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Boglione L, Crobu MG, Pirisi M, Smirne C. Clinical Characteristics and Outcomes in Patients with Chronic HBV Infection and Hospitalized for COVID-19 Pneumonia: A Retrospective Cohort Study. Viruses 2024; 17:40. [PMID: 39861829 PMCID: PMC11769566 DOI: 10.3390/v17010040] [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: 11/06/2024] [Revised: 12/27/2024] [Accepted: 12/27/2024] [Indexed: 01/27/2025] Open
Abstract
The effects of a concomitant infection of hepatitis B virus (HBV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still debated, with a recognized major risk of HBV reactivation during immune-suppressive treatments. The aim of this study was to determine the prevalence and predictive factors of HBV reactivation in a cohort of hospitalized patients with coronavirus disease 2019 (COVID-19) and a current or past hepatitis B infection. In a monocentric retrospective observational study, we enrolled all consecutive hospital admitted patients with COVID-19 pneumonia and a positive HBV serology (N = 84) in our Infectious Diseases Unit from April 2021 to December 2023. We identified 18 (21%) HBsAg-positive/anti-HBc-positive, 41 (49%) HBsAg-negative/anti-HBc-positive/anti-HBs-positive, and 25 (30%) HBsAg-negative/anti-HBc-positive/anti-HBs-negative subjects. The overall rate of hepatitis flare was 10.7%, without any HBsAg seroreversion, severe HBV reactivation, and/or need for new HBV antiviral therapy introduction. Systemic corticosteroid treatment for COVID-19 and baseline anti-HBsAg status were associated with this risk of HBV reactivation. In conclusion, the overall risk of hepatitis flares in hospitalized COVID-19 was reasonably low, with higher doses of corticosteroids treatment being the major risk factor for HBV reactivation, and anti-HBs-positive serological status as a protective element.
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Affiliation(s)
- Lucio Boglione
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (L.B.); (M.P.)
| | - Maria Grazia Crobu
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy;
- Clinical Biochemistry Laboratory, City of Health and Science University Hospital, 10126 Turin, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (L.B.); (M.P.)
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy
| | - Carlo Smirne
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (L.B.); (M.P.)
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy
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Xu W, Langhans SA, Johnson DK, Stauff E, Kandula VVR, Kecskemethy HH, Averill LW, Yue X. Radiotracers for Molecular Imaging of Angiotensin-Converting Enzyme 2. Int J Mol Sci 2024; 25:9419. [PMID: 39273366 PMCID: PMC11395405 DOI: 10.3390/ijms25179419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 08/23/2024] [Accepted: 08/24/2024] [Indexed: 09/15/2024] Open
Abstract
Angiotensin-converting enzymes (ACE) are well-known for their roles in both blood pressure regulation via the renin-angiotensin system as well as functions in fertility, immunity, hematopoiesis, and many others. The two main isoforms of ACE include ACE and ACE-2 (ACE2). Both isoforms have similar structures and mediate numerous effects on the cardiovascular system. Most remarkably, ACE2 serves as an entry receptor for SARS-CoV-2. Understanding the interaction between the virus and ACE2 is vital to combating the disease and preventing a similar pandemic in the future. Noninvasive imaging techniques such as positron emission tomography and single photon emission computed tomography could noninvasively and quantitatively assess in vivo ACE2 expression levels. ACE2-targeted imaging can be used as a valuable tool to better understand the mechanism of the infection process and the potential roles of ACE2 in homeostasis and related diseases. Together, this information can aid in the identification of potential therapeutic drugs for infectious diseases, cancer, and many ACE2-related diseases. The present review summarized the state-of-the-art radiotracers for ACE2 imaging, including their chemical design, pharmacological properties, radiochemistry, as well as preclinical and human molecular imaging findings. We also discussed the advantages and limitations of the currently developed ACE2-specific radiotracers.
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Affiliation(s)
- Wenqi Xu
- Department of Radiology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA; (W.X.); (E.S.); (V.V.R.K.); (H.H.K.); (L.W.A.)
- Diagnostic & Research PET/MR Center, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA;
| | - Sigrid A. Langhans
- Diagnostic & Research PET/MR Center, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA;
- Division of Neurology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA
| | - David K. Johnson
- Computational Chemical Biology Core, Molecular Graphics and Modeling Laboratory, University of Kansas, Lawrence, KS 66047, USA;
| | - Erik Stauff
- Department of Radiology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA; (W.X.); (E.S.); (V.V.R.K.); (H.H.K.); (L.W.A.)
- Diagnostic & Research PET/MR Center, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA;
| | - Vinay V. R. Kandula
- Department of Radiology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA; (W.X.); (E.S.); (V.V.R.K.); (H.H.K.); (L.W.A.)
| | - Heidi H. Kecskemethy
- Department of Radiology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA; (W.X.); (E.S.); (V.V.R.K.); (H.H.K.); (L.W.A.)
- Diagnostic & Research PET/MR Center, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA;
| | - Lauren W. Averill
- Department of Radiology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA; (W.X.); (E.S.); (V.V.R.K.); (H.H.K.); (L.W.A.)
- Diagnostic & Research PET/MR Center, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA;
| | - Xuyi Yue
- Department of Radiology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA; (W.X.); (E.S.); (V.V.R.K.); (H.H.K.); (L.W.A.)
- Diagnostic & Research PET/MR Center, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA;
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Nasir N, Khanum I, Habib K, Wagley A, Arshad A, Majeed A. Insight into COVID-19 associated liver injury: Mechanisms, evaluation, and clinical implications. HEPATOLOGY FORUM 2024; 5:139-149. [PMID: 39006140 PMCID: PMC11237249 DOI: 10.14744/hf.2023.2023.0025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Revised: 07/25/2023] [Accepted: 11/02/2023] [Indexed: 07/16/2024]
Abstract
COVID-19 has affected millions worldwide, causing significant morbidity and mortality. While predominantly involving the respiratory tract, SARS-CoV-2 has also caused systemic illnesses involving other sites. Liver injury due to COVID-19 has been variably reported in observational studies. It has been postulated that liver damage may be due to direct damage by the SARS-CoV-2 virus or multifactorial secondary to hepatotoxic therapeutic options, as well as cytokine release syndrome and sepsis-induced multiorgan dysfunction. The approach to a COVID-19 patient with liver injury requires a thorough evaluation of the pattern of hepatocellular injury, along with the presence of underlying chronic liver disease and concurrent medications which may cause drug-induced liver injury. While studies have shown uneventful recovery in the majority of mildly affected patients, severe COVID-19 associated liver injury has been associated with higher mortality, prolonged hospitalization, and greater morbidity in survivors. Furthermore, its impact on long-term outcomes remains to be ascertained as recent studies report an association with metabolic-fatty liver disease. This present review provides insight into the subject by describing the postulated mechanism of liver injury, its impact in the presence of pre-existing liver disease, and its short- and long-term clinical implications.
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Affiliation(s)
- Nosheen Nasir
- Section of Adult Infectious Diseases, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Iffat Khanum
- Section of Adult Infectious Diseases, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Kiren Habib
- Section of Adult Infectious Diseases, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Abdullah Wagley
- Research Facilitation Office, Medical College, Aga Khan University, Karachi, Pakistan
| | - Aleena Arshad
- Section of Adult Infectious Diseases, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Atif Majeed
- Section of Gastroenterology, Department of Medicine, Aga Khan University, Karachi, Pakistan
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Rodriguez-Espada A, Salgado-de la Mora M, Rodriguez-Paniagua BM, Limon-de la Rosa N, Martinez-Gutierrez MI, Pastrana-Brandes S, Navarro-Alvarez N. Histopathological impact of SARS-CoV-2 on the liver: Cellular damage and long-term complications. World J Gastroenterol 2024; 30:2866-2880. [PMID: 38947288 PMCID: PMC11212712 DOI: 10.3748/wjg.v30.i22.2866] [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: 03/08/2024] [Revised: 05/08/2024] [Accepted: 05/24/2024] [Indexed: 06/05/2024] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and in vitro liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.
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Affiliation(s)
- Alfonso Rodriguez-Espada
- Department of Molecular Biology, Universidad Panamericana School of Medicine, Campus México, Mexico 03920, Mexico
| | - Moises Salgado-de la Mora
- Department of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico 14080, Mexico
| | | | - Nathaly Limon-de la Rosa
- Department of Surgery, University of Colorado Anschutz Medical Campus, Denver, CO 80045, United States
| | | | - Santiago Pastrana-Brandes
- Department of Molecular Biology, Universidad Panamericana School of Medicine, Campus México, Mexico 03920, Mexico
| | - Nalu Navarro-Alvarez
- Department of Molecular Biology, Universidad Panamericana School of Medicine, Campus México, Mexico 03920, Mexico
- Department of Surgery, University of Colorado Anschutz Medical Campus, Denver, CO 80045, United States
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico 14080, Mexico
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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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Quarleri J, Delpino MV. Molecular mechanisms underlying SARS-CoV-2 hepatotropism and liver damage. World J Hepatol 2024; 16:1-11. [PMID: 38313242 PMCID: PMC10835487 DOI: 10.4254/wjh.v16.i1.1] [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: 10/26/2023] [Revised: 12/04/2023] [Accepted: 12/28/2023] [Indexed: 01/23/2024] Open
Abstract
In coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) primarily targets the respiratory system, but evidence suggests extrapulmonary organ involvement, notably in the liver. Viral RNA has been detected in hepatic tissues, and in situ hybridization revealed virions in blood vessels and endothelial cells. Electron microscopy confirmed viral particles in hepatocytes, emphasizing the need for understanding hepatotropism and direct cytopathic effects in COVID-19-related liver injury. Various factors contribute to liver injury, including direct cytotoxicity, vascular changes, inflammatory responses, immune reactions from COVID-19 and vaccinations, and drug-induced liver injury. Although a typical hepatitis presentation is not widely documented, elevated liver biochemical markers are common in hospitalized COVID-19 patients, primarily showing a hepatocellular pattern of elevation. Long-term studies suggest progressive cholestasis may affect 20% of patients with chronic liver disease post-SARS-CoV-2 infection. The molecular mechanisms underlying SARS-CoV-2 infection in the liver and the resulting liver damage are complex. This "Editorial" highlights the expression of the Angiotensin-converting enzyme-2 receptor in liver cells, the role of inflammatory responses, the impact of hypoxia, the involvement of the liver's vascular system, the infection of bile duct epithelial cells, the activation of hepatic stellate cells, and the contribution of monocyte-derived macrophages. It also mentions that pre-existing liver conditions can worsen the outcomes of COVID-19. Understanding the interaction of SARS-CoV-2 with the liver is still evolving, and further research is required.
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Affiliation(s)
- Jorge Quarleri
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1121, Argentina.
| | - M Victoria Delpino
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1121, Argentina
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Zaidi AK, Singh RB, A A Rizvi S, Dehgani-Mobaraki P, Palladino N. COVID-19 pathogenesis. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2024; 202:67-112. [PMID: 38237991 DOI: 10.1016/bs.pmbts.2023.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/23/2024]
Abstract
The pathogenesis of COVID-19 involves a complex interplay between host factors and the SARS-CoV-2 virus, leading to a multitude of clinical manifestations beyond the respiratory system. This chapter provides an overview of the risk factors, genetic predisposition, and multisystem manifestations of COVID-19, shedding light on the underlying mechanisms that contribute to extrapulmonary manifestations. The chapter discusses the direct invasion of SARS-CoV-2 into various organs as well as the indirect mechanisms such as dysregulation of the renin-angiotensin-aldosterone system (RAAS), immune response dysfunctions within the innate and adaptive immune systems, endothelial damage, and immunothrombosis. Furthermore, the multisystem manifestations of COVID-19 across different organ systems, including the cardiovascular, renal, gastrointestinal, hepatobiliary, nervous, endocrine and metabolic, ophthalmic, ear-nose-throat, reproductive, hematopoietic, and immune systems are discussed in detail. Each system exhibits unique manifestations that contribute to the complexity of the disease.
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Affiliation(s)
| | - Rohan Bir Singh
- Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States; Department of Population, Policy and Practice, Greater Ormond Street Institute of Child Health, University College London, United Kingdom; Discipline of Ophthalmology and Visual Sciences, Adelaide Medical School, University of Adelaide, Australia
| | - Syed A A Rizvi
- College of Biomedical Sciences, Larkin University, Miami, Florida, United States.
| | - Puya Dehgani-Mobaraki
- Founder and President, Associazione Naso Sano, Ringgold Institution ID 567754, San Mariano, Italy.
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Wang Y, Shen M, Li Y, Shao J, Zhang F, Guo M, Zhang Z, Zheng S. COVID-19-associated liver injury: Adding fuel to the flame. Cell Biochem Funct 2023; 41:1076-1092. [PMID: 37947373 DOI: 10.1002/cbf.3883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 10/19/2023] [Accepted: 10/21/2023] [Indexed: 11/12/2023]
Abstract
COVID-19 is mainly characterized by respiratory disorders and progresses to multiple organ involvement in severe cases. With expansion of COVID-19 and SARS-CoV-2 research, correlative liver injury has been revealed. It is speculated that COVID-19 patients exhibited abnormal liver function, as previously observed in the SARS and MERS pandemics. Furthermore, patients with underlying diseases such as chronic liver disease are more susceptible to SARS-CoV-2 and indicate a poor prognosis accompanied by respiratory symptoms, systemic inflammation, or metabolic diseases. Therefore, COVID-19 has the potential to impair liver function, while individuals with preexisting liver disease suffer from much worse infected conditions. COVID-19 related liver injury may be owing to direct cytopathic effect, immune dysfunction, gut-liver axis interaction, and inappropriate medication use. However, discussions on these issues are infancy. Expanding research have revealed that angiotensin converting enzyme 2 (ACE2) expression mediated the combination of virus and target cells, iron metabolism participated in the virus life cycle and the fate of target cells, and amino acid metabolism regulated immune response in the host cells, which are all closely related to liver health. Further exploration holds great significance in elucidating the pathogenesis, facilitating drug development, and advancing clinical treatment of COVID-19-related liver injury. This article provides a review of the clinical and laboratory hepatic characteristics in COVID-19 patients, describes the etiology and impact of liver injury, and discusses potential pathophysiological mechanisms.
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Affiliation(s)
- Yingqian Wang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Min Shen
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China
| | - Yujia Li
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiangjuan Shao
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Feng Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Mei Guo
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zili Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shizhong Zheng
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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Pirola CJ, Sookoian S. SARS-CoV-2 targets the liver and manipulates glucose metabolism. Trends Mol Med 2023; 29:681-683. [PMID: 37330366 PMCID: PMC10247144 DOI: 10.1016/j.molmed.2023.06.001] [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: 05/28/2023] [Revised: 06/01/2023] [Accepted: 06/02/2023] [Indexed: 06/19/2023]
Abstract
A recent publication by Barreto and colleagues showed that SARS-CoV-2 directly triggers hyperglycemia by infecting hepatocytes and inducing phosphoenolpyruvate carboxykinase (PEPCK)-dependent gluconeogenesis. Here, we discuss the biological importance of these findings, including the hepatic tropism of SARS-CoV-2. We also comment on the clinical implications of the bidirectional connection between COVID-19 and noncommunicable diseases.
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Affiliation(s)
- Carlos J Pirola
- Systems Biology of Complex Diseases, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
| | - Silvia Sookoian
- Clinical and Molecular Hepatology, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; Maimonides University, Buenos Aires, Argentina.
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Li J, Zhang Q, Xu C, Zhang Y, Lu Y, Ai M, Tan X. Differences in clinical characteristics and liver injury between patients diagnosed with the Omicron subvariant BA.5.2 and the prototype of SARS-CoV-2: a single center retrospective study. BMC Gastroenterol 2023; 23:271. [PMID: 37553605 PMCID: PMC10408107 DOI: 10.1186/s12876-023-02907-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 07/28/2023] [Indexed: 08/10/2023] Open
Abstract
BACKGROUND The purpose of this study was to investigate the differences between the clinical characteristics and the factors influencing liver injury in patients with the Omicron subvariant BA.5.2 (Omicron BA.5.2) and the prototype of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS Between December 30, 2019 and November 30, 2022, 157 patients infected with the SARS-CoV-2 prototype and 199 patients infected with the Omicron BA.5.2 were included in this case-control, single-center, retrospective study. Differences in clinical characteristics and liver injury between the Omicron BA.5.2 patients and the prototype patients were subsequently analyzed. RESULTS None of the Omicron BA.5.2 patients reached the critical state, and showed relatively milder symptoms including fever, cough, headache, muscle soreness, nausea or vomiting, diarrhea, anorexia and hypoxia. The Omicron BA.5.2 had a lower effect on body temperature (T), white blood cell (WBC) count, hematocrit (HCT), C-reactive protein (CRP) level, D-dimer, finger pulse oxygen saturation (SpO2) and lung lesions. The differences in liver injury between the two groups were related to the severity of the disease, T, blood oxygen levels, albumin (ALB), CRP, and medication usage. Gender, body mass index, and CRP levels influenced liver damage in the Omicron BA.5.2 patients. In particular, CRP was an independent risk factor for liver injury. Because the severity of liver function damage was considerably low, only a small number of Omicron BA.5.2 patients required liver-protective treatment. CONCLUSION Liver injury is expected in the COVID-19 patients. The Omicron BA.5.2 patients showed milder symptoms of liver injury than the prototype patients. However, dynamic monitoring of liver function is warranted, especially for individuals presenting with elevated levels of CRP.
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Affiliation(s)
- Jie Li
- Department of Gastroenterology, Jingzhou of Hubei Province, First Hospital of Yangtze University, Jingzhou, China
- Digestive Disease Research Institution of Yangtze University, Jingzhou, China
| | - Qing Zhang
- Department of Gastroenterology, Jingzhou of Hubei Province, First Hospital of Yangtze University, Jingzhou, China
- Digestive Disease Research Institution of Yangtze University, Jingzhou, China
- Clinical medical college, Jingzhou of Hubei Province, Yangtze University, Jingzhou, China
| | - Chao Xu
- Department of Gastroenterology, Jingzhou of Hubei Province, First Hospital of Yangtze University, Jingzhou, China
- Digestive Disease Research Institution of Yangtze University, Jingzhou, China
| | - Yan Zhang
- Department of Gastroenterology, Jingzhou of Hubei Province, First Hospital of Yangtze University, Jingzhou, China
- Digestive Disease Research Institution of Yangtze University, Jingzhou, China
| | - Yueyue Lu
- Department of Gastroenterology, Jingzhou of Hubei Province, First Hospital of Yangtze University, Jingzhou, China
- Digestive Disease Research Institution of Yangtze University, Jingzhou, China
| | - Minghua Ai
- Department of Gastroenterology, Jingzhou of Hubei Province, First Hospital of Yangtze University, Jingzhou, China
- Digestive Disease Research Institution of Yangtze University, Jingzhou, China
| | - Xiaoping Tan
- Department of Gastroenterology, Jingzhou of Hubei Province, First Hospital of Yangtze University, Jingzhou, China.
- Digestive Disease Research Institution of Yangtze University, Jingzhou, China.
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Zhu K, Tsai O, Chahal D, Hussaini T, Yoshida EM. COVID-19 and Liver Disease: An Evolving Landscape. Semin Liver Dis 2023; 43:351-366. [PMID: 37604206 DOI: 10.1055/a-2157-3318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/23/2023]
Abstract
The COVID-19 pandemic has resulted in significant worldwide morbidity and mortality. In this review, we examine the intricate relationships between COVID-19 and liver diseases. While respiratory manifestations of COVID-19 are well known, its impact and consequences in patients with liver diseases remain an area of ongoing investigation. COVID-19 can induce liver injury through various mechanisms and is associated with higher mortality in individuals with preexisting chronic liver disease. Mortality increases with the severity of chronic liver disease and the level of care required. The outcomes in patients with autoimmune hepatitis remain unclear, whereas liver transplant recipients are more likely to experience symptomatic COVID-19 but have comparable outcomes to the general population. Despite suboptimal immunological response, COVID-19 vaccinations are safe and effective in liver disease, although cases of autoimmune hepatitis-like syndrome have been reported. In conclusion, COVID-19 has significant implications in liver diseases; early recognition and treatments are important for improving patient outcomes.
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Affiliation(s)
- Kai Zhu
- Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Olivia Tsai
- Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Daljeet Chahal
- Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
- BC Liver Transplant Program, Vancouver, British Columbia, Canada
| | - Trana Hussaini
- BC Liver Transplant Program, Vancouver, British Columbia, Canada
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
| | - Eric M Yoshida
- Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
- BC Liver Transplant Program, Vancouver, British Columbia, Canada
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12
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Liguori A, Calvez V, D’Ambrosio F, Sciarra A, Marrone G, Biolato M, Grieco A, Gasbarrini A, Alisi A, Miele L. The bidirectional relationship between fatty liver disease and COVID-19. METABOLISM AND TARGET ORGAN DAMAGE 2023; 3. [DOI: 10.20517/mtod.2022.36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/09/2025]
Abstract
COVID-19 and nonalcoholic fatty liver disease (NAFLD) have emerged as global pandemics affecting millions of people worldwide over the past three years. NAFLD is particularly prevalent in individuals with metabolic comorbidities, such as diabetes and obesity, which have been strongly linked to a severe course of Sars-CoV-2 infection. Recently, due to the close association between metabolic abnormalities and NAFLD, the disease has been redefined as metabolic dysfunction-associated fatty liver disease (MAFLD). This review offers an overview of the biological and cellular mechanisms by which COVID-19 can cause liver damage, with a specific focus on the influence of fatty liver in these mechanisms. Additionally, it explores how fatty liver can exacerbate a COVID-19 infection and, conversely, if the presence of COVID-19 may accelerate the development and progression of fatty liver. Finally, the review examines the existing evidence suggesting that NAFLD or MAFLD independently contributes to a heightened severity of COVID-19, while also considering other factors such as age and metabolic comorbidities that may play a role in the disease’s progression.
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13
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Mangoni AA, Zinellu A. An Updated Systematic Review and Meta-Analysis of the Association between the De Ritis Ratio and Disease Severity and Mortality in Patients with COVID-19. Life (Basel) 2023; 13:1324. [PMID: 37374107 DOI: 10.3390/life13061324] [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: 05/16/2023] [Accepted: 06/01/2023] [Indexed: 06/29/2023] Open
Abstract
Patients with Coronavirus disease 2019 (COVID-19) often have elevations in markers of liver injury, particularly serum aspartate transaminase (AST) and alanine transaminase (ALT). Such alterations may affect the AST/ALT ratio (De Ritis ratio) and, potentially, clinical outcomes. We conducted an updated systematic review and meta-analysis of the association between the De Ritis ratio and COVID-19 severity and mortality in hospitalized patients. PubMed, Web of Science, and Scopus were searched between 1 December 2019 and 15 February 2023. The Joanna Briggs Institute Critical Appraisal Checklist and the Grading of Recommendations, Assessment, Development, and Evaluation were used to assess the risk of bias and the certainty of the evidence, respectively. Twenty-four studies were identified. The De Ritis ratio on admission was significantly higher in patients with severe disease and non-survivors vs. patients with non-severe disease and survivors (15 studies, weighted mean difference = 0.36, 95% CI 0.24 to 0.49, p < 0.001). The De Ritis ratio was also associated with severe disease and/or mortality using odds ratios (1.83, 95% CI 1.40 to 2.39, p ˂ 0.001; nine studies). Similar results were observed using hazard ratios (2.36, 95% CI 1.17 to 4.79, p = 0.017; five studies). In six studies, the pooled area under the receiver operating characteristic curve was 0.677 (95% CI 0.612 to 0.743). In our systematic review and meta-analysis, higher De Ritis ratios were significantly associated with severe disease and mortality in COVID-19 patients. Therefore, the De Ritis ratio can be useful for early risk stratification and management in this patient group (PROSPERO registration number: CRD42023406916).
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Affiliation(s)
- Arduino A Mangoni
- Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, Australia
- Department of Clinical Pharmacology, Flinders Medical Centre, Southern Adelaide Local Health Network, Bedford Park, SA 5042, Australia
| | - Angelo Zinellu
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
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14
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Pesti A, Danics K, Glasz T, Várkonyi T, Barbai T, Reszegi A, Kovalszky I, Vályi-Nagy I, Dobi D, Lotz G, Schaff Z, Kiss A. Liver alterations and detection of SARS-CoV-2 RNA and proteins in COVID-19 autopsies. GeroScience 2023; 45:1015-1031. [PMID: 36527584 PMCID: PMC9759055 DOI: 10.1007/s11357-022-00700-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 11/20/2022] [Indexed: 12/23/2022] Open
Abstract
The most severe alterations in Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection are seen in the lung. However, other organs also are affected. Here, we report histopathologic findings in the liver and detection of viral proteins and RNA in COVID-19 autopsies performed at the Semmelweis University (Budapest, Hungary). Between March 2020 through March 2022, 150 autopsies on patients who died of COVID-19 were analyzed. Cause-of-death categories were formed based on the association with SARS-CoV-2 as strong, contributive, or weak. Samples for histopathologic study were obtained from all organs, fixed in formalin, and embedded in paraffin (FFPE). Immunohistochemical study (IHC) to detect SARS-CoV-2 spike protein and nucleocapsid protein (NP), CD31, claudin-5, factor VIII, macrosialin (CD68), and cytokeratin 7, with reverse transcriptase polymerase chain reaction (RT-PCR), and in situ hybridization (ISH, RNAscope®) for SARS-CoV-2 RNA were conducted using FFPE samples of livers taken from 20 autopsies performed ≤ 2 days postmortem. All glass slides were scanned; the digital images were evaluated by semiquantitative scoring and scores were analyzed statistically. Steatosis, single-cell and focal/zonal hepatocyte necrosis, portal fibrosis, and chronic inflammation were found in varying percentages. Sinusoidal ectasia, endothelial cell disruption, and fibrin-filled sinusoids were seen in all cases; these were assessed semiquantitatively for severity (SEF scored). SEF scores did not correlate with cause-of-death categories (p = 0.92) or with severity of lung alterations (p = 0.96). SARS-CoV-2 RNA was detected in 13/20 cases by PCR and in 9/20 by ISH, with IHC demonstration of spike protein in 4/20 cases and NP in 15/20. Viral RNA and proteins were located in endothelial and Kupffer cells, and in portal macrophages, but not in hepatocytes and cholangiocytes. In conclusion, endothelial damage (SEF scores) was the most common alteration in the liver and was a characteristic, but not specific alteration in COVID-19, suggesting an important role in the pathogenesis of COVID-19-associated liver disease. Detection of SARS-CoV-2 RNA and viral proteins in liver non-parenchymal cells suggests that while the most extended primary viral cytotoxic effect occurs in the lung, viral components are present in other organs too, as in the liver. The necrosis/apoptosis and endothelial damage associated with viral infection in COVID-19 suggest that those patients who survive more severe COVID-19 may face prolonged liver repair and accordingly should be followed regularly in the post-COVID period.
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Affiliation(s)
- Adrián Pesti
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Krisztina Danics
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Tibor Glasz
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Tibor Várkonyi
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Tamás Barbai
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Andrea Reszegi
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Ilona Kovalszky
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - István Vályi-Nagy
- Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases, Budapest, Hungary
| | - Deján Dobi
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Gábor Lotz
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Zsuzsa Schaff
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary.
| | - András Kiss
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
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15
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Lücke J, Nawrocki M, Schnell J, Meins N, Heinrich F, Zhang T, Bertram F, Sabihi M, Böttcher M, Blankenburg T, Pfaff M, Notz S, Kempski J, Reeh M, Wolter S, Mann O, Izbicki JR, Lütgehetmann M, Duprée A, Giannou AD, Ondruschka B, Huber S. TNFα aggravates detrimental effects of SARS-CoV-2 infection in the liver. Front Immunol 2023; 14:1151937. [PMID: 37063909 PMCID: PMC10102423 DOI: 10.3389/fimmu.2023.1151937] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 03/14/2023] [Indexed: 04/03/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus does not only lead to pulmonary infection but can also infect other organs such as the gut, the kidney, or the liver. Recent studies confirmed that severe cases of COVID-19 are often associated with liver damage and liver failure, as well as the systemic upregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα). However, the impact these immune mediators in the liver have on patient survival during SARS-CoV-2 infection is currently unknown. Here, by performing a post-mortem analysis of 45 patients that died from a SARS-CoV-2 infection, we find that an increased expression of TNFA in the liver is associated with elevated mortality. Using publicly available single-cell sequencing datasets, we determined that Kupffer cells and monocytes are the main sources of this TNFα production. Further analysis revealed that TNFα signaling led to the upregulation of pro-inflammatory genes that are associated with an unfavorable outcome. Moreover, high levels of TNFA in the liver were associated with lower levels of interferon alpha and interferon beta. Thus, TNFα signaling in the infected SARS-CoV-2 liver correlates with reduced interferon levels and overall survival time.
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Affiliation(s)
- Jöran Lücke
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- *Correspondence: Samuel Huber, ; Jöran Lücke,
| | - Mikolaj Nawrocki
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Josa Schnell
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Nicholas Meins
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Fabian Heinrich
- Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Institute of Medical Microbiology, Virology, and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Tao Zhang
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Franziska Bertram
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Institute of Medical Microbiology, Virology, and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Morsal Sabihi
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marius Böttcher
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Tom Blankenburg
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marie Pfaff
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sara Notz
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jan Kempski
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Matthias Reeh
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Wolter
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Oliver Mann
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jakob R. Izbicki
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marc Lütgehetmann
- Institute of Medical Microbiology, Virology, and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anna Duprée
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anastasios D. Giannou
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Benjamin Ondruschka
- Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Samuel Huber
- Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- *Correspondence: Samuel Huber, ; Jöran Lücke,
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16
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Pirola CJ, Sookoian S. COVID-19 and non-alcoholic fatty liver disease: Biological insights from multi-omics data. Liver Int 2023; 43:580-587. [PMID: 36593576 DOI: 10.1111/liv.15509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/21/2022] [Accepted: 12/27/2022] [Indexed: 01/04/2023]
Abstract
We explored the shared pathophysiological mechanisms between COVID-19 and non-alcoholic fatty liver disease (NAFLD) by integrating multi-omics data. We studied common genetic risk factors and underlying biological processes using functional enrichment analysis. To understand the sex-specific pathways involved in the clinical course of SARS-CoV-2 infection, we processed sex-stratified data from COVID-19 genome-wide association datasets. We further explored the transcriptional signature of the liver cells in healthy and COVID-19 tissue specimens. We also integrated genetic and metabolomic information. We found that COVID-19 and NAFLD share biological disease mechanisms, including pathways that regulate the inflammatory and lipopolysaccharide response. Single-cell transcriptomics revealed enrichment of complement-related pathways in Kupffer cells, syndecan-mediated signalling in plasma cells, and epithelial-to-mesenchymal transition in hepatic stellate cells. The strategy of pathway-level analysis of genomic and metabolomic data uncovered l-lactic acid, Krebs cycle intermediate compounds, arachidonic acid and cortisol among the most prominent shared metabolites.
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Affiliation(s)
- Carlos J Pirola
- Systems Biology of Complex Diseases, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
| | - Silvia Sookoian
- Clinical and Molecular Hepatology, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
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17
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Abstract
SARS-CoV-2 is the viral agent of COVID-19, a pandemic that surfaced in 2019. Although predominantly a respiratory ailment, patients with COVID-19 can have gastrointestinal (GI) and hepatobiliary manifestations. These manifestations are often mild and transient, but they can be severe and consequential. In the GI tract, ischemic enterocolitis is the most common and significant consequence of COVID-19. In the liver, the reported pathologic findings may often be related to consequences of severe systemic viral infection, but reports of hepatitis presumed to be due to SARS-CoV-2 suggest that direct viral infection of the liver may be a rare complication of COVID-19. In both the GI tract and liver, lingering symptoms of GI or hepatic injury after resolution of pulmonary infection may be part of the evolving spectrum of long COVID.
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Affiliation(s)
- Angela R Shih
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
| | - Joseph Misdraji
- Department of Pathology, Yale New Haven Hospital, Yale University, New Haven, CT, 06510, USA.
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18
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Abstract
The coronavirus disease-2019 (COVID-19) pandemic has had a large impact on patients with chronic liver disease (CLD) and liver transplantation (LT) recipients. Patients with advanced CLD are at a significantly increased risk of poor outcomes in the setting of severe acute respiratory syndrome coronavirus 2 infection. The pandemic has also considerably altered the management and care that is provided to patients with CLD, pre-LT patients, and LT recipients. Vaccination against COVID-19 protects patients with CLD and LT recipients from adverse outcomes and is safe in these patients; however, vaccine efficacy may be reduced in LT recipients and other immunosuppressed patients.
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19
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Gupta T, Sharma H. COVID-19 and the liver: Are footprints still there? World J Gastroenterol 2023; 29:656-669. [PMID: 36742164 PMCID: PMC9896610 DOI: 10.3748/wjg.v29.i4.656] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [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: 10/13/2022] [Accepted: 11/21/2022] [Indexed: 01/20/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases. An early trend in higher mortality in patients with acute respiratory distress attracted all researchers to closely monitor patients for the involvement of other systems. It soon became apparent that patients with chronic liver diseases are at increased risk of mortality given their cirrhosis-associated immune dysfunction. Additionally, liver function abnormalities were noted in patients with severe COVID-19. Profound cytokine storm, direct viral infection, drugs and reactivation of viral infections were causes of deranged liver functions. Here, we discuss the relation between COVID-19 and chronic liver disease, specifically cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease (NAFLD), as well as the liver manifestations of COVID-19. The metabolic syndrome, obesity, diabetes mellitus and NAFLD were found to worsen outcome in different studies reported worldwide. Decompensated cirrhosis should be considered a risk factor for death and severe COVID-19. Recently, COVID-19 related cholangiopathy has also been reported with changes of secondary sclerosing cholangitis. The long-term persistence of viral antigens in gut epithelia raises concern regarding the future risk of autoimmune liver diseases.
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Affiliation(s)
- Tarana Gupta
- Department of Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak 124001, Haryana, India
| | - Hemant Sharma
- Department of Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak 124001, Haryana, India
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20
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Liptak P, Nosakova L, Rosolanka R, Skladany L, Banovcin P. Acute-on-chronic liver failure in patients with severe acute respiratory syndrome coronavirus 2 infection. World J Hepatol 2023; 15:41-51. [PMID: 36744167 PMCID: PMC9896507 DOI: 10.4254/wjh.v15.i1.41] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/03/2022] [Accepted: 11/29/2022] [Indexed: 01/16/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a significant impact on the lives of millions of people, especially those with other concomitant diseases, such as chronic liver diseases. To date, seven coronaviruses have been identified to infect humans. The main site of pathological action of these viruses is lung tissue. However, a substantial number of studies have proven that SARS-CoV-2 shows affinity towards several organs, including the gastrointestinal tract and the liver. The current state of evidence points to several proposed mechanisms of liver injury in patients with COVID-19 and their combination. Liver impairment is considered to be the result of the direct effect of the virus on the hepatic tissue cells, a systemic reaction consisting of inflammation, hypoxia and cytokine storm, drug-induced liver injury, with the possible contribution of a perturbed gut-liver axis. Reactivation of chronic hepatic disease could be another factor for liver impairment in patients with SARS-CoV-2 infection. Acute-on-chronic liver failure (ACLF) is a relatively new syndrome that occurs in 10%–30% of all hospitalized patients with chronic liver disease. It is crucial to recognize high-risk patients due to the increased morbidity and mortality in these cases. Several published studies have reported virus infection as a trigger factor for ACLF. However, to date, there are few relevant studies describing the presence of ACLF in patients with acute SARS-CoV-2 infection. In this minireview we summarize the current state of knowledge regarding the relation between ACLF and acute SARS-CoV-2 infection.
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Affiliation(s)
- Peter Liptak
- Clinic of Internal Medicine-Gastroenterology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
| | - Lenka Nosakova
- Clinic of Internal Medicine-Gastroenterology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
| | - Robert Rosolanka
- Clinic of Infectology and Travel Medicine, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
| | - Lubomir Skladany
- Department of Internal Medicine II, Division Hepatology, Gastroenterology and Liver Transplantation, FD Roosevelt University Hospital of Slovak Medical University, Banska Bystrica 97517, Slovakia
| | - Peter Banovcin
- Clinic of Internal Medicine-Gastroenterology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University, Martin 03601, Slovakia
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21
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Farias JP, Codes L, Vinhaes D, Amorim AP, D’Oliveira RC, Farias AQ, Bittencourt PL. Impact of baseline abnormal liver enzymes in the outcome of COVID-19 infection. Transl Gastroenterol Hepatol 2023; 8:5. [PMID: 36704646 PMCID: PMC9813650 DOI: 10.21037/tgh-22-41] [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: 04/24/2022] [Accepted: 10/11/2022] [Indexed: 11/07/2022] Open
Abstract
Background Little is known about the significance of liver function tests (LFT) abnormalities in COVID-19 and their impact on disease outcomes. The aims of the study were to evaluate abnormalities of LFT in patients with COVID-19 and their impact on disease severity, mortality, and correlation with leukocyte markers of inflammation. Methods All patients with COVID-19 admitted to the emergency department (ED) of a single reference center were retrospectively evaluated. Data were collected using an electronic medical database covering the following variables: demographics, baseline complete blood count (CBC) and ratios, neutrophil-lymphocyte (NLR) and monocyte-lymphocyte ratios (MLR), systemic immune-inflammation index (SII), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Disease severity was defined by the presence of organ failure (OF) or requirement for intensive care unit (ICU) support. Mortality was considered as patient death during hospitalization. Results A total of 1,539 subjects (799 women, mean age 57±18 years) with COVID-19 were evaluated. Abnormal AST and/or ALT were seen in 50% of them, with a frequency and magnitude that significantly correlated with leukocyte count and ratios. Both LFT were significantly associated with requirement for hospital and ICU admission and mortality. High AST levels were significantly associated with the presence, number, and types of OFs and in-hospital length of stay (LOS). Elevated ALT was also significantly associated with the aforementioned variables, with the exception of OFs presence, circulatory failure and LOS. Conclusions LFT abnormalities are frequently seen in COVID-19 patients, reflect SARS-CoV-2 associated inflammation and may predict adverse outcomes. LFT may be useful to aid decision-making in the ED for hospital admission or scheduled outpatient reevaluation.
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Affiliation(s)
| | - Liana Codes
- Portuguese Hospital of Bahia, Salvador, Bahia, Brazil;,Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil
| | - Diana Vinhaes
- Portuguese Hospital of Bahia, Salvador, Bahia, Brazil
| | | | - Ricardo Cruz D’Oliveira
- Portuguese Hospital of Bahia, Salvador, Bahia, Brazil;,Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil
| | | | - Paulo Lisboa Bittencourt
- Portuguese Hospital of Bahia, Salvador, Bahia, Brazil;,Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil
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22
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Walia D, Saraya A, Gunjan D. COVID-19 in patients with pre-existing chronic liver disease - predictors of outcomes. World J Virol 2023; 12:30-43. [PMID: 36743659 PMCID: PMC9896592 DOI: 10.5501/wjv.v12.i1.30] [Citation(s) in RCA: 3] [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: 09/13/2022] [Revised: 10/19/2022] [Accepted: 12/06/2022] [Indexed: 01/18/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) has affected patients with pre-existing chronic liver disease (CLD) in various ways. The maximum impact was seen on patients with underlying cirrhosis who have shown to have poor clinical outcomes in the form of increased risk of hepatic decompensation, acute-on-chronic liver failure, and even mortality. It is of paramount importance to identify various factors which are associated with unfavorable outcomes for prognostication and making informed management strategy. Many factors have been evaluated in different studies in patients with underlying CLD. Some of these factors include the severity of underlying chronic liver disease, comorbid conditions, age, and severity of COVID-19. Overall, the outcomes are not fav-orable in patients with cirrhosis as evidenced by data from various studies. The main purpose of this review is to identify the predictors of adverse clinical outcomes including mortality in patients with CLD for risk stratification, prognostication, and appropriate clinical management.
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Affiliation(s)
- Dinesh Walia
- Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi 110029, New Delhi, India
| | - Anoop Saraya
- Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi 110029, New Delhi, India
| | - Deepak Gunjan
- Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi 110029, New Delhi, India
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23
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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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24
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Baldelli L, Marjot T, Barnes E, Barritt AS, Webb GJ, Moon AM. SARS-CoV-2 Infection and Liver Disease: A Review of Pathogenesis and Outcomes. Gut Liver 2023; 17:12-23. [PMID: 36457261 PMCID: PMC9840920 DOI: 10.5009/gnl220327] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/31/2022] [Accepted: 09/07/2022] [Indexed: 12/03/2022] Open
Abstract
The impact of the coronavirus disease 2019 (COVID-19) pandemic has been immense, and it continues to have lasting repercussions. While the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus primarily infects the respiratory system, other organ systems are affected, including the liver. Scientific knowledge on the role of SARS-CoV-2 infection and liver injury has evolved rapidly, with recent data suggesting specific hepatotropism of SARS-CoV-2. Moreover, additional concerns have been raised in regard to long-term liver damage, related to emerging cases of post-COVID-19 cholangiopathy and chronic cholestasis. Great effort has also been focused on studying how specific subpopulations with chronic medical conditions might be disproportionately impacted by COVID-19. One such population includes individuals with chronic liver disease (CLD) and cirrhosis, with an expanding body of research indicating these patients being particularly susceptible to adverse outcomes. In this review, we provide an updated summary on the current pathogenesis and mechanism of liver injury in the setting of SARS-CoV-2 infection, the association between health outcomes and SARS-CoV-2 infection in patients with CLD, and the unique consequences of the COVID-19 pandemic on the routine care of patients with CLD.
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Affiliation(s)
- Luke Baldelli
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Thomas Marjot
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - Eleanor Barnes
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - A. Sidney Barritt
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Gwilym J. Webb
- Cambridge Liver Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Andrew M. Moon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
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25
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Papagiouvanni I, Kotoulas SC, Pataka A, Spyratos DG, Porpodis K, Boutou AK, Papagiouvannis G, Grigoriou I, Vettas C, Goulis I. COVID-19 and liver injury: An ongoing challenge. World J Gastroenterol 2023; 29:257-271. [PMID: 36687117 PMCID: PMC9846934 DOI: 10.3748/wjg.v29.i2.257] [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: 09/12/2022] [Revised: 11/29/2022] [Accepted: 12/21/2022] [Indexed: 01/06/2023] Open
Abstract
The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019, in Wuhan, China. The virus was rapidly spread worldwide, causing coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is presented, usually, with typical respiratory symptoms (i.e., dyspnea, cough) and fever, extrapulmonary manifestations are also encountered. Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and, even, acute liver failure. The pathogenesis of liver damage is not clearly defined; multiple mechanisms contribute to liver disorder, including direct cytopathic viral effect, cytokine storm and immune-mediated hepatitis, hypoxic injury, and drug-induced liver toxicity. Patients with underlying chronic liver disease (i.e., cirrhosis, non-alcoholic fatty liver disease, alcohol-related liver disease, hepatocellular carcinoma, etc.) may have greater risk to develop both severe COVID-19 and further liver deterioration, and, as a consequence, certain issues should be considered during disease management. The aim of this review is to present the prevalence, clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection. Moreover, we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.
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Affiliation(s)
- Ioanna Papagiouvanni
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Thessaloniki, Greece
| | | | - Athanasia Pataka
- Department of Respiratory Medicine, G Papanikolaou Hospital, Resp Failure Unit, Aristotle University of Thessaloniki, Thessaloniki 57001, Greece
| | - Dionisios G Spyratos
- Pulmonary Department, Aristotle University of Thessaloniki, Thessaloniki 57001, Greece
| | - Konstantinos Porpodis
- Pulmonary Department, Aristotle University of Thessaloniki, Thessaloniki 57001, Greece
| | - Afroditi K Boutou
- Pulmonary Department, G Papanikolaou Hospital, Resp Failure Unit, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Georgios Papagiouvannis
- Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia 1036, Cyprus
| | - Ioanna Grigoriou
- Respiratory Failure Clinic, Papanikolaou General Hospital, Thessloniki 57001, Greece
| | - Christos Vettas
- Fourth Department of Internal Medicine, Hippokration General Hospital, Thessaloniki 54642, Greece
| | - Ioannis Goulis
- Fourth Department of Internal Medicine, Hippokration General Hospital, Thessaloniki 54642, Greece
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26
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Khreefa Z, Barbier MT, Koksal AR, Love G, Del Valle L. Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas. Cells 2023; 12:cells12020262. [PMID: 36672197 PMCID: PMC9856332 DOI: 10.3390/cells12020262] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/30/2022] [Accepted: 01/05/2023] [Indexed: 01/11/2023] Open
Abstract
The novel coronavirus, SARS-CoV-2, rapidly spread worldwide, causing an ongoing global pandemic. While the respiratory system is the most common site of infection, a significant number of reported cases indicate gastrointestinal (GI) involvement. GI symptoms include anorexia, abdominal pain, nausea, vomiting, and diarrhea. Although the mechanisms of GI pathogenesis are still being examined, viral components isolated from stool samples of infected patients suggest a potential fecal-oral transmission route. In addition, viral RNA has been detected in blood samples of infected patients, making hematologic dissemination of the virus a proposed route for GI involvement. Angiotensin-converting enzyme 2 (ACE2) receptors serve as the cellular entry mechanism for the virus, and these receptors are particularly abundant throughout the GI tract, making the intestine, liver, and pancreas potential extrapulmonary sites for infection and reservoirs sites for developing mutations and new variants that contribute to the uncontrolled spread of the disease and resistance to treatments. This transmission mechanism and the dysregulation of the immune system play a significant role in the profound inflammatory and coagulative cascades that contribute to the increased severity and risk of death in several COVID-19 patients. This article reviews various potential mechanisms of gastrointestinal, liver, and pancreatic injury.
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Affiliation(s)
- Zaid Khreefa
- Department of Pathology, School of Medicine, Louisiana State University Health School of Medicine, New Orleans, LA 70112, USA
| | - Mallory T. Barbier
- Louisiana Cancer Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
| | - Ali Riza Koksal
- Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA
| | - Gordon Love
- Department of Pathology, School of Medicine, Louisiana State University Health School of Medicine, New Orleans, LA 70112, USA
| | - Luis Del Valle
- Department of Pathology, School of Medicine, Louisiana State University Health School of Medicine, New Orleans, LA 70112, USA
- Louisiana Cancer Research Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
- Correspondence:
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27
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Brandi N, Spinelli D, Granito A, Tovoli F, Piscaglia F, Golfieri R, Renzulli M. COVID-19: Has the Liver Been Spared? Int J Mol Sci 2023; 24:1091. [PMID: 36674607 PMCID: PMC9866733 DOI: 10.3390/ijms24021091] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 01/09/2023] Open
Abstract
The liver is a secondary and often collateral target of COVID-19 disease but can lead to important consequences. COVID-19 might directly cause a high number of complications in patients with pre-existing chronic liver disease, increasing their risk of hepatic decompensation. Moreover, it also determines indirect consequences in the management of patients with liver disease, especially in those suffering from decompensated cirrhosis and HCC, as well as in the execution of their follow-up and the availability of all therapeutic possibilities. Liver imaging in COVID-19 patients proved to be highly nonspecific, but it can still be useful for identifying the complications that derive from the infection. Moreover, the recent implementation of telemedicine constitutes a possible solution to both the physical distancing and the re-organizational difficulties arising from the pandemic. The present review aims to encompass the currently hypothesized pathophysiological mechanisms of liver injury in patients with COVID-19 mediated by both the direct invasion of the virus and its indirect effects and analyze the consequence of the pandemic in patients with chronic liver disease and liver tumors, with particular regard to the management strategies that have been implemented to face this worldwide emergency and that can be further improved.
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Affiliation(s)
- Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Daniele Spinelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
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28
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Naeem M, Bano N, Manzoor S, Ahmad A, Munawar N, Razak SIA, Lee TY, Devaraj S, Hazafa A. Pathogenetic Mechanisms of Liver-Associated Injuries, Management, and Current Challenges in COVID-19 Patients. Biomolecules 2023; 13:99. [PMID: 36671484 PMCID: PMC9855873 DOI: 10.3390/biom13010099] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 11/28/2022] [Accepted: 12/10/2022] [Indexed: 01/06/2023] Open
Abstract
The global outbreak of COVID-19 possesses serious challenges and adverse impacts for patients with progression of chronic liver disease and has become a major threat to public health. COVID-19 patients have a high risk of lung injury and multiorgan dysfunction that remains a major challenge to hepatology. COVID-19 patients and those with liver injury exhibit clinical manifestations, including elevation in ALT, AST, GGT, bilirubin, TNF-α, and IL-6 and reduction in the levels of CD4 and CD8. Liver injury in COVID-19 patients is induced through multiple factors, including a direct attack of SARS-CoV-2 on liver hepatocytes, hypoxia reperfusion dysfunction, cytokine release syndrome, drug-induced hepatotoxicity caused by lopinavir and ritonavir, immune-mediated inflammation, renin-angiotensin system, and coagulopathy. Cellular and molecular mechanisms underlying liver dysfunction are not fully understood in severe COVID-19 attacks. High mortality and the development of chronic liver diseases such as cirrhosis, alcoholic liver disease, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatocellular carcinoma are also associated with patients with liver damage. COVID-19 patients with preexisting or developing liver disease should be managed. They often need hospitalization and medication, especially in conjunction with liver transplants. In the present review, we highlight the attack of SARS-CoV-2 on liver hepatocytes by exploring the cellular and molecular events underlying the pathophysiological mechanisms in COVID-19 patients with liver injury. We also discuss the development of chronic liver diseases during the progression of SARS-CoV-2 replication. Lastly, we explore management principles in COVID-19 patients with liver injury and liver transplantation.
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Affiliation(s)
- Muhammad Naeem
- College of Life Science, Hebei Normal University, Shijiazhuang 050024, China
| | - Naheed Bano
- Department of Fisheries and Aquaculture, Muhammad Nawaz Sharif University of Agriculture, Multan 60000, Pakistan
| | - Saba Manzoor
- Department of Zoology, University of Sialkot, Sialkot 51310, Pakistan
| | - Aftab Ahmad
- Biochemistry/Center for Advanced Studies in Agriculture and Food Security (CAS-AFS), University of Agriculture, Faisalabad 38040, Pakistan
| | - Nayla Munawar
- Department of Chemistry, College of Science, United Arab Emirates University, Al-Ain 15551, United Arab Emirates
| | - Saiful Izwan Abd Razak
- BioInspired Device and Tissue Engineering Research Group (BioInspira), Department of Biomedical Engineering and Health Sciences, Faculty of Electrical Engineering, Universiti Teknologi Malaysia, Johor Bahru 81310, Malaysia
- Sports Innovation & Technology Centre, Institute of Human Centred Engineering, Universiti Teknologi Malaysia, Johor Bahru 81310, Malaysia
| | - Tze Yan Lee
- School of Liberal Arts, Science and Technology (PUScLST) Perdana University, Suite 9.2, 9th Floor, Wisma Chase Perdana, Changkat Semantan Damansara Heights, Kuala Lumpur 50490, Malaysia
| | - Sutha Devaraj
- Faculty of Medicine, AIMST University, Bedong 08100, Malaysia
| | - Abu Hazafa
- Department of Medicine, Surgery and Dentistry, “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
- Department of Biochemistry, University of Agriculture Faisalabad, Faisalabad 38040, Pakistan
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29
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Nowroozi A, Momtazmanesh S, Rezaei N. COVID-19 and MAFLD/NAFLD: An updated review. Front Med (Lausanne) 2023; 10:1126491. [PMID: 37035343 PMCID: PMC10080090 DOI: 10.3389/fmed.2023.1126491] [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] [Received: 02/08/2023] [Accepted: 03/10/2023] [Indexed: 04/11/2023] Open
Abstract
The COVID-19 pandemic is ongoing and places a substantial burden on healthcare systems worldwide. As we further shed light on different disease characteristics, we identify more and more groups of people at higher risk of poor COVID-19 outcomes. Metabolic-associated fatty liver disease (MAFLD) (previously non-alcoholic fatty liver disease or NAFLD) is a common metabolic disorder characterized by fat accumulation and liver fibrosis. Given its close correlation with metabolic syndrome, an established risk factor for severe COVID-19, it is necessary to investigate its interplay with the novel coronavirus. In this study, we review the available data on COVID-19 prognosis, treatment and prevention options in patients with MAFLD, and the effect that the disease and the pandemic have on MAFLD care. Furthermore, we point out the gaps in the current literature to accentuate the work that needs to be done to improve MAFLD care during the pandemic and beyond.
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Affiliation(s)
- Ali Nowroozi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Sara Momtazmanesh
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- *Correspondence: Sara Momtazmanesh,
| | - Nima Rezaei
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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30
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Said KB, Alsolami A, Alreshidi FS, Fathuddin A, Alshammari F, Alrashid F, Aljadani A, Aboras R, Alreshidi F, Alghozwi MH, Alshammari SF, Alharbi NF. Profiles of Independent-Comorbidity Groups in Senior COVID-19 Patients Reveal Low Fatality Associated with Standard Care and Low-Dose Hydroxychloroquine over Antivirals. J Multidiscip Healthc 2023; 16:1215-1229. [PMID: 37153358 PMCID: PMC10162097 DOI: 10.2147/jmdh.s403700] [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: 01/26/2023] [Accepted: 04/03/2023] [Indexed: 05/09/2023] Open
Abstract
Introduction The lack of feasible therapies and comorbidities aggravate the COVID-19 case-fatality rate (CFR). However, reports examining CFR associations with diabetes, concomitant cardiovascular diseases, chronic kidney disease, and chronic liver disease (CLD) are limited. More studies assessing hydroxychloroquine (Hcq) and antivirals are needed. Purpose To examine associations of COVID-19 CFR in comorbid patient groups each with single comorbidities and after treatment with Hcq, favipiravir, and dexamethasone (Dex), either alone or in combination versus standard care. Methods Using statistical analysis, we descriptively determined these associations among 750 COVID-19 patient groups during the last quarter of 2021. Results A diabetes comorbidity (40%, n=299) showed twice the fatality (CFR 14%) of the others (CFR 7%; P=0.001). Hypertension (Htn) was the second-commonest comorbidity (29.5%, n=221), with similar CFR to diabetes (15% and 7% for Htn and non-Htn, respectively), but with higher significance (P=0.0006167). Although only 4% (n=30) heart failure (HF) was reported, the CFR (40%) was much higher than in those without it (8%). A similar rate (4%) for chronic kidney disease was reported, with CFRs of 33% and 9% among those with and without it, respectively (P=0.00048). Ischemic heart disease was 11% (n=74), followed by chronic liver disease (0.4%) and history of smoking (1%); however, these were not significant due to the sample sizes. Treatment indicated standard care and Hcq alone or in combination were superior (CFR of 4% and 0.5%, respectively) compared to favipiravir (25%) or Dex (38.5%) independently or in combination (35.4%). Furthermore, Hcq performed well (CFR 9%) when combined with Dex (9%; P=4.28-26). Conclusion The dominance of diabetes and other comorbidities with significant association with CFR implied existence of a common virulence mechanism. The superiority of low-dose Hcq and standard care over antivirals warrants further studies.
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Affiliation(s)
- Kamaleldin B Said
- Department of Pathology and Microbiology, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
- Genomics, Bioinformatics and Systems Biology, Carleton University, Ottawa, ON K1S 5B6, Canada
- Correspondence: Kamaleldin B Said, Department of Pathology and Microbiology, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia, Tel +966500771459, Email
| | - Ahmed Alsolami
- Department of Internal Medicine, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Fayez Saud Alreshidi
- Deparmtent of Family, Community Medicine, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Anas Fathuddin
- Department of Plastic Surgery, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Fawwaz Alshammari
- Department of Dermatology, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Fauwaz Alrashid
- Department of Surgery, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Ahmed Aljadani
- Department of Internal Medicine, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Rana Aboras
- Deparmtent of Family, Community Medicine, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Fatmah Alreshidi
- Deparmtent of Family, Community Medicine, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Mohammed H Alghozwi
- Department of Pathology and Microbiology, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Suliman F Alshammari
- Department of Pathology and Microbiology, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
| | - Nawaf F Alharbi
- Department of Pathology and Microbiology, College of Medicine, University of Ha’il, Ha’il, 55476, Saudi Arabia
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31
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Quarleri J, Delpino MV. Molecular mechanisms implicated in SARS-CoV-2 liver tropism. World J Gastroenterol 2022; 28:6875-6887. [PMID: 36632318 PMCID: PMC9827585 DOI: 10.3748/wjg.v28.i48.6875] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 11/07/2022] [Accepted: 11/27/2022] [Indexed: 12/26/2022] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hepatic involvement is common in SARS-CoV-2-infected individuals. It is currently accepted that the direct and indirect hepatic effects of SARS-CoV-2 infection play a significant role in COVID-19. In individuals with pre-existing infectious and non-infectious liver disease, who are at a remarkably higher risk of developing severe COVID-19 and death, this pathology is most medically relevant. This review emphasizes the current pathways regarded as contributing to the gastrointestinal and hepatic ailments linked to COVID-19-infected patients due to an imbalanced interaction among the liver, systemic inflammation, disrupted coagulation, and the lung.
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Affiliation(s)
- Jorge Quarleri
- Institute for Biomedical Research on Retroviruses and AIDS, Faculty of Medical Sciences, National Scientific and Technical Research Council-University of Buenos Aires, Buenos Aires 1121, Argentina
| | - M. Victoria Delpino
- Institute for Biomedical Research on Retroviruses and AIDS, Faculty of Medical Sciences, National Scientific and Technical Research Council-University of Buenos Aires, Buenos Aires 1121, Argentina
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32
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Bucurica S, Ionita Radu F, Bucurica A, Socol C, Prodan I, Tudor I, Sirbu CA, Plesa FC, Jinga M. Risk of New-Onset Liver Injuries Due to COVID-19 in Preexisting Hepatic Conditions-Review of the Literature. MEDICINA (KAUNAS, LITHUANIA) 2022; 59:medicina59010062. [PMID: 36676691 PMCID: PMC9864905 DOI: 10.3390/medicina59010062] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/21/2022] [Accepted: 12/23/2022] [Indexed: 12/29/2022]
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted the world and caused the 2019 coronavirus disease (COVID-19) pandemic. The clinical manifestations of the virus can vary from patient to patient, depending on their respective immune system and comorbidities. SARS-CoV-2 can affect patients through two mechanisms: directly by targeting specific receptors or by systemic mechanisms. We reviewed data in the latest literature in order to discuss and determine the risk of new-onset liver injuries due to COVID-19 in preexisting hepatic conditions. The particular expression of angiotensin-converting enzyme 2 (ACE2) receptors is an additional risk factor for patients with liver disease. COVID-19 causes more severe forms in patients with non-alcoholic fatty liver disease (NAFLD), increases the risk of cirrhosis decompensation, and doubles the mortality for these patients. The coinfection SARS-CoV-2-viral hepatitis B or C might have different outcomes depending on the stage of the liver disease. Furthermore, the immunosuppressant treatment administered for COVID-19 might reactivate the hepatic virus. The high affinity of SARS-CoV-2 spike proteins for cholangiocytes results in a particular type of secondary sclerosing cholangitis. The impact of COVID-19 infection on chronic liver disease patients is significant, especially in cirrhosis, influencing the prognosis and outcome of these patients.
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Affiliation(s)
- Sandica Bucurica
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Gastroenterology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Florentina Ionita Radu
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Gastroenterology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
- Correspondence: (F.I.R.); (F.C.P.)
| | - Ana Bucurica
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Calin Socol
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Ioana Prodan
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Gastroenterology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Ioana Tudor
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Gastroenterology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
| | - Carmen Adella Sirbu
- Department of Neurology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
- Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Department of Neurology, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
| | - Florentina Cristina Plesa
- Department of Neurology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
- Department of Preclinical Disciplines, Titu Maiorescu University of Medicine, 031593 Bucharest, Romania
- Correspondence: (F.I.R.); (F.C.P.)
| | - Mariana Jinga
- Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Gastroenterology, ‘Dr. Carol Davila’ Central Military Emergency University Hospital, 010242 Bucharest, Romania
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Jia FJ, Han J. Liver injury in COVID-19: Holds ferritinophagy-mediated ferroptosis accountable. World J Clin Cases 2022; 10:13148-13156. [PMID: 36683648 PMCID: PMC9850986 DOI: 10.12998/wjcc.v10.i36.13148] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 11/20/2022] [Accepted: 12/08/2022] [Indexed: 12/26/2022] Open
Abstract
Even in patients without a history of liver disease, liver injury caused by coronavirus disease 2019 (COVID-19) is gradually becoming more common. However, the precise pathophysiological mechanisms behind COVID-19's liver pathogenicity are still not fully understood. We hypothesize that inflammation may become worse by cytokine storms caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Elevated ferritin levels can initiate ferritinophagy mediated by nuclear receptor coactivator 4 (NCOA4), which leads to iron elevation, and ferroptosis. In COVID-19 patients, ferroptosis can be restricted to reduce disease severity and liver damage by targeting NCOA4-mediated ferritinophagy. To confirm the role of ferritinophagy-mediated ferroptosis in SARS-CoV-2 infection, further research is required.
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Affiliation(s)
- Feng-Ju Jia
- School of Nursing, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Jing Han
- School of Nursing, Qingdao University, Qingdao 266071, Shandong Province, China
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Domovitz T, Ayoub S, Werbner M, Alter J, Izhaki Tavor L, Yahalom-Ronen Y, Tikhonov E, Meirson T, Maman Y, Paran N, Israely T, Dessau M, Gal-Tanamy M. HCV Infection Increases the Expression of ACE2 Receptor, Leading to Enhanced Entry of Both HCV and SARS-CoV-2 into Hepatocytes and a Coinfection State. Microbiol Spectr 2022; 10:e0115022. [PMID: 36314945 PMCID: PMC9769977 DOI: 10.1128/spectrum.01150-22] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 09/28/2022] [Indexed: 11/09/2022] Open
Abstract
Recent studies suggest the enhancement of liver injury in COVID-19 patients infected with Hepatitis C virus (HCV). Hepatocytes express low levels of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor, raising the possibility of HCV-SARS-CoV-2 coinfection in the liver. This work aimed to explore whether HCV and SARS-CoV-2 coinfect hepatocytes and the interplay between these viruses. We demonstrate that SARS-CoV-2 coinfects HCV-infected Huh7.5 (Huh7.5HCV) cells. Both viruses replicated efficiently in the coinfected cells, with HCV replication enhanced in coinfected compared to HCV-mono-infected cells. Strikingly, Huh7.5HCV cells were eight fold more susceptible to SARS-CoV-2 pseudoviruses than naive Huh7.5 cells, suggesting enhanced SARS-CoV-2 entry into HCV-preinfected hepatocytes. In addition, we observed increased binding of spike receptor-binding domain (RBD) protein to Huh7.5HCV cells, as well as enhanced cell-to-cell fusion of Huh7.5HCV cells with spike-expressing Huh7.5 cells. We explored the mechanism of enhanced SARS-CoV-2 entry and identified an increased ACE2 mRNA and protein levels in Huh7.5HCV cells, primary hepatocytes, and in data from infected liver biopsies obtained from database. Importantly, higher expression of ACE2 increased HCV infection by enhancing its binding to the host cell, underscoring its role in the HCV life cycle as well. Transcriptome analysis revealed that shared host signaling pathways were induced in HCV-SARS-CoV-2 coinfection. This study revealed complex interactions between HCV and SARS-CoV-2 infections in hepatocytes, which may lead to the increased liver damage recently reported in HCV-positive COVID-19 patients. IMPORTANCE Here, we provide the first experimental evidence for the coexistence of SARS-CoV-2 infection with HCV, and the interplay between them. The study revealed a complex relationship of enhancement between the two viruses, where HCV infection increased the expression of the SARS-CoV-2 entry receptor ACE2, thus facilitating SARS-CoV-2 entry, and potentially, also HCV entry. Thereafter, SARS-CoV-2 infection enhanced HCV replication in hepatocytes. This study may explain the aggravation of liver damage that was recently reported in COVID-19 patients with HCV coinfection and suggests preinfection with HCV as a risk factor for severe COVID-19. Moreover, it highlights the possible importance of HCV treatment for coinfected patients. In a broader view, these findings emphasize the importance of identifying coinfecting pathogens that increase the risk of SARS-CoV-2 infection and that may accelerate COVID-19-related co-morbidities.
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Affiliation(s)
- Tom Domovitz
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Samer Ayoub
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Michal Werbner
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Joel Alter
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Lee Izhaki Tavor
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Yfat Yahalom-Ronen
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Evgeny Tikhonov
- The Lab of Genomic Instability and Cancer, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Tomer Meirson
- The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
- Davidoff Cancer Center, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel
| | - Yaakov Maman
- The Lab of Genomic Instability and Cancer, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Nir Paran
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Tomer Israely
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Moshe Dessau
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Meital Gal-Tanamy
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
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Polyzogopoulou E, Amoiridou P, Abraham TP, Ventoulis I. Acute liver injury in COVID-19 patients hospitalized in the intensive care unit: Narrative review. World J Gastroenterol 2022; 28:6662-6688. [PMID: 36620339 PMCID: PMC9813941 DOI: 10.3748/wjg.v28.i47.6662] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [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: 11/14/2022] [Accepted: 12/05/2022] [Indexed: 12/19/2022] Open
Abstract
In recent years, humanity has been confronted with a global pandemic due to coronavirus disease 2019 (COVID-19), which has caused an unprecedented health and economic crisis worldwide. Apart from the respiratory symptoms, which are considered the principal manifestations of COVID-19, it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems. Across the spectrum of organ involvement in COVID-19, acute liver injury (ALI) has been gradually gaining increasing attention by the international scientific community. COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course. Indeed, COVID-19 patients hospitalized in the intensive care unit (ICU) run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure. The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature. Several theories have been proposed to explain the occurrence of ALI in the ICU setting, such as hypoperfusion and ischemia due to hemodynamic instability, passive liver congestion as a result of congestive heart failure, ischemia-reperfusion injury, hypoxia due to respiratory failure, mechanical ventilation itself, sepsis and septic shock, cytokine storm, endotheliitis with concomitant coagulopathy, drug-induced liver injury, parenteral nutrition and direct cytopathic viral effect. It should be noted that no specific therapy for COVID-19 induced ALI exists. Therefore, the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues. The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients, explore its clinical implications, shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches. Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues, in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.
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Affiliation(s)
- Effie Polyzogopoulou
- Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens 12462, Greece
| | - Pinelopi Amoiridou
- Department of Intensive Care, AHEPA University Hospital, Thessaloniki 54621, Greece
| | - Theodore P Abraham
- Hypertrophic Cardiomyopathy Center of Excellence, University of California, San Francisco, CA 94117, United States
| | - Ioannis Ventoulis
- Department of Occupational Therapy, University of Western Macedonia, Ptolemaida 50200, Greece
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Choaib A, Issa E, El Choueiry F, Eldin JN, Shbaklo K, Alhajj M, Sawaya RT, Assi G, Nader M, Chatila R, Faour WH. SARS-CoV-2-mediated liver injury: pathophysiology and mechanisms of disease. Inflamm Res 2022; 72:301-312. [PMID: 36539655 PMCID: PMC9767399 DOI: 10.1007/s00011-022-01683-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 12/13/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND SARS-CoV-2-induced severe inflammatory response can be associated with severe medical consequences leading to multi-organ failure, including the liver. The main mechanism behind this assault is the aggressive cytokine storm that induces cytotoxicity in various organs. Of interest, hepatic stellate cells (HSC) respond acutely to liver injury through several molecular mechanisms, hence furthering the perpetuation of the cytokine storm and its resultant tissue damage. In addition, hepatocytes undergo apoptosis or necrosis resulting in the release of pro-inflammatory and pro-fibrogenic mediators that lead to chronic liver inflammation. AIMS The aim of this review is to summarize available data on SARS-CoV-2-induced liver inflammation in addition to evaluate the potential effect of anti-inflammatory drugs in attenuating SARS-CoV-2-induced liver inflammation. METHODS Thorough PubMed search was done to gather and summarize published data on SARS-CoV-2-induced liver inflammation. Additionally, various anti-inflammatory potential treatments were also documented. RESULTS Published data documented SARS-CoV-2 infection of liver tissues and is prominent in most liver cells. Also, histological analysis showed various features of tissues damage, e.g., hepatocellular necrosis, mitosis, cellular infiltration, and fatty degeneration in addition to microvesicular steatosis and inflammation. Finally, the efficacy of the different drugs used to treat SARS-CoV-2-induced liver injury, in particular the anti-inflammatory remedies, are likely to have some beneficial effect to treat liver injury in COVID-19. CONCLUSION SARS-CoV-2-induced liver inflammation is a serious condition, and drugs with potent anti-inflammatory effect can play a major role in preventing irreversible liver damage in COVID-19.
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Affiliation(s)
- Ali Choaib
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Elio Issa
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Francesca El Choueiry
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Jade Nasser Eldin
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Khodor Shbaklo
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Maryline Alhajj
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Ramy Touma Sawaya
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Ghaith Assi
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
| | - Moni Nader
- Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, P.O. Box 127788, Abu Dhabi, United Arab Emirates
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Rajaa Chatila
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon
- Internal Medicine-Gastroenterology, Lebanese American University Medical Center-Rizk Hospital (LAUMC-RH), Beirut, Lebanon
| | - Wissam H Faour
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, P.O. Box 36, Byblos, Lebanon.
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Martínez JA, Alonso-Bernáldez M, Martínez-Urbistondo D, Vargas-Nuñez JA, Ramírez de Molina A, Dávalos A, Ramos-Lopez O. Machine learning insights concerning inflammatory and liver-related risk comorbidities in non-communicable and viral diseases. World J Gastroenterol 2022; 28:6230-6248. [PMID: 36504554 PMCID: PMC9730439 DOI: 10.3748/wjg.v28.i44.6230] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 10/07/2022] [Accepted: 11/16/2022] [Indexed: 11/25/2022] Open
Abstract
The liver is a key organ involved in a wide range of functions, whose damage can lead to chronic liver disease (CLD). CLD accounts for more than two million deaths worldwide, becoming a social and economic burden for most countries. Among the different factors that can cause CLD, alcohol abuse, viruses, drug treatments, and unhealthy dietary patterns top the list. These conditions prompt and perpetuate an inflammatory environment and oxidative stress imbalance that favor the development of hepatic fibrogenesis. High stages of fibrosis can eventually lead to cirrhosis or hepatocellular carcinoma (HCC). Despite the advances achieved in this field, new approaches are needed for the prevention, diagnosis, treatment, and prognosis of CLD. In this context, the scientific com-munity is using machine learning (ML) algorithms to integrate and process vast amounts of data with unprecedented performance. ML techniques allow the integration of anthropometric, genetic, clinical, biochemical, dietary, lifestyle and omics data, giving new insights to tackle CLD and bringing personalized medicine a step closer. This review summarizes the investigations where ML techniques have been applied to study new approaches that could be used in inflammatory-related, hepatitis viruses-induced, and coronavirus disease 2019-induced liver damage and enlighten the factors involved in CLD development.
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Affiliation(s)
- J Alfredo Martínez
- Precision Nutrition and Cardiometabolic Health, Madrid Institute of Advanced Studies-Food Institute, Madrid 28049, Spain
| | - Marta Alonso-Bernáldez
- Precision Nutrition and Cardiometabolic Health, Madrid Institute of Advanced Studies-Food Institute, Madrid 28049, Spain
| | | | - Juan A Vargas-Nuñez
- Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro Majadahonda, Madrid 28222, Majadahonda, Spain
| | - Ana Ramírez de Molina
- Molecular Oncology and Nutritional Genomics of Cancer, Madrid Institute of Advanced Studies-Food Institute, Madrid 28049, Spain
| | - Alberto Dávalos
- Laboratory of Epigenetics of Lipid Metabolism, Madrid Institute of Advanced Studies-Food Institute, Madrid 28049, Spain
| | - Omar Ramos-Lopez
- Medicine and Psychology School, Autonomous University of Baja California, Tijuana 22390, Baja California, Mexico
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Grando M, Balbi M, Zeppieri M. COVID-19-induced liver injury in adult patients: A brief overview. World J Virol 2022; 11:443-452. [PMID: 36483102 PMCID: PMC9724208 DOI: 10.5501/wjv.v11.i6.443] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/07/2022] [Accepted: 10/12/2022] [Indexed: 11/23/2022] Open
Abstract
Coronavirus disease has spread worldwide since 2019, causing important pandemic issues and various social health problems to date. Little is known about the origin of this virus and the effects it has on extra-pulmonary organs. The different mechanisms of the virus and the influence it has on humans are still being studied, with hopes of finding a cure for the disease and the pathologies associated with the infection. Liver damage caused by coronavirus disease 2019 (COVID-19) is sometimes underestimated and has been of important clinical interest in the past few years. Hepatic dysfunctions can manifest in different forms which can sometimes be mild and without specific signs and symptoms or be severe with important clinical implications. There are several studies that have tried to explain the mechanism of entry (hepatotropism) of the virus into hepatocytes and the effects the virus has on this important organ. What clearly emerges from the current literature is that hepatic injury represents an important clinical aspect in the management of patients infected with COVID-19, especially in frail patients and those with comorbidities. The aim of our brief overview is to summarize the current literature regarding the forms of hepatic damage, complications, mechanisms of pathology, clinical features of liver injury, influence of comorbidities and clinical management in patients with COVID-19 infection.
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Affiliation(s)
- Martina Grando
- Department of Internal Medicine, Azienda Sanitaria Friuli Occidentale, San Vito al Tagliamento 33078, Italy
| | - Massimiliano Balbi
- Department of Internal Medicine, Azienda Sanitaria Friuli Occidentale, San Vito al Tagliamento 33078, Italy
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
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Zhang J, Zhao D, Hu J, Huang X, Gu Q, Tao Z. Hepatic dysfunctions in COVID-19 patients infected by the omicron variant of SARS-CoV-2. Front Public Health 2022; 10:1049006. [PMID: 36466505 PMCID: PMC9716022 DOI: 10.3389/fpubh.2022.1049006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 10/24/2022] [Indexed: 11/19/2022] Open
Abstract
Background Presently, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dominates amid the coronavirus disease 2019 (COVID-19) pandemic, but its clinical characteristics with intrinsic severity and organ tropism remain understudied. Methods We reported 1,001 mild COVID-19 patients that were infected with the omicron variant of SARS-CoV-2 and hospitalized in China from February to June 2022, including their demographic information, medical/immunization history, clinical symptom, and hematological profile. Patients with one-, two- and three-dose vaccination were compared to assess the vaccine effectiveness. Importantly, liver damage caused by the omicron variant infection was evaluated, in comparison to that caused by the wild-type or the delta variant SARS-CoV-2 infection. Results For the reported COVID-19 patients infected by the omicron variant of SARS-CoV-2, their median age was 36.0 [interquartile range (IQR): 26.0-50.0] and 49.7% were female. Hypertension, diabetes, and bronchitis were the leading comorbidities, and asymptomatic patients took up a major portion (61.2%). While most hematological parameters revealed the alleviated pathogenicity, full vaccination or booster shot showed effective protection against clinical severity. Furthermore, liver damages caused by viral infection of the omicron variant were largely attenuated when compared to those by infection of the wild-type or the delta variant SARS-CoV-2. Conclusions Our results supported that the viremic effect of the omicron variant tended to be modest, while the liver damage caused by this strain became milder than the previous circulating variants.
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Affiliation(s)
- Jianguo Zhang
- Department of Emergency Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Daguo Zhao
- Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jianhui Hu
- Department of Laboratory Medicine, Zhenjiang Hospital Affiliated to Nanjing University of Chinese Medicine, Zhenjiang Hospital of Traditional Chinese Medicine, Zhenjiang, China
| | - Xing Huang
- Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Qingqing Gu
- Department of Infectious Diseases, The Affiliated Hospital of Kangda College of Nanjing Medical University, The Fourth People's Hospital of Lianyungang, Lianyungang, China
| | - Zhimin Tao
- Department of Emergency Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Jiangsu Province Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
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Krishnan A, Prichett L, Liu Y, Ting PS, Alqahtani SA, Kim AK, Ma M, Hamilton JP, Woreta TA, Chen PH. Risk of Severe Illness and Risk Factors of Outcomes of COVID-19 in Hospitalized Patients with Chronic Liver Disease in a Major U. S. Hospital Network. Can J Gastroenterol Hepatol 2022; 2022:8407990. [PMID: 36387036 PMCID: PMC9649328 DOI: 10.1155/2022/8407990] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 10/01/2022] [Accepted: 10/12/2022] [Indexed: 11/06/2022] Open
Abstract
METHODS We studied 2731 patients with known CLD who were hospitalized at the Johns Hopkins Health System with COVID-19 between March 1, 2020, and December 15, 2021. The primary outcome was all-cause mortality, and secondary outcomes were MV and vasopressors. Multivariable Cox regression models were performed to explore factors associated with the outcomes. RESULTS Overall, 80.1% had severe COVID-19, all-cause mortality was 8.9%, 12.8% required MV, and 11.2% received vasopressor support. Older patients with underlying comorbidities were more likely to have severe COVID-19. There was association between elevated aminotransferases and total bilirubin with more severe COVID-19. Hepatic decompensation was independently associated with all-cause mortality (HR 2.94; 95% CI 1.23-7.06). Alcohol-related liver disease (ALD, HR 2.79, 95% CI, 1.00-8.02) was independently associated with increased risk for MV, and independent factors related to vasopressor support were chronic pulmonary disease and underlying malignancy. CONCLUSIONS COVID-19 infection in patients with CLD is associated with poor outcomes. SARS-CoV-2 infection in patients with hepatic decompensation was associated with an increased risk of in-hospital mortality hazard, and ALD among patients with COVID-19 was associated with an increased hazard for MV.
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Affiliation(s)
- Arunkumar Krishnan
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Laura Prichett
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Yisi Liu
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Peng-sheng Ting
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Saleh A. Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Liver Transplant Center, King Faisal Specialist Hospital and Research Center, Riyadh 12713, Saudi Arabia
| | - Amy K. Kim
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Michelle Ma
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - James P. Hamilton
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Tinsay A. Woreta
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
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Wu HHL, Athwal VS, Kalra PA, Chinnadurai R. COVID-19 and hepatorenal syndrome. World J Gastroenterol 2022; 28:5666-5678. [PMID: 36338894 PMCID: PMC9627428 DOI: 10.3748/wjg.v28.i39.5666] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 09/21/2022] [Accepted: 10/02/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a highly infectious disease which emerged into a global pandemic. Although it primarily causes respiratory symptoms for affected patients, COVID-19 was shown to have multi-organ manifestations. Elevated liver enzymes appear to be commonly observed during the course of COVID-19, and there have been numerous reports of liver injury secondary to COVID-19 infection. It has been established that patients with pre-existing chronic liver disease (CLD) are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD. Co-morbidities such as diabetes, hypertension, obesity, cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD, and a substantial population may also live with some degree of frailty. The mechanisms of how COVID-19 induces liver injury have been postulated. Hepatorenal syndrome (HRS) is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause, and is usually a marker of severe decompensated liver disease. Select reports of HRS following acute COVID-19 infection have been presented, although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data. Evidence discussing the management of HRS in high-dependency care and intensive care contexts is only emerging. In this article, we provide an overview on the speculative pathophysiological mechanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.
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Affiliation(s)
- Henry H L Wu
- Renal Research, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney 2065, New South Wales, Australia
| | - Varinder S Athwal
- Faculty of Biology, Medicine & Health (Division of Diabetes, Metabolism & Gastroenterology), The University of Manchester, Manchester M13 9PL, United Kingdom
| | - Philip A Kalra
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
| | - Rajkumar Chinnadurai
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
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Li P, Liu Y, Cheng Z, Yu X, Li Y. COVID-19-associated liver injury: Clinical characteristics, pathophysiological mechanisms and treatment management. Biomed Pharmacother 2022; 154:113568. [PMID: 36029543 PMCID: PMC9381432 DOI: 10.1016/j.biopha.2022.113568] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/14/2022] [Accepted: 08/15/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global epidemic and poses a major threat to public health. In addition to COVID-19 manifesting as a respiratory disease, patients with severe disease also have complications in extrapulmonary organs, including liver damage. Abnormal liver function is relatively common in COVID-19 patients; its clinical manifestations can range from an asymptomatic elevation of liver enzymes to decompensated hepatic function, and liver injury is more prevalent in severe and critical patients. Liver injury in COVID-19 patients is a comprehensive effect mediated by multiple factors, including liver damage directly caused by SARS-CoV-2, drug-induced liver damage, hypoxia reperfusion dysfunction, immune stress and inflammatory factor storms. Patients with chronic liver disease (especially alcohol-related liver disease, nonalcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma) are at increased risk of severe disease and death after infection with SARS-CoV-2, and COVID-19 aggravates liver damage in patients with chronic liver disease. This article reviews the latest SARS-CoV-2 reports, focusing on the liver damage caused by COVID-19 and the underlying mechanism, and expounds on the risk, treatment and vaccine safety of SARS-CoV-2 in patients with chronic liver disease and liver transplantation.
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Affiliation(s)
- Penghui Li
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Ying Liu
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Ziqi Cheng
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Xiaorui Yu
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Yinxiong Li
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; State Key Laboratory of Respiratory Disease, Guangzhou, China; China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou, China.
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Alnamshan MM. Potential histopathological and immunological effects of SARS-CoV-2 on the liver. BRAZ J BIOL 2022; 82:e262008. [PMID: 36074418 DOI: 10.1590/1519-6984.262008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 07/05/2022] [Indexed: 12/15/2022] Open
Abstract
The coronavirus disease outbreak of 2019 (COVID-19) poses a serious threat to public health worldwide. Lung injury is the most common complication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, other organs, including the liver, can also be affected. Currently, there is limited evidence that liver impairment is associated with severe SARS-CoV-2 infection. Clinicians will need to determine whether liver injury is caused by an underlying liver condition, COVID-19 therapy, the virus directly, or immune-mediated inflammation or represents a complicated disease course in the context of COVID-19. To address the scarcity of data on histopathological changes and immunological effects on the liver with COVID-19 positivity, we analyze and summarize recent findings. We searched PubMed, Medline, Google Scholar, Science Direct, Scopus, and Web of Science databases up to December 1, 2021, identifying published studies with the search terms "Histopathology in COVID-19," "COVID-19," "Pathological changes in liver in COVID-19," "Liver pathology in COVID-19," "immunological effects in liver in COVID-19," and "SARS-CoV-2." This concise review will aid clinicians and researchers in better understanding the tissue histopathology and immunological consequences of SARS-CoV-2 on the liver, enabling improved care planning and avoiding future dangers.
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Affiliation(s)
- M M Alnamshan
- Imam Abdulrahman Bin Faisal University, College of Science, Department of Biology, Dammam, Saudi Arabia
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44
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Hoffmann C, Gerber PA, Cavelti-Weder C, Licht L, Kotb R, Al Dweik R, Cherfane M, Bornstein SR, Perakakis N. Liver, NAFLD and COVID-19. Horm Metab Res 2022; 54:522-531. [PMID: 35468630 DOI: 10.1055/a-1834-9008] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Coronavirus disease 2019 (COVID-19) is characterized by a wide clinical spectrum that includes abnormalities in liver function indicative of liver damage. Conversely, people with liver diseases are at higher risk of severe COVID-19. In the current review, we summarize first the epidemiologic evidence describing the bidirectional relationship between COVID-19 and liver function/liver diseases. Additionally, we present the most frequent histologic findings as well as the most important direct and indirect mechanisms supporting a COVID-19 mediated liver injury. Furthermore, we focus on the most frequent liver disease in the general population, non-alcoholic or metabolic-associated fatty liver disease (NAFLD/MAFLD), and describe how COVID-19 may affect NAFLD/MAFLD development and progression and conversely how NAFLD/MAFLD may further aggravate a COVID-19 infection. Finally, we present the long-term consequences of the pandemic on the development and management of NAFLD.
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Affiliation(s)
- Carlotta Hoffmann
- University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany, Department of Internal Medicine III, Dresden, Germany
| | - Philipp A Gerber
- University Hospital Zurich (USZ) and University of Zurich (UZH), Switzerland, Department of Endocrinology, Diabetology and Clinical Nutrition, Zurich, Switzerland
| | - Claudia Cavelti-Weder
- University Hospital Zurich (USZ) and University of Zurich (UZH), Switzerland, Department of Endocrinology, Diabetology and Clinical Nutrition, Zurich, Switzerland
| | - Louisa Licht
- University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany, Department of Internal Medicine III, Dresden, Germany
| | - Reham Kotb
- Abu Dhabi University, Abu Dhabi, United Arab Emirates, College of Health Sciences, Abu Dhabi, United Arab Emirates
| | - Rania Al Dweik
- Abu Dhabi University, Abu Dhabi, United Arab Emirates, Department of Public Health, Abu Dhabi, United Arab Emirates
| | - Michele Cherfane
- Abu Dhabi University, Abu Dhabi, United Arab Emirates, College of Health Sciences, Abu Dhabi, United Arab Emirates
| | - Stefan R Bornstein
- University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany, Department of Internal Medicine III, Dresden, Germany
| | - Nikolaos Perakakis
- University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany, Department of Internal Medicine III, Dresden, Germany
- University Hospital and Faculty of Medicine, TU Dresden, Dresden, Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, Dresden, Germany
- Neuherberg, German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
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45
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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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46
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Wong CKH, Au ICH, Cheng WY, Man KKC, Lau KTK, Mak LY, Lui SL, Chung MSH, Xiong X, Lau EHY, Cowling BJ. Remdesivir use and risks of acute kidney injury and acute liver injury among patients hospitalised with COVID-19: a self-controlled case series study. Aliment Pharmacol Ther 2022; 56:121-130. [PMID: 35318694 PMCID: PMC9111503 DOI: 10.1111/apt.16894] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 02/04/2022] [Accepted: 03/08/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM To investigate and quantify the risks of AKI and ALI associated with remdesivir use, given the underlying diseases of SARS-CoV-2 infection. METHODS This self-controlled case series (SCCS) study was conducted using electronic hospital records between 23 January 2020 and 31 January 2021 as retrieved from the Hong Kong Hospital Authority which manages all laboratory-confirmed COVID-19 cases in Hong Kong. Outcomes of AKI and ALI were defined using the KDIGO Guideline and Asia Pacific Association of Study of Liver consensus guidelines. Incidence rate ratios (IRR) for AKI and ALI following the administration of remdesivir (exposure) in comparison to a non-exposure period were estimated using the conditional Poisson regression models. RESULTS Of 860 COVID-19 patients administered remdesivir during hospitalisation, 334 (38.8%) and 137 (15.9%) had incident ALI and AKI, respectively. Compared with the baseline period, both ALI and AKI risks were increased significantly during the pre-exposure period (ALI: IRR = 6.169, 95% CI = 4.549-8.365; AKI: IRR = 7.074, 95% CI = 3.763-13.298) and remained elevated during remdesivir treatment. Compared to the pre-exposure period, risks of ALI and AKI were not significantly higher in the first 2 days of remdesivir initiation (ALI: IRR = 1.261, 95% CI = 0.915-1.737; AKI: IRR = 1.261, 95% CI = 0.889-1.789) and between days 2 and 5 of remdesivir treatment (ALI: IRR = 1.087, 95% CI = 0.793-1.489; AKI: IRR = 1.152, 95% CI = 0.821-1.616). CONCLUSION The increased risks of AKI and ALI associated with intravenous remdesivir treatment for COVID-19 may be due to the underlying SARS-CoV-2 infection. The risks of AKI and ALI were elevated in the pre-exposure period, yet no such increased risks were observed following remdesivir initiation when compared to the pre-exposure period.
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Affiliation(s)
- Carlos K. H. Wong
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of MedicineThe University of Hong KongHong Kong SARChina
- Department of Family Medicine and Primary Care, School of Clinical Medicine, LKS Faculty of MedicineThe University of Hong KongHong Kong SARChina
- Laboratory of Data Discovery for Health Limited (D4H), Hong Kong Science ParkHong Kong SARChina
| | - Ivan C. H. Au
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of MedicineThe University of Hong KongHong Kong SARChina
| | - Wing Yiu Cheng
- School of Biomedical Sciences, LKS Faculty of MedicineThe University of Hong KongHong Kong SARChina
| | - Kenneth K. C. Man
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of MedicineThe University of Hong KongHong Kong SARChina
- Research Department of Practice and PolicyUCL School of PharmacyLondonUK
| | - Kristy T. K. Lau
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of MedicineThe University of Hong KongHong Kong SARChina
| | - Lung Yi Mak
- Department of Medicine, School of Clinical Medicine, LKS Faculty of MedicineThe University of Hong KongHong Kong SARChina
- State Key Laboratory of Liver ResearchThe University of Hong KongHong Kong SARChina
| | - Sing Leung Lui
- Department of Medicine, Tung Wah HospitalHong Kong SARChina
| | - Matthew S. H. Chung
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of MedicineThe University of Hong KongHong Kong SARChina
| | - Xi Xiong
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of MedicineThe University of Hong KongHong Kong SARChina
| | - Eric H. Y. Lau
- Laboratory of Data Discovery for Health Limited (D4H), Hong Kong Science ParkHong Kong SARChina
- WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, LKS Faculty of MedicineThe University of Hong KongHong KongSARChina
| | - Benjamin J. Cowling
- Laboratory of Data Discovery for Health Limited (D4H), Hong Kong Science ParkHong Kong SARChina
- WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, LKS Faculty of MedicineThe University of Hong KongHong KongSARChina
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47
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Peiter GC, de Souza CDBT, de Oliveira LM, Pagliarin LG, Dos Anjos VNF, da Silva FAF, de Melo FF, Teixeira KN. COVID-19 liver and gastroenterology findings: An in silico analysis of SARS-CoV-2 interactions with liver molecules. World J Hepatol 2022; 14:1131-1141. [PMID: 35978663 PMCID: PMC9258260 DOI: 10.4254/wjh.v14.i6.1131] [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: 12/03/2021] [Revised: 02/22/2022] [Accepted: 05/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Coronavirus disease 19 (COVID-19) has not only been shown to affect the respiratory system, but has also demonstrated variable clinical presentations including gastrointestinal tract disorders. In addition, abnormalities in liver enzymes have been reported indicating hepatic injury. It is known that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might infect cells via the viral receptor angiotensin-converting enzyme 2 (ACE2) which is expressed in several organs including the liver. The viral Spike glycoprotein binds to ACE2 and must be cleaved by Furin and Type 2 Serine Protease to enter the cells. After that, the Akt/mTOR signaling pathway is activated and several COVID-19 changes are triggered. AIM To analyze liver and gastrointestinal symptoms and cell signaling pathways triggered by SARS-CoV-2 infection due to virus-liver interactions in silico. METHODS In this in silico study, the three-dimensional structures of the Akt, mTORC1 and Furin (receptors) were selected from the Protein Data Bank (PDB) and the structures of inhibitors (ligands) MK-2206, CC-223 and Naphthofluorescein were selected from PubChem and ZINC databases. Ligand files were downloaded as 2D structures and converted to optimized 3D structures using ViewerLite 4.2 software. Marvin Sketch® software was used to calculate prediction of the protonated form of inhibitors in a physiological environment (pH 7.4). AutoDock Tools (ADT) software was used to calculate and delimit the Grid box used in the molecular docking of each structure selected in the PDB. In addition, protonated ligands were prepared for molecular docking using ADT software. Molecular docking was performed using ADT software tools connected to Vina software. Analysis of the amino acid residues involved in ligand interactions, as well as ligand twists, the atoms involved in interactions, bond type and strength of interactions were performed using PyMol® and Discovery Studio® (BIOVIA) software. RESULTS Molecular docking analysis showed that the mTORC1/CC-223 complex had affinity energy between the receptor and ligand of -7.7 kcal/moL with interactions ranging from 2.7 to 4.99 Å. There were four significant chemical bonds which involved two of five polypeptide chains that formed the FKBP12-Rapamycin-Binding (FRB) domain. The strongest was a hydrogen bond, the only polar interaction, and Van der Waals interactions shown to be present in 12 residues of mTORC1's FRB domain. With regard to the Akt/MK-2206 complex there were three Van der Waals interactions and 12 chemical bonds in which seven residues of Akt were involved with all five rings of the MK-2206 structure. In this way, both ASP 388 and GLN 391 bind to the same MK-2206 ring, the smaller one. However, LYS 386 had four chemical bonds with the inhibitor, one with each structure ring, while LYS 387 binds two distinct rings. One of the MK-2206 inhibitor's rings which binds to LYS 387 also binds simultaneously to ILE 367 and LEU 385 residues, and the fifth ring of the structure was involved in a bond with the ALA 382 residue. The hydrogen bonds were the shortest bonds in the complex (2.61 and 3.08 Å) and all interactions had an affinity energy of -8.8 kcal/moL. The affinity energy in the Furin/Naphhofluorescein complex was -9.8 kcal/moL and involved six interactions ranging from 2.57 to 4.98 Å. Among them, two were polar and the others were non-polar, in addition to twelve more Van der Waals interactions. Two distinct hydrogen bonds were formed between Furin and its inhibitor involving GLN 388 and ALA 532 residues. ALA 532 also binds to two distinct rings of Naphthofluorescein, while TRP 531 residue has two simultaneous bonds with the inhibitor. CONCLUSION Liver infection and signaling pathways altered by SARS-CoV-2 can be modulated by inhibitors that demonstrate significant interaction affinity with human proteins, which could prevent the development of infection and symptoms.
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Affiliation(s)
| | | | | | | | | | | | - Fabrício Freire de Melo
- Universidade Federal da Bahia, Campus Anísio Teixeira, Vitória da Conquista 45029-094, Bahia, Brazil
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Sahu T, Pande B, PL M, Verma HK. Liver dysfunction during COVID-19 pandemic: Contributing role of associated factors in disease progression and severity. World J Hepatol 2022; 14:1099-1110. [PMID: 35978661 PMCID: PMC9258249 DOI: 10.4254/wjh.v14.i6.1099] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 02/13/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
In December 2019, a new strain of coronavirus was discovered in China, and the World Health Organization declared it a pandemic in March 2020. The majority of people with coronavirus disease 19 (COVID-19) exhibit no or only mild symptoms such as fever, cough, anosmia, and headache. Meanwhile, approximately 15% develop a severe lung infection over the course of 10 d, resulting in respiratory failure, which can lead to multi-organ failure, coagulopathy, and death. Since the beginning of the pandemic, it appears that there has been consideration that pre-existing chronic liver disease may predispose to deprived consequences in conjunction with COVID-19. Furthermore, extensive liver damage has been linked to immune dysfunction and coagulopathy, which leads to a more severe COVID-19 outcome. Besides that, people with COVID-19 frequently have abnormal liver function, with more significant elevations in alanine aminotransferase and aspartate aminotransferase in patients with severe COVID-19 compared to those with mild/moderate disease. This review focuses on the pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the liver, as well as the use of liver chemistry as a prognostic tool during COVID-19. We also evaluate the findings for viral infection of hepatocytes, and look into the potential mechanisms behind SARS-CoV-2-related liver damage.
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Affiliation(s)
- Tarun Sahu
- Department of Physiology, All India Institute of Medical Sciences, Raipur 492001, Chhattisgarh, India
| | - Babita Pande
- Department of Physiology, All India Institute of Medical Sciences, Raipur 492001, Chhattisgarh, India
| | - Manasa PL
- Center for Basic Sciences, Pt. Ravishankar Shukla University, Raipur 492001, Chhattisgarh, India
| | - Henu Kumar Verma
- Department of Immunopathology, Institute of Lungs Health and Immunity, Munich 85764, Bavaria, Germany
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Săbiescu DM, Kamal AM, Kamal CK, Alexandru DO, Mitruț P. Liver damage in the context of SARS-CoV-2. Covid-19 treatment and its effects on the liver. J Med Life 2022; 15:727-734. [PMID: 35928369 PMCID: PMC9321495 DOI: 10.25122/jml-2022-0177] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 05/16/2022] [Indexed: 11/21/2022] Open
Abstract
Since COVID-19 was declared a pandemic by the World Health Organization, the scientific community has tried to protect the population from the infection and its effects through multiple lines of evidence. Patients at high risk of developing severe disease were advised to protect themselves and practice effective physical distancing. Phenotypes specific to this infection need to be reviewed to understand COVID-19 and its clinical manifestations. When the pandemic began, the scientific community was concerned with the unfavorable outcome of cases with pre-existing liver disease. There have been speculations about risk factors for severe diseases such as liver disease, age, gender, and association with obesity or diabetes.
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Affiliation(s)
- Denisa Marilena Săbiescu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Adina Maria Kamal
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Constantin Kamal Kamal
- Department of Family Medicine, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Dragos Ovidiu Alexandru
- Department of Informatics and Biostatistics, University of Medicine and Pharmacy of Craiova, Craiova, Romania
| | - Paul Mitruț
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, Craiova, Romania
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50
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Grgurevic I, Lucijanić M, Pastrovic F, Barisic Jaman M, Tjesic Drinkovic I, Zelenika M, Milosevic M, Medic B, Kardum D, Bokun T, Luksic I, Piskac Zivkovic N, Keres T, Grabovac V, Persec J, Barsic B. The short-term outcomes of patients with chronic liver disease hospitalized with COVID-19. Intern Med J 2022; 52:1891-1899. [PMID: 35555962 PMCID: PMC9348237 DOI: 10.1111/imj.15817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 04/19/2022] [Accepted: 05/02/2022] [Indexed: 11/28/2022]
Abstract
Background and aims Patients with chronic liver disease (CLD) might have aggravated course upon acquisition of coronavirus disease 2019 (COVID‐19). We aimed to analyse the outcomes of patients with CLD who were hospitalized due to COVID‐19. Methods Medical records of 4014 patients hospitalized due to COVID‐19 in a regional referral hospital over a 12‐month period were analysed. Patients with CLD were identified based on discharge diagnoses according to ICD‐10 classification. Patients were followed for 30 days from admission, and their outcomes (intensive care unit (ICU) admission, mechanical ventilation (MV) or death) were analysed. Results Of the 4014 patients, 110 (2.7%) had CLD and 49 (1.2%) had cirrhosis. Median age of CLD patients was 67.5 years, 79 (71.8%) were males, 224 (23.5%) obese, 56 (50.9%) reported alcohol abuse, 24 (21.8%) had non‐alcoholic fatty liver disease, 11 (10%) viral hepatitis and 98 (89.1%) had pneumonia. Median length of hospitalization was 12 days, 32 (29.1%) patients required ICU admission and 23 (20.9%) MV, while 43 (39.1%) died. In univariate analysis, patients with cirrhosis (45% vs 73%, HR=2.95; P<0.001), but not those with non‐cirrhotic CLD (74% vs 73%, P>0.05), experienced worse 30‐days survival when compared to age, sex and COVID‐19 duration matched cohorts. In a logistic regression analysis conducted on the overall and matched cohorts, liver cirrhosis, but not CLD, predicted inferior survival independently of age, comorbidities and severity of COVID‐19, with a fourfold higher adjusted risk of 30‐day mortality. Conclusion Cirrhosis is independently associated with higher 30‐day mortality of hospitalized patients with COVID‐19. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Ivica Grgurevic
- Department of gastroenterology, hepatology and clinical nutrition, University hospital Dubrava, Zagreb, Croatia.,University of Zagreb School of medicine, Zagreb, Croatia.,University of Zagreb Faculty of pharmacy and biochemistry
| | - Marko Lucijanić
- University of Zagreb School of medicine, Zagreb, Croatia.,Department of hematology, University hospital Dubrava, Zagreb, Croatia
| | - Frane Pastrovic
- Department of gastroenterology, hepatology and clinical nutrition, University hospital Dubrava, Zagreb, Croatia
| | - Mislav Barisic Jaman
- Department of gastroenterology, hepatology and clinical nutrition, University hospital Dubrava, Zagreb, Croatia
| | - Ida Tjesic Drinkovic
- Department of gastroenterology, hepatology and clinical nutrition, University hospital Dubrava, Zagreb, Croatia
| | - Marko Zelenika
- Department of gastroenterology, hepatology and clinical nutrition, University hospital Dubrava, Zagreb, Croatia
| | - Marko Milosevic
- Department of gastroenterology, hepatology and clinical nutrition, University hospital Dubrava, Zagreb, Croatia
| | - Barbara Medic
- Department of gastroenterology, hepatology and clinical nutrition, University hospital Dubrava, Zagreb, Croatia
| | - Dusko Kardum
- Department of gastroenterology, hepatology and clinical nutrition, University hospital Dubrava, Zagreb, Croatia
| | - Tomislav Bokun
- Department of gastroenterology, hepatology and clinical nutrition, University hospital Dubrava, Zagreb, Croatia.,University of Zagreb Faculty of pharmacy and biochemistry
| | - Ivica Luksic
- University of Zagreb School of medicine, Zagreb, Croatia.,Department of maxillofacial surgery, University hospital Dubrava, Zagreb, Croatia
| | | | - Tatjana Keres
- Intensive care unit, Department of internal medicine, University hospital Dubrava, Zagreb, Croatia
| | - Vlatko Grabovac
- Intensive care unit, Department of internal medicine, University hospital Dubrava, Zagreb, Croatia.,Department of emergency medicine, University hospital Dubrava, Zagreb, Croatia
| | - Jasminka Persec
- Intensive care unit, Department of anestesiology, renimatology and intensive care, University hospital Dubrava, Zagreb, Croatia.,University of Zagreb School of Dental medicine
| | - Bruno Barsic
- University of Zagreb School of medicine, Zagreb, Croatia.,Intensive care unit, Department of internal medicine, University hospital Dubrava, Zagreb, Croatia
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