Liver injury in hospitalized patients with COVID-19: An International observational cohort study

Bharath Kumar Tirupakuzhi Vijayaraghavan; Saptarshi Bishnu; ISARIC Clinical Characterization Group; Joaquin Baruch; Barbara Wanjiru Citarella; Christiana Kartsonaki; Aronrag Meeyai; Zubair Mohamed; Shinichiro Ohshimo; Benjamin Lefèvre; Abdulrahman Al-Fares; Jose A. Calvache; Fabio Silvio Taccone; Piero Olliaro; Laura Merson; Neill K.J. Adhikari

doi:10.1371/journal.pone.0277859

Liver injury in hospitalized patients with COVID-19: An International observational cohort study

Bharath Kumar Tirupakuzhi Vijayaraghavan^*, Saptarshi Bishnu, ISARIC Clinical Characterization Group, Joaquin Baruch, Barbara Wanjiru Citarella, Christiana Kartsonaki, Aronrag Meeyai, Zubair Mohamed, Shinichiro Ohshimo, Benjamin Lefèvre, Abdulrahman Al-Fares, Jose A. Calvache, Fabio Silvio Taccone, Piero Olliaro, Laura Merson, Neill K.J. Adhikari

^*Corresponding author for this work

Anesthesiology

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND:

Using a large dataset, we evaluated prevalence and severity of alterations in liver enzymes in COVID-19 and association with patient-centred outcomes.

METHODS:

We included hospitalized patients with confirmed or suspected SARS-CoV-2 infection from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) database. Key exposure was baseline liver enzymes (AST, ALT, bilirubin). Patients were assigned Liver Injury Classification score based on 3 components of enzymes at admission: Normal; Stage I) Liver injury: any component between 1-3x upper limit of normal (ULN); Stage II) Severe liver injury: any component ≥3x ULN. Outcomes were hospital mortality, utilization of selected resources, complications, and durations of hospital and ICU stay. Analyses used logistic regression with associations expressed as adjusted odds ratios (OR) with 95% confidence intervals (CI).

RESULTS:

Of 17,531 included patients, 46.2% (8099) and 8.2% (1430) of patients had stage 1 and 2 liver injury respectively. Compared to normal, stages 1 and 2 were associated with higher odds of mortality (OR 1.53 [1.37-1.71]; OR 2.50 [2.10-2.96]), ICU admission (OR 1.63 [1.48-1.79]; OR 1.90 [1.62-2.23]), and invasive mechanical ventilation (OR 1.43 [1.27-1.70]; OR 1.95 (1.55-2.45). Stages 1 and 2 were also associated with higher odds of developing sepsis (OR 1.38 [1.27-1.50]; OR 1.46 [1.25-1.70]), acute kidney injury (OR 1.13 [1.00-1.27]; OR 1.59 [1.32-1.91]), and acute respiratory distress syndrome (OR 1.38 [1.22-1.55]; OR 1.80 [1.49-2.17]).

CONCLUSIONS:

Liver enzyme abnormalities are common among COVID-19 patients and associated with worse outcomes.

Original language	English
Article number	e0277859
Journal	PLoS ONE
Volume	18
Issue number	9 September
DOIs	https://doi.org/10.1371/journal.pone.0277859
Publication status	Published - 13 Sept 2023

Bibliographical note

Funding Information:
“This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z]; and the Bill & Melinda Gates Foundation [OPP1209135]. The funders had no role in the design, analysis, manuscript preparation or decision to submit for publication.”

Publisher Copyright:
© 2023 Vijayaraghavan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Liver injury in hospitalized patients with COVID-19Final published version, 459 KBLicence: CC BY

Cite this

Tirupakuzhi Vijayaraghavan, B. K., Bishnu, S., ISARIC Clinical Characterization Group, Baruch, J., Citarella, B. W., Kartsonaki, C., Meeyai, A., Mohamed, Z., Ohshimo, S., Lefèvre, B., Al-Fares, A., Calvache, J. A., Taccone, F. S., Olliaro, P., Merson, L., & Adhikari, N. K. J. (2023). Liver injury in hospitalized patients with COVID-19: An International observational cohort study. PLoS ONE, 18(9 September), Article e0277859. https://doi.org/10.1371/journal.pone.0277859

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title = "Liver injury in hospitalized patients with COVID-19: An International observational cohort study",

abstract = "BACKGROUND: Using a large dataset, we evaluated prevalence and severity of alterations in liver enzymes in COVID-19 and association with patient-centred outcomes. METHODS: We included hospitalized patients with confirmed or suspected SARS-CoV-2 infection from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) database. Key exposure was baseline liver enzymes (AST, ALT, bilirubin). Patients were assigned Liver Injury Classification score based on 3 components of enzymes at admission: Normal; Stage I) Liver injury: any component between 1-3x upper limit of normal (ULN); Stage II) Severe liver injury: any component ≥3x ULN. Outcomes were hospital mortality, utilization of selected resources, complications, and durations of hospital and ICU stay. Analyses used logistic regression with associations expressed as adjusted odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Of 17,531 included patients, 46.2% (8099) and 8.2% (1430) of patients had stage 1 and 2 liver injury respectively. Compared to normal, stages 1 and 2 were associated with higher odds of mortality (OR 1.53 [1.37-1.71]; OR 2.50 [2.10-2.96]), ICU admission (OR 1.63 [1.48-1.79]; OR 1.90 [1.62-2.23]), and invasive mechanical ventilation (OR 1.43 [1.27-1.70]; OR 1.95 (1.55-2.45). Stages 1 and 2 were also associated with higher odds of developing sepsis (OR 1.38 [1.27-1.50]; OR 1.46 [1.25-1.70]), acute kidney injury (OR 1.13 [1.00-1.27]; OR 1.59 [1.32-1.91]), and acute respiratory distress syndrome (OR 1.38 [1.22-1.55]; OR 1.80 [1.49-2.17]). CONCLUSIONS: Liver enzyme abnormalities are common among COVID-19 patients and associated with worse outcomes.",

author = "{Tirupakuzhi Vijayaraghavan}, {Bharath Kumar} and Saptarshi Bishnu and {ISARIC Clinical Characterization Group} and Joaquin Baruch and Citarella, {Barbara Wanjiru} and Christiana Kartsonaki and Aronrag Meeyai and Zubair Mohamed and Shinichiro Ohshimo and Benjamin Lef{\`e}vre and Abdulrahman Al-Fares and Calvache, {Jose A.} and Taccone, {Fabio Silvio} and Piero Olliaro and Laura Merson and Adhikari, {Neill K.J.}",

note = "Funding Information: “This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z]; and the Bill & Melinda Gates Foundation [OPP1209135]. The funders had no role in the design, analysis, manuscript preparation or decision to submit for publication.” Publisher Copyright: {\textcopyright} 2023 Vijayaraghavan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2023",

month = sep,

day = "13",

doi = "10.1371/journal.pone.0277859",

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Tirupakuzhi Vijayaraghavan, BK, Bishnu, S, ISARIC Clinical Characterization Group, Baruch, J, Citarella, BW, Kartsonaki, C, Meeyai, A, Mohamed, Z, Ohshimo, S, Lefèvre, B, Al-Fares, A, Calvache, JA, Taccone, FS, Olliaro, P, Merson, L & Adhikari, NKJ 2023, 'Liver injury in hospitalized patients with COVID-19: An International observational cohort study', PLoS ONE, vol. 18, no. 9 September, e0277859. https://doi.org/10.1371/journal.pone.0277859

TY - JOUR

T1 - Liver injury in hospitalized patients with COVID-19

T2 - An International observational cohort study

AU - Tirupakuzhi Vijayaraghavan, Bharath Kumar

AU - Bishnu, Saptarshi

AU - ISARIC Clinical Characterization Group

AU - Baruch, Joaquin

AU - Citarella, Barbara Wanjiru

AU - Kartsonaki, Christiana

AU - Meeyai, Aronrag

AU - Mohamed, Zubair

AU - Ohshimo, Shinichiro

AU - Lefèvre, Benjamin

AU - Al-Fares, Abdulrahman

AU - Calvache, Jose A.

AU - Taccone, Fabio Silvio

AU - Olliaro, Piero

AU - Merson, Laura

AU - Adhikari, Neill K.J.

N1 - Funding Information: “This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z]; and the Bill & Melinda Gates Foundation [OPP1209135]. The funders had no role in the design, analysis, manuscript preparation or decision to submit for publication.” Publisher Copyright: © 2023 Vijayaraghavan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2023/9/13

Y1 - 2023/9/13

N2 - BACKGROUND: Using a large dataset, we evaluated prevalence and severity of alterations in liver enzymes in COVID-19 and association with patient-centred outcomes. METHODS: We included hospitalized patients with confirmed or suspected SARS-CoV-2 infection from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) database. Key exposure was baseline liver enzymes (AST, ALT, bilirubin). Patients were assigned Liver Injury Classification score based on 3 components of enzymes at admission: Normal; Stage I) Liver injury: any component between 1-3x upper limit of normal (ULN); Stage II) Severe liver injury: any component ≥3x ULN. Outcomes were hospital mortality, utilization of selected resources, complications, and durations of hospital and ICU stay. Analyses used logistic regression with associations expressed as adjusted odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Of 17,531 included patients, 46.2% (8099) and 8.2% (1430) of patients had stage 1 and 2 liver injury respectively. Compared to normal, stages 1 and 2 were associated with higher odds of mortality (OR 1.53 [1.37-1.71]; OR 2.50 [2.10-2.96]), ICU admission (OR 1.63 [1.48-1.79]; OR 1.90 [1.62-2.23]), and invasive mechanical ventilation (OR 1.43 [1.27-1.70]; OR 1.95 (1.55-2.45). Stages 1 and 2 were also associated with higher odds of developing sepsis (OR 1.38 [1.27-1.50]; OR 1.46 [1.25-1.70]), acute kidney injury (OR 1.13 [1.00-1.27]; OR 1.59 [1.32-1.91]), and acute respiratory distress syndrome (OR 1.38 [1.22-1.55]; OR 1.80 [1.49-2.17]). CONCLUSIONS: Liver enzyme abnormalities are common among COVID-19 patients and associated with worse outcomes.

AB - BACKGROUND: Using a large dataset, we evaluated prevalence and severity of alterations in liver enzymes in COVID-19 and association with patient-centred outcomes. METHODS: We included hospitalized patients with confirmed or suspected SARS-CoV-2 infection from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) database. Key exposure was baseline liver enzymes (AST, ALT, bilirubin). Patients were assigned Liver Injury Classification score based on 3 components of enzymes at admission: Normal; Stage I) Liver injury: any component between 1-3x upper limit of normal (ULN); Stage II) Severe liver injury: any component ≥3x ULN. Outcomes were hospital mortality, utilization of selected resources, complications, and durations of hospital and ICU stay. Analyses used logistic regression with associations expressed as adjusted odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Of 17,531 included patients, 46.2% (8099) and 8.2% (1430) of patients had stage 1 and 2 liver injury respectively. Compared to normal, stages 1 and 2 were associated with higher odds of mortality (OR 1.53 [1.37-1.71]; OR 2.50 [2.10-2.96]), ICU admission (OR 1.63 [1.48-1.79]; OR 1.90 [1.62-2.23]), and invasive mechanical ventilation (OR 1.43 [1.27-1.70]; OR 1.95 (1.55-2.45). Stages 1 and 2 were also associated with higher odds of developing sepsis (OR 1.38 [1.27-1.50]; OR 1.46 [1.25-1.70]), acute kidney injury (OR 1.13 [1.00-1.27]; OR 1.59 [1.32-1.91]), and acute respiratory distress syndrome (OR 1.38 [1.22-1.55]; OR 1.80 [1.49-2.17]). CONCLUSIONS: Liver enzyme abnormalities are common among COVID-19 patients and associated with worse outcomes.

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U2 - 10.1371/journal.pone.0277859

DO - 10.1371/journal.pone.0277859

M3 - Article

C2 - 37703268

AN - SCOPUS:85171238933

SN - 1932-6203

VL - 18

JO - PLoS ONE

JF - PLoS ONE

IS - 9 September

M1 - e0277859

ER -

Liver injury in hospitalized patients with COVID-19: An International observational cohort study

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