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Luo YW, Huang AL, Tang KF. Angiotensin-converting enzyme 2 and hepatic SARS-CoV-2 infection: Regulation, association, and therapeutic implications. World J Gastroenterol 2025; 31:100864. [PMID: 39958440 PMCID: PMC11752700 DOI: 10.3748/wjg.v31.i6.100864] [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: 08/30/2024] [Revised: 12/07/2024] [Accepted: 12/20/2024] [Indexed: 01/10/2025] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells via the angiotensin-converting enzyme 2 (ACE2) receptor. Mounting evidence has indicated the presence of hepatic SARS-CoV-2 infection and liver injury in patients with coronavirus disease 2019 (COVID-19). Understanding the mechanisms of hepatic SARS-CoV-2 infection is crucial for addressing COVID-19-related liver pathology and developing targeted therapies. This editorial discusses the significance of ACE2 in hepatic SARS-CoV-2 infection, drawing on the research by Jacobs et al. Their findings indicate that hepatic ACE2 expression, frequency of hepatic SARS-CoV-2 infection, and severity of liver injury are elevated in patients with pre-existing chronic liver diseases. These data suggest that hepatic ACE2 could be a promising therapeutic target for COVID-19.
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Affiliation(s)
- Yu-Wei Luo
- Key Laboratory of Molecular Biology on Infectious Disease, Ministry of Education, Chongqing Medical University, Chongqing 400016, China
| | - Ai-Long Huang
- Key Laboratory of Molecular Biology on Infectious Disease, Ministry of Education, Chongqing Medical University, Chongqing 400016, China
| | - Kai-Fu Tang
- Key Laboratory of Molecular Biology on Infectious Disease, Ministry of Education, Chongqing Medical University, Chongqing 400016, China
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2
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Buchynskyi M, Kamyshna I, Oksenych V, Zavidniuk N, Kamyshnyi A. The Intersection of COVID-19 and Metabolic-Associated Fatty Liver Disease: An Overview of the Current Evidence. Viruses 2023; 15:v15051072. [PMID: 37243158 DOI: 10.3390/v15051072] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 04/23/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
The global population is currently experiencing the impact of the SARS-CoV-2 coronavirus, which has caused the Coronavirus Disease 2019 (COVID-19) pandemic. With our profound comprehension of COVID-19, encompassing the involvement sequence of the respiratory tract, gastrointestinal system, and cardiovascular apparatus, the multiorgan symptoms of this infectious disease have been discerned. Metabolic-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a pervasive public health concern intricately linked with metabolic dysregulation and estimated to afflict one-fourth of the global adult population. The burgeoning focus on the association between COVID-19 and MAFLD is justified by the potential role of the latter as a risk factor for both SARS-CoV-2 infection and the subsequent emergence of severe COVID-19 symptoms. Investigations have suggested that changes in both innate and adaptive immune responses among MAFLD patients may play a role in determining the severity of COVID-19. The remarkable similarities observed in the cytokine pathways implicated in both diseases imply the existence of shared mechanisms governing the chronic inflammatory responses characterizing these conditions. The effect of MAFLD on the severity of COVID-19 illness remains uncertain, as indicated by conflicting results in cohort investigations.
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Affiliation(s)
- Mykhailo Buchynskyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Iryna Kamyshna
- Department of Medical Rehabilitation, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Valentyn Oksenych
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway
| | - Nataliia Zavidniuk
- Department of Infectious Diseases with Epidemiology, Dermatology and Venerology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Aleksandr Kamyshnyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
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Elemam NM, Talaat IM, Maghazachi AA, Saber-Ayad M. Liver Injury Associated with COVID-19 Infection: Pathogenesis, Histopathology, Prognosis, and Treatment. J Clin Med 2023; 12:2067. [PMID: 36902854 PMCID: PMC10004475 DOI: 10.3390/jcm12052067] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 02/17/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open
Abstract
Liver injury occurs frequently as a consequence of SARS-CoV-2 infection. Direct infection of the liver leads to hepatic impairment with elevated transaminases. In addition, severe COVID-19 is characterized by cytokine release syndrome, which may initiate or exacerbate liver injury. In patients with cirrhosis, SARS-CoV-2 infection is associated with acute-on-chronic liver failure. The Middle East and North Africa (MENA) region is one of the world's regions characterized by a high prevalence of chronic liver diseases. Both parenchymal and vascular types of injury contribute to liver failure in COVID-19, with a myriad of pro-inflammatory cytokines playing a major role in perpetuating liver injury. Additionally, hypoxia and coagulopathy complicate such a condition. This review discusses the risk factors, and the underlying causes of impaired liver functions in COVID-19, with a focus on key players in the pathogenesis of liver injury. It also highlights the histopathological changes encountered in postmortem liver tissues as well as potential predictors and prognostic factors of such injury, in addition to the management strategies to ameliorate liver damage.
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Affiliation(s)
- Noha Mousaad Elemam
- College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Iman M. Talaat
- College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
- Faculty of Medicine, Alexandria University, Alexandria 21131, Egypt
| | - Azzam A. Maghazachi
- College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Maha Saber-Ayad
- College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
- Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
- Faculty of Medicine, Cairo University, Cairo 11956, Egypt
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Parchwani D, Sonagra AD, Dholariya S, Motiani A, Singh R. COVID-19-related liver injury: Focus on genetic and drug-induced perspectives. World J Virol 2023; 12:53-67. [PMID: 36743658 PMCID: PMC9896591 DOI: 10.5501/wjv.v12.i1.53] [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: 09/13/2022] [Revised: 10/15/2022] [Accepted: 12/01/2022] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Empirical use of potentially hepatotoxic drugs in the management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is considered as one of the major etiopathogenetic factors for liver injury. Recent evidence has shown that an underlying genetic factor may also occur. Hence, it is important to understand the host genetics and iatrogenic-based mechanisms for liver dysfunction to make timely remedial measures. AIM To investigate drug-induced and genetic perspectives for the development of coronavirus disease 2019 (COVID-19)-related liver injury. METHODS Reference Citation Analysis, PubMed, Google Scholar and China National Knowledge Infrastructure were searched by employing the relevant MeSH keywords and pertaining data of the duration, site and type of study, sample size with any subgroups and drug-induced liver injury outcome. Genetic aspects were extracted from the most current pertinent publications. RESULTS In all studies, the hepatic specific aminotransferase and other biochemical indices were more than their prescribed upper normal limit in COVID-19 patients and were found to be significantly related with the gravity of disease, hospital stay, number of COVID-19 treatment drugs and worse clinical outcomes. In addition, membrane bound O-acyltransferase domain containing 7 rs641738, rs11385942 G>GA at chromosome 3 gene cluster and rs657152 C>A at ABO blood locus was significantly associated with severity of livery injury in admitted SARS-CoV-2 patients. CONCLUSION Hepatic dysfunction in SARS-CoV-2 infection could be the result of individual drugs or due to drug-drug interactions and may be in a subset of patients with a genetic propensity. Thus, serial estimation of hepatic indices in hospitalized SARS-CoV-2 patients should be done to make timely corrective actions for iatrogenic causes to avoid clinical deterioration. Additional molecular and translational research is warranted in this regard.
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Affiliation(s)
- Deepak Parchwani
- Department of Biochemistry, All India Institute of Medical Sciences, Rajkot 360001, India
| | - Amit D Sonagra
- Department of Biochemistry, All India Institute of Medical Sciences, Rajkot 360001, India
| | - Sagar Dholariya
- Department of Biochemistry, All India Institute of Medical Sciences, Rajkot 360001, India
| | - Anita Motiani
- Department of Biochemistry, All India Institute of Medical Sciences, Rajkot 360001, India
| | - Ragini Singh
- Department of Biochemistry, All India Institute of Medical Sciences, Rajkot 360001, India
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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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6
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Hu WS, Jiang FY, Shu W, Zhao R, Cao JM, Wang DP. Liver injury in COVID-19: A minireview. World J Gastroenterol 2022; 28:6716-6731. [PMID: 36620342 PMCID: PMC9813934 DOI: 10.3748/wjg.v28.i47.6716] [Citation(s) in RCA: 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: 09/12/2022] [Revised: 11/02/2022] [Accepted: 11/23/2022] [Indexed: 12/19/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has escalated into a global tragedy afflicting human health, life, and social governance. Through the increasing depth of research and a better understanding of this disease, it has been ascertained that, in addition to the lungs, SARS-CoV-2 can also induce injuries to other organs including the liver. Liver injury is a common clinical manifestation of COVID-19, particularly in severe cases, and is often associated with a poorer prognosis and higher severity of COVID-19. This review focuses on the general existing information on liver injury caused by COVID-19, including risk factors and subpopulations of liver injury in COVID-19, the association between preexisting liver diseases and the severity of COVID-19, and the potential mechanisms by which SARS-CoV-2 affects the liver. This review may provide some useful information for the development of therapeutic and preventive strategies for COVID-19-associated liver injury.
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Affiliation(s)
- Wen-Shu Hu
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Fang-Ying Jiang
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Wen Shu
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Rong Zhao
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Ji-Min Cao
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - De-Ping Wang
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
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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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Zha H, Li Q, Chang K, Xia J, Li S, Tang R, Li L. Characterising the Intestinal Bacterial and Fungal Microbiome Associated With Different Cytokine Profiles in Two Bifidobacterium strains Pre-Treated Rats With D-Galactosamine-Induced Liver Injury. Front Immunol 2022; 13:791152. [PMID: 35401547 PMCID: PMC8987000 DOI: 10.3389/fimmu.2022.791152] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 02/28/2022] [Indexed: 12/12/2022] Open
Abstract
Multiple probiotics have protective effects against different types of liver injury. Different intestinal microbes could be beneficial to the protective effects of the probiotics on the treated cohorts in different aspects. The current study was designed to determine the intestinal bacterial and fungal microbiome associated with different cytokine profiles in the Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10 pretreated rats with D-galactosamine-induced liver injury. In this study, partition around medoids clustering analysis determined two distinct cytokine profiles (i.e., CP1 and CP2) comprising the same 11 cytokines but with different levels among the LI09, LI10, positive control (PC), and negative control (NC) cohorts. All rats in PC and NC cohorts were determined with CP1 and CP2, respectively, while the rats with CP1 in LI09 and LI10 cohorts had more severe liver injury than those with CP2, suggesting that CP2 represented better immune status and was the “better cytokine profile” in this study. PERMANOVA analyses showed that the compositions of both bacterial and fungal microbiome were different in the LI10 cohorts with different cytokine profiles, while the same compositions were similar between LI09 cohorts with different cytokine profiles. The phylotype abundances of both bacteria and fungi were different in the rats with different cytokine profiles in LI09 or LI10 cohorts according to similarity percentage (SIMPER) analyses results. At the composition level, multiple microbes were associated with different cytokine profiles in LI09 or LI10 cohorts, among which Flavonifractor and Penicillium were the bacterium and fungus most associated with LI09 cohort with CP2, while Parabacteroides and Aspergillus were the bacterium and fungus most associated with LI10 cohort with CP2. These microbes were determined to influence the cytokine profiles of the corresponding cohorts. At the structure level, Corynebacterium and Cephalotrichiella were determined as the two most powerful gatekeepers in the microbiome networks of LI09 cohort CP2, while Pseudoflavonifractor was the most powerful gatekeeper in LI10 cohort with CP2. These identified intestinal microbes were likely to be beneficial to the effect of probiotic Bifidobacterium on the immunity improvement of the treated cohorts, and they could be potential microbial biomarkers assisting with the evaluation of immune status of probiotics-treated cohorts.
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Affiliation(s)
- Hua Zha
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qian Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kevin Chang
- Department of Statistics, The University of Auckland, Auckland, New Zealand
| | - Jiafeng Xia
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shengjie Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ruiqi Tang
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- *Correspondence: Lanjuan Li,
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Thornton SW, Gosman RE, Sudan DL, Rice HE, Arbogast MK, Fitzgerald TN. Biliary atresia in a neonate with a history of COVID-19: A case report. Int J Surg Case Rep 2022; 90:106705. [PMID: 34952315 PMCID: PMC8685349 DOI: 10.1016/j.ijscr.2021.106705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 12/11/2021] [Accepted: 12/14/2021] [Indexed: 12/01/2022] Open
Abstract
Introduction and importance Biliary Atresia is the progressive destruction of the neonatal intra- and extra- hepatic bile ducts. The novel coronavirus has shown dramatic hepatic tropism, and patients experiencing liver injury appear to have worse outcomes. We present the first documented case of a neonate diagnosed with Biliary Atresia and a prior history of COVID-19. Case presentation A two-month-old female presented with increasing scleral icterus. Her laboratory testing demonstrated direct hyperbilirubinemia, with elevated alkaline phosphatase and increased ALT. She tested positive for COVID-19 at that time, requiring a two-week quarantine during which time she did not develop respiratory symptoms. Two weeks later, she presented to the hospital with emesis and an evaluation concerning for biliary atresia. She ultimately underwent a Kasai repair and recovered well with no significant post-operative complications. Clinical discussion Biliary Atresia is a heterogenous disease of unknown etiology, though viral triggers are suggested to contribute. COVID-19 disease is frequently associated with liver damage, though its relationship to Biliary Atresia is unexplored. We present a case of a neonate who contracted COVID-19 infection, and subsequently developed biliary atresia. Conclusion Considering this child's concurrent COVID-19 infection, viral mediated hepatic and biliary inflammation may have contributed to the development of Biliary Atresia in this case. The proposed relationship requires additional investigation but may suggest value in COVID-19 testing for patients presenting with Biliary Atresia.
Biliary atresia results in a fibrosclerosing, obliterative cholangiopathy Several viruses may play a role in the development of biliary atresia The novel coronavirus SARS-CoV-2 has shown dramatic hepatic tropism It is unknown if COVID-19 disease is related to the development of biliary atresia We present the first case of biliary atresia after diagnosis of COVID-19 disease
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10
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Xu Y, Yang X, Bian H, Xia M. Metabolic dysfunction associated fatty liver disease and coronavirus disease 2019: clinical relationship and current management. Lipids Health Dis 2021; 20:126. [PMID: 34602072 PMCID: PMC8487451 DOI: 10.1186/s12944-021-01564-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 09/20/2021] [Indexed: 02/07/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). At present, the COVID-19 has been prevalent worldwide for more than a year and caused more than four million deaths. Liver injury was frequently observed in patients with COVID-19. Recently, a new definition of metabolic dysfunction associated fatty liver disease (MAFLD) was proposed by a panel of international experts, and the relationship between MAFLD and COVID-19 has been actively investigated. Several previous studies indicated that the patients with MAFLD had a higher prevalence of COVID-19 and a tendency to develop severe type of respiratory infection, and others indicated that liver injury would be exacerbated in the patients with MAFLD once infected with COVID-19. The mechanism underlying the relationship between MAFLD and COVID-19 infection has not been thoroughly investigated, and recent studies indicated that multifactorial mechanisms, such as altered host angiotensin converting enzyme 2 (ACE2) receptor expression, direct viral attack, disruption of cholangiocyte function, systemic inflammatory reaction, drug-induced liver injury, hepatic ischemic and hypoxic injury, and MAFLD-related glucose and lipid metabolic disorders, might jointly contribute to both of the adverse hepatic and respiratory outcomes. In this review, we discussed the relationship between MAFLD and COVID-19 based on current available literature, and summarized the recommendations for clinical management of MAFLD patients during the pandemic of COVID-19.
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Affiliation(s)
- Yanlan Xu
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Department of Geriatrics, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, 201700, China
| | - Xinyu Yang
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Hua Bian
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Fudan Institute for Metabolic Diseases, Shanghai, 200032, China.
| | - Mingfeng Xia
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Fudan Institute for Metabolic Diseases, Shanghai, 200032, China.
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11
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Zhou F, Xia J, Yuan HX, Sun Y, Zhang Y. Liver injury in COVID-19: Known and unknown. World J Clin Cases 2021; 9:4980-4989. [PMID: 34307548 PMCID: PMC8283595 DOI: 10.12998/wjcc.v9.i19.4980] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/13/2021] [Accepted: 05/08/2021] [Indexed: 02/06/2023] Open
Abstract
Since the first report of the coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, the outbreak of the disease is currently continuously evolving. Previous studies have shown varying degrees of liver damage in patients with COVID-19. However, the exact causes of liver injury and the relationship between COVID-19 and liver injury is unclear. This article describes liver injury induced by COVID-19, analyzes its causes, and discusses the treatment and prognosis of liver damage in patients with COVID-19.
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Affiliation(s)
- Feng Zhou
- Department of Endocrinology, Puren Hospital of Wuhan University of Science and Technology, Wuhan 430080, Hubei Province, China
| | - Jian Xia
- Department of Endocrinology, Puren Hospital of Wuhan University of Science and Technology, Wuhan 430080, Hubei Province, China
| | - Hai-Xia Yuan
- Department of Endocrinology, Puren Hospital of Wuhan University of Science and Technology, Wuhan 430080, Hubei Province, China
| | - Ying Sun
- Department of Endocrinology, Puren Hospital of Wuhan University of Science and Technology, Wuhan 430080, Hubei Province, China
| | - Ying Zhang
- Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
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Zhou X, Yu L, Zhou M, Hou P, Yi L, Mi M. Dihydromyricetin ameliorates liver fibrosis via inhibition of hepatic stellate cells by inducing autophagy and natural killer cell-mediated killing effect. Nutr Metab (Lond) 2021; 18:64. [PMID: 34147124 PMCID: PMC8214786 DOI: 10.1186/s12986-021-00589-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 06/10/2021] [Indexed: 12/11/2022] Open
Abstract
Background This study investigated the mechanisms underlying the preventive effect of dihydromyricetin (DHM) against liver fibrosis involving hepatic stellate cells (HSCs) and hepatic natural killer (NK) cells. Methods A carbon tetrachloride (CCl4)-induced liver fibrosis model was established in C57BL/6 mice to study the antifibrotic effect of DHM based on serum biochemical parameters, histological and immunofluorescence stainings, and the expression of several fibrosis-related markers. Based on the immunoregulatory role of DHM, the effect of DHM on NK cell activation ex vivo was evaluated by flow cytometry. Then, we investigated whether DHM-induced autophagy was involved in HSCs inactivation using enzyme-linked immunosorbent assays, transmission electron microscopy, and western blot analysis. Thereafter, the role of DHM in NK cell-mediated killing was studied by in vitro coculture of NK cells and HSCs, with subsequent analysis by flow cytometry. Finally, the mechanism by which DHM regulates NK cells was studied by western blot analysis. Results DHM ameliorated liver fibrosis in C57BL/6 mice, as characterized by decreased serum alanine transaminase and aspartate transaminase levels, decreased expressions of collagen I alpha 1 (CoL-1α1), collagen I alpha 2 (CoL-1α2), tissue inhibitor of metalloproteinases 1 (TIMP-1), α-smooth muscle actin (α-SMA) and desmin, as well as increased expression of matrix metalloproteinase 1 (MMP1). Interestingly, HSCs activation was significantly inhibited by DHM in vivo and in vitro. As expected, DHM also upregulated autophagy-related indicators in liver from CCl4-treated mice. DHM also prevented TGF-β1-induced activation of HSCs in vitro by initiating autophagic flux. In contrast, the autophagy inhibitor 3-methyladenine markedly abolished the antifibrotic effect of DHM. Surprisingly, the frequency of activated intrahepatic NK cells was significantly elevated by DHM ex vivo. Furthermore, DHM enhanced NK cell-mediated killing of HSCs by increasing IFN-γ expression, which was abolished by an anti-IFN-γ neutralizing antibody. Mechanistically, DHM-induced IFN-γ expression was through AhR-NF-κB/STAT3 pathway in NK cells. Conclusion These results demonstrated that DHM can ameliorate the progression of liver fibrosis and inhibition of HSCs activation by inducing autophagy and enhancing NK cell-mediated killing through the AhR-NF-κB/STAT3-IFN-γ signaling pathway, providing new insights into the preventive role of DHM in liver fibrosis. Supplementary Information The online version contains supplementary material available at 10.1186/s12986-021-00589-6.
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Affiliation(s)
- Xi Zhou
- Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University (Army Medical University), NO. 30th Gao Tan Yan Street, Shapingba District, Chongqing, 400038, People's Republic of China
| | - Li Yu
- Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University (Army Medical University), NO. 30th Gao Tan Yan Street, Shapingba District, Chongqing, 400038, People's Republic of China
| | - Min Zhou
- Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University (Army Medical University), NO. 30th Gao Tan Yan Street, Shapingba District, Chongqing, 400038, People's Republic of China
| | - Pengfei Hou
- Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University (Army Medical University), NO. 30th Gao Tan Yan Street, Shapingba District, Chongqing, 400038, People's Republic of China
| | - Long Yi
- Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University (Army Medical University), NO. 30th Gao Tan Yan Street, Shapingba District, Chongqing, 400038, People's Republic of China.
| | - Mantian Mi
- Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University (Army Medical University), NO. 30th Gao Tan Yan Street, Shapingba District, Chongqing, 400038, People's Republic of China.
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Wang M, Fan Y, Chai Y, Cheng W, Wang K, Cao J, Hu X. Association of Clinical and Immunological Characteristics With Disease Severity and Outcomes in 211 Patients With COVID-19 in Wuhan, China. Front Cell Infect Microbiol 2021; 11:667487. [PMID: 34123873 PMCID: PMC8195246 DOI: 10.3389/fcimb.2021.667487] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Accepted: 05/10/2021] [Indexed: 01/08/2023] Open
Abstract
Background Coronavirus disease 2019 (COVID-19) has posed a great threat to global public health. There remains an urgent need to address the clinical significance of laboratory finding changes in predicting disease progression in COVID-19 patients. We aimed to analyze the clinical and immunological features of severe and critically severe patients with COVID-19 in comparison with non-severe patients and identify risk factors for disease severity and clinical outcome in COVID-19 patients. Methods The consecutive records of 211 patients with COVID-19 who were admitted to Zhongnan Hospital of Wuhan University from December 2019 to February 2020 were retrospectively reviewed. Results Of the 211 patients with COVID-19 recruited, 111 patients were classified as non-severe, 59 as severe, and 41 as critically severe cases. The median age was obviously higher in severe and critically severe cases than in non-severe cases. Severe and critically severe patients showed more underlying comorbidities than non-severe patients. Fever was the predominant presenting symptom in COVID-19 patients, and the duration of fever was longer in critically severe patients. Moreover, patients with increased levels of serum aminotransferases and creatinine (CREA) were at a higher risk for severe and critical COVID-19 presentations. The serum levels of IL-6 in severe and critically severe patients were remarkably higher than in non-severe patients. Lymphopenia was more pronounced in severe and critically severe patients compared with non-severe patients. Lymphocyte subset analysis indicated that severe and critically severe patients had significantly decreased count of lymphocyte subpopulations, such as CD4+ T cells, CD8+ T cells and B cells. A multivariate logistic analysis indicated that older age, male sex, the length of hospital stay, body temperature before admission, comorbidities, higher white blood cell (WBC) counts, lower lymphocyte counts, and increased levels of IL-6 were significantly associated with predicting the progression to severe stage of COVID-19. Conclusion Older age, male sex, underlying illness, sustained fever status, abnormal liver and renal functions, excessive expression of IL-6, lymphopenia, and selective loss of peripheral lymphocyte subsets were related to disease deterioration and clinical outcome in COVID-19 patients. This study would provide clinicians with valuable information for risk evaluation and effective interventions for COVID-19.
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Affiliation(s)
- Man Wang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China
| | - Yongzhen Fan
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China
| | - Yuqiong Chai
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China
| | - Wenlin Cheng
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China
| | - Kun Wang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China
| | - Jianlei Cao
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China
| | - Xiaorong Hu
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Institute of Myocardial Injury and Repair, Wuhan University, Wuhan, China
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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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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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