicial" => "1966"
                        "paginaFinal" => "1986"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37363821"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global epidemiology of nonalcoholic fatty liver disease &#8211; meta-analytic assessment of prevalence&#44; incidence&#44; and outcomes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "Z&#46;M&#46; Younossi"
                            1 => "A&#46;B&#46; Koenig"
                            2 => "D&#46; Abdelatif"
                            3 => "Y&#46; Fazel"
                            4 => "L&#46; Henry"
                            5 => "M&#46; Wymer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.28431"
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2016"
                        "volumen" => "64"
                        "paginaInicial" => "73"
                        "paginaFinal" => "84"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26707365"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0883944120303907"
                          "estado" => "S300"
                          "issn" => "08839441"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Significant fibrosis predicts new-onset diabetes mellitus and arterial hypertension in patients with NASH"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Ampuero"
                            1 => "R&#46; Aller"
                            2 => "R&#46; Gallego-Dur&#225;n"
                            3 => "J&#46; Crespo"
                            4 => "J&#46;L&#46; Calleja"
                            5 => "C&#46; Garc&#237;a-Monz&#243;n"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2020.02.028"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2020"
                        "volumen" => "73"
                        "paginaInicial" => "17"
                        "paginaFinal" => "25"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32147361"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Non-alcoholic fatty liver disease&#58; a patient guideline"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;M&#46; Francque"
                            1 => "G&#46; Marchesini"
                            2 => "A&#46; Kautz"
                            3 => "M&#46; Walmsley"
                            4 => "R&#46; Dorner"
                            5 => "J&#46;V&#46; Lazarus"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhepr.2021.100322"
                      "Revista" => array:5 [
                        "tituloSerie" => "JHEP Rep"
                        "fecha" => "2021"
                        "volumen" => "3"
                        "paginaInicial" => "100322"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34693236"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "a systemic metabolic disorder with cardiovascular and malignant complications"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "G&#46; Targher"
                            1 => "C&#46;D&#46; Byrne"
                            2 => "H&#46; Tilg"
                            3 => "MASLD&#58;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gutjnl-2023-330595"
                      "Revista" => array:2 [
                        "tituloSerie" => "Gut"
                        "fecha" => "2024"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;J&#46; Wong"
                            1 => "M&#46; Aguilar"
                            2 => "R&#46; Cheung"
                            3 => "R&#46;B&#46; Perumpail"
                            4 => "S&#46;A&#46; Harrison"
                            5 => "Z&#46;M&#46; Younossi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2014.11.039"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2015"
                        "volumen" => "148"
                        "paginaInicial" => "547"
                        "paginaFinal" => "555"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25461851"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Hagstr&#246;m"
                            1 => "P&#46; Nasr"
                            2 => "M&#46; Ekstedt"
                            3 => "U&#46; Hammar"
                            4 => "P&#46; St&#229;l"
                            5 => "R&#46; Hultcrantz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2017.07.027"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2017"
                        "volumen" => "67"
                        "paginaInicial" => "1265"
                        "paginaFinal" => "1273"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28803953"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "E&#46; Vilar-Gomez"
                            1 => "Y&#46; Martinez-Perez"
                            2 => "L&#46; Calzadilla-Bertot"
                            3 => "A&#46; Torres-Gonzalez"
                            4 => "B&#46; Gra-Oramas"
                            5 => "al&#46; Gonzalez-et"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2015.04.005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2015"
                        "volumen" => "149"
                        "paginaInicial" => "367"
                        "paginaFinal" => "378"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25865049"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Insights into nonalcoholic fatty-liver disease heterogeneity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Arrese"
                            1 => "J&#46;P&#46; Arab"
                            2 => "F&#46; Barrera"
                            3 => "B&#46; Kaufmann"
                            4 => "L&#46; Valenti"
                            5 => "A&#46;E&#46; Feldstein"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1055/s-0041-1730927"
                      "Revista" => array:6 [
                        "tituloSerie" => "Semin Liver Dis"
                        "fecha" => "2021"
                        "volumen" => "41"
                        "paginaInicial" => "421"
                        "paginaFinal" => "434"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34233370"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "International consensus panel MAFLD&#58; a consensus-driven proposed nomenclature for metabolic associated fatty liver disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Eslam"
                            1 => "A&#46;J&#46; Sanyal"
                            2 => "J&#46; George"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2019.11.312"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2020"
                        "volumen" => "158"
                        "paginaInicial" => "1999"
                        "paginaFinal" => "2014"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32044314"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatocellular and extrahepatic cancer risk in people with non-alcoholic fatty liver disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;A&#46; Thomas"
                            1 => "B&#46;J&#46; Kendall"
                            2 => "H&#46;B&#46; El-Serag"
                            3 => "A&#46;P&#46; Thrift"
                            4 => "G&#46;A&#46; Macdonald"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2468-1253(23)00275-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Gastroenterol Hepatol"
                        "fecha" => "2024"
                        "volumen" => "9"
                        "paginaInicial" => "159"
                        "paginaFinal" => "169"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/38215780"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association between fibrosis stage and outcomes of patients with nonalcoholic fatty liver disease&#58; a systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;S&#46; Taylor"
                            1 => "R&#46;J&#46; Taylor"
                            2 => "S&#46; Bayliss"
                            3 => "H&#46; Hagstr&#246;m"
                            4 => "P&#46; Nasr"
                            5 => "J&#46;M&#46; Schattenberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2020.01.043"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2020"
                        "volumen" => "158"
                        "paginaInicial" => "1611"
                        "paginaFinal" => "1625"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32027911"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prospective study of outcomes in adults with nonalcoholic fatty liver disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;J&#46; Sanyal"
                            1 => "M&#46;L&#46; Van Natta"
                            2 => "J&#46; Clark"
                            3 => "B&#46;A&#46; Neuschwander-Tetri"
                            4 => "A&#46; Diehl"
                            5 => "S&#46; Dasarathy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa2029349"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2021"
                        "volumen" => "385"
                        "paginaInicial" => "1559"
                        "paginaFinal" => "1569"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34670043"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease &#40;the LITMUS project&#41;&#58; a comparative diagnostic accuracy study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Vali"
                            1 => "J&#46; Lee"
                            2 => "J&#46; Boursier"
                            3 => "S&#46; Petta"
                            4 => "K&#46; Wonders"
                            5 => "D&#46; Tiniakos"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2468-1253(23)00017-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Gastroenterol Hepatol"
                        "fecha" => "2023"
                        "volumen" => "8"
                        "paginaInicial" => "714"
                        "paginaFinal" => "725"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36958367"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnostic performance of circulating biomarkers for non-alcoholic steatohepatitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;J&#46; Sanyal"
                            1 => "S&#46;S&#46; Shankar"
                            2 => "K&#46;P&#46; Yates"
                            3 => "J&#46; Bolognese"
                            4 => "E&#46; Daly"
                            5 => "C&#46;A&#46; Dehn"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41591-023-02539-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Med"
                        "fecha" => "2023"
                        "volumen" => "29"
                        "paginaInicial" => "2656"
                        "paginaFinal" => "2664"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37679433"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A blood-based biomarker panel &#40;NIS4&#41; for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis&#58; a prospective derivation and global validation study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;A&#46; Harrison"
                            1 => "V&#46; Ratziu"
                            2 => "J&#46; Boursier"
                            3 => "S&#46; Francque"
                            4 => "P&#46; Bedossa"
                            5 => "Z&#46; Majd"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2468-1253(20)30252-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Gastroenterol Hepatol"
                        "fecha" => "2020"
                        "volumen" => "5"
                        "paginaInicial" => "970"
                        "paginaFinal" => "985"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32763196"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "NIS2&#43;&#8482;&#44; an optimisation of the blood-based biomarker NIS4&#174; technology for the detection of at-risk NASH&#58; a prospective derivation and validation study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;A&#46; Harrison"
                            1 => "V&#46; Ratziu"
                            2 => "J&#46; Magnanensi"
                            3 => "Y&#46; Hajji"
                            4 => "S&#46; Deledicque"
                            5 => "Z&#46; Majd"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2023.04.031"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2023"
                        "volumen" => "79"
                        "paginaInicial" => "758"
                        "paginaFinal" => "767"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37224923"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Defining the serum proteomic signature of hepatic steatosis&#44; inflammation&#44; ballooning and fibrosis in non-alcoholic fatty liver disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;J&#46; Sanyal"
                            1 => "S&#46;A&#46; Williams"
                            2 => "J&#46;E&#46; Lavine"
                            3 => "B&#46;A&#46; Neuschwander-Tetri"
                            4 => "L&#46; Alexander"
                            5 => "R&#46; Ostroff"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2022.11.029"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2023"
                        "volumen" => "78"
                        "paginaInicial" => "693"
                        "paginaFinal" => "703"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36528237"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "SOMAscan proteomics identifies serum biomarkers associated with liver fibrosis in patients with NASH"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Luo"
                            1 => "S&#46; Wadhawan"
                            2 => "A&#46; Greenfield"
                            3 => "B&#46;E&#46; Decato"
                            4 => "A&#46;M&#46; Oseini"
                            5 => "R&#46; Collen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep4.1670"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatol Commun"
                        "fecha" => "2021"
                        "volumen" => "5"
                        "paginaInicial" => "760"
                        "paginaFinal" => "773"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34027267"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "FibroScan-AST &#40;FAST&#41; score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis&#58; a prospective derivation and global validation study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;N&#46; Newsome"
                            1 => "M&#46; Sasso"
                            2 => "J&#46;J&#46; Deeks"
                            3 => "A&#46; Paredes"
                            4 => "J&#46; Boursier"
                            5 => "W&#46;K&#46; Chan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2468-1253(19)30383-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Gastroenterol Hepatol"
                        "fecha" => "2020"
                        "volumen" => "5"
                        "paginaInicial" => "362"
                        "paginaFinal" => "373"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32027858"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "MRI-based &#40;MAST&#41; score accurately identifies patients with NASH and significant fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Noureddin"
                            1 => "E&#46; Truong"
                            2 => "J&#46;A&#46; Gornbein"
                            3 => "R&#46; Saouaf"
                            4 => "M&#46; Guindi"
                            5 => "T&#46; Todo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2021.11.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2022"
                        "volumen" => "76"
                        "paginaInicial" => "781"
                        "paginaFinal" => "787"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34798176"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "ADAMTSL2 protein and a soluble biomarker signature identify at-risk non-alcoholic steatohepatitis and fibrosis in adults with NAFLD"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;E&#46; Corey"
                            1 => "R&#46; Pitts"
                            2 => "M&#46; Lai"
                            3 => "J&#46; Loureiro"
                            4 => "R&#46; Masia"
                            5 => "S&#46;A&#46; Osganian"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2021.09.026"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2022"
                        "volumen" => "76"
                        "paginaInicial" => "25"
                        "paginaFinal" => "33"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A proteo-transcriptomic map of non-alcoholic fatty liver disease signatures"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "O&#46; Govaere"
                            1 => "M&#46; Hasoon"
                            2 => "L&#46; Alexander"
                            3 => "S&#46; Cockell"
                            4 => "D&#46; Tiniakos"
                            5 => "M&#46; Ekstedt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s42255-023-00775-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Metab"
                        "fecha" => "2023"
                        "volumen" => "5"
                        "paginaInicial" => "572"
                        "paginaFinal" => "578"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37037945"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serum identification of at-risk MASH&#58; the metabolomics-advanced steatohepatitis fibrosis score &#40;MASEF&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Noureddin"
                            1 => "E&#46; Truong"
                            2 => "R&#46; Mayo"
                            3 => "I&#46; Mart&#237;nez-Arranz"
                            4 => "I&#46; Minchol&#233;"
                            5 => "J&#46;M&#46; Banales"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/HEP.0000000000000542"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2024"
                        "volumen" => "79"
                        "paginaInicial" => "135"
                        "paginaFinal" => "148"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37505221"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack750365"
        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0045" class="elsevierStylePara elsevierViewall">The research leading to these results has received funding from the <span class="elsevierStyleGrantSponsor" id="gs1">Consejer&#237;a de Salud de la Junta de Andaluc&#237;a</span> under grant agreement <span class="elsevierStyleGrantNumber" refid="gs1">PC-0148-2016-0148</span> and <span class="elsevierStyleGrantNumber" refid="gs1">PE-0451-2018</span>&#44; and from <span class="elsevierStyleGrantSponsor" id="gs2">Instituto de Salud Carlos III</span> under grant agreements <span class="elsevierStyleGrantNumber" refid="gs2">CD21&#47;00095</span>&#44; <span class="elsevierStyleGrantNumber" refid="gs2">PI19&#47;01404</span>&#44; <span class="elsevierStyleGrantNumber" refid="gs2">PI19&#47;00589</span>&#44; <span class="elsevierStyleGrantNumber" refid="gs2">PI22&#47;01342</span>&#44; <span class="elsevierStyleGrantNumber" refid="gs2">PI22&#47;01345</span>&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/02105705/0000004700000004/v2_202406091228/S0210570524000530/v2_202406091228/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "96400"
    "tipo" => "SECCION"
    "es" => array:2 [
      "titulo" => "Rinc&#243;n Joven"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "es"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/02105705/0000004700000004/v2_202406091228/S0210570524000530/v2_202406091228/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570524000530?idApp=UINPBA00004N"
]
Indexed in:

Follow us:

Subscribe:

Article

Indexed in:

Follow us:

Subscribe:

Article

Subscribe to our newsletter
