Liver Fibrosis Index FIB-4 Is Associated With Mortality in COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) is associated with adverse outcomes, including need for invasive mechanical ventilation and death in people with risk factors. Liver enzyme elevation is commonly seen in this group, but its clinical significance remains elusive. In this study, we calculated the Fibrosis-4 (FIB-4) score for a cohort of hospitalized patients with COVID-19 and assessed its association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, inflammatory cytokine levels, and clinical outcome. A total of 202 hospitalized participants who tested positive for SARS-CoV-2 by nasopharyngeal sampling were included in this analysis. FIB-4 was calculated for each participant using the alanine aminotransferase, aspartate aminotransferase, age, and platelet count. We evaluated the association between FIB-4 and mortality using both multivariate logistic regression and Cox proportional hazards model. Correlations between FIB-4 and SARS-CoV-2 RNA and cytokine levels were evaluated using the Spearman test. Among the 202 participants, 22 died. The median FIB-4 in participants who survived and died were 1.91 and 3.98 (P < 0.001 by Mann-Whitney U test), respectively. Each one-unit increment in FIB-4 was associated with an increased odds of death (odds ratio, 1.79; 95% confidence interval, 1.36, 2.35; P < 0.001) after adjusting for baseline characteristics including sex, body mass index, hypertension, diabetes, and history of liver diseases. During hospitalization, FIB-4 peaked and then normalized in the survival group but failed to normalize in the death group. FIB-4 was positively correlated with the level of SARS-CoV-2 viral load and monocyte-associated cytokines, especially interleukin-6 and interferon gamma-induced protein 10. Conclusion: FIB-4 is associated with mortality in COVID-19, independent of underlying conditions including liver diseases. FIB-4 may be a simple and inexpensive approach to risk-stratify individuals with COVID-19.

FIG. 1

FIB‐4 was associated with death in COVID‐19. (A‐D) FIB‐4 rather than APRI, ALT, or AST was significantly associated with death in COVID‐19. (E) The association between FIB‐4 and death is consistent across different participant categories.

FIG. 2

Probability of survival during hospitalization is based on initial FIB‐4 score. P value was calculated by Cox proportional model.

FIG. 3

Longitudinal changes in FIB‐4 in MassCPR cohort. (A) FIB‐4 peaked during hospitalization and normalized in most participants. (B) In participants with or without mechanical ventilation from the survival group, FIB‐4 peaked then normalized during hospitalization. In the death group, FIB‐4 was significantly higher than the survival group (*P < 0.005) and failed to normalize. (C) Participants with or without liver diseases had similar trajectory in FIB‐4 temporal changes. Shaded area indicates FIB‐4 < 1.45.

FIG. 4

FIB‐4 is associated with SARS‐CoV‐2 RNAemia. Heatmap summarizing Spearman’s rank correlation rho between SARS‐CoV‐2 RNA level from different body compartments (A) FIB‐4 levels at admission. (B) FIB‐4 levels during RNA sample collection. Higher FIB‐4 levels at admission (C) or RNA sample collection (D) were both associated with SARS‐CoV‐2 RNAemia. *P < 0.05 using Spearman's rank correlation test. NP, nasopharyngeal swab; OP, oropharyngeal swab.