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      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)

      , 1 , 1 , 2 , 2 , 3 , 2 , 4 , 5 , 6 , 7 , 8 , 9 , 9 , 10 , 11 , 11 , 10 , 12 , 10 , 13 , 14 , 15 , 15 , 13 , 16 , 17 , 18 , 19 , 20 , 20 , 21 , 22 , 23 , 5 , 5 , 24 , 25 , 25 , 26 , 27 , 28 , 14 , 29 , 30 , 31 , 24 , 32 , 1 , 33 , 34 , APASL COVID Task Force, APASL COVID Liver Injury Spectrum Study (APCOLIS Study-NCT 04345640)

      Hepatology International

      Springer India

      COVID-19, SARS CoV2, Acute liver injury, Chronic liver disease

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          Abstract

          Background and aims

          COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis.

          Methods

          Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19.

          Results

          Altogether , 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1–3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9–38.8), p = 0.002] predisposed more to liver injury than those without these . Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3–163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients.

          Conclusions

          SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.

          Electronic supplementary material

          The online version of this article (10.1007/s12072-020-10072-8) contains supplementary material, which is available to authorized users.

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          Most cited references 17

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          Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

          Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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            COVID-19: Abnormal liver function tests

            Background & Aims Recent data on the coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has begun to shine light on the impact of the disease on the liver. But no studies to date have systematically described liver test abnormalities in patients with COVID-19. We evaluated the clinical characteristics of COVID-19 in patients with abnormal liver test results. Methods Clinical records and laboratory results were obtained from 417 patients with laboratory-confirmed COVID-19 who were admitted to the only referral hospital in Shenzhen, China from January 11 to February 21, 2020 and followed up to March 7, 2020. Information on clinical features of patients with abnormal liver tests were collected for analysis. Results Of 417 patients with COVID-19, 318 (76.3%) had abnormal liver test results and 90 (21.5%) had liver injury during hospitalization. The presence of abnormal liver tests became more pronounced during hospitalization within 2 weeks, with 49 (23.4%), 31 (14.8%), 24 (11.5%) and 51 (24.4%) patients having alanine aminotransferase, aspartate aminotransferase, total bilirubin and gamma-glutamyl transferase levels elevated to more than 3× the upper limit of normal, respectively. Patients with abnormal liver tests of hepatocellular type or mixed type at admission had higher odds of progressing to severe disease (odds ratios [ORs] 2.73; 95% CI 1.19–6.3, and 4.44, 95% CI 1.93–10.23, respectively). The use of lopinavir/ritonavir was also found to lead to increased odds of liver injury (OR from 4.44 to 5.03, both p <0.01). Conclusion Patients with abnormal liver tests were at higher risk of progressing to severe disease. The detrimental effects on liver injury mainly related to certain medications used during hospitalization, which should be monitored and evaluated frequently. Lay summary Data on liver tests in patients with COVID-19 are scarce. We observed a high prevalence of liver test abnormalities and liver injury in 417 patients with COVID-19 admitted to our referral center, and the prevalence increased substantially during hospitalization. The presence of abnormal liver tests and liver injury were associated with the progression to severe pneumonia. The detrimental effects on liver injury were related to certain medications used during hospitalization, which warrants frequent monitoring and evaluation for these patients.
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              The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients

              Aim To accumulate evidence that indicates the key role played by virus-triggered inflammation in the 2019-novel coronavirus disease (COVID-19) which emerged in Wuhan City and rapidly spread throughout China. Methods Age, neutrophil(NEU)-to-lymphocyte (LYM) ratio (NLR), lymphocyte-to-monocyte(MON) ratio, platelet-to-lymphocyte ratio(PLR), and C-reactive protein(CRP) of 93 patients with laboratory confirmed COVID-19 were investigated and compared. The receiver operating characteristic curve was applied to determine the thresholds for five bio-markers, and their prognostic values were assessed via the Kaplan–Meier curve and multivariate COX regression models. Results The median age was 46.4 years old, and 37cases were females. A total of 26.8% of patients had been to Wuhan, and 73.1% had contacted with people from Wuhan. Fever (83.8%) and cough (70.9%) were the two most common symptoms. Elevated NLR and age were significantly associated with illness severity. The binary logistic analysis identified elevated NLR (hazard risk [HR] 2.46, 95% confidence interval [CI] 1.98–4.57) and age (HR 2.52, 95% CI 1.65–4.83) as independent factors for poor clinical outcome of COVID-19. NLR exhibited the largest area under the curve at 0.841, with the highest specificity (63.6%) and sensitivity (88%). Conclusions Elevated age and NLR can be considered independent biomarkers for indicating poor clinical outcomes.
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                Author and article information

                Contributors
                shivsarin@gmail.com
                Journal
                Hepatol Int
                Hepatol Int
                Hepatology International
                Springer India (New Delhi )
                1936-0533
                1936-0541
                4 July 2020
                : 1-11
                Affiliations
                [1 ]GRID grid.418784.6, ISNI 0000 0004 1804 4108, Department of Hepatology and Liver Transplant, , Institute of Liver and Biliary Sciences, ; New Delhi, 110070 India
                [2 ]Humanity and Health Clinical Trial Center, Hong Kong SAR, China
                [3 ]GRID grid.414906.e, ISNI 0000 0004 1808 0918, Department of Hepatology, NAFLD Research Center, , The First Affiliated Hospital of Wenzhou Medical University, ; Wenzhou, China
                [4 ]Fuyang Second People’s Hospital, Fuyang, China
                [5 ]GRID grid.412258.8, ISNI 0000 0000 9477 7793, Tropical Medicine and Infectious Diseases Department, , Tanta University, ; Tanta, Egypt
                [6 ]GRID grid.412091.f, ISNI 0000 0001 0669 3109, Keimyung University Dongsan Hospital, ; Daegu, South Korea
                [7 ]GRID grid.412643.6, CHESS Center, Institute of Portal Hypertension, , The First Hospital of Lanzhou University, ; Lanzhou, China
                [8 ]GRID grid.416846.9, ISNI 0000 0004 0571 4942, Institute of Digestive and Liver Diseases, St. Luke’s Medical Center, ; Global City, Philippines
                [9 ]GRID grid.255168.d, ISNI 0000 0001 0671 5021, Department of Internal Medicine, , Dongguk University Gyeongju Hospital, ; Gyeongju, South Korea
                [10 ]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Division of Gastroenterology, Department of Medicine, Faculty of Medicine, , Chulalongkorn University and Thai Red Cross, ; Bangkok, Thailand
                [11 ]GRID grid.7130.5, ISNI 0000 0004 0470 1162, Gastroenterology and Hepatology Unit, Department of Medicine, , Prince of Songkla University, ; Songkhla, Thailand
                [12 ]GRID grid.411235.0, ISNI 0000 0004 0647 192X, Kyungpook National University Hospital, ; Daegu, South Korea
                [13 ]Department of Internal Medicine, Fatima University Medical Center, Valenzuela, Philippines
                [14 ]GRID grid.444534.6, Department of Infectious Diseases, School of Medicine, , Mongolian National University of Medical Sciences, ; Ulan Bator, Mongolia
                [15 ]GRID grid.15444.30, ISNI 0000 0004 0470 5454, Severance Hospital, , Yonsei University College of Medicine, ; Seoul, South Korea
                [16 ]National Center for Communicable Diseases, Ulan Bator, Mongolia
                [17 ]Department of Gastroenterology and Hepatology “Dharmais”, National Cancer Hospital, Jakarta, Indonesia
                [18 ]GRID grid.136304.3, ISNI 0000 0004 0370 1101, Chiba University, ; Chiba, Japan
                [19 ]GRID grid.7147.5, ISNI 0000 0001 0633 6224, Department of Medicine, WGO Training Center, , Aga Khan University, ; Karachi, Pakistan
                [20 ]GRID grid.413442.4, ISNI 0000 0004 1802 4561, Department of Hepatology, , Selayang Hospital, ; Batu Caves, Malaysia
                [21 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Division of Gastroenterology, Department of Medicine, Faculty of Siriraj Hospital, , Mahidol University, ; Bangkok, Thailand
                [22 ]GRID grid.9581.5, ISNI 0000000120191471, Division of Hepatobiliary, Cipto Mangunkusuamo Hospital, , University of Indonesia, ; Jakarta, Indonesia
                [23 ]GRID grid.416383.b, ISNI 0000 0004 1768 4525, Hepatologist, , Manipal Hospital, ; New Delhi, India
                [24 ]GRID grid.411509.8, ISNI 0000 0001 2034 9320, Department of Hepatology, , Bangabandhu Sheikh Mujib Medical University, ; Dhaka, Bangladesh
                [25 ]Division of Infectious Diseases, School of Medicine, Kaohsiung Medical University, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
                [26 ]GRID grid.429252.a, ISNI 0000 0004 1764 4857, Liver Transplant Surgery, , Medanta, The Medicity, ; Gurugram, Haryana India
                [27 ]GRID grid.414612.4, ISNI 0000 0004 1804 700X, Hepatologist and Gastroenterologist, , Indraprastha Apollo Hospital, ; New Delhi, India
                [28 ]GRID grid.487294.4, Faculty of Medicine, , Cipto Mangunkusumo Hospitall, Universitas, ; Jakarta, Indonesia
                [29 ]GRID grid.412032.6, ISNI 0000 0001 0744 0787, Kariadi Hospital, , Diponegoro University, ; Semarang, Indonesia
                [30 ]Yerevan Medical University, Yerevan, Armenia
                [31 ]GRID grid.413161.0, ISNI 0000 0004 1766 9130, Department of Gastroenterology, , T.N. Medical College, B.Y.L. Nair. Ch. Hospital, ; Mumbai, India
                [32 ]GRID grid.414807.e, ISNI 0000 0004 1766 8840, Department of Gastroenterology, , Seth GSMC and KEM Hospital, ; Mumbai, India
                [33 ]GRID grid.417333.1, ISNI 0000 0004 0377 4044, Department of Gastroenterology, , Yamanashi Prefectural Central Hospital, ; Kofu, Yamanashi Japan
                [34 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, The University of Tokyo, ; Tokyo, Japan
                Article
                10072
                10.1007/s12072-020-10072-8
                7334898
                32623632
                © Asian Pacific Association for the Study of the Liver 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                Categories
                Original Article

                Gastroenterology & Hepatology

                covid-19, sars cov2, acute liver injury, chronic liver disease

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