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      Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: an international registry study

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      1 , ∗∗ , , 2 , , 3 ,   4 , 5 , 6 , 7 , 8 , 9 , 1 , 10 , 11 , 12 , 13 , 14 , 15 , 1 , 16 , 17 , 18 , 1 , 19 , 7 , 20 , 21 , 22 , 23 , 24 , 25 , 1 , , 2 , , 1 , 18 ,
      Journal of Hepatology
      Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.
      SARS-CoV-2, COVID-19, chronic liver disease, cirrhosis, acute-on-chronic liver failure

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          Abstract

          Background

          Chronic liver disease (CLD) and cirrhosis are associated with immune dysregulation leading to concerns that these patients may be at risk of adverse outcomes following SARS-CoV-2 infection. However, the impact of COVID-19 among patients with pre-existing liver disease remains ill-defined.

          Methods

          Data for CLD patients with SARS-CoV-2 were collected by two international registries. Comparisons were made with non-CLD patients with SARS-CoV-2 from a UK hospital network.

          Results

          Between 25th March and 8th July 2020, 745 CLD patients were reported from 29 countries including 386 with cirrhosis and 359 without. Mortality was 32% in patients with cirrhosis compared with 8% in those without (p<0.001). Mortality in cirrhosis patients increased according to Child-Turcotte-Pugh class (CTP-A (19%), CTP-B (35%), CTP-C (51%)) and the main cause of death was respiratory failure (71%). After adjusting for baseline characteristics, factors associated with death in the total CLD cohort were age (OR 1.02; 1.01–1.04), CTP-A (OR 1.90; 1.03–3.52), CTP-B (OR 4.14; 2.4–7.65), CTP-C cirrhosis (OR 9.32; 4.80–18.08) and alcohol related liver disease (ALD) (OR 1.79; 1.03–3.13). When comparing CLD versus non-CLD (n=620) in propensity-score-matched analysis there were significant increases in mortality with CTP-B +20.0% (8.8%–31.3%) and CTP-C cirrhosis +38.1% (27.1%–49.2%). Acute hepatic decompensation occurred in 46% of patients with cirrhosis, of which 21% had no respiratory symptoms. 50% of those with hepatic decompensation had acute-on-chronic liver failure.

          Conclusions

          This is the largest reported cohort of CLD and cirrhosis patients with SARS-CoV-2 infection to date. We demonstrate that baseline liver disease stage and ALD are independent risk factor for death from COVID-19. These data have important implications for the risk stratification of patients with CLD across the globe during the COVID-19 pandemic.

          Graphical abstract

          Highlights

          • Patients with cirrhosis have high rates of hepatic decompensation and death following SARS-CoV-2 infection.

          • Mortality increased in step-wise fashion according to Child-Turcotte-Pugh class.

          • Other risk factors for death included advancing age and alcohol-related liver disease.

          • Patients with advanced cirrhosis had increased risk of mortality compared to propensity-score-matched patients without liver disease.

          • The majority of deaths in cirrhosis patients were from COVID-19 lung disease.

          Abstract

          This international registry study demonstrates that patients with cirrhosis are at increased risk of death from COVID-19. Mortality from COVID-19 was particularly high among patients with more advanced cirrhosis and those with alcohol-related liver disease.

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          Most cited references33

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          Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis

          Highlights • COVID -19 cases are now confirmed in multiple countries. • Assessed the prevalence of comorbidities in infected patients. • Comorbidities are risk factors for severe compared with non-severe patients. • Help the health sector guide vulnerable populations and assess the risk of deterioration.
            Bookmark
            • Record: found
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            • Article: not found

            Epidemic of COVID-19 in China and associated Psychological Problems

            Highlights • There are higher rate of anxiety, depression, alcohol use disorder, and lower mental wellbeing during the COVID-19 epidemic. • Depression and alcohol use disorder were higher among people from Hubei than other provinces. • Non-significant gender differences in anxiety, depression, and mental wellbeing. • Young people, aged 21–40 years old, were psychologically more vulnerable position during the COVID-19 epidemic.
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              • Article: not found

              SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19

              Background Liver enzyme abnormality is common in patients with coronavirus disease 2019 (COVID-19). Whether or not SARS-CoV-2 infection can lead to liver damage per se remains unknown. Here we reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with liver enzyme abnormality. Methods We received 156 patients diagnosed of COVID-19 from two designated centers in China, and compared clinical features between patients with elevated aminotransferase or not. Postmortem liver biopsies were obtained from two cases who had elevated aminotransferase. We investigated the patterns of liver impairment by electron microscopy, immunohistochemistry, TUNEL assay, and pathological studies. Results 64 of 156 (41.0%) COVID-19 patients had elevated aminotransferase. The median levels of ALT were 50 U/L vs. 19 U/L, respectively, AST were 45.5 U/L vs. 24 U/L, respectively in abnormal and normal aminotransferase groups. The liver enzyme abnormality was associated with disease severity, as well as a series of laboratory tests including higher A-aDO2, higher GGT, lower albumin, decreased CD4+ T cells and B lymphocytes. Ultrastructural examination identified typical coronavirus particles characterized by spike structure in cytoplasm of hepatocytes in two COVID-19 cases. SARS-CoV-2 infected hepatocytes displayed conspicuous mitochondrial swelling, endoplasmic reticulum dilatation, and glycogen granule decrease. Histologically, massive hepatic apoptosis and a certain binuclear hepatocytes were observed. Taken together, both ultrastructural and histological evidence indicated a typical lesion of viral infection. Immunohistochemical results showed scanty CD4+ and CD8+ lymphocytes. No obvious eosinophil infiltration, cholestasis, fibrin deposition, granuloma, massive central necrosis, or interface hepatitis were observed. Conclusions SARS-CoV-2 infection in liver is a crucial cause of hepatic impairment in COVID-19 patients. Hence, a surveillance of viral clearance in liver and long outcome of COVID-19 is required.
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                Author and article information

                Journal
                J Hepatol
                J Hepatol
                Journal of Hepatology
                Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.
                0168-8278
                1600-0641
                6 October 2020
                6 October 2020
                Affiliations
                [1 ]Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
                [2 ]Division of Gastroenterology and Hepatology, University of North Carolina, North Carolina, USA
                [3 ]Centre for Statistics in Medicine, University of Oxford, Oxford, UK
                [4 ]Tropical Medicine and Infectious diseases Department, Tanta University, Tanta, Egypt
                [5 ]Department of Medicine, Section of Hepatology, Rush University Medical Center, Chicago, Illinois, USA
                [6 ]Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK
                [7 ]Liver Unit, Hospital Clínic, Barcelona, Spain; Institut d’Investigacions Biomèdiques, August Pi i Sunyer, Barcelona, Spain
                [8 ]Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
                [9 ]Division of Pediatric Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA
                [10 ]Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
                [11 ]Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA
                [12 ]Shiraz Transplant Center, Abu-Ali Sina Hospital, Shiraz, Iran
                [13 ]Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
                [14 ]Barts Liver Centre, Barts Health NHS Trust & Barts & The London School of Medicine & Dentistry, QMUL, London
                [15 ]Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
                [16 ]Sheila Sherlock Liver Unit, Royal Free Hospital, London, UK
                [17 ]Department of Gastroenterology and Hepatology, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
                [18 ]Cambridge Liver Unit, Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, UK
                [19 ]Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA
                [20 ]CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China
                [21 ]Division of Gastroenterology, University of Washington, Seattle, WA, USA
                [22 ]Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
                [23 ]Department of Gastroenterology & Hepatology, Changi General Hospital; Yong Loo Lin School of Medicine, National University of Singapore
                [24 ]MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
                [25 ]Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease, Zhejiang Province, Wenzhou, Zhejiang, China
                Author notes
                [∗∗ ]Corresponding author Dr Thomas Marjot Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK Tel +44 (0)1865 281547
                [∗]

                These authors contributed equally.

                Article
                S0168-8278(20)33667-9
                10.1016/j.jhep.2020.09.024
                7536538
                33035628
                8c8965ee-6884-498b-9a72-edd25cf5ba8f
                © 2020 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 2 September 2020
                : 22 September 2020
                : 25 September 2020
                Categories
                Article

                Gastroenterology & Hepatology
                sars-cov-2,covid-19,chronic liver disease,cirrhosis,acute-on-chronic liver failure

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