Longitudinal Analysis of the Utility of Liver Biochemistry as Prognostic Markers in Hospitalized Patients With Corona Virus Disease 2019

  1. Tingyan Wang
  2. David A. Smith
  3. Cori Campbell
  4. Steve Harris
  5. Hizni Salih
  6. Kinga A. Várnai
  7. Kerrie Woods
  8. Theresa Noble
  9. Oliver Freeman
  10. Zuzana Moysova
  11. Thomas Marjot
  12. Gwilym J. Webb
  13. Jim Davies
  14. Eleanor Barnes
  15. Philippa C. Matthews

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Abstract

The association of liver biochemistry with clinical outcomes of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is currently unclear, and the utility of longitudinally measured liver biochemistry as prognostic markers for mortality is unknown. We aimed to determine whether abnormal liver biochemistry, assessed at baseline and at repeat measures over time, was associated with death in hospitalized patients with COVID‐19 compared to those without COVID‐19, in a United Kingdom population. We extracted routinely collected clinical data from a large teaching hospital in the United Kingdom, matching 585 hospitalized patients who were SARS‐CoV‐2 real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) positive to 1,165 hospitalized patients who were RT‐PCR negative for age, sex, ethnicity, and preexisting comorbidities. A total of 26.8% (157/585) of patients with COVID‐19 died compared to 11.9% (139/1,165) in the group without COVID‐19 ( P  < 0.001). At presentation, a significantly higher proportion of the group with COVID‐19 had elevated alanine aminotransferase (20.7% vs. 14.6%, P  = 0.004) and hypoalbuminemia (58.7% vs. 35.0%, P  < 0.001) compared to the group without COVID‐19. Within the group with COVID‐19, those with hypoalbuminemia at presentation had 1.83‐fold increased hazards of death compared to those with normal albumin (adjusted hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.25‐2.67), while the hazard of death was ~4‐fold higher in those aged ≥75 years (adjusted HR, 3.96; 95% CI, 2.59‐6.04) and ~3‐fold higher in those with preexisting liver disease (adjusted HR, 3.37; 95% CI, 1.58‐7.16). In the group with COVID‐19, alkaline phosphatase (ALP) increased (R = 0.192, P  < 0.0001) and albumin declined (R = −0.123, P  = 0.0004) over time in patients who died. Conclusion: In this United Kingdom population, liver biochemistry is commonly deranged in patients with COVID‐19. Baseline hypoalbuminemia and rising ALP over time could be prognostic markers for death, but investigation of larger cohorts is required to develop a better understanding of the relationship between liver biochemistry and disease outcome.

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  1. Version published to 10.1002/hep4.1739
  2. ScreenIT

    SciScore for 10.1101/2020.09.15.20194985: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: The management of the dataset is governed by the NIHR HIC Data Sharing Framework. Research Ethics Committee approval was obtained for the database and associated activity: IRAS ID 174658; REC reference 15/SC/0523.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Caveats and limitations: Routinely collected liver biochemistry is not consistent between settings, and therefore the definitions of liver biochemistry derangement may vary across studies. Although AST and GGT have been investigated in previous studies, these parameters are not available for our population. We recognise that analysis can be influenced by missing data, but we report missing values and investigating peak/nadir values as well as baseline. We also undertook sensitivity analysis in a subset of patients with complete BMI measurements to investigate its association with death. Our cohort in the South East of the UK may not be representative of populations elsewhere, especially in terms of ethnic diversity, so caution should be applied in extrapolation of results. Future studies: Further longitudinal studies of COVID-19 outcomes in diverse patient groups, including those with pre-existing liver disease are needed. The NIHR HIC program will continue to benefit the field of COVID-19 research, as data accumulated for further large teaching hospitals can be used to expand this analysis, resulting in a more generalizable study population and increased statistical power. Conclusion: Liver biochemistry derangement is common in COVID-19 patients at the time of a SARS-CoV-2 RT-PCR test and during the clinical course of disease. Baseline and nadir albumin are valuable prognostic factors that are associated with death in COVID-19 patients.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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  3. Version published to 10.1101/2020.09.15.20194985v1 on medRxiv