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Balaji D, Balakrishnan R, Srinivasan D, Subbarayan R, Shrestha R, Srivastava N, Chauhan A. The Impact of SARS-CoV-2 on Liver Diseases and Potential Phytochemical Treatments. INFECTIOUS MICROBES AND DISEASES 2024; 6:177-188. [DOI: 10.1097/im9.0000000000000161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Abstract
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has brought about numerous challenges. One of these challenges is the impact of SARS-CoV-2 on the liver. Although this virus primarily affects the lungs, it can induce elevated transaminase levels and the development of scar tissue in the liver, exacerbating preexisting liver conditions. Individuals with preexisting conditions, such as nonalcoholic fatty liver disease, alcohol-induced liver disease and hepatocellular carcinoma, face an increased risk of mortality from COVID-19. However, drugs currently used to treat COVID-19 have undesirable side effects, which make them unsuitable for patients with preexisting liver conditions. In this review, we explore the potential of phytochemicals, such as apigenin, berberine, curcumin, epigallocatechin-3-gallate, quercetin, resveratrol and silymarin, for treatment of the liver conditions, including nonalcoholic fatty liver disease, alcohol-induced liver disease and hepatocellular carcinoma. We also discuss significant associations between phytochemicals and COVID-19 by depicting their molecular interactions. Based on the discussed overlapping functions, it is important to assess the therapeutic efficacy of phytochemicals that possess hepatoprotective properties as potential alternative treatments for COVID-19.
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Affiliation(s)
- Dhanvee Balaji
- Centre for Advanced Biotherapeutics and Regenerative Medicine, Faculty of Research, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India
| | - Ranjith Balakrishnan
- Centre for Advanced Biotherapeutics and Regenerative Medicine, Faculty of Research, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India
| | - Dhasarathdev Srinivasan
- Centre for Advanced Biotherapeutics and Regenerative Medicine, Faculty of Research, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India
| | | | | | | | - Ankush Chauhan
- Centre for Herbal Pharmacology and Environmental Sustainability, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India
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Mohamed Hassan AS, Abo Gaziah SSA, Ezzelregal Awad HG, Hegab Abdelhady SM, Talaat Elkhafif NA, Hassan Mostafa NB. "Ultrastructural changes of platelets in COVID-19 and chronic viral hepatitis patients ". Ultrastruct Pathol 2024; 48:234-245. [PMID: 38619195 DOI: 10.1080/01913123.2024.2342437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 04/09/2024] [Indexed: 04/16/2024]
Abstract
Platelet-viral interactions are evolving as a new concern. Coagulation disorder is a major consequence of the COVID-19 infection. In chronic hepatitis virus infections, defect in coagulation factors, thrombocytopenia and platelet function abnormalities are common. A SARS-CoV-2 infection on top of chronic viral hepatitis infection can be common in areas where viral hepatitis is endemic. Here, we investigate the platelet ultrastructural changes and estimate the serum platelet factor-4 (PF-4), ferritin, CRP, and D-dimer in COVID-19 patients (n = 60), COVID-19 patients with associated chronic viral hepatitis (n = 20), and healthy subjects (n = 20). Ultrastructural changes were demonstrated in all test groups, denoting platelet activation. In chronic viral hepatitis patients, Platelet ultrastrustural apoptotic changes were also seen. Significantly high levels of PF-4 were confirmed in moderate and severe COVID-19 patients (P.value <0.001), with a cut off value of 17 ng/ml for predicting disease severity. A positive correlation of PF-4 with the level of serum ferritin, CRP, and D-dimer (p value < 0.001) was noted, while negatively correlated with platelet count and platelet granule count (p value < 0.001). In our study, chronic viral hepatitis patients presented mild COVID-19 signs, and their PF-4 level was comparable with the subgroup of mild COVID-19 infection. The platelet's critical role in COVID-19 coagulopathy and chronic viral hepatitis is evidenced by the ultrastructural changes and the high levels of PF4. Moreover, a dual viral infection poses a substantial burden on the platelets, necessitating close monitoring of the patient's coagulation profile.
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3
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Mongare N, Orare K, Busaidy S, Sokwala A, Opio C. Plasma Exchange for Refractory Pruritus Due to Drug-Induced Chronic Cholestasis Following Azithromycin Misuse in COVID-19 Infection. Cureus 2024; 16:e60884. [PMID: 38910696 PMCID: PMC11193081 DOI: 10.7759/cureus.60884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2024] [Indexed: 06/25/2024] Open
Abstract
Azithromycin can result in severe cholestatic liver disease. We describe two cases of intractable pruritus secondary to drug-induced cholestatic liver injury, unresponsive to symptomatic medical therapy, necessitating and responding well to therapeutic plasma exchange (TPE). The first is a case of a 60-year-old male known to have stable chronic lymphocytic leukemia (CLL) and benign prostatic hyperplasia, and the second is a 46-year-old female known to have primary biliary cirrhosis (PBC) who presented at six weeks and two weeks, respectively, post-mild-COVID-19 pneumonia. Their drug histories were positive for over-the-counter (OCT) azithromycin use during the COVID-19 pneumonia period. They presented with a two-week history of severe itching, associated with sleep deprivation and impaired quality of life. Liver function tests revealed a cholestatic pattern of liver injury. Pruritus remained refractory to multiple lines of treatment including bile acid sequestrants and antihistamines. Rapid and long-lasting relief of the patient's symptoms was observed after three sessions of TPE. Our cases highlight medically recalcitrant cholestatic pruritus as an adverse effect of antibiotic misuse during the recent COVID-19 pandemic. Sustained symptomatic improvements were seen after TPE.
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Affiliation(s)
| | - Kelvin Orare
- Internal Medicine, Aga Khan University, Nairobi, KEN
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Singh L, Kumar A, Rai M, Basnet B, Rai N, Khanal P, Lai KS, Cheng WH, Asaad AM, Ansari S. Spectrum of COVID-19 induced liver injury: A review report. World J Hepatol 2024; 16:517-536. [PMID: 38689748 PMCID: PMC11056898 DOI: 10.4254/wjh.v16.i4.517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 01/20/2024] [Accepted: 02/28/2024] [Indexed: 04/24/2024] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has caused changes in the global health system, causing significant setbacks in healthcare systems worldwide. This pandemic has also shown resilience, flexibility, and creativity in reacting to the tragedy. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection targets most of the respiratory tract, resulting in a severe sickness called acute respiratory distress syndrome that may be fatal in some individuals. Although the lung is the primary organ targeted by COVID-19 viruses, the clinical aspect of the disease is varied and ranges from asymptomatic to respiratory failure. However, due to an unorganized immune response and several affected mechanisms, the liver may also experience liver cell injury, ischemic liver dysfunction, and drug-induced liver injury, which can result in respiratory failure because of the immune system's disordered response and other compromised processes that can end in multisystem organ failure. Patients with liver cirrhosis or those who have impaired immune systems may be more likely than other groups to experience worse results from the SARS-CoV-2 infection. We thus intend to examine the pathogenesis, current therapy, and consequences of liver damage concerning COVID-19.
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Affiliation(s)
- Lokjan Singh
- Department of Microbiology, Karnali Academy of Health Science, Teaching Hospital, Jumla 21200, Karnali, Nepal
| | - Anil Kumar
- Department of Microbiology, Karnali Academy of Health Science, Teaching Hospital, Jumla 21200, Karnali, Nepal
| | - Maya Rai
- Department of Microbiology, Karnali Academy of Health Science, Teaching Hospital, Jumla 21200, Karnali, Nepal
| | - Bibek Basnet
- Health Sciences, Asian College of Advance Studies, Purbanchal University, Satdobato 24122, Lalitpur, Nepal
| | - Nishant Rai
- Department of Biotechnology, Graphic Era (Deemed to be University), Dehradun 248002, Uttarakhand, India
| | - Pukar Khanal
- Department of Pharmacology & Toxicology, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Belagavi 590010, Karnataka, India
| | - Kok-Song Lai
- Division of Health Sciences, Abu Dhabi Women's College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates
| | - Wan-Hee Cheng
- Health and Life Sciences, INTI International University, Nilai 71800, Malaysia
| | - Ahmed Morad Asaad
- Department of Microbiology, College of Medicine, Zagazig University, Zagazig 44519, Egypt
| | - Shamshul Ansari
- Division of Health Sciences, Abu Dhabi Women's College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates.
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5
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Lin J, Fan A, Yifu Z, Xie Q, Hong L, Zhou W. BTF3L4 Overexpression Mediates APAP-induced Liver Injury in Mouse and Cellular Models. J Clin Transl Hepatol 2024; 12:245-256. [PMID: 38426192 PMCID: PMC10899873 DOI: 10.14218/jcth.2023.00342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Revised: 11/01/2023] [Accepted: 11/17/2023] [Indexed: 03/02/2024] Open
Abstract
Background and Aims Acetaminophen (APAP)-induced liver injury (AILI) has an increasing incidence worldwide. However, the mechanisms contributing to such liver injury are largely unknown and no targeted therapy is currently available. The study aimed to investigate the effect of BTF3L4 overexpression on apoptosis and inflammation regulation in vitro and in vivo. Methods We performed a proteomic analysis of the AILI model and found basic transcription factor 3 like 4 (BTF3L4) was the only outlier transcription factor overexpressed in the AILI model in mice. BTF3L4 overexpression increased the degree of liver injury in the AILI model. Results BTF3L4 exerts its pathogenic effect by inducing an inflammatory response and damaging mitochondrial function. Increased BTF3L4 expression increases the degree of apoptosis, reactive oxygen species generation, and oxidative stress, which induces cell death and liver injury. The damage of mitochondrial function by BTF3L4 triggers a cascade of events, including reactive oxygen species accumulation and oxidative stress. According to the available AILI data, BTF3L4 expression is positively associated with inflammation and may be a potential biomarker of AILI. Conclusions Our results suggest that BTF3L4 is a pathogenic factor in AILI and may be a potential diagnostic maker for AILI.
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Affiliation(s)
- Junchao Lin
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Military Medical University, Xi’an, Shaanxi, China
| | - Aqiang Fan
- Department of Digestive Surgery, Xijing Hospital, Air Force Military Medical University, Xi’an, Shaanxi, China
| | - Zhujin Yifu
- Department of Digestive Surgery, Xijing Hospital, Air Force Military Medical University, Xi’an, Shaanxi, China
| | - Qibing Xie
- Department of Digestive Surgery, Xijing Hospital, Air Force Military Medical University, Xi’an, Shaanxi, China
| | - Liu Hong
- Department of Digestive Surgery, Xijing Hospital, Air Force Military Medical University, Xi’an, Shaanxi, China
| | - Wei Zhou
- Department of Digestive Surgery, Xijing Hospital, Air Force Military Medical University, Xi’an, Shaanxi, China
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Brilakis L, Theofilogiannakou E, Lykoudis PM. Current remarks and future directions on the interactions between metabolic dysfunction-associated fatty liver disease and COVID-19. World J Gastroenterol 2024; 30:1480-1487. [PMID: 38617460 PMCID: PMC11008415 DOI: 10.3748/wjg.v30.i11.1480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 01/30/2024] [Accepted: 03/04/2024] [Indexed: 03/21/2024] Open
Abstract
During the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, particular interest rose regarding the interaction between metabolic dysfunction-associated fatty liver disease (MAFLD) and the COVID-19 infection. Several studies highlighted the fact that individuals with MAFLD had higher probability of severe acute respiratory syndrome coronavirus 2 infection and more severe adverse clinical outcomes. One of the proposed mechanisms is the inflammatory response pathway, especially the one involving cytokines, such as interleukin 6, which appeared particularly elevated in those patients and was deemed responsible for additional insult to the already damaged liver. This should increase our vigilance in terms of early detection, close follow up and early treatment for individuals with MAFLD and COVID-19 infection. In the direction of early diagnosis, biomarkers such as cytokeratin-18 and scoring systems such as Fibrosis-4 index score are proposed. COVID-19 is a newly described entity, expected to be of concern for the years to come, and MAFLD is a condition with an ever-increasing impact. Delineating the interaction between these two entities should be brought into the focus of research. Reducing morbidity and mortality of patients with COVID-19 and MAFLD should be the ultimate objective, and the optimal way to achieve this is by designing evidence-based prevention and treatment policies.
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Affiliation(s)
- Leonidas Brilakis
- School of Medicine, National & Kapodistrian University of Athens, Athens 11527, Greece
| | | | - Panagis M Lykoudis
- School of Medicine, National & Kapodistrian University of Athens, Athens 11527, Greece
- Division of Surgery & Interventional Science, University College London, London WC1E 6BT, United Kingdom
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Mengual-Moreno E, Nava M, Manzano A, Ariza D, D’Marco L, Castro A, Marquina MA, Hernández M, Corredor-Pereira C, Checa-Ros A, Bermúdez V. Pancreatic and Hepatic Injury in COVID-19: A Worse Prognosis in NAFLD Patients? Biomedicines 2024; 12:283. [PMID: 38397885 PMCID: PMC10887136 DOI: 10.3390/biomedicines12020283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Revised: 12/13/2023] [Accepted: 01/14/2024] [Indexed: 02/25/2024] Open
Abstract
The novel disease produced by SARS-CoV-2 mainly harms the respiratory tract, but it has shown the capacity to affect multiple organs. Epidemiologic evidence supports the relationship between Coronavirus Disease 2019 (COVID-19) and pancreatic and hepatic injury development, identified by alterations in these organ function markers. In this regard, it is important to ascertain how the current prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) might affect COVID-19 evolution and complications. Although it is not clear how SARS-CoV-2 affects both the pancreas and the liver, a multiplicity of potential pathophysiological mechanisms seem to be implicated; among them, a direct viral-induced injury to the organ involving liver and pancreas ACE2 expression. Additionally, immune system dysregulation, coagulopathies, and drugs used to treat the disease could be key for developing complications associated with the patient's clinical decline. This review aims to provide an overview of the available epidemiologic evidence regarding developing liver and pancreatic alterations in patients with COVID-19, as well as the possible role that NAFLD/NASH might play in the pathophysiological mechanisms underlying some of the complications associated with COVID-19. This review employed a comprehensive search on PubMed using relevant keywords and filters. From the initial 126 articles, those aligning with the research target were selected and evaluated for their methodologies, findings, and conclusions. It sheds light on the potential pathophysiological mechanisms underlying this relationship. As a result, it emphasises the importance of monitoring pancreatic and hepatic function in individuals affected by COVID-19.
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Affiliation(s)
- Edgardo Mengual-Moreno
- Biological Research Institute “Doctors Orlando Castejon and Haydee V Castejon”, Universidad del Zulia, Maracaibo 4002, Venezuela;
| | - Manuel Nava
- Endocrine and Metabolic Diseases Research Center, School of Medicine, Universidad del Zulia, Maracaibo 4002, Venezuela; (M.N.); (A.M.); (D.A.); (A.C.); (M.A.M.); (M.H.)
| | - Alexander Manzano
- Endocrine and Metabolic Diseases Research Center, School of Medicine, Universidad del Zulia, Maracaibo 4002, Venezuela; (M.N.); (A.M.); (D.A.); (A.C.); (M.A.M.); (M.H.)
| | - Daniela Ariza
- Endocrine and Metabolic Diseases Research Center, School of Medicine, Universidad del Zulia, Maracaibo 4002, Venezuela; (M.N.); (A.M.); (D.A.); (A.C.); (M.A.M.); (M.H.)
| | - Luis D’Marco
- Grupo de Investigación en Enfermedades Cardiorenales y Metabólicas, Departamento de Medicina y Cirugía, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, Calle Santiago Ramón y Cajal s/n, 46115 Alfara del Patriarca, Valencia, Spain; (L.D.); (A.C.-R.)
| | - Ana Castro
- Endocrine and Metabolic Diseases Research Center, School of Medicine, Universidad del Zulia, Maracaibo 4002, Venezuela; (M.N.); (A.M.); (D.A.); (A.C.); (M.A.M.); (M.H.)
| | - María A. Marquina
- Endocrine and Metabolic Diseases Research Center, School of Medicine, Universidad del Zulia, Maracaibo 4002, Venezuela; (M.N.); (A.M.); (D.A.); (A.C.); (M.A.M.); (M.H.)
| | - Marlon Hernández
- Endocrine and Metabolic Diseases Research Center, School of Medicine, Universidad del Zulia, Maracaibo 4002, Venezuela; (M.N.); (A.M.); (D.A.); (A.C.); (M.A.M.); (M.H.)
| | | | - Ana Checa-Ros
- Grupo de Investigación en Enfermedades Cardiorenales y Metabólicas, Departamento de Medicina y Cirugía, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, Calle Santiago Ramón y Cajal s/n, 46115 Alfara del Patriarca, Valencia, Spain; (L.D.); (A.C.-R.)
| | - Valmore Bermúdez
- Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla 080001, Colombia;
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8
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Tammam MA, Pereira F, Aly O, Sebak M, Diab YM, Mahdy A, El-Demerdash A. Investigating the hepatoprotective potentiality of marine-derived steroids as promising inhibitors of liver fibrosis. RSC Adv 2023; 13:27477-27490. [PMID: 37711373 PMCID: PMC10498675 DOI: 10.1039/d3ra04843h] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 08/27/2023] [Indexed: 09/16/2023] Open
Abstract
It has been reported that organic extracts derived from soft corals belonging to the genus Sarcophyton have exhibited a wide range of therapeutic characteristics. Based on biochemical and histological techniques, we aimed to assess the hepatoprotective role of the organic extract and its principal steroidal contents derived from the Red Sea soft coral Sarcophyton glaucum on acetaminophen-induced liver fibrosis in rats. Serum liver function parameters (ALT, AST, ALP and total bilirubin) were quantified using a spectrophotometer, and both alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) levels were determined by using enzyme-linked immunosorbent assay (ELISA) kits while transformed growth factor beta (TGF-β) and tumor necrosis factor α (TNF-α) in liver tissue homogenate were determined using ELISA, and TGF-β and TNF-α gene expression in liver tissue was determined using real-time PCR following extraction and purification. Histopathological alterations in hepatic tissue were also examined under a microscope. In order to prioritize the isolation and characterization of the most promising marine steroids from the organic extract of the Red Sea soft coral Sarcophyton glaucum as hepatoprotective agents, a computational approach was employed. This approach involved molecular docking (MDock) and analysis of the structure-activity relationship (SAR) against glutathione-S-transferase (GST) and Cu-Zn human superoxide dismutase (Cu-ZnSOD) enzymes. Although the major role in the detoxification of foreign chemicals and toxic metabolites of GST and SOD enzymes is known, there is a lack of knowledge about the mode of action of the hepatoprotective process and those of the targets involved. The present study investigated the multiple interactions of a series of marine steroids with the GST and SOD enzymes, in order to reveal insights into the process of hepatoprotection.
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Affiliation(s)
- Mohamed A Tammam
- Department of Biochemistry, Faculty of Agriculture, Fayoum University Fayoum 63514 Egypt
| | - Florbela Pereira
- LAQV REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa 2829516 Caparica Portugal
| | - Omnia Aly
- Department of Medical Biochemistry, National Research Centre Cairo 12622 Egypt
| | - Mohamed Sebak
- Microbiology and Immunology Department, Faculty of Pharmacy, Beni-Suef University Egypt
| | - Yasser M Diab
- Department of Biochemistry, Faculty of Agriculture, Fayoum University Fayoum 63514 Egypt
| | - Aldoushy Mahdy
- Department of Zoology, Faculty of Science, Al-Azhar University (Assiut Branch) Assiut 71524 Egypt
| | - Amr El-Demerdash
- Division of Organic Chemistry, Department of Chemistry, Faculty of Sciences, Mansoura University Mansoura 35516 Egypt
- Department of Biochemistry and Metabolism, the John Innes Centre Norwich Research Park Norwich NR4 7UH UK
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9
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Shi Y, Wang M, Wu L, Li X, Liao Z. COVID-19 associated liver injury: An updated review on the mechanisms and management of risk groups. LIVER RESEARCH 2023; 7:207-215. [PMID: 39958382 PMCID: PMC11792068 DOI: 10.1016/j.livres.2023.07.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 06/11/2023] [Accepted: 07/09/2023] [Indexed: 09/02/2023]
Abstract
Coronavirus disease 2019 (COVID-19) has been associated with various liver injury cases worldwide. To date, the prevalence, mechanism, clinical manifestations, diagnosis, and outcomes of COVID-19-induced liver injury in various at-risk groups are not well defined. Liver injury may arise in the prevention and treatment of COVID-19 from direct causes such as viral infection and indirect causes such as systemic inflammation, hypoxic changes, and drugs that exacerbate any pre-existing liver disease. Studies have found that patients with underlying liver disease are at higher risk of COVID-19-induced liver injury. Certain condition of cardiopulmonary and metabolic diseases and vulnerable stages in lifespan may also involve in the development of COVID-19-induced liver injury. This review summarized studies of COVID-19-induced liver injury in different at-risk groups regarding their clinical characteristics, parameters, and correlations of the severity with these indicators and signs as well as potential treatment suggestions, to increase attention to physiological and pathological conditions and continue liver function monitoring as they can help in strengthening early supportive treatment and reducing the incidence of adverse outcomes.
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Affiliation(s)
- Yue Shi
- Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Mina Wang
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, China
| | - Liqun Wu
- Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China
| | - Xuexin Li
- Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden
| | - Zehuan Liao
- School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
- Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden
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10
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Aghamohamadi N, Shahba F, Zarezadeh Mehrabadi A, Khorramdelazad H, Karimi M, Falak R, Emameh RZ. Age-dependent immune responses in COVID-19-mediated liver injury: focus on cytokines. Front Endocrinol (Lausanne) 2023; 14:1139692. [PMID: 37654571 PMCID: PMC10465349 DOI: 10.3389/fendo.2023.1139692] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 07/21/2023] [Indexed: 09/02/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is potentially pathogenic and causes severe symptoms; in addition to respiratory syndromes, patients might experience other severe conditions such as digestive complications and liver complications injury. The abnormality in the liver is manifested by hepatobiliary dysfunction and enzymatic elevation, which is associated with morbidity and mortality. The direct cytopathic effect, immune dysfunction, cytokine storm, and adverse effects of therapeutic regimens have a crucial role in the severity of liver injury. According to aging and immune system alterations, cytokine patterns may also change in the elderly. Moreover, hyperproduction of cytokines in the inflammatory response to SARS-CoV-2 can lead to multi-organ dysfunction. The mortality rate in elderly patients, particularly those with other comorbidities, is also higher than in adults. Although the pathogenic effect of SARS-CoV-2 on the liver has been widely studied, the impact of age and immune-mediated responses at different ages remain unclear. This review discusses the association between immune system responses in coronavirus disease 2019 (COVID-19) patients of different ages and liver injury, focusing on cytokine alterations.
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Affiliation(s)
- Nazanin Aghamohamadi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Faezeh Shahba
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Zarezadeh Mehrabadi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Khorramdelazad
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Milad Karimi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Falak
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Zolfaghari Emameh
- Department of Energy and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
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11
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Imam MT, Almalki ZS, Alzahrani AR, Al-Ghamdi SS, Falemban AH, Alanazi IM, Shahzad N, Muhammad Alrooqi M, Jabeen Q, Shahid I. COVID-19 and severity of liver diseases: Possible crosstalk and clinical implications. Int Immunopharmacol 2023; 121:110439. [PMID: 37315370 PMCID: PMC10247890 DOI: 10.1016/j.intimp.2023.110439] [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: 03/20/2023] [Revised: 05/30/2023] [Accepted: 05/31/2023] [Indexed: 06/16/2023]
Abstract
COVID-19-infected individuals and those who recovered from the infection have been demonstrated to have elevated liver enzymes or abnormal liver biochemistries, particularly with preexisting liver diseases, liver metabolic disorders, viral hepatitis, and other hepatic comorbidities. However, possible crosstalk and intricate interplay between COVID-19 and liver disease severity are still elusive, and the available data are murky and confined. Similarly, the syndemic of other blood-borne infectious diseases, chemical-induced liver injuries, and chronic hepatic diseases continued to take lives while showing signs of worsening due to the COVID-19 crisis. Moreover, the pandemic is not over yet and is transitioning to becoming an epidemic in recent years; hence, monitoring liver function tests (LFTs) and assessing hepatic consequences of COVID-19 in patients with or without liver illnesses would be of paramount interest. This pragmatic review explores the correlations between COVID-19 and liver disease severity based on abnormal liver biochemistries and other possible mechanisms in individuals of all ages from the emergence of the COVID-19 pandemic to the post-pandemic period. The review also alludes to clinical perspectives of such interactions to curb overlapping hepatic diseases in people who recovered from the infection or living with long COVID-19.
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Affiliation(s)
- Mohammad T Imam
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Ziyad S Almalki
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Abdullah R Alzahrani
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Saeed S Al-Ghamdi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Alaa H Falemban
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Ibrahim M Alanazi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Naiyer Shahzad
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | | | - Qaisar Jabeen
- Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Imran Shahid
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia.
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12
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Buchynskyi M, Kamyshna I, Oksenych V, Zavidniuk N, Kamyshnyi A. The Intersection of COVID-19 and Metabolic-Associated Fatty Liver Disease: An Overview of the Current Evidence. Viruses 2023; 15:v15051072. [PMID: 37243158 DOI: 10.3390/v15051072] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 04/23/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
The global population is currently experiencing the impact of the SARS-CoV-2 coronavirus, which has caused the Coronavirus Disease 2019 (COVID-19) pandemic. With our profound comprehension of COVID-19, encompassing the involvement sequence of the respiratory tract, gastrointestinal system, and cardiovascular apparatus, the multiorgan symptoms of this infectious disease have been discerned. Metabolic-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a pervasive public health concern intricately linked with metabolic dysregulation and estimated to afflict one-fourth of the global adult population. The burgeoning focus on the association between COVID-19 and MAFLD is justified by the potential role of the latter as a risk factor for both SARS-CoV-2 infection and the subsequent emergence of severe COVID-19 symptoms. Investigations have suggested that changes in both innate and adaptive immune responses among MAFLD patients may play a role in determining the severity of COVID-19. The remarkable similarities observed in the cytokine pathways implicated in both diseases imply the existence of shared mechanisms governing the chronic inflammatory responses characterizing these conditions. The effect of MAFLD on the severity of COVID-19 illness remains uncertain, as indicated by conflicting results in cohort investigations.
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Affiliation(s)
- Mykhailo Buchynskyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Iryna Kamyshna
- Department of Medical Rehabilitation, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Valentyn Oksenych
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway
| | - Nataliia Zavidniuk
- Department of Infectious Diseases with Epidemiology, Dermatology and Venerology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Aleksandr Kamyshnyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
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13
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Montori M, Baroni GS, Santori P, Di Giampaolo C, Ponziani F, Abenavoli L, Scarpellini E. Liver Damage and COVID-19: At Least a “Two-Hit” Story in Systematic Review. Curr Issues Mol Biol 2023; 45:3035-3047. [PMID: 37185723 PMCID: PMC10136465 DOI: 10.3390/cimb45040199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 03/29/2023] [Accepted: 03/30/2023] [Indexed: 04/07/2023] Open
Abstract
COVID-19 pandemic waves have hit on our lives with pulmonary and, also, gastrointestinal symptoms. The latter also includes acute liver damage linked to direct SARS-CoV-2 action and/or drug-induced (DILI) in the frame of pre-existing chronic liver disease. We aimed to review literature data regarding liver damage during COVID-19. We conducted a systematic search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials and case series using the following keywords and acronyms and their associations: liver disease, COVID-19, acute liver damage, drug-induced liver injury, antivirals. Acute liver damage due to SARS-CoV-2 infection is common among COVID-19 patients and is generally self-limiting. However, chronic hepatic diseases, such as metabolic-associated fatty liver disease (MAFLD), are associated with a less favorable prognosis, especially when alkaline phosphatases show a significant rise. Pathophysiology of COVID-19 liver damage is multifaceted and helps understand differences in liver derangement among patients. Thus, early recognition, monitoring and treatment of liver damage are crucial in these patients. In the frame of a not-ending pandemic sustained by SARS-CoV-2, it is crucial to recognize acute hepatic decompensation due to the virus and/or drugs used for COVID-19 treatment.
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Affiliation(s)
- Michele Montori
- Transplant and Hepatic Damage Unit, Polytechincs University of Marche, 60121 Ancona, Italy
| | | | - Pierangelo Santori
- Hepatology and Internal Medicine Unit, Madonna del Soccorso General Hospital, 00168 San Benedetto del Tronto, Italy
| | - Catia Di Giampaolo
- Hepatology and Internal Medicine Unit, Madonna del Soccorso General Hospital, 00168 San Benedetto del Tronto, Italy
| | - Francesca Ponziani
- Digestive Disease Center (C.E.M.A.D.), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Translational Medicine and Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Ludovico Abenavoli
- Department of Health Sciences, University Magna Græcia, 88100 Catanzaro, Italy
| | - Emidio Scarpellini
- Hepatology and Internal Medicine Unit, Madonna del Soccorso General Hospital, 00168 San Benedetto del Tronto, Italy
- Translational Research Center for Gastrointestinal Disorders, Gasthuisberg University Hospital, KULeuven, 3000 Lueven, Belgium
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14
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Qudus MS, Tian M, Sirajuddin S, Liu S, Afaq U, Wali M, Liu J, Pan P, Luo Z, Zhang Q, Yang G, Wan P, Li Y, Wu J. The roles of critical pro-inflammatory cytokines in the drive of cytokine storm during SARS-CoV-2 infection. J Med Virol 2023; 95:e28751. [PMID: 37185833 DOI: 10.1002/jmv.28751] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 03/17/2023] [Accepted: 04/07/2023] [Indexed: 05/17/2023]
Abstract
In patients with severe COVID-19, acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), and even mortality can result from cytokine storm, which is a hyperinflammatory medical condition caused by the excessive and uncontrolled release of pro-inflammatory cytokines. High levels of numerous crucial pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-2, IL-6, tumor necrosis factor-α, interferon (IFN)-γ, IFN-induced protein 10 kDa, granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant protein-1, and IL-10 and so on, have been found in severe COVID-19. They participate in cascade amplification pathways of pro-inflammatory responses through complex inflammatory networks. Here, we review the involvements of these critical inflammatory cytokines in SARS-CoV-2 infection and discuss their potential roles in triggering or regulating cytokine storm, which can help to understand the pathogenesis of severe COVID-19. So far, there is rarely effective therapeutic strategy for patients with cytokine storm besides using glucocorticoids, which is proved to result in fatal side effects. Clarifying the roles of key involved cytokines in the complex inflammatory network of cytokine storm will help to develop an ideal therapeutic intervention, such as neutralizing antibody of certain cytokine or inhibitor of some inflammatory signal pathways.
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Affiliation(s)
- Muhammad Suhaib Qudus
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China
| | - Mingfu Tian
- Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Institute of Medical Microbiology, Jinan University, Guangzhou, China
| | - Summan Sirajuddin
- Department of Health and Biological Sciences, Abasyn University, Peshawar, Pakistan
| | - Siyu Liu
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China
| | - Uzair Afaq
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China
| | - Muneeba Wali
- Department of Allied Health Sciences, CECOS University of IT and Emerging Sciences, Peshawar, Pakistan
| | - Jinbiao Liu
- Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Institute of Medical Microbiology, Jinan University, Guangzhou, China
| | - Pan Pan
- Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Institute of Medical Microbiology, Jinan University, Guangzhou, China
- Foshan Institute of Medical Microbiology, Foshan, China
| | - Zhen Luo
- Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Institute of Medical Microbiology, Jinan University, Guangzhou, China
- Foshan Institute of Medical Microbiology, Foshan, China
| | - Qiwei Zhang
- Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Institute of Medical Microbiology, Jinan University, Guangzhou, China
- Foshan Institute of Medical Microbiology, Foshan, China
| | - Ge Yang
- Foshan Institute of Medical Microbiology, Foshan, China
| | - Pin Wan
- Foshan Institute of Medical Microbiology, Foshan, China
| | - Yongkui Li
- Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Institute of Medical Microbiology, Jinan University, Guangzhou, China
- Foshan Institute of Medical Microbiology, Foshan, China
| | - Jianguo Wu
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China
- Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control, Institute of Medical Microbiology, Jinan University, Guangzhou, China
- Foshan Institute of Medical Microbiology, Foshan, China
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15
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de Lima IC, de Menezes DC, Uesugi JHE, Bichara CNC, da Costa Vasconcelos PF, Quaresma JAS, Falcão LFM. Liver Function in Patients with Long-Term Coronavirus Disease 2019 of up to 20 Months: A Cross-Sectional Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:5281. [PMID: 37047897 PMCID: PMC10094195 DOI: 10.3390/ijerph20075281] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/03/2023] [Accepted: 03/08/2023] [Indexed: 06/19/2023]
Abstract
The long-term laboratory aspects of the effects of coronavirus disease 2019 (COVID-19) on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older admitted during the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. A ferritin level of >300 U/L was observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST level > 25 U/L, and GGT level ≥ 50 or 32 U/L were associated with an ALT level > 29 U/L. A correlation was found between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID-19, especially in those hospitalised during the acute phase. In addition, an ALT level > 29 U/L was associated with changes in the levels of other markers of liver injury, such as LDH, GGT, and ferritin.
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Affiliation(s)
- Igor Costa de Lima
- Center for Biological Health Sciences, State University of Pará, Belém 66087670, Brazil
| | | | | | | | | | - Juarez Antônio Simões Quaresma
- Center for Biological Health Sciences, State University of Pará, Belém 66087670, Brazil
- Tropical Medicine Center, Federal University of Pará, Belém 66055240, Brazil
- School of Medicine, São Paulo University, São Paulo 01246903, Brazil
| | - Luiz Fábio Magno Falcão
- Center for Biological Health Sciences, State University of Pará, Belém 66087670, Brazil
- School of Medicine, São Paulo University, São Paulo 01246903, Brazil
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16
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Sgamato C, Rocco A, Compare D, Minieri S, Marchitto SA, Maurea S, Nardone G. Autoimmune liver diseases and SARS-CoV-2. World J Gastroenterol 2023; 29:1838-1851. [PMID: 37032727 PMCID: PMC10080695 DOI: 10.3748/wjg.v29.i12.1838] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 01/12/2023] [Accepted: 03/14/2023] [Indexed: 03/28/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry. Here we summarise the current knowledge about auto-immune liver diseases (AILDs) and SARS-CoV-2, focusing on: (1) The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs; (2) the role of SARS-CoV-2 in inducing liver damage and triggering AILDs; and (3) the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver. Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine. Although SARS-CoV-2 infection can lead to the development of several autoimmune diseases, few reports correlate it to the appearance of de novo manifestation of immune-mediated liver diseases such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) or AIH/PBC overlap syndrome. Different case series of an AIH-like syndrome with a good prognosis after SARS-CoV-2 vaccination have been described. Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established, these reports suggest that this association could be more than coincidental.
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Affiliation(s)
- Costantino Sgamato
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Alba Rocco
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Debora Compare
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Stefano Minieri
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Stefano Andrea Marchitto
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Simone Maurea
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples 80131, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
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17
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Sadeghi Dousari A, Hosseininasab SS, Sadeghi Dousari F, Fuladvandi M, Satarzadeh N. The impact of COVID-19 on liver injury in various age. World J Virol 2023; 12:91-99. [PMID: 37033149 PMCID: PMC10075051 DOI: 10.5501/wjv.v12.i2.91] [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: 10/14/2022] [Accepted: 01/04/2023] [Indexed: 03/21/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) disease was first detected in December 2019 in Wuhan, China. This disease is currently one of the most important global health problems. The novel coronavirus COVID-19 is a respiratory illness, that has caused a deadly pandemic that is spreading rapidly around the world. It is not only a respiratory system virus that causes severe lung disease, but also a systemic disease agent that can affect all systems. People with COVID-19 disease usually have respiratory signs, however, the liver disorder is not an uncommon presentation. In addition, many studies around the world have revealed that the liver is injured to various degrees in patients with severe acute respiratory syndrome coronavirus 2 disease. This review mainly focuses on the impact of COVID-19 on Liver Injury at various ages.
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Affiliation(s)
- Amin Sadeghi Dousari
- Department of Microbiology, Jiroft University of Medical Sciences, Jiroft 7861634204, Iran
| | | | | | - Masoumeh Fuladvandi
- Department of Nursing, Aligoudarz School of Nursing, Lorestan University of Medical Sciences, Khorramabad 6813833946, Iran
| | - Naghmeh Satarzadeh
- Department of Pharmaceutical Biotechnology, Kerman University of Medical Sciences, Kerman 7616913555, Iran
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18
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Chen Y, Shi C, Zhan H, Yang B, Liu J, Rong P, Luo Y, Yang J. Drug-induced liver injury in COVID-19 patients during hospitalization. Medicine (Baltimore) 2023; 102:e33294. [PMID: 36930097 PMCID: PMC10018522 DOI: 10.1097/md.0000000000033294] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 02/24/2023] [Indexed: 03/18/2023] Open
Abstract
Since coronavirus disease 2019 (COVID-19) outbreaks in December 2019 in Wuhan, almost no studies have systematically described drug-induced liver injury (DILI) in COVID-19 patients. This study aimed to assess the characteristics of liver test abnormality or liver injury in patients with COVID-19, and further to explore DILI in COVID-19 patients during hospitalization. It was a single-center retrospective analysis of confirmed severe acute respiratory syndrome coronavirus 2 infected patients in the hospital from January 2020 to March 2020. Univariate and multivariate logistic regression analysis were used to assess the risk factors associated with liver test abnormality or liver injury. At admission, 148 (48.8%, 148/303) patients had abnormal liver test results and 7 (2.4%, 7/303) had liver injury, while 195 (64.4%, 195/303) had abnormal liver test results and 17 (5.6%, 17/303) had liver injury during hospitalization. After excluding these patients with liver disease and liver function abnormalities or liver injury at admission, 15 (11.1%, 15/135) patients developed DILI during hospitalization. Further regression analysis indicated that methylprednisolone (odds ratio = 4.177, 95% confidence interval [1.106-15.771], P = .035), but not Chinese herbal medicine or other used drug, was associated with DILI in patients during hospitalization. Abnormal liver function results were in more than half of patients with COVID-19, and the incidence of DILI in COVID-19 patients was 11.1% during hospitalization. Liver test abnormality or liver injury in patients might be directly caused by the viral infection at admission, but the detrimental effects on liver injury mainly related to certain medications used during hospitalization, particularly methylprednisolone. Severe COVID-19 could increase the occurrence of liver injury (P = .007) during hospitalization, but not a risk factor of liver injury. However, Chinese herbal medicine was a protective factor for liver injury.
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Affiliation(s)
- Ying Chen
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Cai Shi
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Haiyan Zhan
- Department of Pharmacy, Wuhan Jinyintan Hospital, Wuhan, China
| | - Boning Yang
- Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Jun Liu
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Peipei Rong
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yi Luo
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jian Yang
- Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China
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19
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Chakraborty R, Sharma D, Kapoor DU, Dwivedi A, Khabiya R, Sen S. Implications of metabolic dysfunction associated fatty liver disease in COVID-19. World J Clin Cases 2023; 11:1275-1286. [PMID: 36926128 PMCID: PMC10013103 DOI: 10.12998/wjcc.v11.i6.1275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/20/2022] [Accepted: 01/31/2023] [Indexed: 02/24/2023] Open
Abstract
Metabolic associated fatty liver disorder (MAFLD) characterizes the contributing etiologies (i.e., type 2 diabetes mellitus, metabolic syndrome, overweight) of individuals with fatty liver disease that affects 1/3rd of the world population. In 2020, the coronavirus disease 2019 (COVID-19) crisis was unprecedented, and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2. MAFLD patients are frequently obese with added metabolic menace like diabetes, hypertension, and dyslipidemia leading to greater jeopardy of COVID-19. MAFLD patients are 4 to 6-fold more prone towards infections. COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin. Hence, MAFLD in COVID-19 patients worsens the condition significantly. The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission. Direct hepatic injury, enhanced levels of inflammatory cytokines, declined hepatic mitochondrial activity, and compromised immunity are considered as some underlying mechanisms. The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients. The review systematically analyzes the effect of striking two worldwide pandemics (MAFLD and COVID-19) together in the present era.
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Affiliation(s)
- Raja Chakraborty
- Institute of Pharmacy, Assam Don Bosco University, Guwahati 782402, Assam, India
| | - Deepak Sharma
- School of Medical Sciences, Adamas University, Kolkata 700126, West Bengal, India
| | - Devesh U Kapoor
- Department of Pharmacy, Dr. Dayaram Patel Pharmacy College, Bardoli 394601, Gujarat, India
| | - Akanksha Dwivedi
- Department of Pharmacy, Acropolis Institute of Pharmaceutical Education & Research, Indore 453771, Madhya Pradesh, India
| | - Rakhi Khabiya
- Department of Pharmacy, Acropolis Institute of Pharmaceutical Education & Research, Indore 453771, Madhya Pradesh, India
| | - Saikat Sen
- Faculty of Pharmaceutical Science, Assam down town University, Guwahati 781026, Assam, India
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20
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Miranda C, Garlatti E, Da Porto A, Rinaldo E, Grazioli S, Zanette G, Tonizzo M. Liver injury in COVID-19 patients with non-alcoholic fatty liver disease: an update. Arch Med Sci Atheroscler Dis 2023; 8:e1-e10. [PMID: 37153375 PMCID: PMC10161789 DOI: 10.5114/amsad/160950] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 02/06/2023] [Indexed: 05/09/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has revolutionized the priorities of the medical society worldwide. Although most patients infected with SARS-CoV-2 exhibit respiratory symptoms, other organs may also be involved, including the liver, often resulting in liver injury. Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and its prevalence is expected to increase together with the epidemics of type 2 diabetes and obesity. Data about liver injury during COVID-19 are numerous, while overviews of this infection in patients with NAFLD, both in terms of respiratory and liver, are emerging. In this review, we summarise the current research focusing on COVID-19 in NAFLD patients and discuss the association between liver injury in COVID-19 subjects and non-alcoholic fatty liver disease.
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Affiliation(s)
- Cesare Miranda
- Clinic of Endocrinology and Metabolism Diseases, Pordenone Hospital, Pordenone, Italy
| | - Elena Garlatti
- Internal Medicine, Santa Maria degli Angeli Hospital, Pordenone, Italy
| | - Andrea Da Porto
- Department of Medicine, Clinica Medica, University of Udine, Udine, Italy
| | - Elena Rinaldo
- Clinic of Endocrinology and Metabolism Diseases, Pordenone Hospital, Pordenone, Italy
| | - Silvia Grazioli
- Internal Medicine, Santa Maria degli Angeli Hospital, Pordenone, Italy
| | - Giorgio Zanette
- Clinic of Endocrinology and Metabolism Diseases, Pordenone Hospital, Pordenone, Italy
| | - Maurizio Tonizzo
- Internal Medicine, Santa Maria degli Angeli Hospital, Pordenone, Italy
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21
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Gildea DT, Woo SM, O’Connor CE, Rangnekar AS. COVID-19-Associated Liver Injury. Hepat Med 2023; 15:1-9. [PMID: 36852138 PMCID: PMC9960793 DOI: 10.2147/hmer.s384108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 02/11/2023] [Indexed: 03/01/2023] Open
Abstract
This review analyzes data regarding liver injury associated with COVID-19 infection. We discuss reported effects on the liver from both COVID-19 and COVID-19 treatment as well as pathophysiology, review the potential role of drug-induced liver injury as an etiology of COVID-19-associated liver injury, and touch on other reports of significant outcomes including COVID-19 cholangiopathy and autoimmune hepatitis. Finally, we review the implications of COVID-19 infection in liver transplant recipients.
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Affiliation(s)
- Daniel T Gildea
- Department of Internal Medicine, MedStar Georgetown University Hospital, Washington, DC, USA,Correspondence: Daniel T Gildea, Tel +1 302-985-7777, Email
| | - Stephanie M Woo
- Department of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC, USA
| | | | - Amol S Rangnekar
- MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, DC, USA
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22
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Ali FEM, Abd El-Aziz MK, Ali MM, Ghogar OM, Bakr AG. COVID-19 and hepatic injury: cellular and molecular mechanisms in diverse liver cells. World J Gastroenterol 2023; 29:425-449. [PMID: 36688024 PMCID: PMC9850933 DOI: 10.3748/wjg.v29.i3.425] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/15/2022] [Accepted: 12/23/2022] [Indexed: 01/12/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) represents a global health and economic challenge. Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. The viral tropism pattern of SARS-CoV-2 can induce hepatic injuries either by itself or by worsening the conditions of patients with hepatic diseases. Besides, other factors have been reported to play a crucial role in the pathological forms of hepatic injuries induced by SARS-CoV-2, including cytokine storm, hypoxia, endothelial cells, and even some treatments for COVID-19. On the other hand, several groups of people could be at risk of hepatic COVID-19 complications, such as pregnant women and neonates. The present review outlines and discusses the interplay between SARS-CoV-2 infection and hepatic injury, hepatic illness comorbidity, and risk factors. Besides, it is focused on the vaccination process and the role of developed vaccines in preventing hepatic injuries due to SARS-CoV-2 infection.
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Affiliation(s)
- Fares E M Ali
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt
| | | | - Mahmoud M Ali
- Department of Pharmacology, Al-Azhar University, Assiut 71524, Egypt
| | - Osama M Ghogar
- Department of Biochemistry Faculty of Pharmacy, Badr University in Assiut, Egypt
| | - Adel G Bakr
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt
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Maev IV, Shaburov RI, Pavlov AI, Molodova AI, Karakozov AG, Kazakov SP, Lebedeva EG, Ivolgin AF, Eremin MN, Levchenko OB. Treatment of toxic hepatitis in COVID-19 patients. TERAPEVT ARKH 2023; 94:1413-1420. [PMID: 37167187 DOI: 10.26442/00403660.2022.12.202021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 01/15/2023] [Indexed: 01/17/2023]
Abstract
Background. The article reflects the clinical significance of the early diagnosis of toxic hepatitis in patients who have undergone a new coronavirus infection with the determination of clinical and laboratory predictors of the response to therapy. A dynamic analysis of the effectiveness of toxic hepatitis therapy in patients of three experimental groups and a control group is presented.
Aim. The aim of the present study is to increase the effectiveness of the treatment of toxic hepatitis in patients who have undergone COVID-19.
Materials and methods. On the basis of the newly created infection centers of the Central Clinical Hospital RZhD-Medicine and Vishnevsky 3-rd Central Military Clinical Hospital 996 patients with COVID-19, who had clinical and laboratory signs of toxic liver damage (cytolytic and/or cholestatic syndromes) against the background of COVID-19 therapy.
Results. On the 14th day from the start of therapy in group 3, there was a significant decrease in the clinical manifestations of jaundice in 163 (72.8%) patients, on the 21st day of treatment, this symptom was stopped in all patients. In groups 1 and 2, the decrease in clinical manifestations of jaundice was significantly lower 122 (55.2%) and 134 (58.8%); p0.05. At the end of therapy, no manifestations of jaundice were observed in all experimental groups, while in the control group, symptom reduction was achieved only in 47 (14.5%) patients.
Conclusion. The use of drugs with hepatoprotective effect in the form of monotherapy in groups 1 (UDCA) and 2 (ademethionine) showed a low therapeutic effect with positive dynamics of clinical and laboratory indicators of toxic hepatitis activity. The use of combined treatment in group 3 (UDCA and ademethionine) demonstrated the maximum therapeutic effect, pronounced positive dynamics in the form of normalization of clinical and laboratory indicators of toxic hepatitis activity.
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24
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Al-Rawi TSS, Al-Ani RM. Liver dysfunction-related COVID-19: A narrative review. World J Meta-Anal 2023; 11:5-17. [DOI: 10.13105/wjma.v11.i1.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 11/25/2022] [Accepted: 12/14/2022] [Indexed: 01/11/2023] Open
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Hu WS, Jiang FY, Shu W, Zhao R, Cao JM, Wang DP. Liver injury in COVID-19: A minireview. World J Gastroenterol 2022; 28:6716-6731. [PMID: 36620342 PMCID: PMC9813934 DOI: 10.3748/wjg.v28.i47.6716] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 11/02/2022] [Accepted: 11/23/2022] [Indexed: 12/19/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has escalated into a global tragedy afflicting human health, life, and social governance. Through the increasing depth of research and a better understanding of this disease, it has been ascertained that, in addition to the lungs, SARS-CoV-2 can also induce injuries to other organs including the liver. Liver injury is a common clinical manifestation of COVID-19, particularly in severe cases, and is often associated with a poorer prognosis and higher severity of COVID-19. This review focuses on the general existing information on liver injury caused by COVID-19, including risk factors and subpopulations of liver injury in COVID-19, the association between preexisting liver diseases and the severity of COVID-19, and the potential mechanisms by which SARS-CoV-2 affects the liver. This review may provide some useful information for the development of therapeutic and preventive strategies for COVID-19-associated liver injury.
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Affiliation(s)
- Wen-Shu Hu
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Fang-Ying Jiang
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Wen Shu
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Rong Zhao
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Ji-Min Cao
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - De-Ping Wang
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
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26
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Karlafti E, Paramythiotis D, Pantazi K, Georgakopoulou VE, Kaiafa G, Papalexis P, Protopapas AA, Ztriva E, Fyntanidou V, Savopoulos C. Drug-Induced Liver Injury in Hospitalized Patients during SARS-CoV-2 Infection. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:1848. [PMID: 36557050 PMCID: PMC9782075 DOI: 10.3390/medicina58121848] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/08/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022]
Abstract
In the last few years, the world has had to face the SARS-CoV-2 infection and its multiple effects. Even though COVID-19 was first considered to be a respiratory disease, it has an extended clinical spectrum with symptoms occurring in many tissues, and it is now identified as a systematic disease. Therefore, various drugs are used during the therapy of hospitalized COVID-19 patients. Studies have shown that many of these drugs could have adverse side-effects, including drug-induced liver injury-also known as DILI-which is the focus of our review. Despite the consistent findings, the pathophysiological mechanism behind DILI in COVID-19 disease is still complex, and there are a few risk factors related to it. However, when it comes to the diagnosis, there are specific algorithms (including the RUCAM algorithm) and biomarkers that can assist in identifying DILI and which we will analyze in our review. As indicated by the title, a variety of drugs are associated with this COVID-19-related complication, including systemic corticosteroids, drugs used for the therapy of uncontrolled cytokine storm, as well as antiviral, anti-inflammatory, and anticoagulant drugs. Bearing in mind that hepatotoxicity is very likely to occur during COVID-19, especially in patients treated with multiple medications, we will also refer to the use of other drugs used for DILI therapy in an effort to control and prevent a severe and long-term outcome.
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Affiliation(s)
- Eleni Karlafti
- Emergency Department, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Daniel Paramythiotis
- First Propaedeutic Department of Surgery, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Konstantina Pantazi
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | | | - Georgia Kaiafa
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Petros Papalexis
- Unit of Endocrinology, First Department of Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
- Department of Biomedical Sciences, University of West Attica, 12243 Athens, Greece
| | - Adonis A. Protopapas
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Eleftheria Ztriva
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Varvara Fyntanidou
- Emergency Department, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Christos Savopoulos
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
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Karlafti E, Paramythiotis D, Pantazi K, Georgakopoulou VE, Kaiafa G, Papalexis P, Protopapas AA, Ztriva E, Fyntanidou V, Savopoulos C. Drug-Induced Liver Injury in Hospitalized Patients during SARS-CoV-2 Infection. Medicina (B Aires) 2022; 58:1848. [DOI: https:/doi.org/10.3390/medicina58121848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2025] Open
Abstract
In the last few years, the world has had to face the SARS-CoV-2 infection and its multiple effects. Even though COVID-19 was first considered to be a respiratory disease, it has an extended clinical spectrum with symptoms occurring in many tissues, and it is now identified as a systematic disease. Therefore, various drugs are used during the therapy of hospitalized COVID-19 patients. Studies have shown that many of these drugs could have adverse side-effects, including drug-induced liver injury—also known as DILI—which is the focus of our review. Despite the consistent findings, the pathophysiological mechanism behind DILI in COVID-19 disease is still complex, and there are a few risk factors related to it. However, when it comes to the diagnosis, there are specific algorithms (including the RUCAM algorithm) and biomarkers that can assist in identifying DILI and which we will analyze in our review. As indicated by the title, a variety of drugs are associated with this COVID-19-related complication, including systemic corticosteroids, drugs used for the therapy of uncontrolled cytokine storm, as well as antiviral, anti-inflammatory, and anticoagulant drugs. Bearing in mind that hepatotoxicity is very likely to occur during COVID-19, especially in patients treated with multiple medications, we will also refer to the use of other drugs used for DILI therapy in an effort to control and prevent a severe and long-term outcome.
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Affiliation(s)
- Eleni Karlafti
- Emergency Department, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Daniel Paramythiotis
- First Propaedeutic Department of Surgery, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Konstantina Pantazi
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | | | - Georgia Kaiafa
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Petros Papalexis
- Unit of Endocrinology, First Department of Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
- Department of Biomedical Sciences, University of West Attica, 12243 Athens, Greece
| | - Adonis A. Protopapas
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Eleftheria Ztriva
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Varvara Fyntanidou
- Emergency Department, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Christos Savopoulos
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
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28
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Shiri Aghbash P, Ebrahimzadeh Leylabadlo H, Fathi H, Bahmani M, Chegini R, Bannazadeh Baghi H. Hepatic Disorders and COVID-19: From Pathophysiology to Treatment Strategy. Can J Gastroenterol Hepatol 2022; 2022:4291758. [PMID: 36531832 PMCID: PMC9754839 DOI: 10.1155/2022/4291758] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 10/31/2022] [Accepted: 11/12/2022] [Indexed: 12/13/2022] Open
Abstract
Following the SARS-CoV-2 outbreak and the subsequent development of the COVID-19 pandemic, organs such as the lungs, kidneys, liver, heart, and brain have been identified as priority organs. Liver diseases are considered a risk factor for high mortality from the COVID-19 pandemic. Besides, liver damage has been demonstrated in a substantial proportion of patients with COVID-19, especially those with severe clinical symptoms. Furthermore, antiviral medications, immunosuppressive drugs after liver transplantation, pre-existing hepatic diseases, and chronic liver diseases such as cirrhosis have also been implicated in SARS-CoV-2-induced liver injury. As a result, some precautions have been taken to prevent, monitor the virus, and avoid immunocompromised and susceptible individuals, such as liver and kidney transplant recipients, from being infected with SARS-CoV-2, thereby avoiding an increase in mortality. The purpose of this review was to examine the impairment caused by SARS-CoV-2 infection and the impact of drugs used during the pandemic on the mortality range and therefore the possibility of preventive measures in patients with liver disease.
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Affiliation(s)
- Parisa Shiri Aghbash
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Hamidreza Fathi
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tabriz, Iran
| | - Mohaddeseh Bahmani
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Drug Applied Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Rojin Chegini
- Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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29
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Saeed U, Piracha ZZ, Uppal SR, Waheed Y, Uppal R. SARS-CoV-2 induced hepatic injuries and liver complications. Front Cell Infect Microbiol 2022; 12:726263. [PMID: 36189356 PMCID: PMC9523111 DOI: 10.3389/fcimb.2022.726263] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/23/2022] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is resilient, highly pathogenic, and rapidly transmissible. COVID-19 patients have been reported to have underlying chronic liver abnormalities linked to hepatic dysfunction. DISCUSSION Viral RNAs are detectable in fecal samples by RT-PCR even after negative respiratory samples, which suggests that SARS-CoV-2 can affect the gastrointestinal tract and the liver. The case fatality rates are higher among the elderly and those with underlying comorbidities such as hypertension, diabetes, liver abnormality, and heart disease. There is insufficient research on signaling pathways. Identification of molecular mechanisms involved in SARS-CoV-2-induced damages to hepatocytes is challenging. Herein, we demonstrated the multifactorial effects of SARS-CoV-2 on liver injury such as psychological stress, immunopathogenesis, systemic inflammation, ischemia and hypoxia, drug toxicity, antibody-dependent enhancement (ADE) of infection, and several others which can significantly damage the liver. CONCLUSION During the COVID-19 pandemic, it is necessary for clinicians across the globe to pay attention to SARS-CoV-2-mediated liver injury to manage the rising burden of hepatocellular carcinoma. To face the challenges during the resumption of clinical services for patients with pre-existing liver abnormalities and HCC, the impact of SARS-CoV-2 on hepatocytes should be investigated both in vitro and in vivo.
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Affiliation(s)
- Umar Saeed
- Department of Research and Development, Islamabad Diagnostic Center (IDC), Islamabad, Pakistan
- International Center of Medical Sciences Research(ICMSR), Islamabad, Pakistan
| | - Zahra Zahid Piracha
- Department of Research and Development, Islamabad Diagnostic Center (IDC), Islamabad, Pakistan
- International Center of Medical Sciences Research(ICMSR), Islamabad, Pakistan
| | - Sara Rizwan Uppal
- Department of Research and Development, Islamabad Diagnostic Center (IDC), Islamabad, Pakistan
| | - Yasir Waheed
- Department of ORIC, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan
| | - Rizwan Uppal
- Department of Research and Development, Islamabad Diagnostic Center (IDC), Islamabad, Pakistan
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30
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Aquino-Matus J, Uribe M, Chavez-Tapia N. COVID-19: Current Status in Gastrointestinal, Hepatic, and Pancreatic Diseases—A Concise Review. Trop Med Infect Dis 2022; 7:tropicalmed7080187. [PMID: 36006279 PMCID: PMC9415805 DOI: 10.3390/tropicalmed7080187] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/09/2022] [Accepted: 08/09/2022] [Indexed: 01/08/2023] Open
Abstract
The gastrointestinal tract plays an important role in the pathogenesis of COVID-19. The angiotensin-converting enzyme 2 receptor and the transmembrane protease serine 2 receptor bind and activate SARS-CoV-2 and are present in high concentrations throughout the gastrointestinal tract. Most patients present with gastrointestinal symptoms and/or abnormal liver function tests, both of which have been associated with adverse outcomes. The mechanisms of liver damage are currently under investigation, but the damage is usually transient and nonsevere. Liver transplantation is the only definitive treatment for acute liver failure and end-stage liver disease, and unfortunately, because of the need for ventilators during the COVID-19 pandemic, most liver transplant programs have been suspended. Patients with gastrointestinal autoimmune diseases require close follow-up and may need modification in immunosuppression. Acute pancreatitis is a rare manifestation of COVID-19, but it must be considered in patients with abdominal pain. The gastrointestinal tract, including the liver and the pancreas, has an intimate relationship with COVID-19 that is currently under active investigation.
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Huang J, Zhang Z, Hao C, Qiu Y, Tan R, Liu J, Wang X, Yang W, Qu H. Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor. Front Pharmacol 2022; 13:804189. [PMID: 35979235 PMCID: PMC9377275 DOI: 10.3389/fphar.2022.804189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 06/24/2022] [Indexed: 11/13/2022] Open
Abstract
Of the patients infected with coronavirus disease 2019 (COVID-19), approximately 14–53% developed liver injury resulting in poor outcomes. Drug-induced liver injury (DILI) is the primary cause of liver injury in COVID-19 patients. In this study, we elucidated liver injury mechanism induced by drugs of pharmacologic treatments against SARS-CoV-2 (DPTS) using bioinformatics and systems biology. Totally, 1209 genes directly related to 216 DPTS (DPTSGs) were genes encoding pharmacokinetics and therapeutic targets of DPTS and enriched in the pathways related to drug metabolism of CYP450s, pregnane X receptor (PXR), and COVID-19 adverse outcome. A network, constructed by 110 candidate targets which were the shared part of DPTSGs and 445 DILI targets, identified 49 key targets and four Molecular Complex Detection clusters. Enrichment results revealed that the 4 clusters were related to inflammatory responses, CYP450s regulated by PXR, NRF2-regualted oxidative stress, and HLA-related adaptive immunity respectively. In cluster 1, IL6, IL1B, TNF, and CCL2 of the top ten key targets were enriched in COVID-19 adverse outcomes pathway, indicating the exacerbation of COVID-19 inflammation on DILI. PXR-CYP3A4 expression of cluster 2 caused DILI through inflammation-drug interaction and drug-drug interactions among pharmaco-immunomodulatory agents, including tocilizumab, glucocorticoids (dexamethasone, methylprednisolone, and hydrocortisone), and ritonavir. NRF2 of cluster 3 and HLA targets of cluster four promoted DILI, being related to ritonavir/glucocorticoids and clavulanate/vancomycin. This study showed the pivotal role of PXR associated with inflammation-drug and drug-drug interactions on DILI and highlighted the cautious clinical decision-making for pharmacotherapy to avoid DILI in the treatment of COVID-19 patients.
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Affiliation(s)
- Jingjing Huang
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Zhaokang Zhang
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Chenxia Hao
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Department of Pharmacy, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yuzhen Qiu
- Department of Critical Care, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Ruoming Tan
- Department of Critical Care, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jialin Liu
- Department of Critical Care, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xiaoli Wang
- Department of Critical Care, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- *Correspondence: Xiaoli Wang, ; Wanhua Yang, ; Hongping Qu,
| | - Wanhua Yang
- Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- *Correspondence: Xiaoli Wang, ; Wanhua Yang, ; Hongping Qu,
| | - Hongping Qu
- Department of Critical Care, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- *Correspondence: Xiaoli Wang, ; Wanhua Yang, ; Hongping Qu,
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Chen H, Chen Q. COVID-19 Pandemic: Insights into Interactions between SARS-CoV-2 Infection and MAFLD. Int J Biol Sci 2022; 18:4756-4767. [PMID: 35874945 PMCID: PMC9305262 DOI: 10.7150/ijbs.72461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 06/23/2022] [Indexed: 01/08/2023] Open
Abstract
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an ongoing global health pandemic. Since 2019, the pandemic continues to cast a long shadow on all aspects of our lives, bringing huge health and economic burdens to all societies. With our in-depth understanding of COVID-19, from the initial respiratory tract to the later gastrointestinal tract and cardiovascular systems, the multiorgan involvement of this infectious disease has been discovered. Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named nonalcoholic fatty liver disease (NAFLD), is a major health issue closely related to metabolic dysfunctions, affecting a quarter of the world's adult population. The association of COVID-19 with MAFLD has received increasing attention, as MAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19 symptoms. In this review, we provide an update on the interactions between COVID-19 and MAFLD and its underlying mechanisms.
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Affiliation(s)
- Hanfei Chen
- Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.,Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China
| | - Qiang Chen
- Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.,Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.,MOE Frontier Science Centre for Precision Oncology, University of Macau, Taipa, Macau SAR, China
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The Relationship of Liver and Pancreas Density With Chest Computed Tomography Score Progression and Laboratory Findings in Patients With COVID-19. J Comput Assist Tomogr 2022; 46:848-853. [PMID: 35830381 PMCID: PMC9696684 DOI: 10.1097/rct.0000000000001354] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Abdominal involvement of COVID-19 is a current issue. We aimed to evaluate hepatic and pancreatic density alterations on computed tomography (CT) and to analyze whether these alterations had a relationship with chest CT score and laboratory findings.
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Ahmad R, Haque M. Surviving the Storm: Cytokine Biosignature in SARS-CoV-2 Severity Prediction. Vaccines (Basel) 2022; 10:vaccines10040614. [PMID: 35455363 PMCID: PMC9026643 DOI: 10.3390/vaccines10040614] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/08/2022] [Accepted: 04/12/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary The world has been stricken mentally, physically, and economically by the COVID-19 virus. However, while SARS-CoV-2 viral infection results in mild flu-like symptoms in most patients, a number of those infected develop severe illness. These patients require hospitalization and intensive care. The severe disease can spiral downwards with eventual severe damage to the lungs and failure of multiple organs, leading to the individual’s demise. It is necessary to identify those who are developing a severe form of illness to provide early management. Therefore, it is crucial to learn about the mechanisms and chemical mediators that lead to critical conditions in SARS-CoV-2 infection. This paper reviews studies regarding the individual chemical mediators, pathways, and means that contribute to worsening health conditions in SARS-CoV-2 infection. Abstract A significant part of the world population has been affected by the devastating SARS-CoV-2 infection. It has deleterious effects on mental and physical health and global economic conditions. Evidence suggests that the pathogenesis of SARS-CoV-2 infection may result in immunopathology such as neutrophilia, lymphopenia, decreased response of type I interferon, monocyte, and macrophage dysregulation. Even though most individuals infected with the SARS-CoV-2 virus suffer mild symptoms similar to flu, severe illness develops in some cases, including dysfunction of multiple organs. Excessive production of different inflammatory cytokines leads to a cytokine storm in COVID-19 infection. The large quantities of inflammatory cytokines trigger several inflammation pathways through tissue cell and immune cell receptors. Such mechanisms eventually lead to complications such as acute respiratory distress syndrome, intravascular coagulation, capillary leak syndrome, failure of multiple organs, and, in severe cases, death. Thus, to devise an effective management plan for SARS-CoV-2 infection, it is necessary to comprehend the start and pathways of signaling for the SARS-CoV-2 infection-induced cytokine storm. This article discusses the current findings of SARS-CoV-2 related to immunopathology, the different paths of signaling and other cytokines that result in a cytokine storm, and biomarkers that can act as early signs of warning for severe illness. A detailed understanding of the cytokine storm may aid in the development of effective means for controlling the disease’s immunopathology. In addition, noting the biomarkers and pathophysiology of severe SARS-CoV-2 infection as early warning signs can help prevent severe complications.
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Affiliation(s)
- Rahnuma Ahmad
- Department of Physiology, Medical College for Women and Hospital, Plot No 4 Road 8/9, Sector-1, Dhaka 1230, Bangladesh;
| | - Mainul Haque
- Unit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kem Perdana Sungai Besi, Kuala Lumpur 57000, Malaysia
- Correspondence: or
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35
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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, etc.), 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, nonalcoholic 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
- Unit of Addiction and Hepatology, Alcohological Regional Center, IRCCS Ospedale Policlinico San Martino, ASL3 Liguria, Genoa, Italy -
| | - Antonio DI Biagio
- Unit of Infectious Diseases, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Sharmila Fagoonee
- National Research Council, Molecular Biotechnology Center, Institute for Biostructure and Bioimaging, Turin, Italy
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Zhu X, Wang J, Du J, Chen S, Chen S, Li J, Shen B. Changes in Serum Liver Function for Patients with COVID-19: A 1-Year Follow-Up Study. Infect Drug Resist 2022; 15:1857-1870. [PMID: 35450115 PMCID: PMC9017694 DOI: 10.2147/idr.s356181] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 03/26/2022] [Indexed: 12/17/2022] Open
Abstract
Objective Abnormal liver function and liver injury related to COVID-19 during hospitalization has received widespread attention. However, the long-term observation of patients’ liver functions after discharge has not been investigated. This study intends to analyze the abnormal liver function in patients one year after they are discharged. Methods Serum liver function tests were analyzed for the first time immediately after hospitalization (T1), before discharge (T2), a median of 14.0 (14.0, 15.0) days after discharge (T3) and 1 year (356.0 (347.8, 367.0) days) after discharge (T4). Patients with at least one serum parameter (ALT, AST, ALP, GGT and TB) exceeding the upper limit of reference range were defined as having abnormal liver function. Results For the 118 COVID-19 patients with a median follow-up time of 376.0 (71.5, 385.3) days from onset to the end of the follow-up after discharge, the proportion with abnormal liver function in T1, T2, T3 and T4 were 32.2%, 45.8%, 54.8% and 28.8%, respectively. The proportion of patients with at least once abnormal liver function detected from T1 to T2, T1 to T3, T1 to T4 was 60.2%, 77.4% and 88.9%, respectively. From T1 to T4, the ALT, AST, GGT and BMI at admission were significantly higher in the patients with persistently abnormal liver function than in the patients with persistently normal liver function. Abnormal liver function was mainly manifested in the elevation of GGT and TB levels. Multivariate logistics regression analysis showed that age and gender-adjusted ALT (odds ratio [OR]=2.041, 95% confidence interval [CI]: 1.170–3.561, P=0.012) at admission was a risk factor for abnormal liver function in the T4 stage. Conclusion Abnormal liver function in patients with COVID-19 can persist from admission to one year after discharge, and therefore, the long-term dynamic monitoring of liver function in patients with COVID-19 is necessary.
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Affiliation(s)
- Xiaoli Zhu
- Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China
| | - Jing Wang
- Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China
| | - Juping Du
- Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China
| | - Shuaishuai Chen
- Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China
| | - Shiyong Chen
- Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China
| | - Jun Li
- Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China
| | - Bo Shen
- Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China
- Correspondence: Bo Shen, Department of laboratory medicine, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China, Tel/Fax +86 576 85226374, Email
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Shousha HI, Ramadan A, Lithy R, El-Kassas M. Patterns of liver profile disturbance in patients with COVID-19. World J Clin Cases 2022; 10:2063-2071. [PMID: 35321162 PMCID: PMC8895188 DOI: 10.12998/wjcc.v10.i7.2063] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 07/17/2021] [Accepted: 02/09/2022] [Indexed: 02/06/2023] Open
Abstract
Fever and cough are the most common clinical symptoms of coronavirus disease 2019 (COVID-19), but complications (such as pneumonia, respiratory distress syndrome, and multiorgan failure) can occur in people with additional comorbidities. COVID-19 may be a new cause of liver disease, as liver profile disturbance is one of the most common findings among patients. The molecular mechanism underlying this phenomenon, however, is still unknown. In this paper, we review the most current research on the patterns of change in liver profile among patients with COVID-19, the possible explanation for these findings, and the relation to pre-existing liver disease in these patients.
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Affiliation(s)
- Hend Ibrahim Shousha
- Department of Endemic Medicine, Faculty of Medicine, Cairo University, Cairo 12556, Egypt
| | - Ahmed Ramadan
- Department of Endemic Medicine, Faculty of Medicine, Cairo University, Cairo 12556, Egypt
| | - Rania Lithy
- Department of Endemic Medicine, Faculty of Medicine, Cairo University, Cairo 12556, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
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38
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Cordeiro A, Ribamar A, Ramalho A. Adipose tissue dysfunction and MAFLD in obesity on the scene of COVID-19. Clin Res Hepatol Gastroenterol 2022; 46:101807. [PMID: 34543756 PMCID: PMC8447553 DOI: 10.1016/j.clinre.2021.101807] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 08/19/2021] [Accepted: 09/07/2021] [Indexed: 02/04/2023]
Abstract
Obesity is a known risk factor for respiratory infection and many other chronic diseases, including metabolic dysfunction-associated fatty liver disease (MAFLD), previously known as nonalcoholic fatty liver disease (NAFLD). Recently, it has been considered an important and independent predictor for coronavirus disease 2019 (COVID-19) complications in adults, especially cardiopulmonary, presenting in a great number of individuals in critical care. In obesity, adipose tissue (AT) undergoes expansion via several processes: expansion of adipocytes and insufficient vascularization lead to hypoxia; adipocyte apoptosis/necrosis; irregular fatty acid flux; and enhanced secretion of inflammatory adipokines, cytokines, and chemokines. In individuals with obesity the liver can also become a target of COVID-19 infection, although major liver damage is uncommon. COVID-19 acute pandemic often develops in patients with major metabolic abnormalities, including fatty liver disease, which is part of a chronic pandemic together with body fat accumulation. During metabolic abnormalities, the expansion of metabolically active fat parallels chronic inflammatory changes, the development of Insulin Resistance (IR), and in the liver, the accumulation of fat, possibly, an underlying fibrosis. SARS-Cov-2 virus might affect the liver by direct or indirect mechanisms. The current epidemic of obesity and related metabolic diseases has extensively contributed to increase the number of severe cases and deaths from COVID-19, resulting in a health, political and economic crisis with long-lasting consequences. In this review, the authors explore the relationship between AT dysfunction and MAFLD in obesity on the scene of COVID-19.
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Affiliation(s)
- Adryana Cordeiro
- Department of Social Applied Nutrition, Micronutrients Research Center (NPqM), Institute of Nutrition, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil; Department of Biomedicine, Unit of Biochemistry, Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal.
| | - Amanda Ribamar
- Department of Social Applied Nutrition, Micronutrients Research Center (NPqM), Institute of Nutrition, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil; Faculty of Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Andrea Ramalho
- Department of Social Applied Nutrition, Micronutrients Research Center (NPqM), Institute of Nutrition, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
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39
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Zhao W, Zhang X, Zhu F, Jiang X. Dynamic Changes of Liver Function Indexes in Patients with Different Clinical Types of COVID-19. Int J Gen Med 2022; 15:877-884. [PMID: 35115814 PMCID: PMC8801727 DOI: 10.2147/ijgm.s347291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 01/13/2022] [Indexed: 11/23/2022] Open
Affiliation(s)
- Wei Zhao
- Department of Respiratory and Critical Care Medicine, Wuxi Fifth People’s Hospital, Wuxi, 214000, People’s Republic of China
| | - Xiaoqing Zhang
- Department of Respiratory and Critical Care Medicine, Wuxi Fifth People’s Hospital, Wuxi, 214000, People’s Republic of China
| | - Feng Zhu
- Department of Respiratory and Critical Care Medicine, Wuxi Fifth People’s Hospital, Wuxi, 214000, People’s Republic of China
- Correspondence: Feng Zhu; Xiufeng Jiang, Department of Respiratory and Critical Care Medicine, Wuxi Fifth People’s Hospital, Wuxi, 214000, People’s Republic of China, Tel +86-13914135026; +86-13013630369, Email ;
| | - Xiufeng Jiang
- Department of Respiratory and Critical Care Medicine, Wuxi Fifth People’s Hospital, Wuxi, 214000, People’s Republic of China
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40
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Taneva G, Dimitrov D, Velikova T. Liver dysfunction as a cytokine storm manifestation and prognostic factor for severe COVID-19. World J Hepatol 2021; 13:2005-2012. [PMID: 35070004 PMCID: PMC8727206 DOI: 10.4254/wjh.v13.i12.2005] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 07/02/2021] [Accepted: 11/18/2021] [Indexed: 02/06/2023] Open
Abstract
Liver damage in severe acute respiratory coronavirus 2 infection occurs in patients with or without preexisting liver disorders, posing a significant complication and mortality risk. During coronavirus disease 2019 (COVID-19), abnormal liver function is typically observed. However, liver injury may occur because of the treatment as well. Ischemia, cytokine storm, and hypoxia were identified as the three major factors contributing to liver damage during COVID-19. Indeed, raised liver enzymes during hospitalizations may be attributed to medications used, as well as sepsis and shock. As a result, the proportion of hospitalized patients afflicted with COVID-19 and pathological liver biomarkers varies from 14% to 53%. Aminotransferases and bilirubin are found most often elevated. Usually, increased gamma-glutamyltransferase, alkaline phosphatase, and decreased serum albumin levels are demonstrated. Additionally, although there is no specific treatment for COVID-19, many of the drugs used to treat the infection are hepatotoxic. In this mini-review, we focus on how liver dysfunction can be one of the features associated with the COVID-19 cytokine storm. Furthermore, data show that liver injury can be an independent predictor of severe COVID-19, the need for hospitalization, and death.
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Affiliation(s)
- Gergana Taneva
- Department of Gastroenterology, Sveta Sofia Hospital, Sofia 1618, Bulgaria
| | - Dimitar Dimitrov
- Department of Gastroenterology, Sveta Sofia Hospital, Sofia 1618, Bulgaria
| | - Tsvetelina Velikova
- Department of Clinical Immunology, University Hospital Lozenetz, Sofia 1407, Bulgaria
- Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria.
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Przekop D, Gruszewska E, Chrostek L. Liver function in COVID-19 infection. World J Hepatol 2021; 13:1909-1918. [PMID: 35069997 PMCID: PMC8727219 DOI: 10.4254/wjh.v13.i12.1909] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/07/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) disease affects multiple organs, including anomalies in liver function. In this review we summarize the knowledge about liver injury found during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with special attention paid to possible mechanisms of liver damage and abnormalities in liver function tests allowing for the evaluation of the severity of liver disease. Abnormalities in liver function observed in COVID-19 disease are associated with the age and sex of patients, severity of liver injury, presence of comorbidity and pre-treatment. The method of antiviral treatment can also impact on liver function, which manifests as increasing values in liver function tests. Therefore, analysis of variations in liver function tests is necessary in evaluating the progression of liver injury to severe disease.
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Affiliation(s)
- Dagmara Przekop
- Diagnostics-Experimental Center of Sexually Transmissible Diseases, Bialystok 15-879, Poland
| | - Ewa Gruszewska
- Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok 15-269, Poland
| | - Lech Chrostek
- Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok 15-269, Poland
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The clinical implication of gamma-glutamyl transpeptidase in COVID-19. LIVER RESEARCH 2021; 5:209-216. [PMID: 34603826 PMCID: PMC8464026 DOI: 10.1016/j.livres.2021.09.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 08/11/2021] [Accepted: 09/24/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Coronavirus disease 2019 (COVID-19) is a life-threatening disease that predominantly causes respiratory failure. The impact of COVID-19 on other organs remains elusive. Herein, we aimed to investigate the effects of COVID-19 on the hepatobiliary system. METHODS In the current study, we obtained the clinical records and laboratory results from 66 laboratory-confirmed patients with COVID-19 at the Wuhan Tongji Hospital between 10 February 2020 and 28 February 2020. The detailed clinical features and laboratory findings were collected for analysis. Bioinformatics analysis was conducted to evaluate the correlation between gamma-glutamyl transferase (GGT) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry receptor angiotensin-converting enzyme 2 (ACE2). RESULTS In this cohort, 30 (51.7%) patients had abnormal liver function on admission, which was associated with disease severity and enriched in the male and diabetic patients. The elevated levels of direct bilirubin (P = 0.029) and GGT (P = 0.004) were common in patients with severe pneumonia when compared with those with mild pneumonia. In addition, elevated levels of GGT (P = 0.003) and aspartate aminotransferase (AST) (P = 0.007) were positively associated with longer hospital stay. The expression of ACE2 was closely associated with GGT in various human tissues because they shared the common transcriptional regulator hepatic nuclear factor-1β (HNF1B). CONCLUSIONS Increased GGT levels were common in severe cases and elevated GGT levels were positively associated with prolonged hospital stay and disease severity. Due to the consistent expression with ACE2, GGT is a potent biomarker indicating the susceptibility of SARS-CoV-2 infection.
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43
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Gaspar R, Castelo Branco C, Macedo G. Liver and COVID-19: From care of patients with liver diseases to liver injury. World J Hepatol 2021; 13:1367-1377. [PMID: 34786172 PMCID: PMC8568576 DOI: 10.4254/wjh.v13.i10.1367] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 07/11/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
The global pandemic of coronavirus disease 2019 (COVID-19) changed dramatically all priorities on medical society and created several challenges for clinicians caring for patients with liver diseases. We performed a comprehensive review about how COVID-19 can affect the liver, the influence of liver diseases on the risk of developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 severity and also some strategies to overcome all the challenges clinicians have to face in the management of patients with liver diseases in a period of time when all the focus turned on COVID-19. We analyze the relationship between COVID-19 and non-alcoholic fatty liver disease, alcoholic liver disease, viral hepatitis, autoimmune liver disease, cirrhosis, hepatocellular carcinoma and liver transplantation, as well as the approach to SARS-CoV-2 vaccination.
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Affiliation(s)
- Rui Gaspar
- Department of Gastroenterology and Hepatology, Centro Hospitalar de São João, Porto 4200, Portugal
| | - Catarina Castelo Branco
- Department of Internal Medicine, Centro Hospitalar e Universitário do Porto, Porto 4100, Portugal
| | - Guilherme Macedo
- Department of Gastroenterology and Hepatology, Centro Hospitalar de São João, Porto 4200, Portugal
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Vranić L, Radovan A, Poropat G, Mikolašević I, Milić S. Non-Alcoholic Fatty Liver Disease and COVID-19-Two Pandemics Hitting at the Same Time. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:1057. [PMID: 34684094 PMCID: PMC8540462 DOI: 10.3390/medicina57101057] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 09/29/2021] [Accepted: 10/01/2021] [Indexed: 01/08/2023]
Abstract
The COVID-19 pandemic was and still is a global burden with more than 178,000,000 cases reported so far. Although it mainly affects respiratory organs, COVID-19 has many extrapulmonary manifestations, including, among other things, liver injury. Many hypotheses have been proposed to explain direct and indirect impacts of the SARS-CoV-2 virus on the liver. Studies have shown that around 15-30% of patients with COVID-19 have underlying liver disease, and 20-35% of patients with COVID-19 had altered liver enzymes at admission. One of the hypotheses is reactivation of an underlying liver disease, such as non-alcoholic fatty liver disease (NAFLD). Some studies have shown that NAFLD is associated with severe COVID-19 and poor outcome; nevertheless, other studies showed no significant difference between groups in comparing complications and clinical outcomes. Patients with NAFLD may suffer severe COVID-19 due to other comorbidities, especially cardiovascular diseases. The link between NAFLD and COVID-19 is not clear yet, and further studies and research are needed.
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Affiliation(s)
- Luka Vranić
- Department of Gastroenterology and Hepatology, University Hospital Centre Rijeka, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia; (A.R.); (G.P.); (I.M.)
| | | | | | | | - Sandra Milić
- Department of Gastroenterology and Hepatology, University Hospital Centre Rijeka, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia; (A.R.); (G.P.); (I.M.)
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Mikolasevic I, Bozic D, Pavić T, Ruzic A, Hauser G, Radic M, Radic-Kristo D, Razov-Radas M, Puljiz Z, Milic S. Liver disease in the era of COVID-19: Is the worst yet to come? World J Gastroenterol 2021; 27:6039-6052. [PMID: 34629818 PMCID: PMC8476340 DOI: 10.3748/wjg.v27.i36.6039] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 07/18/2021] [Accepted: 09/01/2021] [Indexed: 02/06/2023] Open
Abstract
The global social, economic and political crises related to coronavirus disease 2019 (COVID-19) presumably had more indirect than direct negative impacts on health systems. Drastic lifestyle changes, social isolation and distancing, and individual and global financial crises resulted in robust populations forfeiting healthy habits and seeking comfort in alcoholic beverages, drugs and unhealthy diets. The inevitable consequences are increases in the incidence of nonalcoholic fatty liver disease, viral hepatitis, acute alcoholic hepatitis, liver cirrhosis decompensation and ultimately liver-related mortality. The inaccessibility of regular clinical and sonographic monitoring systems has caused difficulties in the treatment of patients with chronic liver disease (CLD) and has prevented prompt hepatocellular carcinoma detection and treatment. A dramatic reduction in the number of liver donors and the transformation of numerous transplantation centers into COVID-19 units drastically decreased the rate of orthotopic liver transplantation. The indirect, unavoidable effects of the COVID-19 pandemic in the following years have yet to be determined. Substantial efforts in the management of patients with liver disease in order to overcome the inevitable COVID-19-related morbidity and mortality that will follow have yet to be initiated. Several questions regarding the impact of the COVID-19 pandemic on liver disease remain. The most important question for general CLD patients is: How will the modification of clinical practice during this pandemic affect the outcomes of CLD patients? This article reviews the influence of COVID-19 on patients with liver disease during the pandemic, with particular emphasis on the disease course associated with pandemic resolution.
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Affiliation(s)
- Ivana Mikolasevic
- Department of Gastroenterology, Clinical Hospital Center Rijeka, Rijeka 51000, Croatia
- Department of Gastroenterology, University Hospital Merkur, Zagreb 10000, Croatia
- Faculty of Medicine, University of Rijeka, Rijeka 51000, Croatia
| | - Dorotea Bozic
- Department for Gastroenterology and Hepatology, University Hospital Center Split, Split 21000, Croatia
| | - Tajana Pavić
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Sestre Milosrdnice University Hospital Center, Zagreb 10000, Croatia
| | - Alen Ruzic
- Faculty of Medicine, University of Rijeka, Rijeka 51000, Croatia
- Clinic for Cardiology, University Hospital Center Rijeka, Rijeka 51000, Croatia
| | - Goran Hauser
- Department of Gastroenterology, Clinical Hospital Center Rijeka, Rijeka 51000, Croatia
- Faculty of Medicine, University of Rijeka, Rijeka 51000, Croatia
- Faculty of Health Studies, University of Rijeka, Rijeka 51000, Croatia
| | | | - Delfa Radic-Kristo
- Faculty of Medicine, Zagreb 10000, Croatia
- Department of Hematology, University Hospital Merkur, Zagreb 10000, Croatia
| | | | - Zeljko Puljiz
- Department for Gastroenterology and Hepatology, University Hospital Center Split, Split 21000, Croatia
- University of Split, School of Medicine, Split 21000, Croatia
| | - Sandra Milic
- Department of Gastroenterology, Clinical Hospital Center Rijeka, Rijeka 51000, Croatia
- Faculty of Medicine, University of Rijeka, Rijeka 51000, Croatia
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Ristic-Medic D, Petrovic S, Arsic A, Vucic V. Liver disease and COVID-19: The link with oxidative stress, antioxidants and nutrition. World J Gastroenterol 2021; 27:5682-5699. [PMID: 34629794 PMCID: PMC8473601 DOI: 10.3748/wjg.v27.i34.5682] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/11/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023] Open
Abstract
Varying degrees of liver injuries have been reported in patients infected with the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). In general, oxidative stress is actively involved in initiation and progression of liver damage. The liver metabolizes various compounds that produce free radicals. Maintaining the oxidative/antioxidative balance is important in coronavirus disease 2019 (COVID-19) patients. Antioxidant vitamins, essential trace elements and food compounds, such as polyphenols, appear to be promising agents, with effects in oxidative burst. Deficiency of these nutrients suppresses immune function and increases susceptibility to COVID-19. Daily micronutrient intake is necessary to support anti-inflammatory and antioxidative effects but for immune function may be higher than current recommended dietary intake. Antioxidant supplements (β-carotene, vitamin A, vitamin C, vitamin E, and selenium) could have a potential role in patients with liver damage. Available evidence suggests that supplementing the diet with a combination of micronutrients may help to optimize immune function and reduce the risk of infection. Clinical trials based on the associations of diet and SARS-CoV-2 infection are lacking. Unfortunately, it is not possible to definitively determine the dose, route of administration and best timing to intervene with antioxidants in COVID-19 patients because clinical trials are still ongoing. Until then, hopefully, this review will enable clinicians to understand the impact of micronutrient dietary intake and liver status assessment in COVID-19 patients.
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Affiliation(s)
- Danijela Ristic-Medic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, National Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Snjezana Petrovic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, National Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Aleksandra Arsic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, National Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Vesna Vucic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, National Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
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47
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Mohapatra RK, Dhama K, Mishra S, Sarangi AK, Kandi V, Tiwari R, Pintilie L. The microbiota-related coinfections in COVID-19 patients: a real challenge. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2021; 10:47. [PMID: 34458380 PMCID: PMC8380112 DOI: 10.1186/s43088-021-00134-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 07/29/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of ongoing global pandemic of coronavirus disease 2019 (COVID-19), has infected millions of people around the world, especially the elderly and immunocompromised individuals. The infection transmission rate is considered more rapid than other deadly pandemics and severe epidemics encountered earlier, such as Ebola, Zika, Influenza, Marburg, SARS, and MERS. The public health situation therefore is really at a challenging crossroads. MAIN BODY The internal and external and resident microbiota community is crucial in human health and is essential for immune responses. This community tends to be altered due to pathogenic infections which would lead to severity of the disease as it progresses. Few of these resident microflora become negatively active during infectious diseases leading to coinfection, especially the opportunistic pathogens. Once such a condition sets in, it is difficult to diagnose, treat, and manage COVID-19 in a patient. CONCLUSION This review highlights the various reported possible coinfections that arise in COVID-19 patients vis-à-vis other serious pathological conditions. The local immunity in lungs, nasal passages, oral cavity, and salivary glands are involved with different aspects of COVID-19 transmission and pathology. Also, the role of adaptive immune system is discussed at the site of infection to control the infection along with the proinflammatory cytokine therapy.
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Affiliation(s)
- Ranjan K. Mohapatra
- Department of Chemistry, Government College of Engineering, Keonjhar, Odisha 758002 India
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh 243122 India
| | - Snehasish Mishra
- School of Biotechnology, KIIT University, Bhubaneswar, Odisha 751024 India
| | - Ashish K. Sarangi
- Department of Chemistry, School of Applied Sciences, Centurion University of Technology and Management, Odisha, India
| | - Venkataramana Kandi
- Department of Microbiology, Prathima Institute of Medical Sciences, Karimnagar, Telangana India
| | - Ruchi Tiwari
- Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, Uttar Pradesh Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go Anusandhan Sansthan (DUVASU), Mathura, 281001 India
| | - Lucia Pintilie
- Department of Synthesis of Bioactive Substances and Pharmaceutical Technologies, National Institute for Chemical and Pharmaceutical Research and Development, Bucharest, Romania
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Levy E, Stintzi A, Cohen A, Desjardins Y, Marette A, Spahis S. Critical appraisal of the mechanisms of gastrointestinal and hepatobiliary infection by COVID-19. Am J Physiol Gastrointest Liver Physiol 2021; 321:G99-G112. [PMID: 34009033 PMCID: PMC8289353 DOI: 10.1152/ajpgi.00106.2021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
COVID-19 represents a novel infectious disease induced by SARS-CoV-2. It has to date affected 24,240,000 individuals and killed 2,735,805 people worldwide. The highly infectious virus attacks mainly the lung, causing fever, cough, and fatigue in symptomatic patients, but also pneumonia in severe cases. However, growing evidence highlights SARS-CoV-2-mediated extrarespiratory manifestations, namely, gastrointestinal (GI) and hepatic complications. The detection of 1) the virus in the GI system (duodenum, colon, rectum, anal region, and feces); 2) the high expression of additional candidate coreceptors/auxiliary proteins to facilitate the virus entry; 3) the abundant viral angiotensin-converting enzyme 2 receptor; 4) the substantial expression of host transmembrane serine protease 2, necessary to induce virus-cell fusion; 5) the viral replication in the intestinal epithelial cells; and 6) the primarily GI disorders in the absence of respiratory symptoms lead to increased awareness of the risk of disease transmission via the fecal-oral route. The objectives of this review are to provide a brief update of COVID-19 pathogenesis and prevalence, present a critical overview of its GI and liver complications that affect clinical COVID-19 outcomes, clarify associated mechanisms (notably microbiota-related), define whether gut/liver disorders occur more frequently among critically ill patients with COVID-19, determine the impact of COVID-19 on preexisting gut/liver complications and vice versa, and discuss the available strategies for prevention and treatment to improve prognosis of the patients. The novel SARS-CoV-2 can cause gastrointestinal and hepatobiliary manifestations. Metagenomics studies of virobiota in response to SARS-CoV-2 infection are necessary to highlight the contribution of bacterial microflora to COVID-19 phenotype, which is crucial for developing biomarkers and therapeutics.
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Affiliation(s)
- Emile Levy
- 1Research Centre, Sainte-Justine University Health Center, Université de Montréal, Quebec, Canada,2Department of Nutrition, Université de Montréal, Quebec, Canada,3Department of Pediatrics, Gastroenterology and Hepatology Unit, Université de Montréal, Quebec, Canada,4Institute of Nutrition and Functional Foods, Laval University, Quebec, Canada
| | - Alain Stintzi
- 5Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ontario, Canada
| | - Albert Cohen
- 6Division of Gastroenterology, Jewish General Hospital, Quebec, Canada
| | - Yves Desjardins
- 4Institute of Nutrition and Functional Foods, Laval University, Quebec, Canada
| | - André Marette
- 4Institute of Nutrition and Functional Foods, Laval University, Quebec, Canada
| | - Schohraya Spahis
- 1Research Centre, Sainte-Justine University Health Center, Université de Montréal, Quebec, Canada,2Department of Nutrition, Université de Montréal, Quebec, Canada,4Institute of Nutrition and Functional Foods, Laval University, Quebec, Canada
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A case of secondary sclerosing cholangitis due to COVID-19. Clin Imaging 2021; 80:239-242. [PMID: 34364072 PMCID: PMC8314797 DOI: 10.1016/j.clinimag.2021.07.017] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 06/24/2021] [Accepted: 07/20/2021] [Indexed: 02/06/2023]
Abstract
COVID-19 was first recognized by the World Health Organization (WHO) in December 2019 and declared a global pandemic in March 2020. Although COVID-19 primarily results in pulmonary symptoms, it is becoming apparent that it can lead to multisystemic manifestations. Liver damage with elevated AST and ALT is seen in patients with COVID-19. Although the etiology of liver damage is still debated, biliary damage is rarely seen. This case demonstrates a potential complication of COVID-19 in a previously healthy patient. The patient contracted COVID-19 in March 2020 and endured a complicated course including intubation, multiple readmissions, and chronic abdominal pain. He is now awaiting a liver transplant. Our case portrays biliary damage as an additional possible complication of COVID-19 and the importance of imaging in its diagnosis.
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Huang YK, Li YJ, Li B, Wang P, Wang QH. Dysregulated liver function in SARS-CoV-2 infection: Current understanding and perspectives. World J Gastroenterol 2021; 27:4358-4370. [PMID: 34366609 PMCID: PMC8316914 DOI: 10.3748/wjg.v27.i27.4358] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 05/15/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Abstract
Since it was first reported in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread rapidly around the world to cause the ongoing pandemic. Although the clinical manifestations of SARS-CoV-2 infection are predominantly in the respiratory system, liver enzyme abnormalities exist in around half of the cases, which indicate liver injury, and raise clinical concern. At present, there is no consensus whether the liver injury is directly caused by viral replication in the liver tissue or indirectly by the systemic inflammatory response. This review aims to summarize the clinical manifestations and to explore the underlying mechanisms of liver dysfunction in patients with SARS-CoV-2 infection.
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Affiliation(s)
- Yi-Ke Huang
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory for Transfusion-transmitted Infectious Diseases of the Health Commission of Sichuan Province, Chengdu 610052, Sichuan Province, China
| | - Yu-Jia Li
- Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory for Transfusion-transmitted Infectious Diseases of the Health Commission of Sichuan Province, Chengdu 610052, Sichuan Province, China
- Joint laboratory on Transfusion-transmitted Diseases between Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Nanning Blood Center, Nanning 530007, Guangxi Zhuang Autonomous Region, China
| | - Bin Li
- Joint laboratory on Transfusion-transmitted Diseases between Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Nanning Blood Center, Nanning 530007, Guangxi Zhuang Autonomous Region, China
| | - Pan Wang
- Department of Emergency, The Traditional Chinese Medicine Hospital of Wenjiang District, Chengdu 611130, Sichuan Province, China
| | - Qing-Hua Wang
- Department of Emergency, The Traditional Chinese Medicine Hospital of Wenjiang District, Chengdu 611130, Sichuan Province, China
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