COVID-19
Regístrese
metricas
covid
Annals of Hepatology
Buscar en
Annals of Hepatology
Toda la web
Inicio Annals of Hepatology Liver disease and outcomes among COVID-19 hospitalized patients – A systematic...
Journal Information
Back to article

Statistics

Follow this link to access the full text of the article

Original article
Liver disease and outcomes among COVID-19 hospitalized patients – A systematic review and meta-analysis
Ashish Sharmaa,1, Pragya Jaiswalb,1, Yasameen Kerakhanc, Lakshmi Saravanand, Zeba Murtazae, Azka Zerghamf, Nagaraj-Sanchitha Honganurg, Aelia Akbarh, Aran Deoli, Benedict Francisj, Shakumar Patelk, Deep Mehtal, Richa Jaiswalb, Jagmeet Singhm, Urvish Pateln,2, Preeti Malikn,2,
Corresponding author
pmalik.ma@gmail.com

Corresponding author at: Department of Public Health, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York City, NY 10029, USA.
a Department of Internal Medicine, Yuma Regional Medicine, Yuma, AZ, USA
b Department of Internal Medicine, Medical University of South Carolina, Charleston, SC, USA
c Department of Internal Medicine, Abrazo Central Campus, Phoenix, AZ, USA
d American University of Antigua, Jabberwock Road, Osbourn, Antigua & Barbuda, USA
e Department of Neurosciences and Internal Medicine, University of California School of Medicine, San Diego, CA, USA
f Department of Internal Medicine, Larkin Community Hospital, FL, USA
g Department of Internal Medicine and Cardiology, University of Illinois, Chicago, IL, USA
h Department of Internal Medicine, Loyola University, Chicago, IL, USA
i Department of Internal Medicine, Swedish Covenant Hospital, Chicago, IL, USA
j Department of Internal Medicine, Jackson Park Hospital, Chicago, IL, USA
k Department of Internal Medicine, Hackensack Ocean Medical Center, Brick Township, NJ, USA
l Clinical Research Program, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
m Department of Internal Medicine, Geisinger Commonwealth School of Medicine, Scranton, PA, USA
n Department of Public Health, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
Ver más
Read
11536
Times
was read the article
1865
Total PDF
9671
Total HTML
Share statistics
 array:24 [
  "pii" => "S1665268120301885"
  "issn" => "16652681"
  "doi" => "10.1016/j.aohep.2020.10.001"
  "estado" => "S300"
  "fechaPublicacion" => "2021-03-01"
  "aid" => "273"
  "copyright" => "AEDV"
  "copyrightAnyo" => "2020"
  "documento" => "article"
  "crossmark" => 1
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "fla"
  "cita" => "Ann Hepatol. 2021;21C:"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S1665268120301824"
    "issn" => "16652681"
    "doi" => "10.1016/j.aohep.2020.09.011"
    "estado" => "S300"
    "fechaPublicacion" => "2021-03-01"
    "aid" => "267"
    "copyright" => "Fundación Clínica Médica Sur, A.C."
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Ann Hepatol. 2021;21C:"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Clinical features and risk factors of COVID-19-associated liver injury and function&#58; A retrospective analysis of 830 cases"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0010"
          "etiqueta" => "Fig&#46; 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 1982
              "Ancho" => 3167
              "Tamanyo" => 497063
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0010"
              "detalle" => "Fig&#46; "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Mechanism of liver injury in patients with coronavirus disease 2019 &#40;COVID-19&#41;&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Faxiang Chen, Wei Chen, Jianpu Chen, Dan Xu, Wei Xie, Xiang Wang, Yuanliang Xie"
          "autores" => array:7 [
            0 => array:2 [
              "nombre" => "Faxiang"
              "apellidos" => "Chen"
            ]
            1 => array:2 [
              "nombre" => "Wei"
              "apellidos" => "Chen"
            ]
            2 => array:2 [
              "nombre" => "Jianpu"
              "apellidos" => "Chen"
            ]
            3 => array:2 [
              "nombre" => "Dan"
              "apellidos" => "Xu"
            ]
            4 => array:2 [
              "nombre" => "Wei"
              "apellidos" => "Xie"
            ]
            5 => array:2 [
              "nombre" => "Xiang"
              "apellidos" => "Wang"
            ]
            6 => array:2 [
              "nombre" => "Yuanliang"
              "apellidos" => "Xie"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268120301824?idApp=UINPBA00004N"
    "url" => "/16652681/000000210000000C/v1_202102250957/S1665268120301824/v1_202102250957/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S1665268120301897"
    "issn" => "16652681"
    "doi" => "10.1016/j.aohep.2020.10.002"
    "estado" => "S300"
    "fechaPublicacion" => "2021-03-01"
    "aid" => "274"
    "copyright" => "AEDV"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Ann Hepatol. 2021;21C:"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Aminotransferases disorders associated with venous thromboembolic events in patients infected with COVID-19"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0010"
          "etiqueta" => "Fig&#46; 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 1742
              "Ancho" => 1508
              "Tamanyo" => 137046
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0055"
              "detalle" => "Fig&#46; "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">AST disorders in the cohort &#40;46 patients&#41; and in the patients with VTE &#40;10 patients&#41; AST UI&#47;L&#44; normal &#60; 37 UI&#47;L&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Amer Hamad&#233;, Bastien Woehl, Marjolaine Talbot, Naouel Bensalah, Pierre Michel, Golnaz Obringer, Mich&#232;le Lehn-Hogg, Nathalie Buschenrieder, Mahdi Issa, Jonathan Tousch, Dominique Stephan, Lucas Jambert"
          "autores" => array:12 [
            0 => array:2 [
              "nombre" => "Amer"
              "apellidos" => "Hamad&#233;"
            ]
            1 => array:2 [
              "nombre" => "Bastien"
              "apellidos" => "Woehl"
            ]
            2 => array:2 [
              "nombre" => "Marjolaine"
              "apellidos" => "Talbot"
            ]
            3 => array:2 [
              "nombre" => "Naouel"
              "apellidos" => "Bensalah"
            ]
            4 => array:2 [
              "nombre" => "Pierre"
              "apellidos" => "Michel"
            ]
            5 => array:2 [
              "nombre" => "Golnaz"
              "apellidos" => "Obringer"
            ]
            6 => array:2 [
              "nombre" => "Mich&#232;le"
              "apellidos" => "Lehn-Hogg"
            ]
            7 => array:2 [
              "nombre" => "Nathalie"
              "apellidos" => "Buschenrieder"
            ]
            8 => array:2 [
              "nombre" => "Mahdi"
              "apellidos" => "Issa"
            ]
            9 => array:2 [
              "nombre" => "Jonathan"
              "apellidos" => "Tousch"
            ]
            10 => array:2 [
              "nombre" => "Dominique"
              "apellidos" => "Stephan"
            ]
            11 => array:2 [
              "nombre" => "Lucas"
              "apellidos" => "Jambert"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268120301897?idApp=UINPBA00004N"
    "url" => "/16652681/000000210000000C/v1_202102250957/S1665268120301897/v1_202102250957/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "Liver disease and outcomes among COVID-19 hospitalized patients &#8211; A systematic review and meta-analysis"
    "tieneTextoCompleto" => true
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Ashish Sharma, Pragya Jaiswal, Yasameen Kerakhan, Lakshmi Saravanan, Zeba Murtaza, Azka Zergham, Nagaraj-Sanchitha Honganur, Aelia Akbar, Aran Deol, Benedict Francis, Shakumar Patel, Deep Mehta, Richa Jaiswal, Jagmeet Singh, Urvish Patel, Preeti Malik"
        "autores" => array:16 [
          0 => array:3 [
            "nombre" => "Ashish"
            "apellidos" => "Sharma"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">1</span>"
                "identificador" => "fn0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Pragya"
            "apellidos" => "Jaiswal"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">1</span>"
                "identificador" => "fn0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Yasameen"
            "apellidos" => "Kerakhan"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Lakshmi"
            "apellidos" => "Saravanan"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Zeba"
            "apellidos" => "Murtaza"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Azka"
            "apellidos" => "Zergham"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">f</span>"
                "identificador" => "aff0030"
              ]
            ]
          ]
          6 => array:3 [
            "nombre" => "Nagaraj-Sanchitha"
            "apellidos" => "Honganur"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">g</span>"
                "identificador" => "aff0035"
              ]
            ]
          ]
          7 => array:3 [
            "nombre" => "Aelia"
            "apellidos" => "Akbar"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">h</span>"
                "identificador" => "aff0040"
              ]
            ]
          ]
          8 => array:3 [
            "nombre" => "Aran"
            "apellidos" => "Deol"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">i</span>"
                "identificador" => "aff0045"
              ]
            ]
          ]
          9 => array:3 [
            "nombre" => "Benedict"
            "apellidos" => "Francis"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">j</span>"
                "identificador" => "aff0050"
              ]
            ]
          ]
          10 => array:3 [
            "nombre" => "Shakumar"
            "apellidos" => "Patel"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">k</span>"
                "identificador" => "aff0055"
              ]
            ]
          ]
          11 => array:3 [
            "nombre" => "Deep"
            "apellidos" => "Mehta"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">l</span>"
                "identificador" => "aff0060"
              ]
            ]
          ]
          12 => array:3 [
            "nombre" => "Richa"
            "apellidos" => "Jaiswal"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          13 => array:3 [
            "nombre" => "Jagmeet"
            "apellidos" => "Singh"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">m</span>"
                "identificador" => "aff0065"
              ]
            ]
          ]
          14 => array:3 [
            "nombre" => "Urvish"
            "apellidos" => "Patel"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">n</span>"
                "identificador" => "aff0070"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">2</span>"
                "identificador" => "fn0010"
              ]
            ]
          ]
          15 => array:4 [
            "nombre" => "Preeti"
            "apellidos" => "Malik"
            "email" => array:1 [
              0 => "pmalik.ma@gmail.com"
            ]
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">n</span>"
                "identificador" => "aff0070"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">2</span>"
                "identificador" => "fn0010"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:14 [
          0 => array:3 [
            "entidad" => "Department of Internal Medicine&#44; Yuma Regional Medicine&#44; Yuma&#44; AZ&#44; USA"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Department of Internal Medicine&#44; Medical University of South Carolina&#44; Charleston&#44; SC&#44; USA"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Department of Internal Medicine&#44; Abrazo Central Campus&#44; Phoenix&#44; AZ&#44; USA"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "American University of Antigua&#44; Jabberwock Road&#44; Osbourn&#44; Antigua &#38; Barbuda&#44; USA"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Department of Neurosciences and Internal Medicine&#44; University of California School of Medicine&#44; San Diego&#44; CA&#44; USA"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
          5 => array:3 [
            "entidad" => "Department of Internal Medicine&#44; Larkin Community Hospital&#44; FL&#44; USA"
            "etiqueta" => "f"
            "identificador" => "aff0030"
          ]
          6 => array:3 [
            "entidad" => "Department of Internal Medicine and Cardiology&#44; University of Illinois&#44; Chicago&#44; IL&#44; USA"
            "etiqueta" => "g"
            "identificador" => "aff0035"
          ]
          7 => array:3 [
            "entidad" => "Department of Internal Medicine&#44; Loyola University&#44; Chicago&#44; IL&#44; USA"
            "etiqueta" => "h"
            "identificador" => "aff0040"
          ]
          8 => array:3 [
            "entidad" => "Department of Internal Medicine&#44; Swedish Covenant Hospital&#44; Chicago&#44; IL&#44; USA"
            "etiqueta" => "i"
            "identificador" => "aff0045"
          ]
          9 => array:3 [
            "entidad" => "Department of Internal Medicine&#44; Jackson Park Hospital&#44; Chicago&#44; IL&#44; USA"
            "etiqueta" => "j"
            "identificador" => "aff0050"
          ]
          10 => array:3 [
            "entidad" => "Department of Internal Medicine&#44; Hackensack Ocean Medical Center&#44; Brick Township&#44; NJ&#44; USA"
            "etiqueta" => "k"
            "identificador" => "aff0055"
          ]
          11 => array:3 [
            "entidad" => "Clinical Research Program&#44; Icahn School of Medicine at Mount Sinai&#44; New York City&#44; NY&#44; USA"
            "etiqueta" => "l"
            "identificador" => "aff0060"
          ]
          12 => array:3 [
            "entidad" => "Department of Internal Medicine&#44; Geisinger Commonwealth School of Medicine&#44; Scranton&#44; PA&#44; USA"
            "etiqueta" => "m"
            "identificador" => "aff0065"
          ]
          13 => array:3 [
            "entidad" => "Department of Public Health&#44; Icahn School of Medicine at Mount Sinai&#44; New York City&#44; NY&#44; USA"
            "etiqueta" => "n"
            "identificador" => "aff0070"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author at&#58; Department of Public Health&#44; Icahn School of Medicine at Mount Sinai&#44; 1 Gustave L&#46; Levy Place&#44; New York City&#44; NY 10029&#44; USA&#46;"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:8 [
        "identificador" => "fig0025"
        "etiqueta" => "Fig&#46; 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 711
            "Ancho" => 2508
            "Tamanyo" => 211555
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0055"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Forest plot of alanine aminotransferase &#40;ALT&#41; with outcome in COVID-19 hospitalizations&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The WHO declared coronavirus disease 2019 &#40;COVID-19&#41; as a global pandemic on March 11&#44; 2020 <a class="elsevierStyleCrossRef" href="#bib0005">&#91;1&#93;</a>&#46; With approximately 5 million cases and over 160&#44;220 deaths&#44; the USA remains the worst affected country as of August 8&#44; 2020 <a class="elsevierStyleCrossRef" href="#bib0010">&#91;2&#93;</a>&#46; Following this&#44; India &#40;4&#46;3M&#41;&#44; Brazil &#40;4&#46;1M&#41;&#44; and Russia &#40;1M&#41;&#44; are among the other countries that are greatly affected&#46; Total cases worldwide are around 27 million&#44; and thus it remains an emergency of international concern <a class="elsevierStyleCrossRef" href="#bib0015">&#91;3&#93;</a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Severe acute respiratory syndrome coronavirus 2 &#40;SARS-CoV2&#41; mainly affects the respiratory system but as we are gaining more insight about this novel disease&#44; many published studies have also provided evidence of its organotropism and multisystem organ inflammation nature <a class="elsevierStyleCrossRefs" href="#bib0020">&#91;4&#44;5&#93;</a>&#46; Multiple studies have observed association of elevated liver enzymes in patients with COVID-19 infection assuming that it can cause liver damage either via direct hepatotoxic injury with viral infection&#44; or drug toxicity&#44; or immune mediated response&#46; In the past&#44; it has been reported that 60&#37; of patients developed liver damage due to the SARS epidemic <a class="elsevierStyleCrossRef" href="#bib0030">&#91;6&#93;</a>&#46; Since SARS-CoV-2 belongs to the same coronavirus family&#44; we assume it may cause liver injury&#46; The biliary epithelium has expression of angiotensin-converting enzyme &#40;ACE-2&#41; receptor&#44; which is also the binding site of SARS-CoV-2 <a class="elsevierStyleCrossRef" href="#bib0035">&#91;7&#93;</a>&#46; The ACE2 receptor expression in hepatocytes has been shown to be upregulated in animals&#8217; models of liver injury but hepatocytes have lower expression in humans <a class="elsevierStyleCrossRefs" href="#bib0040">&#91;8&#44;9&#93;</a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Current literature has many published clinical studies focusing on implications of hepatic involvement in COVID-19&#46; However&#44; most of them are diverse because of variation in definition of liver injury&#44; different clinical presentations and severity of the disease in individual studies&#46; Additionally&#44; there is no strong evidence showing association of outcomes of COVID-19 in patients with pre-existing chronic liver disease or liver injury&#46; One study in China reported that of patients who had preexisting hepatitis B infection&#44; 32&#46;1&#37; of them got severe COVID 19 infection in comparison to 15&#46;7&#37; of patients who had no hepatitis B <a class="elsevierStyleCrossRef" href="#bib0050">&#91;10&#93;</a>&#46; Hence&#44; we aim to systematically study the occurrence of liver injury&#44; comorbid liver disease and elevated liver enzymes in COVID-19 confirmed hospitalizations and also identify their association with outcomes&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2</span><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0045">Endpoint</span><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of the study is to evaluate the role of the comorbid chronic liver disease &#40;CM-CLD&#41;&#44; elevated liver enzymes and COVID-19 associated acute liver injury &#40;COVID-19 ALI&#41; in predicting the outcomes in confirmed COVID-19 hospitalized patients&#46; COVID-19 confirmation was evaluated by combined findings of RT-PCR&#44; serology&#44; symptoms&#44; and MRI chest in majority of those studies&#46; Poor outcomes were defined by intensive care unit &#40;ICU&#41; admission&#44; oxygen saturation &#60;90&#37;&#44; invasive mechanical ventilation &#40;IMV&#41; utilization&#44; severe disease&#44; and in-hospital mortality&#46; Study-specific poor outcomes and definitions of CM-CLD&#44; COVID-19 ALI and cut-off levels of liver enzymes in each individual study are mentioned in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;2</span><span class="elsevierStyleSectionTitle" id="sect0050">Search strategy and selection criteria</span><p id="par0025" class="elsevierStylePara elsevierViewall">A systematic search was conducted on published studies using PRISMA guidelines <a class="elsevierStyleCrossRef" href="#bib0055">&#91;11&#93;</a> and followed MOOSE checklist <a class="elsevierStyleCrossRef" href="#bib0060">&#91;12&#93;</a> from December 1&#44; 2019 to June 30&#44; 2020&#46; We searched PubMed&#44; Web of Science&#44; Scopus&#44; and medRxiv for observational studies that described comorbidities&#44; complications and laboratory findings of COVID-19 patients following keyword&#47;MESH terms&#58; &#40;&#40;COVID-19&#91;Title&#47;Abstract&#93;&#41; OR coronavirus &#91;Title&#47;Abstract&#93;&#41; OR SARS-CoV-2&#91;Title&#47;Abstract&#93; OR 2019-nCoV &#91;Title&#47;Abstract&#93;&#46; Studies were included in this meta-analysis if they had comorbid liver disease&#44; elevated liver enzymes&#44; acute liver injury and outcomes of COVID-19 hospitalized patients&#46; Literature other than observational studies&#44; non-English literature&#44; non-full text&#44; and animal studies were excluded&#46; Flow diagram of the literature search and study selection process is described in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;3</span><span class="elsevierStyleSectionTitle" id="sect0055">Study selection</span><p id="par0030" class="elsevierStylePara elsevierViewall">Abstracts were reviewed&#44; and articles were retrieved and reviewed for availability of data on comorbid liver disease&#44; elevated liver enzymes&#44; acute liver injury and outcomes of COVID-19 patients&#46; Studies which gave details on outcomes were selected for quantitative analysis&#46; PM and DM independently screened all identified studies and assessed full-texts to decide eligibility&#46; Any disagreement was resolved through discussion with another reviewer UP&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;4</span><span class="elsevierStyleSectionTitle" id="sect0060">Data collection</span><p id="par0035" class="elsevierStylePara elsevierViewall">From the included studies&#44; we extracted the following variables including comorbid liver disease&#44; elevated AST and ALT levels&#44; acute liver injury and outcomes&#46; Details on binary outcomes like ICU vs&#46; non-ICU admission&#44; severe vs non-severe disease&#44; IMV vs no-IMV use&#44; oxygen saturation &#60;90&#37; vs &#62;90&#37;&#44; in-hospital mortality vs discharged alive and survivors were collected using prespecified data collection forms by two authors &#40;PM and DM&#41; with a common consensus of author &#40;UP&#41; upon disagreement&#46; We have presented the study characteristics like the first author&#39;s last name&#44; publication month and year&#44; country of origin&#44; sample size&#44; mean or median age&#44; males&#44; outcomes and definitions of comorbid liver disease and acute liver injury and cut offs for elevated AST and ALT levels assessed in that individual study in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> &#40;references for the studies are in Supplemental file 1&#46;1&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;5</span><span class="elsevierStyleSectionTitle" id="sect0065">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Data analysis was performed using Review Manager version 5&#46;3 &#40;The Nordic Cochrane Centre&#44; The Cochrane Collaboration&#44; Copenhagen&#44; Denmark&#41;&#46; If the study has more than one outcome comparison then we have used data from the most severe outcome in the analysis to minimize the overall selection bias of our study&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The Maentel&#8211;Haenszel formula was used to calculate dichotomous variables to obtain odds ratios &#40;ORs&#41; along with its 95&#37; confidence intervals to describe the association of comorbid liver disease&#44; elevated liver enzymes&#44; acute liver injury and outcomes of COVID-19 patients in each study&#46; Random-effect models were used regardless of heterogeneity to estimate the combined effect and its precision&#44; to give a more conservative estimate of the ORs and 95&#37; CI&#46; The <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> statistic was used to assess statistical heterogeneity and <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>50&#37; was considered significant heterogeneity&#46; The <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered significant&#46; Publication bias was assessed visually using funnel plots and the Newcastle-Ottawa Scale &#40;NOS&#41;&#46; Newcastle-Ottawa Scale &#40;NOS&#41; <a class="elsevierStyleCrossRef" href="#bib0065">&#91;13&#93;</a> was used to assess the quality and bias in the included studies&#44; which rates selection&#44; comparability and outcome &#40;Supplemental file 1&#46;2&#41;&#46; All studies were assessed to be of high quality&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The pooled OR and 95&#37; CI are represented in the form of forest plots&#46; Each square on the chart area represents individual study and the area of each square is equivalent to the weight of the study&#44; which is the inverse of the study variance&#46; The diamond represents the pooled OR and the width corresponds to the 95&#37; CI&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3</span><span class="elsevierStyleSectionTitle" id="sect0070">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">Review of the databases identified 45&#44;377 articles on July 1&#44; 2020&#44; out of which 200 full text articles were assessed for eligibility after removing duplicated articles&#44; non-human studies&#44; non-observational studies&#44; and articles with non-English language by July 7&#46; During the second round&#44; 150 articles with insufficient clinical information on COVID-19 outcomes and comorbid liver disease&#44; elevated liver enzymes&#44; acute liver injury were excluded and 50 articles on comorbidity&#44; complications and outcomes were extracted for final evaluation by July 15&#46; So&#44; after detailed assessment and considering strict inclusion and exclusion criteria&#44; we included 24 observational studies with 12&#44;882 confirmed cases of COVID-19 patients detailing comorbid liver disease or elevated liver enzymes or acute liver injury and outcomes&#46; Meta-analysis random effects models quantified the study level impact of liver disease and liver injury on outcomes in COVID-19 hospitalized patients&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The overall prevalence of acute liver injury was 26&#46;5&#37; &#91;&#40;129&#47;485&#41;<span class="elsevierStyleHsp" style=""></span>&#42;<span class="elsevierStyleHsp" style=""></span>100&#93;&#44; comorbid chronic liver disease was 2&#46;6&#37; &#91;&#40;229&#47;8800&#41;<span class="elsevierStyleHsp" style=""></span>&#42;<span class="elsevierStyleHsp" style=""></span>100&#93;&#44; elevated AST was 41&#46;1&#37; &#91;&#40;2115&#47;5135&#41;<span class="elsevierStyleHsp" style=""></span>&#42;<span class="elsevierStyleHsp" style=""></span> 100&#93; and elevated ALT was 29&#46;1&#37; &#91;&#40;1485&#47;5094&#41;<span class="elsevierStyleHsp" style=""></span>&#42;<span class="elsevierStyleHsp" style=""></span>100&#93; in our meta-analysis &#40;<a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2&#8211;5</a>&#41;&#46;</p><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0075">Chronic liver disease</span><p id="par0065" class="elsevierStylePara elsevierViewall">A total of 17 studies reported data on chronic liver disease with outcomes giving a sample size of 8800 COVID-19 patients for evaluation&#46; Meta-analysis of all 17 studies showed that chronic liver disease had no significant association with poor outcomes compared to better outcomes &#40;pooled OR&#58; 0&#46;96&#59; 95&#37; CI&#58; 0&#46;71&#8211;1&#46;29&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;78&#41; with no heterogeneity in the data &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;93&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;2</span><span class="elsevierStyleSectionTitle" id="sect0080">Acute liver injury</span><p id="par0070" class="elsevierStylePara elsevierViewall">We found 4 studies that provided data on acute liver injury and outcomes with a sample size of 485 patients for evaluation&#46; Meta-analysis of all 4 studies showed that acute liver injury had higher odds of poor outcomes compared to better outcomes with a pooled OR of 1&#46;68 &#40;95&#37; CI&#58; 1&#46;04&#8211;2&#46;70&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#44; with no heterogeneity between studies &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;55&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;3</span><span class="elsevierStyleSectionTitle" id="sect0085">Aspartate aminotransferase &#40;AST&#41;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Out of 23 studies&#44; meta-analysis of 12 studies who have reported data on elevated AST and outcomes giving a total sample size of 5135 patients for evaluation&#44; showed that increased AST values are associated with 3 times more risk of poor outcomes in COVID-19 patients &#40;pooled OR&#58; 2&#46;98&#59; 95&#37; CI&#58; 2&#46;35&#8211;3&#46;77&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;00001&#41;&#44; with 36&#37; heterogeneity between studies &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;10&#41;&#46; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;4</span><span class="elsevierStyleSectionTitle" id="sect0090">Alanine aminotransferase &#40;ALT&#41;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Similarly&#44; in 10 studies meta-analysis with reported elevated ALT and outcomes including 5094 patients for evaluation&#44; we found an approx&#46; 2-fold increased likelihood of poor outcomes &#40;pooled OR&#58; 1&#46;73&#59; 95&#37; CI&#58; 1&#46;32&#8211;2&#46;27&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#44; with significant heterogeneity between studies &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>51&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46; Sensitivity analysis was performed by removing outlying study &#40;Mikami et al&#46;&#41; on funnel plots to account for heterogeneity&#46; The results after sensitivity analysis did not change and still showed significant association of elevated ALT with poor outcomes &#40;pooled OR&#58; 1&#46;85&#59; 95&#37; CI&#58; 1&#46;49&#8211;2&#46;29&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;00001&#41;&#44; with no heterogeneity between studies &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;50&#59; <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#37;&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">4</span><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">In our meta-analysis&#44; we found that acute liver injury and elevated ALT and AST levels were associated with poor outcomes&#46; However&#44; our study could not provide significant evidence of the effect of pre-existing chronic liver disease on COVID-19 patient outcomes&#46; In support of our findings&#44; a recent meta-analysis found that the frequency of underlying chronic liver disease was not statistically different between severe and non-severe diseases <a class="elsevierStyleCrossRef" href="#bib0070">&#91;14&#93;</a>&#46; However&#44; another study by Singh et al&#46; reported that patients with preexisting liver disease&#44; particularly cirrhosis&#44; are at higher risk for hospitalizations and mortality <a class="elsevierStyleCrossRef" href="#bib0075">&#91;15&#93;</a>&#46; Few studies have reported that the frequency of patients with liver injury was higher in severe cases compared to mild cases&#44; consistent with our findings of liver injury associated with poor outcomes <a class="elsevierStyleCrossRefs" href="#bib0080">&#91;16&#8211;18&#93;</a>&#46; There are several theories proposed for liver damage in COVID-19 such as direct effect of the virus on hepatocytes or biliary epithelium via Angiotensin-converting enzyme 2 &#40;ACE 2&#41; receptors expression&#44; liver injury related to increased immune response &#40;cytokine storm&#41; and immune mediated damage&#44; drug toxicity &#40;because of drugs like acetaminophen&#44; antivirals and hydroxychloroquine&#41;&#44; and liver failure occurring in patients having multiorgan dysfunction <a class="elsevierStyleCrossRefs" href="#bib0095">&#91;19&#8211;21&#93;</a>&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">A study by Chai et al&#46;&#44; has reported that expression of ACE 2 receptors was 57&#46;9&#37; in bile duct cells &#40;Cholangiocytes&#41; and 2&#46;6&#37; in hepatocytes <a class="elsevierStyleCrossRef" href="#bib0035">&#91;7&#93;</a>&#46; Cholangiocytes play a vital role in liver regeneration and immune response <a class="elsevierStyleCrossRef" href="#bib0110">&#91;22&#93;</a>&#46; Hence one possible theory for liver injury in COVID-19 patients is destruction of Cholangiocytes by SARS-CoV-2 virus via ACE 2 receptors&#46; Additionally&#44; it was also observed that expression of ACE 2 in hepatocytes increases in cases of liver injury <a class="elsevierStyleCrossRef" href="#bib0045">&#91;9&#93;</a>&#46; Recently&#44; post mortem liver biopsies of COVID-19 patients have shown moderate microvesicular steatosis and mild lobular and portal activity&#44; indicating the injury could have been caused by either SARS-CoV-2 infection or drug-induced liver injury <a class="elsevierStyleCrossRef" href="#bib0115">&#91;23&#93;</a>&#46; Whether this liver injury is caused by the virus itself or is due to a severe inflammatory response with liver damage or sepsis or multisystem organ failure or drug toxicity is not well understood <a class="elsevierStyleCrossRef" href="#bib0120">&#91;24&#93;</a>&#46; Therefore&#44; temporal relationship of COVID-19 induced liver damage cannot be established&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Furthermore&#44; increased liver enzymes &#40;AST and ALT&#41; occur in the setting of hepatocyte damage &#40;abnormal liver function&#41;&#46; According to initial studies&#44; more than a third of patients had elevated AST and ALT &#40;Transaminitis&#41; which was associated with longer hospital stay <a class="elsevierStyleCrossRefs" href="#bib0085">&#91;17&#44;25&#44;26&#93;</a>&#46; In a study done by Cai et al&#46;&#44; 76&#46;3&#37; of COVID-19 patients had abnormal liver tests while 21&#46;5&#37; developed liver injury during hospitalization&#44; which was defined by ALT&#44; AST&#44; total bilirubin and gamma-glutamyl transferase levels elevated to more than 3&#215; the upper limit of normal <a class="elsevierStyleCrossRef" href="#bib0135">&#91;27&#93;</a>&#46; The study also found that patients with abnormal liver tests had significantly higher odds of developing severe pneumonia <a class="elsevierStyleCrossRef" href="#bib0135">&#91;27&#93;</a>&#46; These findings are also consistent with our study that shows a significant elevation in AST and ALT among COVID-19 patients may be helpful in predicting poor outcomes among these patients&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">SARS-CoV-2 is phylogenetically similar to SARS-CoV and MERS and&#44; studies have given evidence of association of SARS-CoV and MERS with liver injury&#46; and elevated transaminases associated with severe disease <a class="elsevierStyleCrossRefs" href="#bib0100">&#91;20&#44;28&#8211;32&#93;</a>&#46; Additionally&#44; autopsies of SARS patients found not only virus particles in the hepatocytes and hepatic vascular endothelial cells but also significant increase in mitotic cells&#44; with eosinophilic bodies and ballooning hepatocytes&#44; suggesting that SARS-CoV may induce liver cells apoptosis and thus cause liver injury <a class="elsevierStyleCrossRefs" href="#bib0165">&#91;33&#44;34&#93;</a>&#46; Hence&#44; liver injury due to SARS-CoV&#44; MERS and SARS-CoV-2 diagnosed at the early stage may be direct effect of virus or systemic inflammatory response syndrome associated with the infection is not elucidated and requires future prospective and properly designed studies&#46;</p><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">4&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0100">Strengths&#44; limitations and future directions</span><p id="par0105" class="elsevierStylePara elsevierViewall">There are few limitations in our systematic review and meta-analysis&#46; The most important limitation was the variability among studies in regards to definition of liver dysfunction&#44; acute liver injury&#44; different cut off values for elevated liver enzymes&#44; type of chronic liver disease and different definitions of disease severity and outcomes&#46; Additionally&#44; due to lack of data from prospective studies&#44; all the studies that we included were from retrospective studies&#46; Also&#44; there were no studies reporting changing levels of AST and ALT during the disease course&#44; which is significant to predict the clinical course of the COVID-19 during hospital admission&#46; Most of our studies included in analysis are from China&#44; there may be a chance of overlap of study population as well as results may not be representative of the general population&#46; However few strengths of the study are&#44; our meta-analysis suggests that acute liver injury in patients and elevated AST&#44; ALT levels are associated with poor outcomes along with their high prevalence in COVID-19 patients&#46; Meta-analysis of 17 studies could not establish a significant effect of chronic liver diseases on outcomes in COVID-19 patients&#46; The other main strength of this meta-analysis is the low heterogeneity of the included studies&#46; Future prospective studies should focus on the timeline of the changes in levels of AST and ALT and the severity of the COVID-19 disease and associated liver injury&#46; In addition&#44; stratification of chronic liver diseases would further help to understand the relation of different chronic liver conditions and their effects on COVID-19 affected individuals&#46; Furthermore&#44; we suggest that COVID-19 patients with pre-existing liver disease or liver damage could possibly be treated with drugs that could both protect liver functions and inhibit inflammatory responses&#44; which may aid in the process of disease recovery&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">5</span><span class="elsevierStyleSectionTitle" id="sect0105">Conclusion</span><p id="par0110" class="elsevierStylePara elsevierViewall">To conclude acute liver injury&#44; liver function abnormalities specially elevated levels of AST and ALT are not only frequent in COVID-19 but are also associated with poor outcomes&#46; Hence&#44; future studies should carefully investigate the cause of liver injury during COVID-19 infection especially if it is treatment drug related&#46; From a clinical perspective&#44; these findings may help in early triage&#44; close monitoring of the occurrence of liver injury&#44; and careful use of drugs which can cause liver toxicity in COVID-19 patients&#46;AbbreviationsCOVID-19coronavirus disease 2019CM-CLDcomorbid chronic liver diseaseCOVID-19 ALICOVID-19 associated acute liver injuryASTaspartate aminotransferaseALTalanine aminotransferaseICUintensive care unit &#40;ICU&#41;IMVinvasive mechanical ventilationSARS-CoV2severe acute respiratory syndrome coronavirus 2ACE-2angiotensin-converting enzyme 2</p><p id="par0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleDefList"><span class="elsevierStyleSectionTitle" id="sect0110">Abbreviations</span><span class="elsevierStyleDefTerm">COVID-19</span><span class="elsevierStyleDefDescription"><p id="par0120" class="elsevierStylePara elsevierViewall">coronavirus disease 2019</p></span><span class="elsevierStyleDefTerm">CM-CLD</span><span class="elsevierStyleDefDescription"><p id="par0125" class="elsevierStylePara elsevierViewall">comorbid chronic liver disease</p></span><span class="elsevierStyleDefTerm">COVID-19 ALI</span><span class="elsevierStyleDefDescription"><p id="par0130" class="elsevierStylePara elsevierViewall">COVID-19 associated acute liver injury</p></span><span class="elsevierStyleDefTerm">AST</span><span class="elsevierStyleDefDescription"><p id="par0135" class="elsevierStylePara elsevierViewall">aspartate aminotransferase</p></span><span class="elsevierStyleDefTerm">ALT</span><span class="elsevierStyleDefDescription"><p id="par0140" class="elsevierStylePara elsevierViewall">alanine aminotransferase</p></span><span class="elsevierStyleDefTerm">ICU</span><span class="elsevierStyleDefDescription"><p id="par0145" class="elsevierStylePara elsevierViewall">intensive care unit &#40;ICU&#41;</p></span><span class="elsevierStyleDefTerm">IMV</span><span class="elsevierStyleDefDescription"><p id="par0150" class="elsevierStylePara elsevierViewall">invasive mechanical ventilation</p></span><span class="elsevierStyleDefTerm">SARS-CoV2</span><span class="elsevierStyleDefDescription"><p id="par0155" class="elsevierStylePara elsevierViewall">severe acute respiratory syndrome coronavirus 2</p></span><span class="elsevierStyleDefTerm">ACE-2</span><span class="elsevierStyleDefDescription"><p id="par0160" class="elsevierStylePara elsevierViewall">angiotensin-converting enzyme 2</p></span></span></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Funding</span><p id="par0165" class="elsevierStylePara elsevierViewall">The study had no internal or external funding source&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Authors&#8217; contributions</span><p id="par0170" class="elsevierStylePara elsevierViewall">Conceptualization&#58; PM&#44; UP&#59; Methodology&#58; AS&#44; PM&#44; UP&#44; PJ&#59; Acquisition of data&#58; DM&#44; RJ&#59; Formal analysis and investigation&#58; PM&#44; UP&#59; Writing &#8211; original draft preparation&#58; AS&#44; PJ&#44; AZ&#44; AD&#44; AK&#44; ZM&#44; LS&#44; NSH&#44; BF&#44; YK&#44; SP&#44; DM&#44; RJ&#59; Writing &#8211; review&#44; critical feedback&#44; and editing&#58; JS&#44; PM&#44; UP&#59; Funding acquisition&#58; None&#59; Resources&#58; AS&#59; Supervision&#58; UP and PM&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Ethical approval</span><p id="par0175" class="elsevierStylePara elsevierViewall">Though this article does not contain any studies with direct involvement of human participants or animals performed by any of the authors&#44; all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and&#47;or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Informed consent</span><p id="par0180" class="elsevierStylePara elsevierViewall">The data used in this study is deidentified and collected from the studies published online thus informed consent or IRB approval was not needed for this study&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Availability of data and material</span><p id="par0185" class="elsevierStylePara elsevierViewall">The data is collected from the studies published online&#44; publicly available&#44; and specific details related to data and&#47;or analysis will be made available upon request&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conflicts of interest</span><p id="par0190" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:14 [
        0 => array:3 [
          "identificador" => "xres1471607"
          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Introduction and objectives"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Materials and methods"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Results"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Conclusion"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1340237"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        3 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Methods"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Endpoint"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Search strategy and selection criteria"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Study selection"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Data collection"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        4 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Results"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Chronic liver disease"
            ]
            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Acute liver injury"
            ]
            2 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Aspartate aminotransferase &#40;AST&#41;"
            ]
            3 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Alanine aminotransferase &#40;ALT&#41;"
            ]
          ]
        ]
        5 => array:3 [
          "identificador" => "sec0065"
          "titulo" => "Discussion"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Strengths&#44; limitations and future directions"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Conclusion"
        ]
        7 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Funding"
        ]
        8 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Authors&#8217; contributions"
        ]
        9 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Ethical approval"
        ]
        10 => array:2 [
          "identificador" => "sec0095"
          "titulo" => "Informed consent"
        ]
        11 => array:2 [
          "identificador" => "sec0100"
          "titulo" => "Availability of data and material"
        ]
        12 => array:2 [
          "identificador" => "sec0105"
          "titulo" => "Conflicts of interest"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-08-19"
    "fechaAceptado" => "2020-10-05"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1340237"
          "palabras" => array:8 [
            0 => "COVID-19"
            1 => "Coronavirus disease"
            2 => "SARS-CoV-2"
            3 => "2019-nCoV"
            4 => "Outcomes"
            5 => "Chronic liver disease"
            6 => "Acute liver injury"
            7 => "Biomarkers"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The coronavirus disease 2019 &#40;COVID-19&#41; pandemic has been a challenge globally&#46; In severe acute respiratory syndrome &#40;SARS&#41; epidemic 60&#37; of patients had hepatic injury&#44; due to phylogenetic similarities of the viruses it is assumed that COVID-19 is associated with acute liver injury&#46; In this meta-analysis&#44; we aim to study the occurrence and association of liver injury&#44; comorbid liver disease and elevated liver enzymes in COVID-19 confirmed hospitalizations with outcomes&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Data from observational studies describing comorbid chronic liver disease&#44; acute liver injury&#44; elevated aspartate aminotransferase &#40;AST&#41;&#44; alanine aminotransferase &#40;ALT&#41; levels and outcomes of COVID-19 hospitalized patients from December 1&#44; 2019&#44; to June 30&#44; 2020 was extracted following PRISMA guidelines&#46; Adverse outcomes were defined as admission to intensive care unit &#40;ICU&#41;&#44; oxygen saturation &#60;90&#37;&#44; invasive mechanical ventilation &#40;IMV&#41;&#44; severe disease and in-hospital mortality&#46; Odds ratio &#40;OR&#41; and 95&#37; confidence interval &#40;95&#37; CI&#41; were obtained&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">24 studies with 12&#44;882 confirmed COVID-19 patients were included&#46; Overall prevalence of CM-CLD was 2&#46;6&#37;&#44; COVID-19-ALI was 26&#46;5&#37;&#44; elevated AST was 41&#46;1&#37; and elevated ALT was 29&#46;1&#37;&#46; CM-CLD had no significant association with poor outcomes &#40;pooled OR&#58; 0&#46;96&#59; 95&#37; CI&#58; 0&#46;71&#8211;1&#46;29&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;78&#41;&#46; COVID-19-ALI &#40;1&#46;68&#59;1&#46;04&#8211;2&#46;70&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#44; elevated AST &#40;2&#46;98&#59; 2&#46;35&#8211;3&#46;77&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;00001&#41; and elevated ALT &#40;1&#46;85&#59;1&#46;49&#8211;2&#46;29&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;00001&#41; were significantly associated with higher odds of poor outcomes&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Our meta-analysis suggests that acute liver injury and elevated liver enzymes were significantly associated with COVID-19 severity&#46; Future studies should evaluate changing levels of biomarkers amongst liver disease patients to predict poor outcomes of COVID-19 and causes of liver injury during COVID-19 infection&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction and objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Materials and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
          ]
        ]
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:3 [
        "etiqueta" => "1"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0065">Ashish Sharma and Pragya Jaiswal are equally contributing first author&#46;</p>"
        "identificador" => "fn0005"
      ]
      1 => array:3 [
        "etiqueta" => "2"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0070">Equally contributed senior authors&#46;</p>"
        "identificador" => "fn0010"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0200" class="elsevierStylePara elsevierViewall">The following are Supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0115"
          ]
        ]
      ]
    ]
    "multimedia" => array:7 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2882
            "Ancho" => 2508
            "Tamanyo" => 499105
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0035"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Flow diagram of literature search and study selection process of COVID-19 outcomes and liver disease&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1000
            "Ancho" => 2508
            "Tamanyo" => 305932
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0040"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Forest plot of comorbid chronic liver disease &#40;CM-CLD&#41; with outcome in COVID-19 hospitalizations&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 478
            "Ancho" => 2508
            "Tamanyo" => 133839
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0045"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Forest plot of acute liver injury &#40;COVID-19-ALI&#41; with outcome in COVID-19 hospitalizations&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 783
            "Ancho" => 2508
            "Tamanyo" => 225539
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0050"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Forest plot of aspartate aminotransferase &#40;AST&#41; with outcome in COVID-19 hospitalizations&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "fig0025"
        "etiqueta" => "Fig&#46; 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 711
            "Ancho" => 2508
            "Tamanyo" => 211555
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0055"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Forest plot of alanine aminotransferase &#40;ALT&#41; with outcome in COVID-19 hospitalizations&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0060"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Country&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sample size &#40;<span class="elsevierStyleItalic">n</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mean&#47;median age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Males &#40;<span class="elsevierStyleItalic">n</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study design&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Outcomes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comorbid liver disease<a class="elsevierStyleCrossRefs" href="#tblfn0030"><span class="elsevierStyleSup">&#36;</span></a>&#47;acute liver injury and AST and ALT levels<span class="elsevierStyleSup">&#64;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Huang et al&#46;&#44; January 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICU vs&#46; non-ICU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLDAST&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Guan et al&#46;&#44; February 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1099&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">637&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective multi-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe vs non-severe<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLDASTALT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Wang et al&#46;&#44; February 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">138&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICU vs&#46; non-ICU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zhang et al&#46;&#44; February 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">140&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe vs non-severe<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chen et al&#46;&#44; March 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe vs&#46; moderate<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ALI&#94;&#94;&#94;AST&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mo et al&#46;&#44; March 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">155&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refractory vs&#46; general<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">&#35;&#35;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Qin et al&#46;&#44; March 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">452&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">235&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe vs non-severe<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruan et al&#46;&#44; Mar 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67 &#40;died&#41;50 &#40;discharged&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">102&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective multi-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Died vs&#46; discharged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Wang et al&#46;&#44; March 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SpO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>90 vs&#46; SpO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLDASTALT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Wang et al&#46;&#44; March 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">339&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">166&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Survivor vs&#46; non-survivor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLDALI&#94;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zheng et al&#46;&#44; March 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">161&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe vs non-severe<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLDASTALT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zhou et al&#46;&#44; March 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">191&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">119&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective multi-center cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Survivor vs&#46; non-survivor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ALT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Colaneri et al&#46;&#44; April 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Italy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe vs&#46; mild<a class="elsevierStyleCrossRef" href="#tblfn0015">&#42;&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Goyal et al&#46;&#44; April 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">393&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">238&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective multi-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Invasive mechanical ventilation vs&#46; no invasive mechanical ventilation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLDASTALT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zhang et al&#46;&#44; April 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">663&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">321&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>critical vs&#46; mild<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>moderate<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ASTALT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zhao et al&#44; April 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe vs&#46; mild<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#35;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ALI&#94;&#42;ASTALT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Du et al&#46;&#44; May 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">179&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective single-center case cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Deceased vs survivors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AST&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hong et al&#46;&#44; May 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">South Korea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICU vs&#46; non-ICU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLDASTALT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Huang et&#46; al&#46;&#44; May 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">202&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">116&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective multi-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe vs non-severe<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Zheng et al&#46;&#44; May 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">invasive mechanical ventilation vs non-invasive mechanical ventilation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLDALI&#94;&#94;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Deng et al&#46;&#44; June 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;5 &#40;severe<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>critical&#41;&#44; 35 &#40;moderate&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective cohort study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#40;Severe<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>critical&#41; vs&#46; moderate<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ASTALT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Marcello et al&#46;&#44; June 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3055&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective multi-center study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Died vs&#46; discharged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mikami et al&#46;&#44; June 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">USA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2820&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62 &#40;survivor&#41;&#44; 76 &#40;Non-survivor&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1611&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective multi-center cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Survivor vs&#46; non-survivor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ASTALT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Wang et al&#46;&#44; June 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">China&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">275&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">128&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective single-center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe vs non-severe<a class="elsevierStyleCrossRef" href="#tblfn0010">&#42;&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CM-CLD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12882&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"></td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2532345.png"
              ]
            ]
          ]
          "notaPie" => array:7 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Using the American Thoracic Society guidelines for community-acquired pneumonia&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "&#42;&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">World Health Organization and the National Health Commission of China interim guidelines defined disease severity and improvement as follows&#58; Mild cases&#58; The mild clinical symptoms and no pneumonia in imaging&#46; Moderate cases&#58; symptoms like fever and respiratory tract symptoms&#44; etc&#46;&#44; and pneumonia can be seen in imaging&#46; Severe cases&#58; Meeting any of the following &#8211; respiratory distress&#44; respiratory rate<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>breaths&#47;min&#59; SpO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>93&#37; at rest&#59; and PaO<span class="elsevierStyleInf">2</span>&#47;FIO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>300&#46; Patients with &#62;50&#37; lesion progression within 24&#8211;48<span class="elsevierStyleHsp" style=""></span>h&#46; Critical&#47;extremely severe cases&#58; if they have one of the following&#58; respiratory failure requiring mechanical ventilation&#44; shock&#44; and other organ failure requiring ICU treatment&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "&#42;&#42;&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Patients were included in the mild disease group if they did not need high-flow oxygen support and in the severe disease group if they were provided with high-flow oxygen support&#46;</p>"
            ]
            3 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "&#35;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Not mentioned&#46;</p>"
            ]
            4 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "&#35;&#35;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">General COVID-19 included following criteria&#58;&#40;i&#41; obvious alleviation of respiratory symptoms &#40;e&#46;g&#46; cough&#44; chest distress and breath shortness&#41; after treatment&#59; &#40;ii&#41; maintenance of normal body temperature for &#8805;3 days without the use of corticosteroid or antipyretics&#59; &#40;iii&#41; improvement in radiological abnormalities on chest CT or X-ray after treatment&#59; &#40;iv&#41; a hospital stays of &#8804;10 days&#46; Otherwise&#44; it was classified as refractory COVID-19&#46;</p>"
            ]
            5 => array:3 [
              "identificador" => "tblfn0030"
              "etiqueta" => "&#36;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">All the studies mentioned chronic liver disease as a comorbidity&#46;</p> <p class="elsevierStyleNotepara" id="npar0035">&#94; Liver enzyme abnormalities&#46;</p> <p class="elsevierStyleNotepara" id="npar0040">&#94;&#94; Acute liver injury defined as an increase in alanine aminotransferase &#40;ALT&#41; over two times the upper limit of the range &#40;ULN&#41; or an increase in conjugated bilirubin or a combined increase in aspartate aminotransferase &#40;AST&#41;&#44; alkaline phosphatase and total bilirubin provided that one of them was above two times ULN&#46;</p> <p class="elsevierStyleNotepara" id="npar0045">&#94;&#94;&#94; Acute liver injury was defined as Jaundice with a total bilirubin level of 3<span class="elsevierStyleHsp" style=""></span>mg&#47;dl or higher and an acute increase in ALT of at least 5 times the upper limit of the normal range and&#47;or an increase alkaline phosphatase of at least twice the upper limit of the normal range&#46;</p> <p class="elsevierStyleNotepara" id="npar0050">&#94;&#42; Liver injury was judged ALT and AST levels&#46;</p>"
            ]
            6 => array:3 [
              "identificador" => "tblfn0035"
              "etiqueta" => "&#64;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0055">Studies considered AST &#40;aspartate aminotransferase&#41; and ALT &#40;alanine aminotransferase&#41; levels &#62;40<span class="elsevierStyleHsp" style=""></span>IU&#47;L as elevated levels&#46;</p> <p class="elsevierStyleNotepara" id="npar0060">References of the included studies in meta-analysis is in eSupplemental file 1&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Study characteristics&#44; outcomes and Liver disease&#46;</p>"
        ]
      ]
      6 => array:5 [
        "identificador" => "upi0005"
        "tipo" => "MULTIMEDIAECOMPONENTE"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "Ecomponente" => array:2 [
          "fichero" => "mmc1.docx"
          "ficheroTamanyo" => 20786
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:34 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "&#91;1&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "WHO Director-General&#39;s opening remarks at the media briefing on COVID-19 &#8211; 11 March 2020"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "World Health Organization"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "&#91;2&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cases in the U&#46;S&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Centers for Disease Control and Prevention"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "&#91;3&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "COVID-19 CORONAVIRUS PANDEMIC"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Worldometer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "&#91;4&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Multiorgan and renal tropism of SARS-CoV-2"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46;G&#46; Puelles"
                            1 => "M&#46; L&#252;tgehetmann"
                            2 => "M&#46;T&#46; Lindenmeyer"
                            3 => "J&#46;P&#46; Sperhake"
                            4 => "M&#46;N&#46; Wong"
                            5 => "L&#46; Allweiss"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMc2011400"
                      "Revista" => array:7 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2020"
                        "volumen" => "383"
                        "numero" => "6"
                        "paginaInicial" => "590"
                        "paginaFinal" => "592"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32402155"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "&#91;5&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Age-adjusted risk factors associated with mortality and mechanical ventilation utilization amongst COVID-19 hospitalizations &#8211; a systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "U&#46; Patel"
                            1 => "P&#46; Malik"
                            2 => "M&#46;S&#46; Usman"
                            3 => "D&#46; Mehta"
                            4 => "A&#46; Sharma"
                            5 => "F&#46;A&#46; Malik"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "SN Comprehen Clin Med"
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "&#91;6&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "COVID-19 and liver"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46; Jothimani"
                            1 => "R&#46; Venugopal"
                            2 => "M&#46;F&#46; Abedin"
                            3 => "I&#46; Kaliamoorthy"
                            4 => "M&#46; Rela"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2013.10.028"
                      "Revista" => array:3 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2020"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24211739"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "&#91;7&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Specific ACE2 expression in Cholangiocytes may cause liver damage after 2019-nCoV infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "X&#46; Chai"
                            1 => "L&#46; Hu"
                            2 => "Y&#46; Zhang"
                            3 => "W&#46; Han"
                            4 => "Z&#46; Lu"
                            5 => "A&#46; Ke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "bioRxiv"
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "&#91;8&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Paizis"
                            1 => "C&#46; Tikellis"
                            2 => "M&#46;E&#46; Cooper"
                            3 => "J&#46;M&#46; Schembri"
                            4 => "R&#46;A&#46; Lew"
                            5 => "A&#46;I&#46; Smith"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/gut.2004.062398"
                      "Revista" => array:7 [
                        "tituloSerie" => "Gut"
                        "fecha" => "2005"
                        "volumen" => "54"
                        "numero" => "December &#40;12&#41;"
                        "paginaInicial" => "1790"
                        "paginaFinal" => "1796"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16166274"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "&#91;9&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Upregulation of hepatic angiotensin-converting enzyme 2 &#40;ACE2&#41; and angiotensin-&#40;1-7&#41; levels in experimental biliary fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;B&#46; Herath"
                            1 => "F&#46;J&#46; Warner"
                            2 => "J&#46;S&#46; Lubel"
                            3 => "R&#46;G&#46; Dean"
                            4 => "Z&#46; Jia"
                            5 => "R&#46;A&#46; Lew"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2007.03.008"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2007"
                        "volumen" => "47"
                        "numero" => "September &#40;3&#41;"
                        "paginaInicial" => "387"
                        "paginaFinal" => "395"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17532087"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "&#91;10&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comorbidity and its impact on 1590 patients with COVID-19 in China&#58; a nationwide analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;J&#46; Guan"
                            1 => "W&#46;H&#46; Liang"
                            2 => "Y&#46; Zhao"
                            3 => "H&#46;R&#46; Liang"
                            4 => "Z&#46;S&#46; Chen"
                            5 => "Y&#46;M&#46; Li"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2020"
                        "volumen" => "55"
                        "numero" => "May &#40;5&#41;"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "&#91;11&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Preferred reporting items for systematic reviews and meta-analyses&#58; the PRISMA statement"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46; Moher"
                            1 => "A&#46; Liberati"
                            2 => "J&#46; Tetzlaff"
                            3 => "D&#46;G&#46; Altman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pmed.1000097"
                      "Revista" => array:6 [
                        "tituloSerie" => "PLoS Med"
                        "fecha" => "2009"
                        "volumen" => "6"
                        "numero" => "July &#40;7&#41;"
                        "paginaInicial" => "e1000097"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19621072"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "&#91;12&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Meta-analysis of observational studies in epidemiology&#58; a proposal for reporting&#46; Meta-analysis Of Observational Studies in Epidemiology &#40;MOOSE&#41; group"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;F&#46; Stroup"
                            1 => "J&#46;A&#46; Berlin"
                            2 => "S&#46;C&#46; Morton"
                            3 => "I&#46; Olkin"
                            4 => "G&#46;D&#46; Williamson"
                            5 => "D&#46; Rennie"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.283.15.2008"
                      "Revista" => array:7 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2000"
                        "volumen" => "283"
                        "numero" => "April &#40;15&#41;"
                        "paginaInicial" => "2008"
                        "paginaFinal" => "2012"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10789670"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "&#91;13&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Newcastle-Ottawa Scale &#40;NOS&#41; for assessing the quality of nonrandomised studies in meta-analyses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;A&#46; Wells"
                            1 => "B&#46; Shea"
                            2 => "D&#46; O&#8217;Connell"
                            3 => "J&#46; Peterson"
                            4 => "V&#46; Welch"
                            5 => "M&#46; Losos"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2020"
                        "editorial" => "Professor GA Wells&#44; Department of Epidemiology and Community Medicine"
                        "editorialLocalizacion" => "University of Ottawa&#44; Ontario K1J 8M5&#44; Canada"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "&#91;14&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Coronavirus disease &#40;COVID-19&#41; and the liver&#58; a comprehensive systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;P&#46; Kumar"
                            1 => "S&#46; Mishra"
                            2 => "D&#46;K&#46; Jha"
                            3 => "J&#46; Shukla"
                            4 => "A&#46; Choudhury"
                            5 => "R&#46; Mohindra"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Hepatol Int"
                        "fecha" => "2020"
                        "numero" => "July"
                        "paginaInicial" => "1"
                        "paginaFinal" => "12"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "&#91;15&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical characteristics and outcomes of coronavirus disease 2019 among patients with preexisting liver disease in the United States&#58; a multicenter research network study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46; Singh"
                            1 => "A&#46; Khan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2020"
                        "numero" => "May"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "&#91;16&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical features of patients infected with 2019 novel coronavirus in Wuhan&#44; China"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Huang"
                            1 => "Y&#46; Wang"
                            2 => "X&#46; Li"
                            3 => "L&#46; Ren"
                            4 => "J&#46; Zhao"
                            5 => "Y&#46; Hu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(20)30183-5"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2020"
                        "volumen" => "395"
                        "numero" => "February &#40;10223&#41;"
                        "paginaInicial" => "497"
                        "paginaFinal" => "506"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31986264"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "&#91;17&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan&#44; China&#58; a descriptive study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Chen"
                            1 => "M&#46; Zhou"
                            2 => "X&#46; Dong"
                            3 => "J&#46; Qu"
                            4 => "F&#46; Gong"
                            5 => "Y&#46; Han"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "The Lancet"
                        "fecha" => "2020"
                        "volumen" => "395"
                        "numero" => "10223"
                        "paginaInicial" => "507"
                        "paginaFinal" => "513"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "&#91;18&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "COVID-19 in a designated infectious diseases hospital outside Hubei Province&#44; China"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Q&#46; Cai"
                            1 => "D&#46; Huang"
                            2 => "P&#46; Ou"
                            3 => "H&#46; Yu"
                            4 => "Z&#46; Zhu"
                            5 => "Z&#46; Xia"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/all.14309"
                      "Revista" => array:7 [
                        "tituloSerie" => "Allergy"
                        "fecha" => "2020"
                        "volumen" => "75"
                        "numero" => "7"
                        "paginaInicial" => "1742"
                        "paginaFinal" => "1752"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32239761"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "&#91;19&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tissue distribution of ACE2 protein&#44; the functional receptor for SARS coronavirus&#46; A first step in understanding SARS pathogenesis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "I&#46; Hamming"
                            1 => "W&#46; Timens"
                            2 => "M&#46;L&#46; Bulthuis"
                            3 => "A&#46;T&#46; Lely"
                            4 => "G&#46; Navis"
                            5 => "H&#46; van Goor"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/path.1570"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Pathol"
                        "fecha" => "2004"
                        "volumen" => "203"
                        "numero" => "June &#40;2&#41;"
                        "paginaInicial" => "631"
                        "paginaFinal" => "637"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15141377"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "&#91;20&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical characteristics and mechanism of liver injury in patients with severe acute respiratory syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Z&#46;P&#46; Duan"
                            1 => "Y&#46; Chen"
                            2 => "J&#46; Zhang"
                            3 => "J&#46; Zhao"
                            4 => "Z&#46;W&#46; Lang"
                            5 => "F&#46;K&#46; Meng"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Zhonghua Gan Zang Bing Za Zhi"
                        "fecha" => "2003"
                        "volumen" => "11"
                        "numero" => "August &#40;8&#41;"
                        "paginaInicial" => "493"
                        "paginaFinal" => "496"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12939186"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "&#91;21&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk factors related to hepatic injury in patients with corona virus disease 2019"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Li"
                            1 => "S&#46; Li"
                            2 => "M&#46; Xu"
                            3 => "P&#46; Yu"
                            4 => "S&#46; Zheng"
                            5 => "Z&#46; Duan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "medRxiv"
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "&#91;22&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cholangiocyte pathobiology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46;M&#46; Banales"
                            1 => "R&#46;C&#46; Huebert"
                            2 => "T&#46; Karlsen"
                            3 => "M&#46; Strazzabosco"
                            4 => "N&#46;F&#46; LaRusso"
                            5 => "G&#46;J&#46; Gores"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41575-019-0125-y"
                      "Revista" => array:7 [
                        "tituloSerie" => "Nat Rev Gastroenterol Hepatol"
                        "fecha" => "2019"
                        "volumen" => "16"
                        "numero" => "May &#40;5&#41;"
                        "paginaInicial" => "269"
                        "paginaFinal" => "281"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30850822"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "&#91;23&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pathological findings of COVID-19 associated with acute respiratory distress syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Z&#46; Xu"
                            1 => "L&#46; Shi"
                            2 => "Y&#46; Wang"
                            3 => "J&#46; Zhang"
                            4 => "L&#46; Huang"
                            5 => "C&#46; Zhang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-2600(20)30076-X"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet Respir Med"
                        "fecha" => "2020"
                        "volumen" => "8"
                        "numero" => "4"
                        "paginaInicial" => "420"
                        "paginaFinal" => "422"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32085846"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "&#91;24&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "COVID-19 and liver dysfunction&#58; current insights and emergent therapeutic strategies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Feng"
                            1 => "K&#46;I&#46; Zheng"
                            2 => "Q&#46;Q&#46; Yan"
                            3 => "R&#46;S&#46; Rios"
                            4 => "G&#46; Targher"
                            5 => "C&#46;D&#46; Byrne"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.14218/JCTH.2020.00018"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Transl Hepatol"
                        "fecha" => "2020"
                        "volumen" => "8"
                        "numero" => "March &#40;1&#41;"
                        "paginaInicial" => "18"
                        "paginaFinal" => "24"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32274342"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "&#91;25&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical features of COVID-19-related liver functional abnormality"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Z&#46; Fan"
                            1 => "L&#46; Chen"
                            2 => "J&#46; Li"
                            3 => "X&#46; Cheng"
                            4 => "J&#46; Yang"
                            5 => "C&#46; Tian"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cgh.2020.04.002"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Gastroenterol Hepatol"
                        "fecha" => "2020"
                        "volumen" => "18"
                        "numero" => "June &#40;7&#41;"
                        "paginaInicial" => "1561"
                        "paginaFinal" => "1566"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32283325"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "&#91;26&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical features of patients infected with 2019 novel coronavirus in Wuhan&#44; China"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Huang"
                            1 => "Y&#46; Wang"
                            2 => "X&#46; Li"
                            3 => "L&#46; Ren"
                            4 => "J&#46; Zhao"
                            5 => "Y&#46; Hu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "The Lancet"
                        "fecha" => "2020"
                        "volumen" => "395"
                        "numero" => "10223"
                        "paginaInicial" => "497"
                        "paginaFinal" => "506"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "&#91;27&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "COVID-19&#58; abnormal liver function tests"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Q&#46; Cai"
                            1 => "D&#46; Huang"
                            2 => "H&#46; Yu"
                            3 => "Z&#46; Zhu"
                            4 => "Z&#46; Xia"
                            5 => "Y&#46; Su"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jhep.2020.04.006"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "2020"
                        "volumen" => "73"
                        "numero" => "3"
                        "paginaInicial" => "566"
                        "paginaFinal" => "574"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32298767"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "&#91;28&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Organ distribution of severe acute respiratory syndrome &#40;SARS&#41; associated coronavirus &#40;SARS-CoV&#41; in SARS patients&#58; implications for pathogenesis and virus transmission pathways"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Ding"
                            1 => "L&#46; He"
                            2 => "Q&#46; Zhang"
                            3 => "Z&#46; Huang"
                            4 => "X&#46; Che"
                            5 => "J&#46; Hou"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/path.1560"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Pathol"
                        "fecha" => "2004"
                        "volumen" => "203"
                        "numero" => "June &#40;2&#41;"
                        "paginaInicial" => "622"
                        "paginaFinal" => "630"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15141376"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "&#91;29&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical significance of hepatic derangement in severe acute respiratory syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46;L&#46; Chan"
                            1 => "A&#46;C&#46; Kwan"
                            2 => "K&#46;F&#46; To"
                            3 => "S&#46;T&#46; Lai"
                            4 => "P&#46;K&#46; Chan"
                            5 => "W&#46;K&#46; Leung"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3748/wjg.v11.i14.2148"
                      "Revista" => array:7 [
                        "tituloSerie" => "World J Gastroenterol"
                        "fecha" => "2005"
                        "volumen" => "11"
                        "numero" => "April &#40;14&#41;"
                        "paginaInicial" => "2148"
                        "paginaFinal" => "2153"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15810082"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "&#91;30&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical characteristics and mechanism of liver damage in patients with severe acute respiratory syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Z&#46; Yang"
                            1 => "M&#46; Xu"
                            2 => "J&#46;Q&#46; Yi"
                            3 => "W&#46;D&#46; Jia"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatobiliary Pancreat Dis Int"
                        "fecha" => "2005"
                        "volumen" => "4"
                        "numero" => "February &#40;1&#41;"
                        "paginaInicial" => "60"
                        "paginaFinal" => "63"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15730921"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "&#91;31&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection&#58; a single-center experience in Saudi Arabia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Saad"
                            1 => "A&#46;S&#46; Omrani"
                            2 => "K&#46; Baig"
                            3 => "A&#46; Bahloul"
                            4 => "F&#46; Elzein"
                            5 => "M&#46;A&#46; Matin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ijid.2014.09.003"
                      "Revista" => array:7 [
                        "tituloSerie" => "Int J Infect Dis"
                        "fecha" => "2014"
                        "volumen" => "29"
                        "numero" => "December"
                        "paginaInicial" => "301"
                        "paginaFinal" => "306"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25303830"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "&#91;32&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Critically ill patients with the middle east respiratory syndrome&#58; a multicenter retrospective cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46;M&#46; Arabi"
                            1 => "A&#46; Al-Omari"
                            2 => "Y&#46; Mandourah"
                            3 => "F&#46; Al-Hameed"
                            4 => "A&#46;A&#46; Sindi"
                            5 => "B&#46; Alraddadi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/CCM.0000000000002621"
                      "Revista" => array:7 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2017"
                        "volumen" => "45"
                        "numero" => "October &#40;10&#41;"
                        "paginaInicial" => "1683"
                        "paginaFinal" => "1695"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28787295"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "&#91;33&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46; Li"
                            1 => "M&#46;J&#46; Moore"
                            2 => "N&#46; Vasilieva"
                            3 => "J&#46; Sui"
                            4 => "S&#46;K&#46; Wong"
                            5 => "M&#46;A&#46; Berne"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature02145"
                      "Revista" => array:7 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2003"
                        "volumen" => "426"
                        "numero" => "November &#40;6965&#41;"
                        "paginaInicial" => "450"
                        "paginaFinal" => "454"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14647384"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "&#91;34&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "SARS-associated viral hepatitis caused by a novel coronavirus&#58; report of three cases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;N&#46; Chau"
                            1 => "K&#46;C&#46; Lee"
                            2 => "H&#46; Yao"
                            3 => "T&#46;Y&#46; Tsang"
                            4 => "T&#46;C&#46; Chow"
                            5 => "Y&#46;C&#46; Yeung"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/hep.20111"
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "2004"
                        "volumen" => "39"
                        "numero" => "February &#40;2&#41;"
                        "paginaInicial" => "302"
                        "paginaFinal" => "310"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14767982"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/16652681/000000210000000C/v1_202102250957/S1665268120301885/v1_202102250957/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "78265"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original Articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/16652681/000000210000000C/v1_202102250957/S1665268120301885/v1_202102250957/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268120301885?idApp=UINPBA00004N"
]
Article information
ISSN: 16652681
Original language: English
DOI:10.1016/j.aohep.2020.10.001
The statistics are updated each day
Year/Month Html Pdf Total
2024 November 5 2 7
2024 October 45 8 53
2024 September 54 19 73
2024 August 59 15 74
2024 July 59 4 63
2024 June 57 4 61
2024 May 49 4 53
2024 April 39 16 55
2024 March 97 9 106
2024 February 117 15 132
2024 January 161 15 176
2023 December 109 11 120
2023 November 120 15 135
2023 October 124 19 143
2023 September 126 13 139
2023 August 119 14 133
2023 July 58 10 68
2023 June 59 11 70
2023 May 120 8 128
2023 April 69 4 73
2023 March 45 8 53
2023 February 45 12 57
2023 January 63 19 82
2022 December 69 17 86
2022 November 94 26 120
2022 October 73 22 95
2022 September 113 34 147
2022 August 108 38 146
2022 July 103 31 134
2022 June 90 35 125
2022 May 262 48 310
2022 April 158 40 198
2022 March 155 36 191
2022 February 335 26 361
2022 January 683 94 777
2021 December 423 91 514
2021 November 584 153 737
2021 October 579 134 713
2021 September 727 96 823
2021 August 1054 136 1190
2021 July 760 110 870
2021 June 609 116 725
2021 May 473 99 572
2021 April 248 82 330
2021 March 86 86 172
2021 February 25 17 42
2021 January 32 14 46
2020 December 21 16 37
2020 November 8 13 21
Show all

Follow this link to access the full text of the article

Subscribe to our newsletter

Publish in
Annals of Hepatology
Affiliated societies

 

es en pt

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

Are you a health professional able to prescribe or dispense drugs?

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