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.

Proinflammatory and Hepatic Features Related to Morbidity and Fatal Outcomes in COVID-19 Patients

“…Moreover, FIB-4 was also related with increased risk of mortality in hospitalized patients with COVID-19 as well as with lower survival [ 23 , 24 ]. In addition, FIB-4 positively correlated to SARS-CoV-2 viral load and the levels of inflammatory cytokines [ 25 ]. Besides FIB-4, AAR was another liver marker also associated (equal or higher than 1.29) with an increased risk of ICU plus death in this research.…”

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

“…Several pieces of evidence suggest the prognostic value of the FIB-4 index in COVID-19 cases [ 12 , 16 , 24 , 25 ]. Liver injury in COVID-19 cases has been observed more frequently in severe cases [ 26 ].…”

Liver stiffness is associated with disease severity and worse clinical scenarios in coronavirus disease 2019: A prospective transient elastography study

“…Previous studies have demonstrated that non‐invasive liver fibrosis indicators, including FIB‐4 index and neutrophil to lymphocyte ratio, are associated with poor clinical outcomes in COVID‐19 21‐26 . Based on the evidence from these recent studies, it is rational to anticipate that patients with fibrosing NAFLD could be more prone to more severe COVID‐19.…”

“…Previous studies have demonstrated that non-invasive liver fibrosis indicators, including FIB-4 index and neutrophil to lymphocyte ratio, are associated with poor clinical outcomes in COVID-19. [21][22][23][24][25][26] Based on the evidence from these recent studies, it is rational to anticipate that patients with fibrosing NAFLD could be more prone to more severe COVID-19. In this regard, we aimed to confirm this hypothesis by investigating the associations of liver stiffness measurement (LSM) determined via vibration-controlled transient elastography (VCTE) (FibroScan; Echosens, Paris, France); which is a simple, reliable, and non-invasive ultrasound-based procedure to assess the severity of liver fibrosis, 27 with disease severity and clinical outcomes.…”