Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: An international registry study

Abstract

Background & aims: Chronic liver disease (CLD) and cirrhosis are associated with immune dysregulation, leading to concerns that affected patients may be at risk of adverse outcomes following SARS-CoV-2 infection. We aimed to determine the impact of COVID-19 on patients with pre-existing liver disease, which currently remains ill-defined.

Methods: Between 25th March and 8th July 2020, data on 745 patients with CLD and SARS-CoV-2 (including 386 with and 359 without cirrhosis) were collected by 2 international registries and compared to data on non-CLD patients with SARS-CoV-2 from a UK hospital network.

Results: Mortality was 32% in patients with cirrhosis compared to 8% in those without (p <0.001). Mortality in patients with cirrhosis increased according to Child-Pugh class (A [19%], B [35%], C [51%]) and the main cause of death was from respiratory failure (71%). After adjusting for baseline characteristics, factors associated with death in the total CLD cohort were age (odds ratio [OR] 1.02; 1.01-1.04), Child-Pugh A (OR 1.90; 1.03-3.52), B (OR 4.14; 2.4-7.65), or C (OR 9.32; 4.80-18.08) cirrhosis and alcohol-related liver disease (OR 1.79; 1.03-3.13). Compared to patients without CLD (n = 620), propensity-score-matched analysis revealed significant increases in mortality in those with Child-Pugh B (+20.0% [8.8%-31.3%]) and C (+38.1% [27.1%-49.2%]) cirrhosis. Acute hepatic decompensation occurred in 46% of patients with cirrhosis, of whom 21% had no respiratory symptoms. Half of those with hepatic decompensation had acute-on-chronic liver failure.

Conclusions: In the largest such cohort to date, we demonstrate that baseline liver disease stage and alcohol-related liver disease are independent risk factors for death from COVID-19. These data have important implications for the risk stratification of patients with CLD across the globe during the COVID-19 pandemic.

Lay summary: This international registry study demonstrates that patients with cirrhosis are at increased risk of death from COVID-19. Mortality from COVID-19 was particularly high among patients with more advanced cirrhosis and those with alcohol-related liver disease.

Keywords: Acute-on-chronic liver failure; COVID-19; Chronic liver disease; Cirrhosis; SARS-CoV-2.

Graphical abstract

Fig. 1

Chronic liver disease cohort selection. Total combined submissions to the online reporting registries (https://COVID-Hep.net and http://COVIDCirrhosis.org) and number of patients with chronic liver disease and SARS-CoV-2 infection included in the final analysis after exclusions.

Fig. 2

Major outcomes according to liver disease stage. Rates of major outcomes following SARS-CoV-2 infection in patients with CLD separated by liver disease stage. Chi squared test for trend was used to compare outcome proportions between the stages of liver disease (CLD without cirrhosis, Child-Pugh A, Child-Pugh B, Child-Pugh C) including hospitalisation (p = 0.690), requirement for ICU (p <0.001), admission to ICU (p <0.001), RRT (p <0.001), invasive ventilation (p = 0.227), and death (p <0.001). Error bars represent 95% CIs. The discrepancy between the rates of ICU requirement and ICU admission are accounted for by a proportion of severe cases being deemed inappropriate for ICU admission or due to lack of ICU availability. CLD, chronic liver disease; ICU, intensive care unit; RRT, new requirement for renal replacement therapy.

Fig. 3

Case fatality rates following SARS-CoV-2 infection per 10-year age group. Comparison of case fatality rates following SARS-CoV-2 infection per 10-year age group between patients with CLD, with and without cirrhosis. CLD, chronic liver disease.

Fig. 4

Clinical course of SARS-CoV-2 infection in patients with CLD according to presence/absence of cirrhosis. Sankey diagrams displaying the clinical course of patients with CLD and SARS-CoV-2 infection separated into those with and without cirrhosis. Bar widths are proportional to number/percentage of patients and the outcome of survived vs. died are displayed in green and red for each group respectively. CLD, chronic liver disease; ICU, intensive care unit.

Fig. 5

Propensity score-matched analysis of mortality from SARS-CoV-2 infection by stage of liver disease in comparison to non-CLD cohort. Plots show propensity-score matched analyses for risk of death for each CLD stage compared to non-CLD patients with SARS-CoV-2 infection. Variables selected for propensity score matching were age in years, interactions with age, sex, COPD, diabetes mellitus, and heart disease. Error bars represent Clopper-Pearson binomial CIs at 95%. Identical analyses were performed for the total CLD cohort (A) and then restricted to UK CLD cases (B). In the total CLD cohort, the risk of death for each disease stage was; CLD without cirrhosis -3.4% (95% CI -7.2 to 0.31%; p = 0.248), Child-Pugh A +2.0% (95% CI -6.2% to 10.2%; p = 0.631), Child-Pugh B +20.0% (95% CI 8.8%–31.3%; p <0.001), Child-Pugh C +38.1% (95% CI 27.1%–49.2%; p <0.001) (A). In the UK CLD cohort, the risk of death for each disease stage was; CLD without cirrhosis +4.4% (95% CI -6.9% to 15.8%; p = 0.445), Child-Pugh A +8.5% (95% CI -9.2 to 26.2; p = 0.349), Child-Pugh B +17.8% (95% CI 2.5–33.1%; p = 0.023), and Child-Pugh C +50.5% (95% CI 28.1%–72.8%; p ≤0.001) (B).

Fig. 6

Rates of acute hepatic decompensation and case fatality rates according to CLIF-C organ failure score. (A) Rates of acute hepatic decompensation separated according to liver disease stage. Acute hepatic decompensation was defined as one or more of new or worsening ascites, new or worsening hepatic encephalopathy, spontaneous bacterial peritonitis, or variceal haemorrhage. (B) Case fatality rates separated according to CLIF-C organ failure score (using EASL-Chronic Liver Failure Consortium organ failures definition).