Non-alcoholic fatty liver disease (NAFLD) and risk of hospitalization for Covid-19

  1. Carolyn T. Bramante
  2. Christopher J. Tignanelli
  3. Nirjhar Dutta
  4. Emma Jones
  5. Leonardo Tamaritz
  6. Jeanne Clark
  7. Genevieve Melton-Meaux
  8. Michael Usher
  9. Sayeed Ikramuddin

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Abstract

Background

Covid-19 disease causes significant morbidity and mortality through increase inflammation and thrombosis. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are states of chronic inflammation and indicate advanced metabolic disease. We sought to understand the risk of hospitalization for Covid-19 associated with NAFLD/NASH.

Methods

Retrospective analysis of electronic medical record data of 6,700 adults with a positive SARS-CoV-2 PCR from March 1, 2020 to Aug 25, 2020. Logistic regression and competing risk were used to assess odds of being hospitalized. Additional adjustment was added to assess risk of hospitalization among patients with a prescription for metformin use within the 3 months prior to the SARS-CoV-2 PCR result, history of home glucagon-like-peptide 1 receptor agonist (GLP-1 RA) use, and history of metabolic and bariatric surgery (MBS). Interactions were assessed by gender and race.

Results

A history of NAFLD/NASH was associated with increased odds of admission for Covid-19: logistic regression OR 2.04 (1.55, 2.96, p<0.01), competing risks OR 1.43 (1.09-1.88, p<0.01); and each additional year of having NAFLD/NASH was associated with a significant increased risk of being hospitalized for Covid-19, OR 1.86 (1.43-2.42, p<0.01). After controlling for NAFLD/NASH, persons with obesity had decreased odds of hospitalization for Covid-19, OR 0.41 (0.34-0.49, p<0.01). NAFLD/NASH increased risk of hospitalization in men and women, and in all racial/ethnic subgroups. Mediation treatments for metabolic syndrome were associated with non-significant reduced risk of admission: OR 0.42 (0.18-1.01, p=0.05) for home metformin use and OR 0.40 (0.14-1.17, p=0.10) for home GLP-1RA use. MBS was associated with a significant decreased risk of admission: OR 0.22 (0.05-0.98, p<0.05).

Conclusions

NAFLD/NASH is a significant risk factor for hospitalization for Covid-19, and appears to account for risk attributed to obesity. Treatments for metabolic disease mitigated risks from NAFLD/NASH. More research is needed to confirm risk associated with visceral adiposity, and patients should be screened for and informed of treatments for metabolic syndrome.

Key Questions

Question

Does NAFLD/NASH independently increase risk for poor outcomes from Covid-19?

Findings

In this observational study, a history of NAFLD/NASH was associated with a significantly increased odds of hospitalization. Metabolic surgery was protective against admission in persons with NAFLD/NASH and Covid-19. Metformin and glucagon like peptide 1 receptor agonists were associated with non-significant protecting against admission.

Meaning

Treatment for metabolic syndrome greatly reduce the elevated risk of hospitalization for Covid-19 among persons with NAFLD/NASH.

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  1. ScreenIT

    SciScore for 10.1101/2020.09.01.20185850: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analyses were performed using Stata MP, version 16 (StataCorp, College Station, TX).
    StataCorp
    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:
    Our study has several limitations: there may be unmeasured confounders and residual bias. Findings in a sample in the upper Midwest may not be generalizable. Hepatitis B and C were not excluded as they may co-occur with NAFLD/NASH in persons with BMI>=30kg/m2, and the prevalence in this region is low: 0.78% of adults with hepatitis C and 0.59% with chronic hepatitis B. Further selection bias may be present in that there are likely many more individuals in this population who have NAFLD/NASH but who did not have 3 elevated ALT readings.4 Conclusions: NAFLD/NASH is a state of chronic inflammation due to visceral adiposity, is a significant risk factor for hospitalization for Covid-19, and appears to account for risk attributed to obesity. Treatments for metabolic disease mitigated risks from NAFLD/NASH. More research is needed to confirm these findings. Patients with elevated BMI should be screened for NAFLD/NASH and informed of the risks associated with visceral adiposity and Covid-19, as well as opportunities for mitigating this risk such as bariatric surgery, GLP-1RA, and metformin.9,14

    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.

    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 10.1101/2020.09.01.20185850v1 on medRxiv