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Antar SA, Ashour NA, Hamouda AO, Noreddin AM, Al-Karmalawy AA. Recent advances in COVID-19-induced liver injury: causes, diagnosis, and management. Inflammopharmacology 2024:10.1007/s10787-024-01535-7. [PMID: 39126569 DOI: 10.1007/s10787-024-01535-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Accepted: 03/29/2024] [Indexed: 08/12/2024]
Abstract
Since the start of the pandemic, considerable advancements have been made in our understanding of the effects of SARS-CoV-2 infection and the associated COVID-19 on the hepatic system. There is a broad range of clinical symptoms for COVID-19. It affects multiple systems and has a dominant lung illness depending on complications. The progression of COVID-19 in people with pre-existing chronic liver disease (CLD) has also been studied in large multinational groups. Notably, SARS-CoV-2 infection is associated with a higher risk of hepatic decompensation and death in patients with cirrhosis. In this review, the source, composition, mechanisms, transmission characteristics, clinical characteristics, therapy, and prevention of SARS-CoV-2 were clarified and discussed, as well as the evolution and variations of the virus. This review briefly discusses the causes and effects of SARS-CoV-2 infection in patients with CLD. As part of COVID-19, In addition, we assess the potential of liver biochemistry as a diagnostic tool examine the data on direct viral infection of liver cells, and investigate potential pathways driving SARS-CoV-2-related liver damage. Finally, we explore how the pandemic has had a significant impact on patient behaviors and hepatology services, which may increase the prevalence and severity of liver disease in the future. The topics encompassed in this review encompass the intricate relationships between SARS-CoV-2, liver health, and broader health management strategies, providing valuable insights for both current clinical practice and future research directions.
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Affiliation(s)
- Samar A Antar
- Center for Vascular and Heart Research, Fralin Biomedical Research Institute, Virginia Tech, Roanoke, VA, 24016, USA
- Department of Pharmacology, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt
| | - Nada A Ashour
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt
| | - Amir O Hamouda
- Department of Biochemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt
| | - Ayman M Noreddin
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ahram Canadian University, 6Th of October City, Giza, 12566, Egypt
- Department of Internal Medicine, School of Medicine, University of California -Irvine, Irvine, USA
| | - Ahmed A Al-Karmalawy
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, New Damietta, 34518, Egypt.
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6Th of October City, Giza, 12566, Egypt.
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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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Michalak A, Lach T, Szczygieł K, Cichoż-Lach H. COVID-19, Possible Hepatic Pathways and Alcohol Abuse-What Do We Know up to 2023? Int J Mol Sci 2024; 25:2212. [PMID: 38396888 PMCID: PMC10888568 DOI: 10.3390/ijms25042212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 01/23/2024] [Accepted: 01/26/2024] [Indexed: 02/25/2024] Open
Abstract
The pandemic period due to coronavirus disease 2019 (COVID-19) revolutionized all possible areas of global health. Significant consequences were also related to diverse extrapulmonary manifestations of this pathology. The liver was found to be a relatively common organ, beyond the respiratory tract, affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple studies revealed the essential role of chronic liver disease (CLD) in the general outcome of coronavirus infection. Present concerns in this field are related to the direct hepatic consequences caused by COVID-19 and pre-existing liver disorders as risk factors for the severe course of the infection. Which mechanism has a key role in this phenomenon-previously existing hepatic disorder or acute liver failure due to SARS-CoV-2-is still not fully clarified. Alcoholic liver disease (ALD) constitutes another not fully elucidated context of coronavirus infection. Should the toxic effects of ethanol or already developed liver cirrhosis and its consequences be perceived as a causative or triggering factor of hepatic impairment in COVID-19 patients? In the face of these discrepancies, we decided to summarize the role of the liver in the whole picture of coronavirus infection, paying special attention to ALD and focusing on the pathological pathways related to COVID-19, ethanol toxicity and liver cirrhosis.
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Affiliation(s)
- Agata Michalak
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
| | - Tomasz Lach
- Department of Orthopedics and Traumatology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
| | - Karolina Szczygieł
- Clinical Dietetics Unit, Department of Bioanalytics, Medical University of Lublin, Chodźki 7, 20-093 Lublin, Poland;
| | - Halina Cichoż-Lach
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland;
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Ying-Hao P, Rui-Han L, Hai-Dong Z, Qiu-Hua C, Yuan-Yuan G, Yu-Shan Y, Hai-Qi Z, Hua J. Different effects of vaccine on VST in critical and non-critical COVID-19 patients: A retrospective study of 363 cases. Heliyon 2023; 9:e16017. [PMID: 37153418 PMCID: PMC10151027 DOI: 10.1016/j.heliyon.2023.e16017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 04/20/2023] [Accepted: 04/28/2023] [Indexed: 05/09/2023] Open
Abstract
Aim To explore the risk factors of prolonged viral shedding time (VST) in critical/non-critical COVID-19 patients during hospitalization. Methods In this retrospective study, we enrolled 363 patients with SARS-CoV-2 infection admitted in a designated hospital during the COVID-19 outbreak in Nanjing Lukou International Airport. Patients were divided into critical (n = 54) and non-critical (n = 309) groups. We analyzed the relationship between the VST and demographics, clinical characteristics, medications, and vaccination histories, respectively. Results The median duration of VST was 24 d (IQR, 20-29) of all patients. The VST of critical cases was longer than non-critical cases (27 d, IQR, 22.0-30.0 vs. 23 d, IQR 20-28, P < 0.05). Cox proportional hazards model showed that ALT (HR = 1.610, 95%CI 1.186-2.184, P = 0.002) and EO% (HR = 1.276, 95%CI 1.042-1.563, P = 0.018) were independent factors of prolonged VST in total cases; HGB (HR = 0.343, 95%CI 0.162-0.728, P = 0.005) and ALP (HR = 0.358, 95%CI 0.133-0.968, P = 0.043) were independent factors of prolonged VST in critical cases, while EO% (HR = 1.251, 95%CI 1.015-1.541, P = 0.036) was the independent factor of prolonged VST in non-critical cases. Vaccinated critical cases showed higher levels of SARS-CoV-2-IgG (1.725 S/CO, IQR 0.3975-28.7925 vs 0.07 S/CO, IQR 0.05-0.16, P < 0.001) and longer VSTs (32.5 d, IQR 20.0-35.25 vs 23 d, IQR 18.0-30.0, P = 0.011) compared with unvaccinated critical patients. Fully vaccinated non-critical cases, however, presented higher levels of SARS-CoV-2-IgG (8.09 S/CO, IQR 1.6975-55.7825 vs 0.13 S/CO IQR 0.06-0.41, P < 0.001) and shorter VSTs (21 d, IQR 19.0-28.0 vs 24 d, IQR 21.0-28.5, P = 0.013) compared with unvaccinated non-critical patients. Conclusions Our results suggested that risk factors of prolonged VST were different between critical and non-critical COVID-19 patients. Increased level of SARS-CoV-2-IgG and vaccination did not shorten the VST and hospital stay in critical COVID-19 patients.
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Affiliation(s)
- Pei Ying-Hao
- Department of Intensive Care Unit, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, China
| | - Li Rui-Han
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, China
| | - Zhang Hai-Dong
- Department of Intensive Care Unit, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, China
| | - Chen Qiu-Hua
- Department of Intensive Care Unit, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, China
| | - Gu Yuan-Yuan
- Department of Intensive Care Unit, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, China
| | - Yang Yu-Shan
- First School of Clinical Medicine, Nanjing University of Chinese Medicine, Jiangsu Province, China
| | - Zhou Hai-Qi
- Department of Intensive Care Unit, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, China
| | - Jiang Hua
- Department of Intensive Care Unit, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province, China
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Sanyaolu A, Marinkovic A, Abbasi AF, Prakash S, Patidar R, Desai P, Williams M, Jan A, Hamdy K, Solomon R, Balendra V, Ansari M, Shazley O, Khan N, Annan R, Dixon Y, Okorie C, Antonio A. Effect of SARS-CoV-2 infection on the liver. World J Virol 2023; 12:109-121. [PMID: 37033147 PMCID: PMC10075054 DOI: 10.5501/wjv.v12.i2.109] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 01/04/2023] [Accepted: 02/01/2023] [Indexed: 03/21/2023] Open
Abstract
There have been numerous concerns about the disease and how it affects the human body since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic began in December 2019. The impact of SARS-CoV-2 on the liver is being carefully investigated due to an increase in individuals with hepatitis and other liver illnesses, such as alcoholic liver disease. Additionally, the liver is involved in the metabolism of numerous drugs used to treat comorbidities and coronavirus disease 2019 (COVID-19). Determining how SARS-CoV-2 affects the liver and what factors place individuals with COVID-19 at a higher risk of developing liver problems are the two main objectives of this study. This evaluation of the literature included research from three major scientific databases. To provide an update on the current impact of COVID-19 on the liver, data was collected and relevant information was incorporated into the review. With more knowledge about the effect of the disease on the liver, better management and therapeutics can be developed, and education can ultimately save lives and reduce the long-term impact of the pandemic on our population.
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Affiliation(s)
- Adekunle Sanyaolu
- Department of Public Health, Federal Ministry of Health, Abuja, Nigeria, Abuja 0000, FCT, Nigeria
| | - Aleksandra Marinkovic
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Abu Fahad Abbasi
- Department of Internal Medicine, Loyola University Medical Center, Maywood, Illinois, IL 60153, United States
| | - Stephanie Prakash
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Risha Patidar
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Priyank Desai
- Department of Basic Medical Science, American University of Saint Vincent School of Medicine, Saint Vincent and the Grenadines 0000, Saint Vincent and the Grenadines
| | - Martina Williams
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Abdul Jan
- Department of Basic Medical Science, Windsor University School of Medicine, Cayon 0000, Saint Kitts and Nevis
| | - Kareem Hamdy
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Rachael Solomon
- Department of Basic Medical Science, Caribbean Medical University School of Medicine, Willemstad 0000, Curaçao, Netherlands Antilles
| | - Vyshnavy Balendra
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Maaz Ansari
- Department of Basic Medical Science, Saint James School of Medicine, The Quarter 2640 0000, Anguilla
| | - Omar Shazley
- Basic Medical Science, Saint James School of Medicine, Saint Vincent and the Grenadines 0000, Saint Vincent and the Grenadines
| | - Nasar Khan
- Department of Basic Medical Science, Windsor University School of Medicine, Cayon 0000, Saint Kitts and Nevis
| | - Rochelle Annan
- University of Health Sciences Antigua School of Medicine, Piccadilly, St. John's Antigua
| | - Yashika Dixon
- Department of Basic Medical Science, Windsor University School of Medicine, Cayon 0000, Saint Kitts and Nevis
| | - Chuku Okorie
- Department of Science, Union County College, Plainfield, New Jersey, NJ 07016, United States
| | - Afolabi Antonio
- Department of Internal Medicine, Lloydminster Regional Hospital, Lloydminster S9V 1Y5, Saskatchewan, Canada
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Said ZNA, El Habashy SA, Zaky S, ESCMID Study Group for Viral Hepatitis. COVID-19-induced transaminitis and hyperbilirubinemia: Presentation and outcomes. World J Gastroenterol 2023; 29:1123-1130. [PMID: 36926664 PMCID: PMC10011958 DOI: 10.3748/wjg.v29.i7.1123] [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: 09/10/2022] [Revised: 12/29/2022] [Accepted: 02/13/2023] [Indexed: 02/21/2023] Open
Abstract
The risk of liver injury in patients with coronavirus disease 2019 (COVID-19) infection is quite evident. Furthermore, liver function test abnormalities are still detected in COVID-19 patients despite the development of antivirals and the availability of several types of vaccines. This editorial describes liver involvement during COVID-19 infection in patients with or without preexisting liver injury, such as chronic liver disease, to elucidate COVID-19-induced liver function abnormalities and their severity, pathophysiology, clinical manifestations, and clinical and laboratory outcomes. We also discuss the effect of vaccination against COVID-19 to better understand host factors, such as age, gender, and race, on the incidence and severity of liver dysfunction at initial presentation and during the illness. Finally, we summarize the results of relevant meta-analyses published to date and highlight the importance of adequate liver function monitoring in the current climate of the overwhelming COVID-19 pandemic.
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Affiliation(s)
- Zeinab Nabil Ahmed Said
- Department of Medical Microbiology and Immunology, Faculty of Medicine (For Girls), Al-Azhar University, Cairo 11754, Nasr City, Egypt
| | | | - Samy Zaky
- Department of Hepato-gastroenterology and Infectious Diseases, Faculty of Medicine (For Girls), Al-Azhar University, Cairo 11754, Egypt
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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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Zanon M, Neri M, Pizzolitto S, Radaelli D, Concato M, Peruch M, D'Errico S. Liver pathology in COVID-19 related death and leading role of autopsy in the pandemic. World J Gastroenterol 2023; 29:200-220. [PMID: 36683722 PMCID: PMC9850946 DOI: 10.3748/wjg.v29.i1.200] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [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: 12/21/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Information on liver involvement in patients with coronavirus disease 2019 is currently fragmented. AIM To highlight the pathological changes found during the autopsy of severe acute respiratory syndrome coronavirus 2 positive patients. METHODS A systematic literature search on PubMed was carried out until June 21, 2022. RESULTS A literature review reveals that pre-existing liver disease and elevation of liver enzyme in these patients are not common; liver enzyme elevations tend to be seen in those in critical conditions. Despite the poor expression of viral receptors in the liver, it seems that the virus is able to infect this organ and therefore cause liver damage. Unfortunately, to date, the search for the virus inside the liver is not frequent (16% of the cases) and only a small number show the presence of the virus. In most of the autopsy cases, macroscopic assessment is lacking, while microscopic evaluation of livers has revealed the frequent presence of congestion (42.7%) and steatosis (41.6%). Less frequent is the finding of hepatic inflammation or necrosis (19%) and portal inflammation (18%). The presence of microthrombi, frequently found in the lungs, is infrequent in the liver, with only 12% of cases presenting thrombotic formations within the vascular tree. CONCLUSION To date, the greatest problem in interpreting these modifications remains the association of the damage with the direct action of the virus, rather than with the inflammation or alterations induced by hypoxia and hypovolemia in patients undergoing oxygen therapy and decompensated patients.
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Affiliation(s)
- Martina Zanon
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Margherita Neri
- Department of Medical Sciences, University of Ferrara, Ferrara 44121, Italy
| | - Stefano Pizzolitto
- Department of Pathology, Santa Maria della Misericordia University Hospital, Udine 33100, Italy
| | - Davide Radaelli
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Monica Concato
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Michela Peruch
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Stefano D'Errico
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
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9
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Philips CA, Madhu D, Augustine P. Investigating the correlation between COVID-19 and the progression of chronic liver disease. Expert Rev Gastroenterol Hepatol 2023; 17:603-613. [PMID: 37086388 DOI: 10.1080/17474124.2023.2206564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 04/20/2023] [Indexed: 04/23/2023]
Abstract
INTRODUCTION The novel coronavirus disease 2019 has thrown light on various heterogeneous afflictions of newly emerging viruses on the human body. Early reports demonstrated direct effect of novel coronavirus on the liver, but subsequently, this did not stand up to validation. The SARS-CoV-2 virus affects the liver differentially; in healthy compared to those with preexisting liver disease. AREAS COVERED This exhaustive paper reviews the current, literature on mechanisms by which COVID-19 affects the healthy liver and those with preexisting liver disease such as alcohol-related and nonalcoholic fatty liver, autoimmune liver disease, chronic liver disease and cirrhosis, hepatocellular carcinoma, viral hepatitis, and liver transplant recipients, with special mention on drug-and herb-induced liver injury with COVID-19 therapies. Search methodology: the review (Dec. 2022 - Jan. 2023) is based on PubMed (NLM) search using the keyword 'COVID' with supplementary searches using 'fibrosis;' 'liver;' 'cirrhosis;' 'CLD;' 'NAFLD;' 'NASH;' 'hepatocellular carcinoma;' 'hepatitis;' 'fatty liver;' 'alcohol;' 'viral;' 'transplant;' and 'liver failure.' EXPERT OPINION Direct liver tropism of SARS-CoV-2 does not cause liver damage. Adverse events following infection depend on the severity of liver disease, the severity of COVID-19, and other risk factors such as metabolic syndrome and older age. Alcohol-related liver disease independently predicts adverse outcomes.
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Affiliation(s)
- Cyriac Abby Philips
- Clinical and Translational Hepatology and The Monarch Liver Laboratory, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, Kerala, India
| | - Deepak Madhu
- Department of Gastroenterology, Lisie Hospital, Ernakulam, Kerala, India
| | - Philip Augustine
- Department of Gastroenterology and Advanced GI Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, Kerala, India
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10
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Aquino-Matus J, Uribe M, Chavez-Tapia N. COVID-19: Current Status in Gastrointestinal, Hepatic, and Pancreatic Diseases—A Concise Review. Trop Med Infect Dis 2022; 7:tropicalmed7080187. [PMID: 36006279 PMCID: PMC9415805 DOI: 10.3390/tropicalmed7080187] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/09/2022] [Accepted: 08/09/2022] [Indexed: 01/08/2023] Open
Abstract
The gastrointestinal tract plays an important role in the pathogenesis of COVID-19. The angiotensin-converting enzyme 2 receptor and the transmembrane protease serine 2 receptor bind and activate SARS-CoV-2 and are present in high concentrations throughout the gastrointestinal tract. Most patients present with gastrointestinal symptoms and/or abnormal liver function tests, both of which have been associated with adverse outcomes. The mechanisms of liver damage are currently under investigation, but the damage is usually transient and nonsevere. Liver transplantation is the only definitive treatment for acute liver failure and end-stage liver disease, and unfortunately, because of the need for ventilators during the COVID-19 pandemic, most liver transplant programs have been suspended. Patients with gastrointestinal autoimmune diseases require close follow-up and may need modification in immunosuppression. Acute pancreatitis is a rare manifestation of COVID-19, but it must be considered in patients with abdominal pain. The gastrointestinal tract, including the liver and the pancreas, has an intimate relationship with COVID-19 that is currently under active investigation.
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Canillas L, Broquetas T, Carrión JA, Pagano G, Soriano A, Garrido E, Fernández R, Viu A, Romero J, Díaz G, Cañete N, Coll S, Naranjo D, Bessa X, Garcia‐Retortillo M, Puigvehí M. Follow-up evaluation of patients with liver test abnormalities detected during SARS-CoV2 infection. J Viral Hepat 2022; 29:823-834. [PMID: 35708160 PMCID: PMC9350227 DOI: 10.1111/jvh.13718] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 05/31/2022] [Accepted: 06/07/2022] [Indexed: 01/08/2023]
Abstract
Abnormal liver function tests (A-LFTs) during admission for coronavirus disease-19 (COVID-19) are frequent, but its evolution after COVID-19 resolution remains unexplored. We evaluated factors related to A-LFTs during COVID-19 and assessed the liver outcome after patients' discharge. This is a observational study including: (1) retrospective analysis of variables related to A-LFTs during COVID-19; and (2) follow-up evaluation with blood test, transient elastography and liver biopsy in those with persistent A-LFTs. A-LFTs were defined according to CTCAEv4.0. Among 595 patients, 366 (61.5%) showed A-LFTs. The ratio of partial pressure of oxygen and inspired oxygen fraction (P/F) below 200, ferritin ≥1000 ng/mL, male gender and antibiotic and immunomodulatory treatments were related to A-LFTs. Follow-up evaluation was performed in 153 individuals. Persistent A-LFTs at follow-up was similar in patients with/without A-LFTs during admission (14.1% vs. 4.9%, p = 0.104). Fifteen (93%) and 58 (39%) patients with/without A-LFTs at follow-up showed metabolic fatty liver disease criteria (p < 0.001), which were histologically confirmed. In conclusion, A-LFTs during COVID-19 were related to infection severity. Abnormalities remitted at follow-up in >80% of patients, and no correlation between A-LFTs at admission and at follow-up was found. Most patients with A-LFTs at follow-up had non-invasive and histologically proven fatty liver disease.
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Affiliation(s)
- Lidia Canillas
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain,IMIM (Hospital del Mar Medical Research Institute)BarcelonaSpain
| | - Teresa Broquetas
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain,IMIM (Hospital del Mar Medical Research Institute)BarcelonaSpain
| | - José A. Carrión
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain
| | - Giulia Pagano
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain
| | - Agnès Soriano
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain
| | - Esther Garrido
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain,IMIM (Hospital del Mar Medical Research Institute)BarcelonaSpain
| | - Rosa Fernández
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain,IMIM (Hospital del Mar Medical Research Institute)BarcelonaSpain
| | - Ana Viu
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain,IMIM (Hospital del Mar Medical Research Institute)BarcelonaSpain
| | - Judit Romero
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain,IMIM (Hospital del Mar Medical Research Institute)BarcelonaSpain
| | - Gemma Díaz
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain,IMIM (Hospital del Mar Medical Research Institute)BarcelonaSpain
| | - Nuria Cañete
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain,IMIM (Hospital del Mar Medical Research Institute)BarcelonaSpain
| | - Susana Coll
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain,IMIM (Hospital del Mar Medical Research Institute)BarcelonaSpain
| | | | - Xavier Bessa
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain,IMIM (Hospital del Mar Medical Research Institute)BarcelonaSpain
| | - Montserrat Garcia‐Retortillo
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain,IMIM (Hospital del Mar Medical Research Institute)BarcelonaSpain
| | - Marc Puigvehí
- Liver Section, Gastroenterology DepartmentHospital del MarBarcelonaSpain,IMIM (Hospital del Mar Medical Research Institute)BarcelonaSpain
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12
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Sahin T, Simsek C, Balaban HY. Practical points that gastrointestinal fellows should know in management of COVID-19. World J Clin Cases 2022; 10:5133-5145. [PMID: 35812670 PMCID: PMC9210885 DOI: 10.12998/wjcc.v10.i16.5133] [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: 03/17/2021] [Revised: 07/31/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
Pandemics obligate providers to transform their clinical practice. An extensive effort has been put to find out feasible approaches for gastrointestinal diseases and also to manage coronavirus disease 2019 (COVID-19) related gastrointestinal conditions. Diarrhea, hepatitis, and pancreatitis can be seen in the COVID-19 course. Endoscopic procedures increase the risk of contamination for medical staff and patients despite precautions, therefore indications should be tailored to balance risks vs benefits. Furthermore, whether the immunosupression in inflammatory bowel diseases, liver transplantation, and autoimmune liver diseases increases COVID-19 related risks and how to modify immunosupression are topics of ongoing debate. This review aims to provide most up to date practical approaches that a gastrointestinal fellow should be aware on the problems and management of gastrointestinal and hepatobiliary diseases during the COVID-19 pandemic.
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Affiliation(s)
- Tevhide Sahin
- Department of Gastroenterology, Hacettepe University, Faculty of Medicine, Ankara 06100, Turkey
| | - Cem Simsek
- Department of Gastroenterology, Hacettepe University, Faculty of Medicine, Ankara 06100, Turkey
| | - Hatice Yasemin Balaban
- Department of Gastroenterology, Hacettepe University, Faculty of Medicine, Ankara 06100, Turkey
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13
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Wang MK, Yu XL, Zhou LY, Si HM, Hui JF, Hou DY, Li WP, Yang JS. COVID-19 and liver dysfunction: What nutritionists need to know. World J Gastroenterol 2022; 28:1526-1535. [PMID: 35582132 PMCID: PMC9048466 DOI: 10.3748/wjg.v28.i15.1526] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/24/2021] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 has brought serious challenges for the medical field. Patients with COVID-19 usually have respiratory symptoms. However, liver dysfunction is not an uncommon presentation. Additionally, the degree of liver dysfunction is associated with the severity and prognosis of COVID-19. Prevention, diagnosis, and treatment of malnutrition should be routinely recommended in the management of patients with COVID-19, especially in those with liver dysfunction. Recently, a large number of studies have reported that nutrition therapy measures, including natural dietary supplements, vitamins, minerals and trace elements, and probiotics, might have potential hepatoprotective effects against COVID-19-related liver dysfunction via their antioxidant, antiviral, anti-inflammatory, and positive immunomodulatory effects. This review mainly focuses on the possible relationship between COVID-19 and liver dysfunction, nutritional and metabolic characteristics, nutritional status assessment, and nutrition therapy to provide a reference for the nutritionists while making evidence-based nutritional decisions during the COVID-19 pandemic.
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Affiliation(s)
- Ming-Ke Wang
- Department of Disease Control and Prevention, Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
| | - Xue-Lu Yu
- Department of Disease Control and Prevention, Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
| | - Li-Yun Zhou
- Department of Disease Control and Prevention, Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
| | - Hong-Mei Si
- Department of Disease Control and Prevention, Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
| | - Ju-Fen Hui
- Department of Disease Control and Prevention, Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
| | - Deng-Yong Hou
- Department of Disease Control and Prevention, Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
| | - Wei-Peng Li
- Department of Disease Control and Prevention, Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
| | - Ji-Shun Yang
- Medical Care Center, Naval Medical Center of PLA, Naval Medical University, Shanghai 200052, China
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14
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Yao L, Lu L, Ma W. Immunopathological changes, complications, sequelae and immunological memory in COVID-19 patients. Heliyon 2022; 8:e09302. [PMID: 35497026 PMCID: PMC9040416 DOI: 10.1016/j.heliyon.2022.e09302] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 11/25/2021] [Accepted: 04/14/2022] [Indexed: 01/09/2023] Open
Abstract
Confirmed SARS-CoV-2-caused disease (COVID-19) cases have reached 275.65 million worldwide. Although the majority of COVID-19 patients present mild to moderate symptoms, some have severe complications including death. We first reviewed the pathogenesis on ACE2, a binding receptor of SARS-CoV-2 expressed in multiple organs, and prevalent multinucleate syncytia in the lung tissues of COVID-19 patients. Then, we evaluated the pathological, immunological changes and sequelae in the major organs. Finally, we reviewed the immunological memory after SARS-CoV-2 infection and vaccination. The binding of SARS-Cov-2 to ACE2 receptor results in reduced ACE2 protein levels, which may lead to elevated susceptibility to inflammation, cell death, organ failure, and potentially severe illness. These damages increase the risk of health problems over a long period, which result in many complications. The complications in multiple organs lead to the increased risk of long-term health problems that require additional attention. A multidisciplinary care team is necessary for further management and recovery of the COVID-19 survivors. Many COVID-19 patients will probably make antibodies against SARS-CoV-2 virus for most of their lives, and the immunity against reinfection would last for 3-61 months.
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Affiliation(s)
- Liqin Yao
- Department of Thyroid and Breast Surgery, The First Affiliated Hospital, Huzhou University School of Medicine, Huzhou, Zhejiang, 313000, China
| | - Lingeng Lu
- Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, New Haven, CT, 06520, USA
- Center for Biomedical Data Science and Yale Cancer Center, Yale University, 60 College Street, New Haven, CT, 06520, USA
| | - Wenxue Ma
- Department of Medicine, Moores Cancer Center and Sanford Stem Cell Clinical Center, University of California San Diego, La Jolla, CA, 92093, USA
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15
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Limon-De La Rosa N, Cervantes-Alvarez E, Navarro-Alvarez N. Increased Hepatic Expression of SARS-CoV-2 Entry Points and Proinflammatory Cytokines in Cirrhosis. Clin Gastroenterol Hepatol 2022; 20:239-241.e3. [PMID: 34481957 PMCID: PMC8410674 DOI: 10.1016/j.cgh.2021.08.053] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 08/27/2021] [Accepted: 08/30/2021] [Indexed: 02/07/2023]
Abstract
It has been recently reported that patients with cirrhosis have significantly higher mortality following severe acute respiratory syndrome coronavrisu 2 (SARS-CoV-2) infection compared with those without.1,2 Specifically, it was demonstrated that mortality was greater in those with advanced cirrhosis (Child-Pugh B and C), and that from cirrhotic patients experiencing SARS-CoV-2 infection, close to half suffer acute decompensation including acute-on-chronic liver failure (ACLF).2 Unfortunately, the presence of hepatic decompensation at baseline has been shown to be an independent predictor of all-cause mortality in patients with coronavirus disease 2019 (COVID-19).1 Patients with decompensated cirrhosis contracting COVID-19 have a poor outcome, with an overall reported mortality of over 30%.1.
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Affiliation(s)
- Nathaly Limon-De La Rosa
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Eduardo Cervantes-Alvarez
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; El Plan de Estudios Combinados en Medecina, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Nalu Navarro-Alvarez
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Molecular Biology, School of Medicine, Universidad Panamericana Campus México, Mexico City, Mexico; Department of Surgery, University of Colorado Anschutz Medical Campus, Denver, Colorado.
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16
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Guler-Margaritis S, Mercan-Stanciu A, Toma L, Rusie D, Isac T, Dodot M, Zgura A, Bacalbasa N, Haineala B, Badiu DC, Serban D, Iliescu EL. COVID-19 Mid-term Impact on Hepatocellular Carcinoma in Patients With Hepatitis C Chronic Infection. In Vivo 2021; 35:3377-3383. [PMID: 34697172 PMCID: PMC8627777 DOI: 10.21873/invivo.12636] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 08/20/2021] [Accepted: 08/23/2021] [Indexed: 11/10/2022]
Abstract
BACKGROUND/AIM Liver injury has been frequently reported in association with SARS-CoV-2 infection, but data are still lacking regarding the impact of pre-existing liver damage and neoplasia on SARS-CoV-2 infection outcome and vice-versa. This study aimed to assess the effects of SARS-CoV-2 infection on hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infected patients, both in therapeutic-naïve and patients treated with direct acting antivirals. PATIENTS AND METHODS We conducted a retrospective cohort study on 21 patients with a personal history of HCV infection, that have been diagnosed with different forms of HCC and who were subsequently infected with SARS-CoV-2. Patients were monitored by liver function tests, tumoral markers, blood cell count, and coagulation profile periodically. RESULTS Solitary HCC nodules were predominant among the subjects who achieved sustained virologic response, while multinodular and infiltrative patterns were mostly prevalent among the treatment-naïve group. Most patients had mild and moderate COVID-19 infections. CONCLUSION Within the current global pandemic crisis, cancer patients are highly vulnerable and in need of constant monitoring. Among patients with HCC, the ones with cured HCV infection may be at a lower risk of fatality than those with active HCV infection, when diagnosed with SARS-CoV-2 infection.
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Affiliation(s)
- Silviu Guler-Margaritis
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Urology, Fundeni Clinical Institute, Bucharest, Romania
| | - Adriana Mercan-Stanciu
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine II, Fundeni Clinical Institute, Bucharest, Romania
| | - Letitia Toma
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine II, Fundeni Clinical Institute, Bucharest, Romania
| | - Daniel Rusie
- Department of General Surgery, Clinical Emergency Hospital, Bucharest, Romania
| | - Teodora Isac
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine II, Fundeni Clinical Institute, Bucharest, Romania
| | - Mihai Dodot
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine II, Fundeni Clinical Institute, Bucharest, Romania
| | - Anca Zgura
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Oncology-Radiotherapy, "Prof Dr Alexandru Trestioreanu" Institute of Oncology, Bucharest, Romania
| | - Nicolae Bacalbasa
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Bogdan Haineala
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Urology, Fundeni Clinical Institute, Bucharest, Romania
| | - Dumitru Cristinel Badiu
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;
- General Surgery Department, Bagdasar Arseni Clinical Emergency Hospital, Bucharest, Romania
| | - Dragos Serban
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Surgery, University Emergency Hospital, Bucharest, Romania
| | - Elena Laura Iliescu
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine II, Fundeni Clinical Institute, Bucharest, Romania
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17
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Ristic-Medic D, Petrovic S, Arsic A, Vucic V. Liver disease and COVID-19: The link with oxidative stress, antioxidants and nutrition. World J Gastroenterol 2021; 27:5682-5699. [PMID: 34629794 PMCID: PMC8473601 DOI: 10.3748/wjg.v27.i34.5682] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/11/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023] Open
Abstract
Varying degrees of liver injuries have been reported in patients infected with the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). In general, oxidative stress is actively involved in initiation and progression of liver damage. The liver metabolizes various compounds that produce free radicals. Maintaining the oxidative/antioxidative balance is important in coronavirus disease 2019 (COVID-19) patients. Antioxidant vitamins, essential trace elements and food compounds, such as polyphenols, appear to be promising agents, with effects in oxidative burst. Deficiency of these nutrients suppresses immune function and increases susceptibility to COVID-19. Daily micronutrient intake is necessary to support anti-inflammatory and antioxidative effects but for immune function may be higher than current recommended dietary intake. Antioxidant supplements (β-carotene, vitamin A, vitamin C, vitamin E, and selenium) could have a potential role in patients with liver damage. Available evidence suggests that supplementing the diet with a combination of micronutrients may help to optimize immune function and reduce the risk of infection. Clinical trials based on the associations of diet and SARS-CoV-2 infection are lacking. Unfortunately, it is not possible to definitively determine the dose, route of administration and best timing to intervene with antioxidants in COVID-19 patients because clinical trials are still ongoing. Until then, hopefully, this review will enable clinicians to understand the impact of micronutrient dietary intake and liver status assessment in COVID-19 patients.
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Affiliation(s)
- Danijela Ristic-Medic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, National Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Snjezana Petrovic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, National Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Aleksandra Arsic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, National Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Vesna Vucic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, National Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
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18
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Ihlow J, Seelhoff A, Corman VM, Gruber AD, Dökel S, Meinhardt J, Radbruch H, Späth-Schwalbe E, Elezkurtaj S, Horst D, Herbst H. COVID-19: a fatal case of acute liver failure associated with SARS-CoV-2 infection in pre-existing liver cirrhosis. BMC Infect Dis 2021; 21:901. [PMID: 34479499 PMCID: PMC8414454 DOI: 10.1186/s12879-021-06605-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Accepted: 08/23/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is challenging, particularly in post-mortem human tissues. However, there is increasing evidence for viral SARS-CoV-2 manifestation in non-respiratory tissues. In this context, it is a current matter of debate, whether SARS-CoV-2 shows hepatotropism. CASE PRESENTATION Here, we report a case of an 88-year-old women with massive SARS-CoV-2 viremia, severe jaundice and clinical signs of an acute hepatitis, who died within a few days from an acute liver failure without showing any clinical signs of pneumonia. Autopsy revealed a severe chronic and acute liver damage with bile duct infestation by SARS-CoV-2 that was accompanied by higher expressions of angiotensin-converting enzyme-2 (ACE2), Cathepsin L and transmembrane serine protease 2 (TMPRSS2). CONCLUSION Our findings indicate an enhanced biliary susceptibility to viral infection with SARS-CoV-2, that might have resulted from pre-existing severe liver damage. Furthermore, our findings emphasize the differential diagnosis of coronavirus disease 2019 (COVID-19)-associated liver failure in the clinical setting of an inexplicable jaundice.
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Affiliation(s)
- Jana Ihlow
- Institute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
| | - Alexander Seelhoff
- Department of Gastroenterology, Vivantes Netzwerk für Gesundheit GmbH Berlin, Vivantes Hospital Spandau, Neue Bergstraße 6, 13585, Berlin, Germany
| | - Victor M Corman
- Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Achim D Gruber
- Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Straße 15, 14163, Berlin, Germany
| | - Simon Dökel
- Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Straße 15, 14163, Berlin, Germany
| | - Jenny Meinhardt
- Institute of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Helena Radbruch
- Institute of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Ernst Späth-Schwalbe
- Department of Hematology, Oncology and Palliative Care, Vivantes Netzwerk für Gesundheit GmbH Berlin, Vivantes Hospital Spandau, Neue Bergstraße 6, 13585, Berlin, Germany
| | - Sefer Elezkurtaj
- Institute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - David Horst
- Institute of Pathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Hermann Herbst
- Department of Pathology, Vivantes Netzwerk für Gesundheit GmbH Berlin, Vivantes Hospital Neukölln, Rudower Straße 48, 12351, Berlin, Germany
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19
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Remes‐Troche JM, Velarde‐Ruiz Velasco JA. The Liver and COVID-19 in Mexico. Clin Liver Dis (Hoboken) 2021; 19:49-52. [PMID: 34900238 PMCID: PMC8653117 DOI: 10.1002/cld.1153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Content available: Author Interview and Audio Recording.
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Affiliation(s)
- José María Remes‐Troche
- Laboratorio de Fisiología Digestiva y Motilidad GastrointestinalInstituto de Investigaciones Médico‐BiológicasUniversidad Veracruzana MéxicoVeracruzMéxico
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20
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Pyne JD, Brickman AM. The Impact of the COVID-19 Pandemic on Dementia Risk: Potential Pathways to Cognitive Decline. NEURODEGENER DIS 2021; 21:1-23. [PMID: 34348321 PMCID: PMC8678181 DOI: 10.1159/000518581] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 07/19/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19), the far-reaching pandemic, has infected approximately 185 million of the world's population to date. After infection, certain groups, including older adults, men, and people of color, are more likely to have adverse medical outcomes. COVID-19 can affect multiple organ systems, even among asymptomatic/mild severity individuals, with progressively worse damage for those with higher severity infections. SUMMARY The COVID-19 virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily attaches to cells through the angiotensin-converting enzyme 2 (ACE2) receptor, a universal receptor present in most major organ systems. As SARS-CoV-2 binds to the ACE2 receptor, its bioavailability becomes limited, thus disrupting homeostatic organ function and inducing an injury cascade. Organ damage can then arise from multiple sources including direct cellular infection, overactive detrimental systemic immune response, and ischemia/hypoxia through thromboembolisms or disruption of perfusion. In the brain, SARS-CoV-2 has neuroinvasive and neurotropic characteristics with acute and chronic neurovirulent potential. In the cardiovascular system, COVID-19 can induce myocardial and systemic vascular damage along with thrombosis. Other organ systems such as the lungs, kidney, and liver are all at risk for infection damage. Key Messages: Our hypothesis is that each injury consequence has the independent potential to contribute to long-term cognitive deficits with the possibility of progressing to or worsening pre-existing dementia. Already, reports from recovered COVID-19 patients indicate that cognitive alterations and long-term symptoms are prevalent. This critical review highlights the injury pathways possible through SARS-CoV-2 infection that have the potential to increase and contribute to cognitive impairment and dementia.
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Affiliation(s)
- Jeffrey D. Pyne
- Department of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA
| | - Adam M. Brickman
- Department of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, USA
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21
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Chinnici CM, Russelli G, Bulati M, Miceli V, Gallo A, Busà R, Tinnirello R, Conaldi PG, Iannolo G. Mesenchymal stromal cell secretome in liver failure: Perspectives on COVID-19 infection treatment. World J Gastroenterol 2021; 27:1905-1919. [PMID: 34007129 PMCID: PMC8108038 DOI: 10.3748/wjg.v27.i17.1905] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/05/2021] [Accepted: 04/05/2021] [Indexed: 02/06/2023] Open
Abstract
Due to their immunomodulatory potential and release of trophic factors that promote healing, mesenchymal stromal cells (MSCs) are considered important players in tissue homeostasis and regeneration. MSCs have been widely used in clinical trials to treat multiple conditions associated with inflammation and tissue damage. Recent evidence suggests that most of the MSC therapeutic effects are derived from their secretome, including the extracellular vesicles, representing a promising approach in regenerative medicine application to treat organ failure as a result of inflammation/fibrosis. The recent outbreak of respiratory syndrome coronavirus, caused by the newly identified agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has forced scientists worldwide to use all available instruments to fight the infection, including the inflammatory cascade caused by this pandemic disease. The use of MSCs is a valid approach to combat organ inflammation in different compartments. In addition to the lungs, which are considered the main inflammatory target for this virus, other organs are compromised by the infection. In particular, the liver is involved in the inflammatory response to SARS-CoV-2 infection, which causes organ failure, leading to death in coronavirus disease 2019 (COVID-19) patients. We herein summarize the current implications derived from the use of MSCs and their soluble derivatives in COVID-19 treatment, and emphasize the potential of MSC-based therapy in this clinical setting.
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Affiliation(s)
- Cinzia Maria Chinnici
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
- Department of Regenerative Medicine, Fondazione Ri.MED, Palermo 90127, Italy
| | - Giovanna Russelli
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Matteo Bulati
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Vitale Miceli
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Alessia Gallo
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Rosalia Busà
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Rosaria Tinnirello
- Neuroscience Unit, CNR Institute of Biomedicine and Molecular Immunology, Palermo 90146, Italy
| | - Pier Giulio Conaldi
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
| | - Gioacchin Iannolo
- Department of Research, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS-ISMETT), Palermo 90127, Italy
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22
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Frater JL, Wang T, Lee YS. Laboratory hematologic features of COVID-19 associated liver injury: A systematic review. World J Meta-Anal 2021; 9:193-207. [DOI: 10.13105/wjma.v9.i2.193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/31/2021] [Accepted: 04/23/2021] [Indexed: 02/06/2023] Open
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23
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Frater JL, Wang T, Lee YS. Laboratory hematologic features of COVID-19 associated liver injury: A systematic review. World J Meta-Anal 2021; 9:192-206. [DOI: 10.13105/wjma.v9.i2.192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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24
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Cichoż-Lach H, Michalak A. Liver injury in the era of COVID-19. World J Gastroenterol 2021; 27:377-390. [PMID: 33584070 PMCID: PMC7856845 DOI: 10.3748/wjg.v27.i5.377] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 12/25/2020] [Accepted: 01/08/2021] [Indexed: 02/06/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undoubtedly revolutionized the whole globe and given a new point of view on respiratory tract infections. Nevertheless, coronavirus disease 2019 (COVID-19) cannot be perceived as a disease limited only to pneumonia with diverse severity. More and more reports have demonstrated a wide range of possible systemic symptoms, including hepatic complications. Liver injury has been observed in a significant proportion of patients, especially in those with a severe or critical illness. COVID-19 might provoke a deterioration of liver function in patients with already diagnosed chronic liver diseases and without pre-existing liver disorders. The deterioration of liver function worsens the prognosis, increases the risk of a severe course of SARS-CoV-2 infection and prolongs the hospital stay. In general, patients who develop liver dysfunction in COVID-19 are mainly males, elderly people, and those with higher body mass index. The underlying mechanisms for hepatic failure in patients infected with SARS-CoV-2 are still unclear, nevertheless liver damage appears to be directly connected with virus-induced cytopathic effects. A liver injury observed during hospitalization might be simultaneously caused by the use of potentially hepatotoxic drugs, mainly antiviral agents. This minireview focuses on a possible relationship between COVID-19 and the liver, potential molecular mechanisms of liver damage, the characteristics of liver injury and suggested factors predisposing to hepatic manifestations in COVID-19 patients.
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Affiliation(s)
- Halina Cichoż-Lach
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Jaczewskiego 8, Lublin 20-954, Poland
| | - Agata Michalak
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Jaczewskiego 8, Lublin 20-954, Poland
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25
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Lopez-Mendez I, Aquino-Matus J, Gall SMB, Prieto-Nava JD, Juarez-Hernandez E, Uribe M, Castro-Narro G. Association of liver steatosis and fibrosis with clinical outcomes in patients with SARS-CoV-2 infection (COVID-19). Ann Hepatol 2021; 20:100271. [PMID: 33099028 PMCID: PMC7577265 DOI: 10.1016/j.aohep.2020.09.015] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 09/21/2020] [Accepted: 09/22/2020] [Indexed: 02/06/2023]
Abstract
INTRODUCTION AND OBJECTIVES Liver function tests (LFT) abnormalities are reported in up to 50% of COVID-19 patients, and metabolic comorbidities are associated with poorer outcomes. The aim of the study was to determine the prevalence of liver steatosis and fibrosis in patients with COVID-19 and their association with clinical outcomes. MATERIAL AND METHODS Retrospective study in hospitalized COVID-19 patients was conducted. The risk for liver steatosis was estimated by HSI > 36, and risk for advanced liver fibrosis with APRI > 1.0, NAFLD FS > 0.675 and/or FIB-4 > 3.25. Clinical outcomes were admission to Intensive Care Unit (ICU) and mortality. RESULTS Of 155 patients, 71.6% were male (n = 111), and 28.4% (n = 44) were obese. Abnormal LFT were present in 96.8% (n = 150), prevalence of steatosis was 42.6% (n = 66) and of significative liver fibrosis was 44.5% (n = 69). Liver fibrosis by FIB-4 was associated with risk of ICU admission (OR 1.74 [95%CI 1.74-2.68; p = 0.023]) and mortality (OR 6.45 [95%CI 2.01-20.83, p = 0.002]); no independent associations were found. CONCLUSIONS The prevalence of steatosis and significant liver fibrosis was high in COVID-19 patients but was not associated with clinical outcomes.
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Affiliation(s)
- Ivan Lopez-Mendez
- Transplants and Hepatology Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, Toriello Guerra, Tlalpan, Mexico City, ZC 14050 Mexico.
| | - Jorge Aquino-Matus
- Obesity and Digestive Diseases Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, Toriello Guerra, Tlalpan, Mexico City, ZC 14050 Mexico
| | - Sofia Murua-Beltrán Gall
- Department of Internal Medicine, Medica Sur Clinic and Foundation, Puente de Piedra 150, Toriello Guerra, Tlalpan, Mexico City, ZC 14050 Mexico
| | - Jose D Prieto-Nava
- Department of Internal Medicine, Medica Sur Clinic and Foundation, Puente de Piedra 150, Toriello Guerra, Tlalpan, Mexico City, ZC 14050 Mexico
| | - Eva Juarez-Hernandez
- Translational Research Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, Toriello Guerra, Tlalpan, Mexico City, ZC 14050 Mexico
| | - Misael Uribe
- Obesity and Digestive Diseases Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, Toriello Guerra, Tlalpan, Mexico City, ZC 14050 Mexico
| | - Graciela Castro-Narro
- Transplants and Hepatology Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, Toriello Guerra, Tlalpan, Mexico City, ZC 14050 Mexico.
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