Background Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19). Methods We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD. Results Of the 978 patients in our cohort, 867 patients (mean age 56.9±14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29-4.55), decompensated cirrhosis (HR 2.91 [1.70-5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53-7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47-3.70]) and decompensated cirrhosis (OR 2.50 [1.20-5.21]) were independently associated with risk for severe COVID-19. Conclusions The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in the fall of 2019 and has since become a global pandemic. This virus, which causes coronavirus disease 2019 (COVID-19), has led to over 4.8 million infections and 316,000 deaths worldwide to date. 1 Prior studies have demonstrated advanced age, chronic cardiopulmonary diseases, immunosuppression and obesity as potential risk factors for worse clinical outcomes among patients with COVID-19-with mortality often driven by disease-associated cardiopulmonary failure. 2,3 While the virus primarily affects the lungs, experience from China and the USA also suggests that SARS-CoV-2 may impact extra-pulmonary systems, including the gastrointestinal and hepatobiliary systems. 4,5 Chronic liver disease (CLD), including non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease and chronic viral hepatitis, comprise a large global burden of disease. 6 Published reports indicate that up to half of adults hospitalized with COVID-19 have abnormal aminotransferase levels and 2%-11% have underlying liver conditions. 7-12 A meta-analysis of 11 observational studies of 2034 adults with COVID-19 from China revealed an overall CLD prevalence of 3%. 13 However, there are limited reports on the nature of liver disease among COVID-19 patients and it remains unclear how underlying CLD influences hepatic injury and clinical outcomes in these patients. Higher rates of liver dysfunction have been observed in patients with more severe cases of COVID-19 and among those requiring admission to the intensive care unit (ICU). 12,14 Given the high prevalence of NAFLD in the USA, as well as metabolic syndrome and

National Center for Advancing Translational Sciences and National Institutes of Health.