key: cord-0834608-u51u1ab3 authors: Moon, Andrew M.; Webb, Gwilym J.; Aloman, Costica; Armstrong, Matthew J.; Cargill, Tamsin; Dhanasekaran, Renumathy; Genescà, Joan; Gill, Upkar S.; James, Theodore W.; Jones, Patricia D.; Marshall, Aileen; Mells, George; Perumalswami, Ponni V.; Qi, Xiaolong; Su, Feng; Ufere, Nneka N.; Barnes, Eleanor; Barritt, A Sidney; Marjot, Thomas title: High Mortality Rates for SARS-CoV-2 Infection in Patients with Pre-existing Chronic Liver Disease and Cirrhosis: Preliminary Results from an International Registry date: 2020-05-21 journal: J Hepatol DOI: 10.1016/j.jhep.2020.05.013 sha: ed6179aa4571a724249822740b5712ab00b3460c doc_id: 834608 cord_uid: u51u1ab3 nan To the Editor: Chronic liver disease (CLD) and cirrhosis are common conditions 1 associated with immune dysregulation 2 leading to concerns that these patients are at increased risk for complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and resulting coronavirus disease 2019 . 3 However, the effects of COVID-19 among patients with pre-existing liver disease are currently undefined. We report the outcomes of the first 152 consecutive submissions of clinician-reported cases of laboratory-confirmed COVID-19 in patients with CLD to two international reporting registries (COVID-Hep.net and COVIDCirrhosis.org) between 25 March 2020 and 20 April 2020. Our combined database includes 103 patients with cirrhosis and 49 with non-cirrhotic CLD from 21 countries across 4 continents (59.9% male, median age 61 years, aetiology 22.4% non-alcoholic fatty liver disease, 19.7% alcohol, 11.8% hepatitis B, 10.5% hepatitis C, 35.6% other/combination). Contributors were encouraged to enter data at the end of the patient's disease course. For patients admitted to hospital, cases were only included in the analysis if a definitive outcome of death or discharge was reported. 95.2% of patients with cirrhosis were hospitalised with a median length of hospital stay until discharge or death of 10 days (IQR 5-14 days). Outcomes for patients with cirrhosis included admission to intensive care unit (ICU) in 23.3%, invasive ventilation in 17.5%, non-invasive ventilatory support in 18.6%, renal replacement therapy 4.9% and death in 39.8%. Mortality far exceeded that reported in unselected populations 4 , hospitalised patients with cirrhosis in the era preceding COVID-19 5 , and in patients with cirrhosis admitted with influenza. 6 In patients not admitted to ICU, 59.5 % had non-severe disease, 27.8% had severe disease but escalation of care was deemed inappropriate, and 3.7% were considered to require ICU but were not admitted due to lack of availability. Targeted antiviral therapy was used in 38.1% of total cases. The most frequently used treatments were chloroquine/hydroxychloroquine (23.0%), lopinovir/ritonavir (6.6%), tocilizumab (3.3%), and interferon-alpha (3.3%). Cause of death in patients with cirrhosis was reported as COVID-19 lung disease in 78.7%, cardiac-related in 4.3%, and liver-related in 12.2%. Risk factors for poor COVID-19 outcomes in the general population including advanced age, obesity, renal impairment, heart disease, and diabetes mellitus were over-represented among those who died, although male sex and non-white ethnicity were not. 7 Mortality correlated strongly with baseline Child-Turcotte-Pugh (CTP) class and model for end-stage liver disease (MELD) score (Table 1) . Deaths occurred in 12.2% of CLD without cirrhosis, 23.9% CTP-A cirrhosis, 43.3% CTP-B cirrhosis, and 63.0% CTP-C cirrhosis (Fig. 1A) . CTP-B and CTP-C cirrhosis remained associated with death after adjusting for baseline characteristics including comorbidities (Table 1) . CTP-B and CTP-C cirrhosis remained significant predictors of mortality even when analysis was restricted to those with cirrhosis. Hepatic decompensation occurred in 36.9% and was associated with baseline CTP class (Fig. 1B) . This large, multicentre, international cohort of patients with chronic liver disease and cirrhosis allows for in depth assessment of the clinical factors associated with poor outcomes from COVID-19. Accepting that data from registries are subject to selection bias, preliminary findings suggest that baseline liver disease severity is strongly associated with COVID-19-related morbidity and mortality. Furthermore, many SARS-CoV-2-infected patients with cirrhosis experienced hepatic decompensation even in the absence of respiratory symptoms. These findings have important implications for clinicians regarding risk stratification and prognostication for patients with cirrhosis and COVID-19 and suggest the need to maintain a low threshold for SARS-CoV-2 testing in the presence of new hepatic decompensation. Addenbrooke's Hospital, Cambridge University Hospitals Contemporary Epidemiology of Chronic Liver Disease and Cirrhosis Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 Decreasing Mortality Among Patients Hospitalized With Cirrhosis in the United States From Influenza virus infection as precipitating event of acute-on-chronic liver failure Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Division of Internal Medicine, Azienda Ospedaliero-Universitaria Maggiore della Carità Sant'Orsola Hospital / Sant'Orsola Hospital University of Health Sciences Philippines Juozas Kupcinskas Addenbrooke's Hospital / Cambridge University Hospitals Addenbrooke's Hospital / Cambridge University Hospitals Addenbrooke's Hospital / Cambridge University Hospitals Addenbrooke's Hospital / Cambridge University Hospitals Addenbrooke's Hospital / Cambridge University Hospitals Addenbrooke's Hospital / Cambridge University Hospitals Addenbrooke's Hospital / Cambridge University Hospitals Hepatology Unit Jean Verdier Hospital, Bondy / Avicenne Hospital Mount Sinai Hospital Mount Sinai Hospital Mount Sinai Hospital Royal Victoria Hospital Whipps Cross University Hospital (Barts Health NHS Trust) / Whipps Cross University Hospital (Barts Health NHS Trust), UK Upkar Gill / Janet Dearden Upkar Gill / Sushma Saksena The Medical City / The Medical City net and COVIDCirrhosis.org would also like to thank the following societies for their endorsement British Association for Study of the Liver (BASL) Chinese Portal Hypertension Diagnosis and Monitoring Study Group (CHESS)