Endocrinol Metab.  2021 Aug;36(4):800-809. 10.3803/EnM.2021.1040.

High Fibrosis-4 Index Is Related with Worse Clinical Outcome in Patients with Coronavirus Disease 2019 and Diabetes Mellitus: A Multicenter Observational Study

• Kim SW
• Jeon JH
• Moon JS
• Kim MK

• KMID: 2519668
• DOI: http://doi.org/10.3803/EnM.2021.1040

Abstract

Background
Based on recent evidence on the importance of the presence of diabetes mellitus (DM) and fibrosis-4 (FIB-4) index in coronavirus disease 2019 (COVID-19) mortality, we analyzed whether these factors could additively predict such mortality.
Methods
This multicenter observational study included 1,019 adult inpatients admitted to university hospitals in Daegu. The demographic and laboratory findings, mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM and/or a high FIB-4 index. The mortality risk and corresponding hazard ratio (HR) were analyzed using the Kaplan-Meier method and Cox proportional hazard models.
Results
The patients with DM (n=217) exhibited significantly higher FIB-4 index and mortality compared to those without DM. Although DM (HR, 2.66; 95% confidence interval [CI], 1.63 to 4.33) and a high FIB-4 index (HR, 4.20; 95% CI, 2.21 to 7.99) were separately identified as risk factors for COVID-19 mortality, the patients with both DM and high FIB-4 index had a significantly higher mortality (HR, 9.54; 95% CI, 4.11 to 22.15). Higher FIB-4 indices were associated with higher mortality regardless of DM. A high FIB-4 index with DM was more significantly associated with a severe clinical course with mortality (odds ratio, 11.24; 95% CI, 5.90 to 21.41) than a low FIB-4 index without DM, followed by a high FIB-4 index alone and DM alone. The duration of quarantine and hospital stay also tended to be longer in those with both DM and high FIB-4 index.
Conclusion
Both DM and high FIB-4 index are independent and additive risk factors for COVID-19 mortality.

Keyword

Non-alcoholic fatty liver disease; Diabetes mellitus; COVID-19; Mortality

Figure

• 

  Fig. 1 Mortality of coronavirus disease 2019 (COVID-19) patients according to (A) diabetes mellitus (DM), (B) fibrosis-4 (FIB-4) index, and (C) diabetes mellitus (DM) and FIB-4 index. (A) Red line, patients with diabetes; blue line, patients without diabetes. (B) Red line, patients with high FIB-4 index; blue line, patients with low FIB-4 index. (C) Red solid line, patents with diabetes and high FIB-4 index; red dashed line, non-diabetes patients with high FIB-4 index; blue solid line, patents with diabetes and low FIB-4 index; blue dashed line, non-diabetes patients with low FIB-4 index. Data were analyzed using Cox proportional hazards model and all data are expressed as hazard ratio (HR) (95% confidence interval). Model was adjusted for age, sex, and underlying diseases.

• 

  Fig. 2 Mortality of coronavirus disease 2019 (COVID-19) according to the presence of diabetes mellitus (DM) in patient (A) with low fibrosis-4 (FIB-4) index and (B) with high FIB-4 index. Red line, patients with diabetes; blue line, patients without diabetes. Data were analyzed using Cox proportional hazards model and all data are expressed as hazard ratio (HR) (95% confidence interval). Model was adjusted for age, sex, and underlying diseases.

• 

  Fig. 3 Mortality of coronavirus disease 2019 (COVID-19) according to fibrosis-4 (FIB-4) index in patient (A) without diabetes mellitus (DM) and (B) with DM. Red line, patients with high FIB-4 index; blue line, patients with low FIB-4 index. Data were analyzed using Cox proportional hazards model all data are expressed as hazard ratio (HR) (95% confidence interval). Model was adjusted for age, sex, and underlying diseases.

• 

  Fig. 4 Odds ratio (OR) of severe clinical course (A) and severe clinical course or death (B) according to patients group stratified according to the presence of diabetes mellitus (DM) or fibrosis-4 (FIB-4) index. Data were analyzed using multivariate logistic regression and all data are expressed as OR (95% confidence intervals). Model was adjusted for age, sex, and underlying diseases. HR, hazard ratio.

• 

  Fig. 5 The estimated mean of duration of confirmation to (A) release and (B) hospital length. Data were analyzed using general linear model and all data are expressed as the mean±standard error. Model was adjusted for age, sex, and underlying diseases. NS, not significant; DM, diabetes mellitus; FIB-4, fibrosis-4. aP<0.01; bP<0.05.

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