COVID-19 mortality in cirrhosis is determined by cirrhosis-associated comorbidities and extrahepatic organ failure: Results from the multinational LEOSS registry

Abstract

Background and objective: International registries have reported high mortality rates in patients with liver disease and COVID-19. However, the extent to which comorbidities contribute to excess COVID-19 mortality in cirrhosis is controversial.

Methods: We used the multinational Lean European Open Survey on SARS-CoV-2-infected patients (LEOSS) to identify patients with cirrhosis documented between March 2020 and March 2021, when the wild-type and alpha variant were predominant. We compared symptoms, disease progression and mortality after propensity score matching (PSM) for age, sex, obesity, smoking status, and concomitant diseases. Mortality was also compared with that of patients with spontaneous bacterial peritonitis (SBP) without SARS-CoV-2 infection, a common bacterial infection and well-described precipitator of acute-on-chronic liver failure.

Results: Among 7096 patients with SARS-CoV-2 infection eligible for analysis, 70 (0.99%) had cirrhosis, and all were hospitalized. Risk factors for severe COVID-19, such as diabetes, renal disease, and cardiovascular disease were more frequent in patients with cirrhosis. Case fatality rate in patients with cirrhosis was 31.4% with the highest odds of death in patients older than 65 years (43.6% mortality; odds ratio [OR] 4.02; p = 0.018), Child-Pugh class C (57.1%; OR 4.00; p = 0.026), and failure of two or more organs (81.8%; OR 19.93; p = 0.001). After PSM for demographics and comorbidity, the COVID-19 case fatality of patients with cirrhosis did not significantly differ from that of matched patients without cirrhosis (28.8% vs. 26.1%; p = 0.644) and was similar to the 28-day mortality in a comparison group of patients with cirrhosis and SBP (33.3% vs. 31.5%; p = 1.000).

Conclusions: In immunologically naïve patients with cirrhosis, mortality from wild-type SARS-CoV-2 and the alpha variant is high and is largely determined by cirrhosis-associated comorbidities and extrahepatic organ failure.

Keywords: ACLD; COVID-19; SARS-CoV-2; SBP; chronic liver disease; cirrhosis.

FIGURE 1

Case fatality rates in SARS‐CoV‐2‐infected patients with cirrhosis stratified for age, disease severity, and organ failure. Case fatality rates of 70 SARS‐CoV‐2 infected patients with cirrhosis are depicted and stratified for (a) age, (b) Child‐Pugh class, (c) types of organ failure, and (d) number of organ failures. Organ failures were defined according to the EF CLIF criteria based on the CLIF SOFA score. Case fatality rates were colour coded as follows: ≤25%: green, >25% and ≤40%: yellow, >40% orange. For statistical comparisons and significance levels see Table 4. B, Brain; Ci, Circulatory; Co, Coagulation; K, Kidney; L, Liver; R, Respiratory failure

FIGURE 2

COVID‐19 disease phases (LEOSS) and phase transition in patients with cirrhosis. Sankey flow diagram of disease courses of patients with cirrhosis and COVID‐19 in the UC, the complicated phase and the CR. ALT, alanine aminotransferase; AST, aspartate aminotransferase; INR, International Normalized Ratio; NIV, non‐invasive ventilation; paO2, partial pressure of oxygen; qSOFA, quick Sequential Organ Failure Assessment; SO2, blood oxygen saturation; ULN, upper limit of the norm. The flow diagram was build using the SankeyMATIC diagram builder (https://sankeymatic.com, as accessed on 16 August 2021)