Possible unrecognised liver injury is associated with mortality in critically ill COVID-19 patients

Abstract

Background: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has not been investigated. We aimed to explore the association of pre-admission liver fibrosis indices with the prognosis of critically ill COVID-19 patients.

Methods: The work presented was an observational study in 214 patients with COVID-19 consecutively admitted to the intensive care unit (ICU). Pre-admission liver fibrosis indices were calculated. In-hospital mortality and predictive factors were explored with Kaplan-Meier and Cox regression analysis.

Results: The mean age was 59.58 (13.79) years; 16 patients (7.48%) had previously recognised chronic liver disease. Up to 78.84% of patients according to Forns, and 45.76% according to FIB-4, had more than minimal fibrosis. Fibrosis indices were higher in non-survivors [Forns: 6.04 (1.42) versus 4.99 (1.58), p < 0.001; FIB-4: 1.77 (1.17) versus 1.41 (0.91), p = 0.020)], but no differences were found in liver biochemistry parameters. Patients with any degree of fibrosis either by Forns or FIB-4 had a higher mortality, which increased according to the severity of fibrosis (p < 0.05 for both indexes). Both Forns [HR 1.41 (1.11-1.81); p = 0.006] and FIB-4 [HR 1.31 (0.99-1.72); p = 0.051] were independently related to survival after adjusting for the Charlson comorbidity index, APACHE II, and ferritin.

Conclusion: Unrecognised liver fibrosis, assessed by serological tests prior to admission, is independently associated with a higher risk of death in patients with severe COVID-19 admitted to the ICU.

Keywords: biomarkers; coronavirus; critical care; liver diseases; survival analysis.

Figure 1.

(a) Distribution of patients according to the different fibrosis categories established by baseline Forns and FIB-4 indices. (b) Stratification of the NAFLD fibrosis score values (n = 95) according to the fibrosis severity determined by the Forns and FIB-4 indices. p-value for mean comparison between categories <0.01 for both indices. NAFLD, nonalcoholic fatty liver disease.

Figure 2.

(a–d) Kaplan–Meier survival curves according to pre-existing fibrosis. Survival curves according to the severity of fibrosis (a,c) or the presence or absence of fibrosis (b,d) estimated by the Forns index (a,b) or the FIB-4 index (c,d).

Figure 3.

Distribution of the liver laboratory tests in survivors and non-survivors at different time points during hospitalisation. Kernel density estimates were used for graphical representation; p values were nonsignificant in all cases.