Early Elevation of Fibrosis-4 Liver Fibrosis Score Is Associated With Adverse Outcomes Among Patients With Coronavirus Disease 2019

  1. Fangfei Xiang
  2. Jing Sun
  3. Po-Hung Chen
  4. Peijin Han
  5. Haipeng Zheng
  6. Shuijiang Cai
  7. Gregory D Kirk

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background

Limited prior data suggest that preexisting liver disease is associated with adverse outcomes among patients with coronavirus disease 2019 (COVID-19). Fibrosis-4 (FIB-4) is a noninvasive index of readily available laboratory measurements that represents hepatic fibrosis. We evaluated the association between FIB-4 at the early stage of infection and COVID-19 outcomes.

Methods

FIB-4 was evaluated at admission in a cohort of 267 patients admitted with early-stage COVID-19 confirmed through reverse-transcription polymerase chain reaction assay. Hazard of ventilator use and of high-flow oxygen was estimated using Cox regression models controlled for covariates. Risks of progression to severe disease and of death/prolonged hospitalization were estimated using multivariable logistic regression models.

Results

Forty-one (15%) patients progressed to severe disease, 36 (14%) required high-flow oxygen support, 10 (4%) required mechanical ventilator support, and 1 died. FIB-4 between 1.45 and 3.25 was associated with a greater than 5-fold (95% confidence interval [CI], 1.2–28) increased hazard of high-flow oxygen use, a greater than 4-fold (95% CI, 1.5–14.6) increased odds of progression to severe disease, and an over 3-fold (95% CI, 1.4–7.7) increased odds of death or prolonged hospitalization. FIB-4 >3.25 was associated with a greater than 12-fold (95% CI, 2.3–68. 7) increased hazard of high-flow oxygen use and an over 11-fold (95% CI, 3.1–45) increased risk of progression to severe disease. All associations were independent of sex, number of comorbidities, and inflammatory markers (D-dimer, C-reactive protein).

Conclusions

FIB-4 at the early-stage of COVID-19 had an independent and dose-dependent association with adverse outcomes during hospitalization. FIB-4 provided significant prognostic value for estimating adverse outcomes among COVID-19 patients.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.09.01.20186080: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the Institutional Review Board of Guangzhou No. 8 People’s Hospital.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Values that had substantial missing data (e.g., SS-A/Ro antibodies) were excluded from the analysis; all laboratory tests included in the analysis had ≤ 10% missing.
    SS-A/Ro
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis and figures were performed in STATA 15 (College Station, TX) and R.
    STATA
    suggested: (Stata, RRID:SCR_012763)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The current study has several limitations. We were not able to confirm liver fibrosis using ultrasound, elastography, or biopsy to better characterize liver disease severity among patients. Therefore, the association should be interpreted with caution. In addition, this is a single-site study with relatively low sample size. Thus, the external validity should be further evaluated in other cohorts with larger sample sizes. However, despite the limited sample size, we were still able to observe strong associations between high FIB-4 scores early on and multiple adverse outcomes during follow-up. Third, FIB-4 score comprised platelet count, ALT, and AST, which could fluctuate especially during acute inflammation, and severe COVID-19 cases could have elevated aminotransferases and thrombocytopenia during infection [1, 11]. Elevated FIB-4 score could be a product of acute inflammation rather than a reflection of hepatic fibrosis. However, we have limited our study cohort to only patients in the early-stage of COVID-19 infection, and the distributions of ALT and AST at admission were within the normal range in our study. We also controlled for multiple inflammatory markers in our final models. Based on our results, the independent association between FIB-4 score and adverse outcomes was not confounded or completely mediated by the inflammatory markers at admission, so the inflammation alone is unlikely to explain this association. Furthermore, even if FIB-4 is not fully representat...

    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.
    • Thank you for including a protocol registration statement.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1093/cid/ciaa1710
  3. Version published to 10.1101/2020.09.01.20186080v1 on medRxiv