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

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.

Keywords: COVID-19; FIB-4 score; liver enzyme; mechanical ventilator; prolonged hospitalization.