Outcomes of SARS-CoV-2 Infection in Patients With Chronic Liver Disease and Cirrhosis: A National COVID Cohort Collaborative Study

Abstract

Background and Aims In chronic liver disease (CLD) patients with or without cirrhosis, existing studies on the outcomes with SARS-CoV-2 infection have limited generalizability. We used the National COVID Cohort Collaborative (N3C), a harmonized electronic health record (EHR) dataset of 6.4 million, to describe SARS-CoV-2 outcomes in patients with CLD and cirrhosis. Methods We identified all CLD patients with or without cirrhosis who had SARS-CoV-2 testing in the N3C Data Enclave as of 7/1/2021. We used survival analyses to associate SARS-CoV-2 infection, presence of cirrhosis, and clinical factors with the primary outcome of 30-day mortality. Results We isolated 220,727 patients with CLD and SARS-CoV-2 test status: 128,864 (58%) Non-Cirrhosis/Negative, 29,446 (13%) Non-Cirrhosis/Positive, 53,476 (24%) Cirrhosis/Negative, and 8,941 (4%) Cirrhosis/Positive patients. Thirty-day all-cause mortality rates were 3.9% in Cirrhosis/Negative and 8.9% in Cirrhosis/Positive patients. Compared to Cirrhosis/Negative, Cirrhosis/Positive had 2.38-times adjusted hazard of death at 30 days. Compared to Non-Cirrhosis/Positive, Cirrhosis/Positive had 3.31-times adjusted hazard of death at 30 days. In stratified analyses among patients with cirrhosis with increased age, obesity, and comorbid conditions (diabetes, heart failure, and pulmonary disease); SARS-CoV-2 infection was associated with increased adjusted hazards of death. Conclusions In this study of ∼221,000 nationally-representative, diverse, and gender-balanced CLD patients; we found SARS-CoV-2 infection in patients with cirrhosis was associated with 2.38-times mortality hazard, and the presence of cirrhosis among CLD patients infected with SARS-CoV-2 was associated with 3.31-times mortality hazard. These results provide an additional impetus for increasing vaccination uptake and further research regarding immune responses to vaccines in patients with severe liver disease.

Clinical outcomes in COVID-19 and cirrhosis: a systematic review and meta-analysis of observational studies

“…When compared with SARS-COV-2 patients with non-cirrhotic CLD, they report an adjusted 30-day mortality HR of 3.31. 14 This risk is higher than adjusted risks for hospitalised patients identified in our systematic review, likely due to the high proportion of non-hospitalised patients in this study and the difference in risk of hospitalisation between groups (CLD 22.9% vs cirrhosis 50.1%). 14 Observational studies within our meta-analysis include predominantly patients who were hospitalised or presented to hospitals.…”

“…Ge et al have reported data from the N3C Consortium in the USA which uses electronic healthcare record data to identify patients who underwent SARS-CoV-2 testing or had related symptoms. 14 In total, 8941 patients with cirrhosis and COVID-19 were identified. When compared with SARS-COV-2 patients with non-cirrhotic CLD, they report an adjusted 30-day mortality HR of 3.31.…”

COVID-19 and Cirrhosis: A Combination We Must Strive to Prevent

“…9 Although these studies have been limited by issues of selection bias, generalizability, and imperfect control groups, they have been critical in establishing cirrhosis as a major risk factor for poor outcomes from COVID-19. The study by Ge and colleagues 4 confirms the main findings of these studies using a larger and nationally representative patient cohort with more recent follow-up data.…”

“…3 In this issue of Gastroenterology, Ge and colleagues 4 conduct a retrospective cohort study to evaluate the outcomes of patients with cirrhosis and COVID-19 using electronic health record data from the National COVID Cohort Collaborative Data Enclave, or N3C. 4 The N3C is a novel, centralized, curated, national repository of harmonized electronic health record data from clinical sites across the United States, with the National Center for Advancing Translational Sciences at the National Institutes of Health serving as data steward. It was formed in response to the need for rapid accrual of large-scale data on COVID-19.…”

“…The 220,727 patients included in Ge et al's study 4 were adults with chronic liver disease who underwent testing for SARS-CoV-2 via nucleic acid amplification testing or culture between January 1, 2020 and July 1, 2021. Among patients with cirrhosis, COVID-19 was associated with a 2.38-fold (95% CI, 2.18-2.59) increased risk of 30-day mortality after adjusting for age, race and ethnicity, chronic liver disease etiology, comorbidities as quantified by a modified Charlson Comorbidity Index, and geographical region.…”