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• W3118156749 abstract "Acute-on-chronic liver failure (ACLF) is a condition associated with hepatic and extrahepatic organ failure with high short-term mortality.2Bajaj J.S. Garcio-Tsao G. Biggins S.W. et al.Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort.Gut Publ Online First. 13 July 2020; https://doi.org/10.1136/gutjnl-2020-322118Crossref Scopus (148) Google Scholar The data regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related ACLF (S-ACLF) are scarce.2Bajaj J.S. Garcio-Tsao G. Biggins S.W. et al.Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort.Gut Publ Online First. 13 July 2020; https://doi.org/10.1136/gutjnl-2020-322118Crossref Scopus (148) Google Scholar, 3Kulkarni A.V. Kumar P. Tevethia H.V. et al.Systematic review with meta-analysis: liver manifestations and outcomes in COVID-19.Aliment Pharmacol Ther. 2020; 52: 584-599Crossref PubMed Scopus (156) Google Scholar, 4Qiu H. Wander P. Bernstein D. et al.Acute on chronic liver failure from novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Liver Int. 2020; 40: 1590-1593Crossref PubMed Scopus (32) Google Scholar, 5Marjot T. Moon A.M. Cook J.A. et al.Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: an international registry study.J Hepatol Publ Online First. 1 Oct 2020; https://doi.org/10.1016/j.jhep.2020.09.024Abstract Full Text Full Text PDF Scopus (295) Google Scholar, 6Sarin S.K. Choudhury A. Lau G.K. et al.Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; the APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study).Hepatol Int. 2020; 14: 690-700Crossref PubMed Scopus (170) Google Scholar, 7Shalimar Elhence A. Vaishnav M. et al.Poor outcomes in patients with cirrhosis and corona virus disease-19.Indian J Gastroenterol. 2020; 39: 285-291Crossref PubMed Scopus (35) Google Scholar, 8Iavarone M. D'Ambrosio R. Soria A. et al.High rates of 30-day mortality in patients with cirrhosis and COVID-19.J Hepatol. 2020; 73: 1063-1071Abstract Full Text Full Text PDF PubMed Scopus (224) Google Scholar Whether patients with cirrhosis are at a high risk of developing ACLF after coronavirus disease 2019 (COVID-19) needs further elucidation. Here, we report our observation of patients with COVID-19 and ACLF (as per European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) definition).2Bajaj J.S. Garcio-Tsao G. Biggins S.W. et al.Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort.Gut Publ Online First. 13 July 2020; https://doi.org/10.1136/gutjnl-2020-322118Crossref Scopus (148) Google Scholar We prospectively collected the clinical and laboratory data between 1st June and 10th October of 2020. Fifty seven (2.3%) of 2460 patients with COVID-19 had underlying cirrhosis, and 60% of patients had cirrhosis-related symptoms at presentation. The clinical and laboratory data are described in Table 1. Patients with S-ACLF (35%) had significantly prolonged hospital stay (14.7 ±17.3 days vs. 5.4 ±5.3 days, p-0.004), severe COVID-19 illness (25% vs. 3%, p-0.03), need for intensive care unit (45% vs. 11%, p-0.003), and higher mortality (30% vs. 5%, p-0.01) as compared with patients without ACLF. The cause of death was respiratory failure in 5 (67%) and liver failure in 3 (37%) patients. There were no differences in laboratory parameters between those who died and survived in the S-ACLF group. Patients who died had significantly higher Chronic Liver Failure Consortium (CLIF C) score (56.8 ±4.8 vs.43.3 ±6.4, p-<0.001), CLIF C organ failure score (12.1 ±1.4 vs.9.7 ±1.6,p-0.005), and ACLF grade (3.1 ±0.9 vs.1.9 ±0.6,p-0.003).Table 1Comparison of Patients with S-ACLF and Patients with COVID-19 and without ACLF.ParametersS-ACLF (n-20)Non-ACLF (n-37)P valueAge (years)48.4 ± 10.953 ± 12.30.174Male (n, %)19 (95)32 (86)0.318Comorbidities (n, %) Diabetes mellitus2 (10)19 (51)0.002 Hypertension2 (10)12 (32)0.060 Coronary artery disease1 (5)3 (8)0.661Etiology of cirrhosis (n, %) Alcohol13 (65)12 (32.4)0.094 Cryptogenic3 (15)6 (16.2) Nonalcoholic steatohepatitis1 (5)12 (32.4) Viral2 (10)5 (13.5) Autoimmune1 (5)2 (5.5)Compensated cirrhosisaBefore the onset of COVID-19 illness. (n, %)10 (50)20 (54)0.770Severity of cirrhosis Child Pugh score, A/B/C (%)11 ± 1.7, 0/25/758 ± 2.4,29.7/40.6/29.7<0.001 Sodium MELD28.4 ± 7.515.2 ± 8.7<0.001Acute hepatic decompensation (%) Ascites/hepatic encephalopathy/variceal bleed70/50/540/8/20.002/<0.001/0.065ACLF severity scores CLIF C ACLF score48 ± 8.6 ACLF CLIF C organ failure score10 ± 1.9 ACLF grade – 1/2/3 (%)15/50/35COVID-19 severity grade (%) Mild (no hypoxia)/moderate (SpO2 90–94%)/severe (SpO2<90%) on room air45/30/2554/33/30.030Laboratory parameters Hemoglobin (g/dL)9.1 ± 1.810.4 ± 2.20.031 Total leukocyte count/μL9.9 ± 9.26 ± 3.70.028 Lymphocytopenia, <1000/μL (n, %)4 (20)18 (48.6)0.034 Platelets/μLaBefore the onset of COVID-19 illness.1031.1 ± 0.41.2 ± 0.80.756 Sodium (meq/l)130.8 ± 5.6132.8 ± 4.80.169 Creatinine (mg/dl)1.5 ± 11 ± 0.30.003 Total/direct bilirubin(mg/dL)14.9 ± 10.6/7.6 ± 6.62.9 ± 2.4/1.3 ± 1.5<0.001 Aspartate transaminase (<40 U/L)173 ± 204109 ± 1710.212 Alanine transaminase (<40 U/L)73.6 ± 77.857 ± 66.50.402 Alkaline phosphatase (30–120 U/L)141.5 ± 65.2114 ± 56.50.103 Total protein (g/dL)6 ± 16.5 ± 0.70.048 Serum albumin (g/dL)2.7 ± 0.43 ± 0.50.082 International normalized ratio2.5 ± 1.31.5 ± 0.6<0.001Inflammatory biomarkers (reference range) Interleukin-6 (pg/ml, <7)64.5 ± 97.649.5 ± 890.558 D-dimer (ng/ml, <232)2534.4 ± 2019.71406.4 ± 16880.029 C-reactive protein (mg/l, <6)17.8 ± 25.915.9 ± 27.60.809 Lactate dehydrogenase (U/L,225–450)523.4 ± 463.5405.4 ± 417.10.331 Ferritin(ng/ml,30–400)906.6 ± 1262.5560.7 ± 1227.20.319Hospital admission (n, %)16 (80)22 (59)0.116 Intensive care unit9 (45)4 (11)0.003 Oxygen requirement11 (55)13 (65)0.147 Mechanical ventilation7 (35)1 (2)0.001COVID-19 treatment Supportive4 (20)12 (32) Remdesivir6 (30)14 (38)0.130 Doxycycline10 (50)11 (30)0.554 Steroids13 (65)16 (43)0.114Length of hospital stay (days)14.7 ± 17.35.4 ± 5.30.004 Mortality (n, %)6 (30)2 (5)0.011All results are expressed in mean ± standard deviation unless otherwise specified. ACLF, acute-on-chronic liver failure; MELD, Model for End-Stage Liver Disease; CLIF C, Chronic Liver Failure Consortium; COVID-19, coronavirus disease 2019; SpO2, oxygen saturation in pulse oximeter.Bold describes the Significant values.a Before the onset of COVID-19 illness. Open table in a new tab All results are expressed in mean ± standard deviation unless otherwise specified. ACLF, acute-on-chronic liver failure; MELD, Model for End-Stage Liver Disease; CLIF C, Chronic Liver Failure Consortium; COVID-19, coronavirus disease 2019; SpO2, oxygen saturation in pulse oximeter. Bold describes the Significant values. Patients with ACLF are more prone to develop severe COVID-19 illness because of profound immune dysregulation.1Arroyo V. Moreau R. Jalan R. Acute-on-Chronic liver failure.N Engl J Med. 2020; 382: 2137-2145Crossref PubMed Scopus (272) Google Scholar It is unclear whether outcomes in S-ACLF will be different compared with the other causes of ACLF. Our cohort demonstrated lower mortality in patients with cirrhosis, contrary to other studies despite having similar disease severity. Our cohort's better outcomes could be due to prompt usage of steroids in patients with moderate or severe COVID-19.4Qiu H. Wander P. Bernstein D. et al.Acute on chronic liver failure from novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Liver Int. 2020; 40: 1590-1593Crossref PubMed Scopus (32) Google Scholar, 5Marjot T. Moon A.M. Cook J.A. et al.Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: an international registry study.J Hepatol Publ Online First. 1 Oct 2020; https://doi.org/10.1016/j.jhep.2020.09.024Abstract Full Text Full Text PDF Scopus (295) Google Scholar, 6Sarin S.K. Choudhury A. Lau G.K. et al.Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; the APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study).Hepatol Int. 2020; 14: 690-700Crossref PubMed Scopus (170) Google Scholar, 7Shalimar Elhence A. Vaishnav M. et al.Poor outcomes in patients with cirrhosis and corona virus disease-19.Indian J Gastroenterol. 2020; 39: 285-291Crossref PubMed Scopus (35) Google Scholar, 8Iavarone M. D'Ambrosio R. Soria A. et al.High rates of 30-day mortality in patients with cirrhosis and COVID-19.J Hepatol. 2020; 73: 1063-1071Abstract Full Text Full Text PDF PubMed Scopus (224) Google Scholar The patients tolerated steroids well, and four patients developed gram-negative sepsis, which responded to broad-spectrum antibiotics. The exact mechanism of S-ACLF is unclear, and the cytokine storm might serve as a trigger in these patients. It is also hypothesized that direct SARS-CoV-2 infection can cause significant liver injury because of the upregulated Angiotensin converting enzyme 2 (ACE2) expression and higher ACE2 internalization in hepatocytes, causing worsening of liver fibrosis and portal hypertension to ACLF in decompensated cirrhosis.9Gao F. Zheng K.I. Fan Y.C. et al.ACE2: a linkage for the interplay between COVID-19 and decompensated cirrhosis.Am J Gastroenterol. 2020; 115: 1544Crossref PubMed Scopus (14) Google Scholar In addition, a liver biopsy might have helped in better understanding of the cause and severity of S-ACLF. Excessive systemic inflammation is a hallmark in ACLF, and these patients had higher leukocyte count and elevated D-dimer in our study. The inflammatory response observed in our study is comparable with that of patients with COVID-19 without cirrhosis, as described in recent metanalysis.10Leisman D.E. Ronner L. Pinotti R. et al.Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndrome.Lancet Respir Med Publ Online First. 2020; 8: 1233-1244https://doi.org/10.1016/S2213-2600(20)30404-5Abstract Full Text Full Text PDF PubMed Scopus (535) Google Scholar Whether immune dysregulation in S-ACLF is different from ACLF of other causes and cirrhosis needs further evaluation. We speculate that the SARS-CoV-2 infection predominantly determines immune dysregulation and outcomes irrespective of cirrhosis severity. In conclusion, S-ACLF is associated with a poor outcome, and early recognition and aggressive treatment of COVID-19 is warranted. Further multicentre studies with a larger sample size will provide more robust data on S-ACLF outcomes. Pramod Kumar: Conceptualization, Methodology, Writing – original draft, Writing – review & editing. Mithun Sharma: Reviewing and editing. Syeda F. Sulthana: Compilation. Anand Kulkarni: Reviewing and editing. Padaki N. Rao: Supervision. Duvvuru N. Reddy: Supervision. The authors have none to declare. The authors thank the Department of Gastroenterology, Department Emergency Medicine, Department of Internal Medicine, Department of Pulmonary Medicine, and Department of Anesthesiology and Critical Care, Asian Institute of Gastroenterology Hospitals, Hyderabad." @default.
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• W3118156749 title "Severe Acute Respiratory Syndrome Coronavirus 2–related Acute-on-chronic Liver Failure" @default.
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