SARS-CoV-2 infection in patients with underlying chronic liver disease is associated with significantly greater risk of liver decompensation and acute on chronic liver failure

ABSTRACT

Objectives: Chronic liver disease (CLD) patients are hypothesized to have greater risks of liver decompensation following SARS-CoV-2 infection. Data evaluating COVID-19 in CLD patients remains sparse. We aim to evaluate whether SARS-CoV-2 infection in CLD patients is associated with increased risks of liver decompensation or acute on chronic liver failure (ACLF). Materials and Methods: Using the Common Data Schema from COVID-19 Research Database, a large U.S. database containing over 72 million linked patients with both electronic health records and claims data, we evaluated CLD patients with (CLD - COVID-19) vs. without COVID-19 (CLD without COVID-19). Patients had minimum 6-months follow-up until censoring event or end of study period (August 31, 2021) to evaluate incident liver decompensation (i.e. ascites, hepatic encephalopathy, variceal bleeding, hepatorenal syndrome, liver failure) and incident ACLF (EASL-CLIF definition). Outcomes were evaluated using adjusted multivariate Cox proportional hazards models. Results: Among 923,671 adults with CLD (44.7% women, 12.4% cirrhosis), 3.8% had CLD - COVID-19 and 96.3% had CLD without COVID-19. Over a median follow-up of 242-267 days, when compared to CLD without COVID-19, CLD - COVID-19 patients had significantly greater risk of liver decompensation (HR 1.22, 95% CI 1.13-1.32, p<0.001) and ACLF (HR 1.54, 95% CI 1.17-2.03, p<0.01). Among CLD patients with cirrhosis at baseline, COVID- 19 was similarly associated with higher risk of ACLF (HR 1.66, 95% CI 1.26-2.19, p<0.001). When evaluating individual organ failures in patients with ACLF, CLD - COVID-19 vs. CLD without COVID- 19 was associated with significantly greater risks of cardiovascular failure (HR 4.75, p<0.001), respiratory failure (HR 5.80, p<0.001), and renal failure (HR 3.93, p<0.001). Conclusion: Among a large U.S. cohort evaluating COVID-19 in CLD patients, SARS-CoV-2 infection was associated with significantly greater risks of liver decompensation and ACLF in patients with underlying CLD. The primary drivers of ACLF were the increased risks of cardiovascular failure, respiratory failure, and renal failure associated with COVID-19.