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Abenavoli L, Aquila I, Sacco MA, Scarlata GGM, Procopio AC, Boccuto L, Scarpellini E, Greco M, Foti DP, Ricci P, Luzza F. Liver Damage and Impaired Coagulation in COVID-19 Patients: A Case Series. Diseases 2023; 11:141. [PMID: 37873785 PMCID: PMC10594514 DOI: 10.3390/diseases11040141] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 10/02/2023] [Accepted: 10/12/2023] [Indexed: 10/25/2023] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated an unprecedented challenge for healthcare systems worldwide. Currently, the scientific community wonders if liver injury in patients suffering from severe forms is a direct consequence of the virus or secondary manifestations of systemic inflammation. The liver plays an essential role in the development of the inflammatory storm typical of this disease, and its involvement is associated with worse clinical outcomes and a higher risk of morbidity and mortality from Coronavirus disease 2019 (COVID-19). METHODS Ten patients suffering from severe COVID-19 disease who died between January 2020 and December 2021 were included in the present analysis. These subjects underwent a post mortem examination with a focused evaluation of the hepatic injury. Also, several laboratory parameters have been evaluated, with a primary focus on prothrombin time, partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers to detect coagulative changes. RESULTS The main cause of death was represented by pulmonary thromboembolism events (50%). The analysis of coagulation laboratory parameters and liver biomarkers revealed a statistically significant rise in aPTT and ALP, and a decrease in albumin, when comparing the blood value at admission and death. We also found high levels of D-dimers in most of the subjects at the time of hospitalization. Interestingly, the post mortem analysis of the liver showed ample morphologic variability, with several disease features. In detail, the liver histology revealed the following: the presence of a variable degree of micro- and macrovacuolar steatosis, inflammation (also, hepato-cholangitis), and variable fibrosis. Of mention, we were also able to detect organized fibrinous material. CONCLUSIONS Our results indicate that in subjects with a severe form of COVID-19, liver disease is related to changes in coagulative and fibrinolytic pathways. In particular, we noted low fibrinogen levels and high D-dimer levels with histological liver findings. Our data suggest that fibrinogen and D-dimers may be used as prognostic markers to detect the severity of liver disease in patients with COVID-19. Finally, we underline the crucial role of coagulation balance in subjects with severe forms of COVID-19.
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Affiliation(s)
- Ludovico Abenavoli
- Department of Health Sciences, University “Magna Græcia”, Viale Europa, 88100 Catanzaro, Italy; (G.G.M.S.); (A.C.P.); (M.G.); (F.L.)
| | - Isabella Aquila
- Institute of Legal Medicine, Department of Medical and Surgical Sciences, University “Magna Graecia”, Viale Europa, 88100 Catanzaro, Italy; (I.A.); (M.A.S.); (P.R.)
| | - Matteo Antonio Sacco
- Institute of Legal Medicine, Department of Medical and Surgical Sciences, University “Magna Graecia”, Viale Europa, 88100 Catanzaro, Italy; (I.A.); (M.A.S.); (P.R.)
| | - Giuseppe Guido Maria Scarlata
- Department of Health Sciences, University “Magna Græcia”, Viale Europa, 88100 Catanzaro, Italy; (G.G.M.S.); (A.C.P.); (M.G.); (F.L.)
| | - Anna Caterina Procopio
- Department of Health Sciences, University “Magna Græcia”, Viale Europa, 88100 Catanzaro, Italy; (G.G.M.S.); (A.C.P.); (M.G.); (F.L.)
| | - Luigi Boccuto
- Healthcare Genetics and Genomics Doctoral Program, School of Nursing, College of Behavioral, Social and Health Sciences, Clemson University, Clemson, SC 29631, USA;
| | - Emidio Scarpellini
- Translationeel Onderzoek van Gastroenterologische Aandoeningen (T.A.R.G.I.D.), Gasthuisberg University Hospital, KU Leuven, Herestraat 49, 3000 Leuven, Belgium;
| | - Marta Greco
- Department of Health Sciences, University “Magna Græcia”, Viale Europa, 88100 Catanzaro, Italy; (G.G.M.S.); (A.C.P.); (M.G.); (F.L.)
| | - Daniela Patrizia Foti
- Department of Experimental and Clinical Medicine, University “Magna Græcia”, Viale Europa, 88100 Catanzaro, Italy;
| | - Pietrantonio Ricci
- Institute of Legal Medicine, Department of Medical and Surgical Sciences, University “Magna Graecia”, Viale Europa, 88100 Catanzaro, Italy; (I.A.); (M.A.S.); (P.R.)
| | - Francesco Luzza
- Department of Health Sciences, University “Magna Græcia”, Viale Europa, 88100 Catanzaro, Italy; (G.G.M.S.); (A.C.P.); (M.G.); (F.L.)
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Testino G, Bottaro LC, Andorno E, Bandini F, Balbinot P, Beltramini S, Bottino S, Caltabellotta M, Caputo F, Caviglia E, Curone P, DI Biagio A, Gagliano C, Gandolfo N, Pestarino L, Rollero A, Romairone E, Sampietro L, Torre E, Zuccarelli S, Pellicano R. Hepatic encephalophathy: management and diagnostic therapeutic assistance path of Ligurian Local Health Company 3 (ASL3). Minerva Med 2023; 114:698-718. [PMID: 36952221 DOI: 10.23736/s0026-4806.22.08408-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/24/2023]
Abstract
Hepatic encephalophathy (HE) is a neuropsychiatric syndrome with a prevalence in the cirrhotic population ranging from 20 to 80%. HE is a cause of inappropriate hospitalization, caregiver burdening and increased social costs. There is need to create dedicated care pathways to better manage patients and support family caregivers. The data used for the preparation of this diagnostic therapeutic assistance path (DTAP) are based on a detailed analysis of the scientific literature published before June 30, 2022 (PubMed, Web of Science, Scopus, Google Scholar). Furthermore, in the process of developing this work, we consulted in particular the guidelines/ position papers of International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN), Italian Association for the Study of the Liver (AISF), European Association for the Study of the Liver (EASL), American Association for the Study of Liver Diseases (AASLD), Italian Society on Alcohol (Società Italiana di Alcologia [SIA]) and other relevant papers. DTAP was created based on the most recent recommendations of the international scientific literature. The present DTAP highlight the need for a multidisciplinary activity integrated with territorial medicine in close connection with caregivers. This guarantees improved therapeutic adherence, hospital readmission reduction, improved quality of life for patients and caregivers and a significant reduction in costs.
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Affiliation(s)
- Gianni Testino
- Addiction and Hepatology Unit/Alcohological Regional Centre and Study Centre "Self Help, Community Program and Caregiver Training" ASL3, Genoa, Italy -
| | | | - Enzo Andorno
- Liver Transplantation Unit, San Martino Polyclinic Hospital, Genoa, Italy
| | | | - Patrizia Balbinot
- Addiction and Hepatology Unit/Alcohological Regional Centre and Study Centre "Self Help, Community Program and Caregiver Training" ASL3, Genoa, Italy
| | | | | | | | - Fabio Caputo
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Center for the Study and Treatment of Chronic Inflammatory Intestinal Diseases (IBD) and Gastroenterological Manifestations of Rare Diseases, Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Center for the Study and Treatment of Alcohol-Related Diseases, Department of Translational Medicine, University of Ferrara, Ferrara, Italy
- Department of Internal Medicine, Santissima Annunziata Hospital, University of Ferrara, Ferrara, Italy
| | | | | | - Antonio DI Biagio
- Department of Health Sciences, Infectious Diseases Clinic, IRCCS San Martino Polyclinic Hospital, University of Genoa, Genoa, Italy
| | | | | | | | | | | | | | - Enrico Torre
- Unit of Endocrinology, Metabolic Diseases and Diabetology, ASL3 Liguria, Genoa, Italy
| | | | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy
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Abenavoli L, Aquila I, Sacco MA, Procopio AC, Cinaglia P, Zanza C, Longhitano Y, Arena V, Fagoonee S, Ricci P, Luzza F. Liver injury associated with high value of D-dimer plasmatic level in COVID-19 patients. Minerva Gastroenterol (Torino) 2023; 69:141-148. [PMID: 35470356 DOI: 10.23736/s2724-5985.22.03189-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causal agent of the coronavirus disease (COVID-19), has infected millions of people worldwide. Currently, the scientific community debates on the direct viral responsibility of liver damage or whether the observed changes are secondary manifestations of systemic inflammation triggered by COVID-19. The hepatic involvement is associated with worse clinical outcomes and higher risk of COVID-19 related morbidity and mortality. Furthermore, SARS-CoV-2 infection may predispose patients to thrombotic disease due to excessive inflammation, platelet activation, and endothelial dysfunction. METHODS In this paper, we reported a cross-sectional analysis of five patients affected by a severe form of COVID-19, who died between April 11 and May 1, 2020. Each patient has been subjected to a medico-legal autopsy in which both gross and histological liver changes were evaluated, as well as the correlation with the related coagulation profile. RESULTS In three cases of our cohort, the thromboembolism was recognized as cause of death. Furthermore, a significant statistical difference between D-dimer values at hospital admission and death among enrolled patients (P=0.033), was evaluated. No patient has recorded a pre-existing liver disease. CONCLUSIONS Our results support the evidence that hepatic damage in subjects with severe form of COVID-19 is related to the changes in coagulative and fibrinolytic pathways. Hence, the evaluation of D-dimer blood levels may be useful in clinical practice to predict the involvement of the liver and the prognosis of these patients. This data highlights the fundamental role of coagulation balance in subjects with advanced form of COVID-19.
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Affiliation(s)
- Ludovico Abenavoli
- Department of Health Sciences, Magna Grecia University, Catanzaro, Italy -
| | - Isabella Aquila
- Department of Surgical and Medical Sciences, Magna Grecia University, Catanzaro, Italy
| | - Matteo A Sacco
- Department of Surgical and Medical Sciences, Magna Grecia University, Catanzaro, Italy
| | - Anna C Procopio
- Department of Health Sciences, Magna Grecia University, Catanzaro, Italy
| | - Pietro Cinaglia
- Department of Health Sciences, Magna Grecia University, Catanzaro, Italy
| | - Christian Zanza
- Department of Emergency, Anesthesia and Critical Care, Foundation "Ospedale Alba-Bra", Michele and Pietro Ferrero Hospital, Verduno, Cuneo, Italy
| | - Yaroslava Longhitano
- Department of Emergency Medicine, Section of Anesthesia and Critical Care, St Giacomo Hospital, Novi Ligure, Alessandria, Italy
| | - Vincenzo Arena
- Department of Woman and Child Health and Public Health, IRCCS A. Gemelli University Polyclinic Foundation, Rome, Italy
| | - Sharmila Fagoonee
- Institute of Biostructure and Bioimaging, National Research Council, Molecular Biotechnology Center, Turin, Italy
| | - Pietrantonio Ricci
- Department of Surgical and Medical Sciences, Magna Grecia University, Catanzaro, Italy
| | - Francesco Luzza
- Department of Health Sciences, Magna Grecia University, Catanzaro, Italy
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Liptak P, Nosakova L, Rosolanka R, Skladany L, Banovcin P. Acute-on-chronic liver failure in patients with severe acute respiratory syndrome coronavirus 2 infection. World J Hepatol 2023; 15:41-51. [PMID: 36744167 PMCID: PMC9896507 DOI: 10.4254/wjh.v15.i1.41] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/03/2022] [Accepted: 11/29/2022] [Indexed: 01/16/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a significant impact on the lives of millions of people, especially those with other concomitant diseases, such as chronic liver diseases. To date, seven coronaviruses have been identified to infect humans. The main site of pathological action of these viruses is lung tissue. However, a substantial number of studies have proven that SARS-CoV-2 shows affinity towards several organs, including the gastrointestinal tract and the liver. The current state of evidence points to several proposed mechanisms of liver injury in patients with COVID-19 and their combination. Liver impairment is considered to be the result of the direct effect of the virus on the hepatic tissue cells, a systemic reaction consisting of inflammation, hypoxia and cytokine storm, drug-induced liver injury, with the possible contribution of a perturbed gut-liver axis. Reactivation of chronic hepatic disease could be another factor for liver impairment in patients with SARS-CoV-2 infection. Acute-on-chronic liver failure (ACLF) is a relatively new syndrome that occurs in 10%–30% of all hospitalized patients with chronic liver disease. It is crucial to recognize high-risk patients due to the increased morbidity and mortality in these cases. Several published studies have reported virus infection as a trigger factor for ACLF. However, to date, there are few relevant studies describing the presence of ACLF in patients with acute SARS-CoV-2 infection. In this minireview we summarize the current state of knowledge regarding the relation between ACLF and acute SARS-CoV-2 infection.
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Affiliation(s)
- Peter Liptak
- Clinic of Internal Medicine-Gastroenterology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
| | - Lenka Nosakova
- Clinic of Internal Medicine-Gastroenterology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
| | - Robert Rosolanka
- Clinic of Infectology and Travel Medicine, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
| | - Lubomir Skladany
- Department of Internal Medicine II, Division Hepatology, Gastroenterology and Liver Transplantation, FD Roosevelt University Hospital of Slovak Medical University, Banska Bystrica 97517, Slovakia
| | - Peter Banovcin
- Clinic of Internal Medicine-Gastroenterology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
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TESTINO G, PELLICANO R. SARS-CoV-2 infection and alcohol consumption: a warning for pulmonologists. MINERVA RESPIRATORY MEDICINE 2022; 61. [DOI: 10.23736/s2784-8477.22.02008-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
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Marano G, Traversi G, Gaetani E, Pola R, Claro AE, Mazza M. Alcohol use disorder and liver injury related to the COVID-19 pandemic. World J Hepatol 2022; 14:1875-1883. [PMID: 36340751 PMCID: PMC9627438 DOI: 10.4254/wjh.v14.i10.1875] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 09/26/2022] [Accepted: 10/11/2022] [Indexed: 02/06/2023] Open
Abstract
Alcohol use disorder is a complex and heterogeneous phenomenon that can be studied from several points of view by focusing on its different components. Alcohol is a hepatotoxin whose metabolism creates profound alterations within the hepatocyte. The liver is the central organ in the metabolism of alcohol, a process that also involves other organs and tissues such as the brain, heart and muscles, but the most relevant organ is the liver. The anatomopathological alterations in the liver associated with the prolonged use of alcohol range from the simple accumulation of neutral fats in the hepatocytes, to cirrhosis and hepatocellular carcinoma. Alcohol abuse frequently leads to liver disease such as steatosis, steatohepatitis, fibrosis, cirrhosis, and tumors. Following the spread of coronavirus disease 2019 (COVID-19), there was an increase in alcohol consumption, probably linked to the months of lockdown and smart working. It is known that social isolation leads to a considerable increase in stress, and it is also recognized that high levels of stress can result in an increase in alcohol intake. Cirrhotic patients or subjects with liver cancer are immunocompromised, so they may be more exposed to COVID-19 infection with a worse prognosis. This review focuses on the fact that the COVID-19 pandemic has made the emergence of alcohol-induced liver damage a major medical and social problem.
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Affiliation(s)
- Giuseppe Marano
- Department of Geriatrics, Neuroscience and Orthopedics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Gianandrea Traversi
- Dipartimento di Medicina di Laboratorio, UOSD Genetica Medica, Ospedale Generale “San Giovanni Calibita” Fatebenefratelli, Rome 00186, Italy
| | - Eleonora Gaetani
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Roberto Pola
- Division of Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Angelo Emilio Claro
- Department of Geriatrics, Neuroscience and Orthopedics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Marianna Mazza
- Department of Geriatrics, Neuroscience and Orthopedics, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
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Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology/Alcohological Regional Centre, ASL3 Liguria c/o San Martino Hospital, Genoa, Italy - .,Centro Studi "Mutual-self-help, community programs and caregiver training", ASL3 Liguria, Genoa, Italy -
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Testino G, Pellicano R. SARS-CoV-2, autoimmunity and liver disease. Minerva Gastroenterol (Torino) 2022; 68:338-339. [PMID: 35144366 DOI: 10.23736/s2724-5985.22.03147-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology, Alcohological Regional Center, ASL3, IRCCS San Martino University Hospital, Genoa, Italy -
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette-S. Giovanni Antica Sede Hospital, Turin, Italy
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Testino G, Pellicano R. Alcohol consumption: confirmed as cause of increased COVID-19 disease severity. Minerva Gastroenterol (Torino) 2022; 68:232-233. [PMID: 35754394 DOI: 10.23736/s2724-5985.22.03143-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology, Alcohological Regional Center, Polyclinic San Martino Hospital, ASL3, Genoa, Italy -
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy
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Elnaggar M, Abomhya A, Elkhattib I, Dawoud N, Doshi R. COVID-19 and liver diseases, what we know so far. World J Clin Cases 2022; 10:3969-3980. [PMID: 35665122 PMCID: PMC9131221 DOI: 10.12998/wjcc.v10.i13.3969] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 10/15/2021] [Accepted: 03/26/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) pneumonia outbreak started in December 2019. On March 12, 2020, the World Health Organization (WHO) declared that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a pandemic, and as of May 2021, SARS-CoV-2 has infected over 167.3 million patients, including 3.4 million deaths, reported to WHO. In this review, we will focus on the relationship between SARS-CoV-2 infection and the liver. We will discuss how chronic liver diseases affect the COVID-19 disease course and outcomes. We will also discuss the SARS-CoV-2 effects on the liver, mechanisms of acute liver injury, and potential management plans.
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Affiliation(s)
- Mohamed Elnaggar
- Department of Internal Medicine, University of Nevada Reno School of Medicine, Reno, NV 89052, United States
| | - Ahmed Abomhya
- Department of Internal Medicine, The Brooklyn Hospital Center, Brooklyn, NY 11200, United States
| | - Ismail Elkhattib
- Department of Internal Medicine, University of Connecticut, Farmington, CT 06030, United States
| | - Nabila Dawoud
- Department of Internal Medicine, University of Kentucky, Lexington, KY 40508, United States
| | - Rajkumar Doshi
- Department of Cardiology, St Joseph's University Medical Center, Paterson, NJ 07503, United States
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Testino G, DI Biagio A, Fagoonee S, Pellicano R. SARS-CoV-2, alcohol consumption and liver injury. Minerva Med 2021; 113:333-342. [PMID: 34672164 DOI: 10.23736/s0026-4806.21.07809-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Angiotensin converting enzyme 2 (ACE2) receptor sites for severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), responsible for the disease called Covid-19 are present in the liver, especially in correspondence with cholangiocytes. Liver damage during SARS-Cov-2 infection can be due to several mechanism including direct cytopathic effect, synergy of intestinal damage / liver damage (lipopolysaccharides / Kupfer and other cells interaction), uncontrolled immune reaction (lymphopenia and significant increase in C reactive protein, ferritin, lactate dehydrogenase, D-dimer, interleukin (IL)-6, IL- 10, IL-2, interferon-gamma ...), sepsis, drug-induced liver injury, hypoxia and thromboembolic events. An increase in aspartate aminotransferase (AST) from 14 to 58% and alanine transaminase (ALT) from 21 to 76% has been reported. The mean level of AST and ALT has been reported to be higher in patients admitted to the intensive care unit than in those hospitalized in the ordinary hospital unit. The correlation of liver damage with worse prognosis is now a known fact, confirmed by numerous studies, in all pandemic phases. The consumption of alcohol reduces both innate and acquired immune activity and it has been hypothesized that this habit is correlated with liver increase of ACE2 receptors. Furthermore, non-alcoholic and alcoholic steatosis / steatohepatitis is a breeding ground for the development of oxidative stress. In this context, any encounter with SARS-Cov-2 infection can support and aggravate the systemic cytokine tsunami.
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Affiliation(s)
- Gianni Testino
- Addiction and Hepatology Unit, Alcohological Regional Centre, ASL3 Liguria c/o Polyclinic San Martino Hospital, Genova, Italy -
| | - Antonio DI Biagio
- Infectious Diseases Unit, University of Genoa and Polyclinic San Martino Hospital, Genova, Italy
| | - Sharmila Fagoonee
- Institute for Biostructure and Bioimaging, National Research Council, Molecular Biotechnology Center, Turin, Italy
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