Association of liver abnormalities with in-hospital mortality in patients with COVID-19

Abstract

Background & aims: The evolution and clinical significance of abnormal liver chemistries and the impact of hepatitis B infection on outcome in patients with COVID-19 is not well characterized. This study aimed to explore these issues.

Methods: This large retrospective cohort study included 2,073 patients with coronavirus disease 2019 (COVID-19) and definite outcomes in Wuhan, China. Longitudinal liver function tests were conducted, with associated factors and risk of death determined by multivariate regression analyses. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. The characteristics of liver abnormalities and outcomes of patients with COVID-19, with and without hepatitis B, were compared after 1:3 propensity score matching.

Results: Of the 2,073 patients, 1,282 (61.8%) had abnormal liver chemistries during hospitalization, and 297 (14.3%) had a liver injury. The mean levels of aspartate aminotransferase (AST) and direct bilirubin (D-Bil) increased early after symptom onset in deceased patients and showed disparity compared to levels in discharged patients throughout the clinical course of the disease. Abnormal AST (adjusted hazard ratio [HR] 1.39; 95% CI 1.04-1.86, p = 0.027) and D-Bil (adjusted HR 1.66; 95% CI 1.22-2.26; p = 0.001) levels at admission were independent risk factors for mortality due to COVID-19. A nomogram was established based on the results of multivariate analysis and showed sufficient discriminatory power and good consistency between the prediction and the observation. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes.

Conclusions: Abnormal AST and D-Bil levels at admission were independent predictors of COVID-19-related mortality. Therefore, monitoring liver chemistries, especially AST and D-Bil levels, is necessary in hospitalized patients with COVID-19.

Lay summary: Liver test abnormalities (in particular elevations in the levels of aspartate aminotransferase [AST] and direct bilirubin [D-Bil]) were observed after symptom onset in patients who went on to die of coronavirus disease 2019 (COVID-19). Abnormal levels of AST and D-Bil at admission were independent predictors of COVID-19-related mortality. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes.

Keywords: Aspartate aminotransferase; COVID-19; Direct bilirubin; Hepatitis B; Liver injury.

Graphical abstract

Fig. 1

Temporal changes of liver chemistries in the clinical course of patients with COVID-19. Trajectories of mean (A) ALT, (B) AST, (C) ALP, (D) GGT, (E) T-Bil and (F) D-Bil in the clinical course of deceased and discharged patients with COVID-19, with 95% confidence band (grey) based on generalized additive model. ALP, alkaline phosphatase; ALT, alanine aminotransferases; AST, aspartate aminotransferase; D-Bil, direct bilirubin; GGT, gamma-glutamyltransferase; T-Bil, total bilirubin.

Fig. 2

Prognostic models for the fatal outcome in COVID-19. Two prognostic models, based on multivariable cox regression analyses, which included (A) liver injury at admission, or (B) abnormal AST and D-Bil levels at admission, and other baseline findings, were obtained after backward stepwise selection with Akaike information criterion. The hazard ratios and the 95% CIs associated with COVID-19 mortality in each model were presented. ALB, albumin; AST, aspartate aminotransferase; COVID-19, coronavirus disease 2019; CRP, C-reactive protein; cTnI, cardiac troponin I; D-Bil, direct bilirubin; PLT, platelet count; PT, prothrombin time.

Fig. 3

Prognostic nomogram for predicting the overall survival probability of patients with COVID-19. To use the nomogram, based on the multivariable cox regression model, an individual patient’s value (all values of variables are measured at admission) is located on each value axis, and a line is drawn upward to determine the number of points and to predict the overall survival probability of patients with COVID-19. The sum of these numbers is located on the Total Points axis, and a line is drawn downward to the survival axes to determine the likelihood of 14-day, 21-day, and 28-day survival. AST, aspartate aminotransferase; CRP, C-reactive protein; cTnI, cardiac troponin I; D-Bil, direct bilirubin; PLT, platelet count.

Fig. 4

Kaplan-Meier survival curve for in-hospital mortality of COVID-19 patients with hepatitis B and without liver diseases after propensity score matching. COVID-19, coronavirus disease 2019; HR, hazard ratio.