Background and Aims In patients with chronic liver diseases (CLD) with or without cirrhosis, existing data on the risk of adverse outcomes with SARS-CoV-2 infection have been mixed or have limited generalizability. We used the National COVID Cohort Collaborative (N3C) Data Enclave, a harmonized electronic health record (EHR) dataset of 5.9 million nationally-representative, diverse, and gender-balanced patients, to describe outcomes in patients with CLD and cirrhosis with SARS-CoV-2.

Methods We identified all chronic liver diseases patients with and without cirrhosis who had SARS-CoV-2 testing documented in the N3C Data Enclave as of data release date 5/15/2021. The primary outcome was 30-day all-cause mortality. Survival analysis methods were used to estimate cumulative incidences of death, hospitalization, and mechanical ventilation, and to calculate the associations of SARS-CoV-2 infection, presence of cirrhosis, and demographic and clinical factors to 30-day mortality.

Results We isolated 217,143 patients with CLD: 129,097 (59%) without cirrhosis and SARS-CoV-2 negative, 25,844 (12%) without cirrhosis and SARS-CoV-2 positive, 54,065 (25%) with cirrhosis and SARS-CoV-2 negative, and 8,137 (4%) with cirrhosis and SARS-CoV-2 positive. Among CLD patients without cirrhosis, 30-day all-cause mortality rates were 0.4% in SARS-CoV-2 negative patients and 1.8% in positive patients. Among CLD patients with cirrhosis, 30-day all-cause mortality rates were 4.0% in SARS-CoV-2 negative patients and 9.7% in positive patients.

Compared to those who tested SARS-CoV-2 negative, SARS-CoV-2 positivity was associated with more than two-fold (aHR 2.43, 95% CI 2.23-2.64) hazard of death at 30 days among patients with cirrhosis. Compared to patients without cirrhosis, the presence of cirrhosis was associated with a three-fold (aHR 3.39, 95% CI 2.96-3.89) hazard of death at 30 days among patients who tested SARS-CoV-2 positive. Age (aHR 1.03 per year, 95% CI 1.03-1.04) was associated with death at 30 days among patients with cirrhosis who were SARS-CoV-2 positive.

Conclusions In this study of nearly 220,000 CLD patients, we found SARS-CoV-2 infection in patients with cirrhosis was associated with 2.43-times mortality hazard, and the presence of cirrhosis among CLD patients infected with SARS-CoV-2 were associated with 3.39-times mortality hazard. Compared to previous studies, our use of a nationally-representative, diverse, and gender-balanced dataset enables wide generalizability of these findings.