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1
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Mataix RP, Morillo JSG, Martín JMS. Hepatic phenomena associated with SARS-CoV-2: Acute liver injury, autoimmune hepatitis and post-vaccination. Med Clin (Barc) 2025:S0025-7753(25)00011-9. [PMID: 39909769 DOI: 10.1016/j.medcli.2024.12.006] [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: 10/09/2024] [Revised: 12/11/2024] [Accepted: 12/16/2024] [Indexed: 02/07/2025]
Abstract
The infection with SARS-CoV-2, primarily recognized for its respiratory effects, reveals itself as a multifaceted clinical phenomenon, extending beyond the pulmonary realm. Accompanied by gastrointestinal, neurological, thromboembolic, cardiovascular, and immune-related manifestations, the complexity of the systemic repercussions of the disease becomes apparent. Genetic predisposition is a significant factor in the development of autoimmune hepatitis, as both viruses, such as SARS-CoV-2, and drugs, including vaccines, can act as triggers in genetically susceptible individuals. A profound understanding of these mechanisms is essential to effectively address the clinical complexity of SARS-CoV-2 infection.
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Affiliation(s)
- Roberto Pertusa Mataix
- Unit of Systemic and Rare Autoimmune Diseases in Adults, Internal Medicine Service, Virgen del Rocío University Hospital, Manuel Siurot Avenue, S/n, 41013 Sevilla, Spain.
| | - José Salvador García Morillo
- Unit of Systemic and Rare Autoimmune Diseases in Adults, Internal Medicine Service, Virgen del Rocío University Hospital, Manuel Siurot Avenue, S/n, 41013 Sevilla, Spain
| | - José Manuel Sousa Martín
- Digestive Department, Virgen del Rocío University Hospital, Manuel Siurot Avenue, S/n, 41013 Sevilla, Spain
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2
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Yu C, Wang W, Zhang Q, Jin Z. Autoimmune hepatitis under the COVID-19 veil: an analysis of the nature of potential associations. Front Immunol 2025; 16:1510770. [PMID: 39958350 PMCID: PMC11825795 DOI: 10.3389/fimmu.2025.1510770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 01/14/2025] [Indexed: 02/18/2025] Open
Abstract
In recent years, the novel coronavirus infectious disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has led to over 670 million infections and nearly 7 million deaths worldwide. The global pandemic of COVID-19 has precipitated a significant public health crisis. The prevalence of liver function abnormalities associated with SARS-CoV-2 is as high as 53% among healthy individuals or patients with autoimmune hepatitis (AIH) and shows a positive correlation with disease severity; moreover, specific adaptive immune responses can influence the trajectory and outcomes of COVID-19. For instance, SARS-CoV-2 may impact autoimmunity through mechanisms such as excessive stimulation of immune responses and molecular mimicry, particularly in genetically predisposed individuals. Currently, the overall mutational trend of SARS-CoV-2 indicates heightened infectivity and immune evasion capabilities. Consequently, vaccination remains crucial for universal protection against this disease. Nevertheless, alongside the widespread implementation of vaccination programs globally, an increasing number of cases have been documented where COVID-19 vaccination appears to trigger new-onset autoimmune hepatitis; yet definitive evidence is still pending elucidation regarding causality. In this review, we analyse the clinical-immunological characteristics, risks associated with severe disease progression, and prognosis for AIH patients infected with SARS-CoV-2; discuss the detrimental effects exerted by SARS-CoV-2 on hepatic function; summarise the mechanisms and attributes leading to new-onset AIH; as well as provide insights into how vaccination may interfere with autoimmunity processes. We continue to underscore the significance of vaccination while aiming to enhance awareness concerning potential risks associated with it-this could facilitate better management strategies for autoimmune diseases along with appropriate adjustments in vaccination protocols. Although the precise triggering mechanism linking COVID-19-related events to AIH remains unclear, existing evidence suggests that this relationship is far from coincidental.
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Affiliation(s)
| | | | | | - Zhenjing Jin
- Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
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3
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Fischer AK, Stippel D, Canbay A, Nierhoff D, Thomas M, Best J, Büttner R, Drebber U. COVID-19-associated secondary sclerosing cholangitis with liver transplantation. Virchows Arch 2024; 485:371-377. [PMID: 38526652 PMCID: PMC11329547 DOI: 10.1007/s00428-024-03753-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/22/2024] [Accepted: 01/27/2024] [Indexed: 03/27/2024]
Abstract
We report on two cases of orthotopic liver transplantation (OLTX) due to SARS-Cov2-associated secondary sclerosing cholangitis (SSC) following long-term artificial respiration and extra-corporal membrane oxygenation in intensive care. Under these conditions, SSC is a rapidly progredient biliary disease featuring degenerative cholangiopathy, loss of bile ducts, ductular and parenchymal cholestasis, biliary fibrosis, and finally cirrhosis. Reduced perfusion and oxygenation of the peribiliary plexus, severe concurrent infections, and secondary medico-toxic effects appear to play a crucial role in the pathogenesis of the disease. A direct cytopathic effect of SARS-Cov2 on endothelial cells followed by thrombosis and fibrosing obliteration in all parts of the vascular bed of the liver may enhance the virus-associated liver disease and particularly SSC.
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Affiliation(s)
- Anne Kristin Fischer
- Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
| | - Dirk Stippel
- Department of Surgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Ali Canbay
- Department of Internal Medicine, Transplant Medicine, Gastroenterology and Hepatology, University of Bochum, In Der Schornau 23-25 44892, Bochum, Germany
| | - Dirk Nierhoff
- Department of Internal Medicine, Gastroenterology and Hepatology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Michael Thomas
- Department of Surgery, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Jan Best
- Department of Internal Medicine, Transplant Medicine, Gastroenterology and Hepatology, University of Bochum, In Der Schornau 23-25 44892, Bochum, Germany
| | - Reinhard Büttner
- Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Uta Drebber
- Institute of Pathology, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
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Rasheed MA, Ballotin VR, Bigarella LG, Soldera J. Post-COVID-19 cholangiopathy: Systematic review. World J Methodol 2023; 13:296-322. [PMID: 37771872 PMCID: PMC10523251 DOI: 10.5662/wjm.v13.i4.296] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 06/07/2023] [Accepted: 08/23/2023] [Indexed: 09/20/2023] Open
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on global health, primarily characterized by severe respiratory illness. However, emerging evidence suggests that COVID-19 can also lead to secondary sclerosing cholangitis (SC), referred to as post-COVID-19 cholangiopathy. AIM To synthesize currently reported cases to assess the current state of knowledge on post-COVID-19 cholangiopathy. METHODS Medical Subject Headings and Health Sciences Descriptors were used to retrieve relevant studies, which were combined using Boolean operators. Searches were conducted on electronic databases including Scopus, Web of Science, and MEDLINE (PubMed). Studies published in English, Spanish, or Portuguese were included, with no restrictions on the publication date. Additionally, the reference lists of retrieved studies were manually searched. Simple descriptive analyses were used to summarize the results. Then the data were extracted and assessed based on Reference Citation Analysis (https://www.referencecitationanalysis.com/). RESULTS The initial search yielded a total of 192 articles. After screening, 85 articles were excluded due to duplication, leaving 107 articles for further review. Of these, 63 full-length articles met the inclusion criteria and were included in the analyses. Most of the patients were male and exhibited elevated liver function tests (93.8%). Magnetic resonance imaging revealed duct thickening with contrast enhancement (47.7%), as well as beading of the intrahepatic ducts (45.7%) with peribiliary contrast enhancement on diffusion (28.7%). Liver biopsy results confirmed SC in most cases (74.4%). Sixteen patients underwent liver transplantation, with three experiencing successful outcomes. CONCLUSION Post-COVID-19 cholangiopathy is a serious condition that is expected to become increasingly concerning in the coming years, particularly considering long COVID syndromes. Although liver transplantation has been proposed as a potential treatment option, more research is necessary to establish its efficacy and explore other potential treatments.
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Affiliation(s)
| | | | | | - Jonathan Soldera
- Acute Medicine, University of South Wales, Cardiff CF37 1DL, United Kingdom
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Saeedi N, Gohari NSF, Ghalibaf AAM, Dehghan A, Owlia MB. COVID-19 infection: a possible induction factor for development of autoimmune diseases? Immunol Res 2023; 71:547-553. [PMID: 37316687 DOI: 10.1007/s12026-023-09371-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 02/14/2023] [Indexed: 06/16/2023]
Abstract
Following the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the importance of investigation of the pathogenesis and immunological characteristics of COVID-19 became quite clear. Currently, there are reports indicating that COVID-19 is able to induce autoimmune responses. Abnormal immune reactions are a cornerstone in the pathogenicity of both conditions. Detection of autoantibodies in COVID-19 patients may suggest a link between COVID-19 and autoimmunity. In this study, we focused on the similarities and possible differences between COVID-19 and autoimmune disorders to explore the relationship between them. Comparing the pathogenicity of SARS-CoV-2 infection with autoimmune conditions revealed significant immunological properties of COVID-19 including the presence of several autoantibodies, autoimmunity-related cytokines, and cellular activities that could be useful in future clinical studies aiming at managing this pandemic.
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Affiliation(s)
- Nikoo Saeedi
- Student Research Committee, Islamic Azad University, Mashhad Branch, Mashhad, Iran.
| | - Narjes Sadat Farizani Gohari
- Interest Group of CoronaVirus 2019 (IGCV-19), Universal Scientific Education and Research Network (USERN), Yazd, Iran
- Student Research Committee, Faculty of Medicine, Yazd University of Medical Sciences, Yazd, Iran
| | - Amir Ali Moodi Ghalibaf
- Student Research Committee, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
- Interest Group of CoronaVirus 2019 (IGCV-19), Universal Scientific Education and Research Network (USERN), Birjand, Iran
| | - Ali Dehghan
- Division of Rheumatology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mohammad Bagher Owlia
- Division of Rheumatology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Sgamato C, Rocco A, Compare D, Minieri S, Marchitto SA, Maurea S, Nardone G. Autoimmune liver diseases and SARS-CoV-2. World J Gastroenterol 2023; 29:1838-1851. [PMID: 37032727 PMCID: PMC10080695 DOI: 10.3748/wjg.v29.i12.1838] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 01/12/2023] [Accepted: 03/14/2023] [Indexed: 03/28/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry. Here we summarise the current knowledge about auto-immune liver diseases (AILDs) and SARS-CoV-2, focusing on: (1) The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs; (2) the role of SARS-CoV-2 in inducing liver damage and triggering AILDs; and (3) the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver. Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine. Although SARS-CoV-2 infection can lead to the development of several autoimmune diseases, few reports correlate it to the appearance of de novo manifestation of immune-mediated liver diseases such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) or AIH/PBC overlap syndrome. Different case series of an AIH-like syndrome with a good prognosis after SARS-CoV-2 vaccination have been described. Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established, these reports suggest that this association could be more than coincidental.
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Affiliation(s)
- Costantino Sgamato
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Alba Rocco
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Debora Compare
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Stefano Minieri
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Stefano Andrea Marchitto
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Simone Maurea
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples 80131, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
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Quan L, Tan J, Hua L, You X. Genetic predisposition between coronavirus disease 2019 and rheumatic diseases: A 2-sample Mendelian randomization study. Int J Rheum Dis 2023; 26:710-717. [PMID: 36890668 DOI: 10.1111/1756-185x.14624] [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: 01/10/2023] [Revised: 01/30/2023] [Accepted: 02/07/2023] [Indexed: 03/10/2023]
Abstract
OBJECTIVE The causalities between the coronavirus disease 2019 (COVID-19) and the risk of rheumatic diseases remain unclear. The purpose of this study was to investigate the causal effect of COVID-19 on rheumatic disease occurrence. METHODS Single nucleotide polymorphisms (SNPs), acquired from published genome-wide association studies, were used to perform 2-sample Mendelian randomization (MR) on cases diagnosed with COVID-19 (n = 13 464), rheumatic diseases (n = 444 199), juvenile idiopathic arthritis (JIA, n = 15 872), gout (n = 69 374), systemic lupus erythematosus (SLE, n = 3094), ankylosing spondylitis (n = 75 130), primary biliary cholangitis (PBC, n = 11 375) and primary Sjögren's syndrome (n = 95 046). Three MR methods were used in the analysis based on different heterogeneity and pleiotropy using the Bonferroni correction. RESULTS The results revealed a causality between COVID-19 and rheumatic diseases with an odds ratio (OR) of 1.010 (95% confidence interval [CI], 1.006-1.013; P = .014). In addition, we observed that COVID-19 was causally associated with an increased risk of JIA (OR 1.517; 95%CI, 1.144-2.011; P = .004), PBC (OR 1.370; 95%CI, 1.149-1.635; P = .005), but a decreased risk of SLE (OR 0.732; 95%CI, 0.590-0.908; P = .004). Using MR, 8 SNPs were identified to associate with COVID-19 and recognized as significant variables. None of them were previously reported in any other diseases. CONCLUSIONS This is the first study to use MR to explore the impact of COVID-19 on rheumatic diseases. From a genetic perspective, we found that COVID-19 could increase the risk of rheumatic diseases, such as PBC and JIA, but decrease that of SLE, thereby suggesting a potential surge in the disease burden of PBC and JIA following the COVID-19 pandemic.
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Affiliation(s)
- Liuliu Quan
- Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Jiangshan Tan
- Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and National Clinical Research Center of Cardiovascular Diseases, Beijing, China
| | - Lu Hua
- Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and National Clinical Research Center of Cardiovascular Diseases, Beijing, China
| | - Xin You
- Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.,Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, China
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8
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Ture HY, Kim NR, Nam EJ. New-onset retroperitoneal fibrosis following COVID-19 mRNA vaccination: Coincidental or vaccine-induced phenomenon? Int J Rheum Dis 2023. [PMID: 36814401 DOI: 10.1111/1756-185x.14621] [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: 01/01/2023] [Revised: 01/28/2023] [Accepted: 02/07/2023] [Indexed: 02/24/2023]
Abstract
The Pfizer-BioNTech mRNA vaccine is a US Food and Drug Administration-approved coronavirus disease 2019 (COVID-19) vaccine. Although it is reported to be safe and effective, immune dysregulation leading to autoimmunity has become an area of concern. Retroperitoneal fibrosis (RPF) is an immune-mediated fibroinflammatory disease characterized by the deposition of fibrous tissues, primarily around the abdominal aorta and iliac arteries. Herein, we report a case of RPF following Pfizer BioNTech COVID-19 mRNA vaccination. To the best of our knowledge, there have been no published reports on RPF after COVID-19 mRNA vaccination. A 58-year-old woman with no history of autoimmune diseases presented with acute onset of epigastric pain 5 weeks after the second dose of the Pfizer-BioNTech vaccine. She had been diagnosed with stage I breast cancer 9 years ago and was in complete remission on admission. Abdominal computed tomography showed preaortic soft-tissue infiltration around the origin of the superior mesenteric artery but no evidence of breast cancer recurrence. Considering the temporal relationship between current symptoms and vaccination and the absence of other possible causes, she was diagnosed with RPF secondary to Pfizer-BioNTech vaccine-induced autoimmunity. This case may raise awareness of the possibility of RPF development following COVID-19 mRNA vaccination.
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Affiliation(s)
- Hirut Yadeta Ture
- Division of Rheumatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea
| | - Na Ri Kim
- Division of Rheumatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea
| | - Eon Jeong Nam
- Division of Rheumatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea
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Li X, Li Y, Xiao J, Wang H, Guo Y, Mao X, Shi P, Hou Y, Zhang X, Zhao N, Zheng M, He Y, Ding J, Tan Y, Liao M, Li L, Peng Y, Li X, Pan Q, Xie Q, Li Q, Li J, Li Y, Chen Z, Huang Y, Assis DN, Cai SY, Boyer JL, Huang X, Tang CE, Liu X, Peng S, Chai J. Unique DUOX2 +ACE2 + small cholangiocytes are pathogenic targets for primary biliary cholangitis. Nat Commun 2023; 14:29. [PMID: 36759512 PMCID: PMC9911648 DOI: 10.1038/s41467-022-34606-w] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 10/31/2022] [Indexed: 02/11/2023] Open
Abstract
Cholangiocytes play a crucial role in bile formation. Cholangiocyte injury causes cholestasis, including primary biliary cholangitis (PBC). However, the etiology of PBC remains unclear despite being characterized as an autoimmune disease. Using single-cell RNA sequencing (scRNA-seq), fluorescence-activated-cell-sorting, multiplex immunofluorescence (IF) and RNAscope analyses, we identified unique DUOX2+ACE2+ small cholangiocytes in human and mouse livers. Their selective decrease in PBC patients was associated with the severity of disease. Moreover, proteomics, scRNA-seq, and qPCR analyses indicated that polymeric immunoglobulin receptor (pIgR) was highly expressed in DUOX2+ACE2+ cholangiocytes. Serum anti-pIgR autoantibody levels were significantly increased in PBC patients, regardless of positive and negative AMA-M2. Spatial transcriptomics and multiplex IF revealed that CD27+ memory B and plasma cells accumulated in the hepatic portal tracts of PBC patients. Collectively, DUOX2+ACE2+ small cholangiocytes are pathogenic targets in PBC, and preservation of DUOX2+ACE2+ cholangiocytes and targeting anti-pIgR autoantibodies may be valuable strategies for therapeutic interventions in PBC.
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Affiliation(s)
- Xi Li
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
- Department of Hematology, the Third Affiliated Hospital (Daping Hospital), Third Military Medical University (Army Medical University), Chongqing, 400042, PR China
| | - Yan Li
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Jintao Xiao
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, 410008, PR China
| | - Huiwen Wang
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
- Department of Hepatology and Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, PR China
| | - Yan Guo
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
- Department of Endocrinology, Xiangya Hospital, Central South University, Changsha, 410008, PR China
| | - Xiuru Mao
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
- Department of Hepatology and Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, PR China
| | - Pan Shi
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Yanliang Hou
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, 410008, PR China
| | - Xiaoxun Zhang
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Nan Zhao
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Minghua Zheng
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, PR China
| | - Yonghong He
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Jingjing Ding
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Ya Tan
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Min Liao
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Ling Li
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Ying Peng
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Xuan Li
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Qiong Pan
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Qiaoling Xie
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Qiao Li
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Jianwei Li
- Institute of Hepatobiliary Surgery, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Ying Li
- Institute of Hepatobiliary Surgery, the Second Affiliated Hospital (Xinqiao Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Zhe Chen
- Department of Hematology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - Yongxiu Huang
- Department of Hematology, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, PR China
| | - David N Assis
- Department of Internal Medicine and Liver Center, Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA
| | - Shi-Ying Cai
- Department of Internal Medicine and Liver Center, Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA
| | - James L Boyer
- Department of Internal Medicine and Liver Center, Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA
| | - Xuequan Huang
- Center of Minimally Invasive Intervention, the First Affiliated Hospital (Southwest Hospital), Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.
| | - Can-E Tang
- Institute of Medical Science Research, Xiangya Hospital, Central South University, Changsha, 410008, PR China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, PR China.
| | - Xiaowei Liu
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, 410008, PR China.
| | - Shifang Peng
- Department of Hepatology and Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, PR China.
| | - Jin Chai
- Department of Gastroenterology, Institute of Digestive Diseases of PLA, Cholestatic Liver Diseases Certer, and Center for Metabolic Associated Fatty Liver Disease, the First Affiliated Hospital (Southwest Hospital) to Third Military Medical University (Army Medical University), Chongqing, 400038, PR China.
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10
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Abstract
SARS-CoV-2 is the viral agent of COVID-19, a pandemic that surfaced in 2019. Although predominantly a respiratory ailment, patients with COVID-19 can have gastrointestinal (GI) and hepatobiliary manifestations. These manifestations are often mild and transient, but they can be severe and consequential. In the GI tract, ischemic enterocolitis is the most common and significant consequence of COVID-19. In the liver, the reported pathologic findings may often be related to consequences of severe systemic viral infection, but reports of hepatitis presumed to be due to SARS-CoV-2 suggest that direct viral infection of the liver may be a rare complication of COVID-19. In both the GI tract and liver, lingering symptoms of GI or hepatic injury after resolution of pulmonary infection may be part of the evolving spectrum of long COVID.
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Affiliation(s)
- Angela R Shih
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
| | - Joseph Misdraji
- Department of Pathology, Yale New Haven Hospital, Yale University, New Haven, CT, 06510, USA.
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11
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Asgarzdeh A, Habibzadeh S, Asghariazar V, Safarzadeh E. Drug-induced hepatitis (DIH) after SARS-CoV-2 vaccination. Clin Res Hepatol Gastroenterol 2023; 47:102028. [PMID: 36195274 PMCID: PMC9527185 DOI: 10.1016/j.clinre.2022.102028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 09/17/2022] [Accepted: 09/30/2022] [Indexed: 02/07/2023]
Key Words
- alp, alkaline phosphatase
- alt, alanine aminotransferase
- ama, anti-mitochondrial antibody
- ana, anti-nuclear antibodies
- apca, anti-parietal cell antibody
- asa, acetylsalicylic acid
- asma, anti-smooth muscle antibodies
- ast, aspartate aminotransferase
- covid-19, coronavirus disease 2019
- ct, computerized tomography
- dih, drug-induced hepatitis
- ds-dna, double-stranded dna antibodies
- ggt, gamma-glutamyl transferase
- hav ab, hepatitis a virus antibody
- igg, immunoglobulins g
- lc, liver cytosol
- lkm-1 ab, liver-kidney microsome type 1 antibody
- mrcp, magnetic resonance cholangiopancreatography
- pbc, primary biliary cholangitis
- psc, primary sclerosing cholangitis
- sars-cov-2, severe acute respiratory syndrome coronavirus 2
- sla, soluble liver antigen
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Affiliation(s)
- Ali Asgarzdeh
- Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Shahram Habibzadeh
- Department of Internal Medicine, Emam Khomeini Hospital, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Vahid Asghariazar
- Deputy of Research and Technology, Ardabil University of Medical Sciences, Ardabil, Iran; Immunology Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Elham Safarzadeh
- Department of Microbiology, Parasitology, and Immunology, Ardabil University of Medical Sciences, Ardabil, Iran.
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12
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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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13
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Cunha-Silva M, de França EVC, Greca RD, Mazo DFDC, da Costa LBE, de Moraes PBS, Veiga CT, Assis-Mendonça GR, Boin IDFSF, Stucchi RSB, Sevá-Pereira T. Autoimmune hepatitis and primary biliary cholangitis overlap syndrome after COVID-19. Autops Case Rep 2023; 13:e2023422. [PMID: 37034275 PMCID: PMC10075219 DOI: 10.4322/acr.2023.422] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Accepted: 02/10/2023] [Indexed: 04/07/2023]
Abstract
COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.
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Affiliation(s)
- Marlone Cunha-Silva
- Universidade Estadual de Campinas (UNICAMP), School of Medical Sciences, Centro de Diagnóstico de Doenças do Aparelho Digestivo (GASTROCENTRO), Department of Internal Medicine, Division of Gastroenterology, Campinas, SP, Brasil
| | - Eloy Vianey Carvalho de França
- Universidade Estadual de Campinas (UNICAMP), School of Medical Sciences, Centro de Diagnóstico de Doenças do Aparelho Digestivo (GASTROCENTRO), Department of Internal Medicine, Division of Gastroenterology, Campinas, SP, Brasil
| | - Raquel Dias Greca
- Universidade Estadual de Campinas (UNICAMP), School of Medical Sciences, Centro de Diagnóstico de Doenças do Aparelho Digestivo (GASTROCENTRO), Department of Internal Medicine, Division of Gastroenterology, Campinas, SP, Brasil
| | - Daniel Ferraz de Campos Mazo
- Universidade Estadual de Campinas (UNICAMP), School of Medical Sciences, Centro de Diagnóstico de Doenças do Aparelho Digestivo (GASTROCENTRO), Department of Internal Medicine, Division of Gastroenterology, Campinas, SP, Brasil
| | - Larissa Bastos Eloy da Costa
- Universidade Estadual de Campinas (UNICAMP), School of Medical Sciences, Department of Pathology, Campinas, SP, Brasil
| | - Priscilla Brito Sena de Moraes
- Universidade Estadual de Campinas (UNICAMP), School of Medical Sciences, Centro de Diagnóstico de Doenças do Aparelho Digestivo (GASTROCENTRO), Department of Internal Medicine, Division of Gastroenterology, Campinas, SP, Brasil
| | - Clauber Teles Veiga
- Universidade Estadual de Campinas (UNICAMP), School of Medical Sciences, Centro de Diagnóstico de Doenças do Aparelho Digestivo (GASTROCENTRO), Department of Internal Medicine, Division of Gastroenterology, Campinas, SP, Brasil
| | | | | | - Raquel Silveira Bello Stucchi
- Universidade Estadual de Campinas (UNICAMP), School of Medical Sciences, Department of Internal Medicine, Division of Infectious Diseases, Campinas, SP, Brasil
| | - Tiago Sevá-Pereira
- Universidade Estadual de Campinas (UNICAMP), School of Medical Sciences, Centro de Diagnóstico de Doenças do Aparelho Digestivo (GASTROCENTRO), Department of Internal Medicine, Division of Gastroenterology, Campinas, SP, Brasil
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14
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Abstract
Knowledge on SARS-CoV-2 infection and its resultant COVID-19 in liver diseases has rapidly increased during the pandemic. Hereby, we review COVID-19 liver manifestations and pathophysiological aspects related to SARS-CoV-2 infection in patients without liver disease as well as the impact of COVID-19 in patients with chronic liver disease (CLD), particularly cirrhosis and liver transplantation (LT). SARS-CoV-2 infection has been associated with overt proinflammatory cytokine profile, which probably contributes substantially to the observed early and late liver abnormalities. CLD, particularly decompensated cirrhosis, should be regarded as a risk factor for severe COVID-19 and death. LT was impacted during the pandemic, mainly due to concerns regarding donation and infection in recipients. However, LT did not represent a risk factor per se of worse outcome. Even though scarce, data regarding COVID-19 specific therapy in special populations such as LT recipients seem promising. COVID-19 vaccine-induced immunity seems impaired in CLD and LT recipients, advocating for a revised schedule of vaccine administration in this population.
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Affiliation(s)
- Jean-François Dufour
- Hepatology, Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Thomas Marjot
- Oxford Liver Unit, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK
- Nuffield Department of Medicine, Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | - Chiara Becchetti
- Department of Hepatology and Gastroenterology, ASST Grande Ospedale Metropolitano Niguarda, Bern, Italy
- Department of Visceral Surgery and Medicine, Inselspital, University Hospital of Bern, Bern, Switzerland
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University Innsbruck, Innsbruck, Austria
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15
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Cho JY, Lee YS, Kim SS, Song DS, Lee JH, Kim JH. Forms of cholangitis to be considered after SARS-CoV-2 infection. Clin Mol Hepatol 2022; 28:929-930. [PMID: 36096495 PMCID: PMC9597223 DOI: 10.3350/cmh.2022.0260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 08/31/2022] [Indexed: 01/05/2023] Open
Affiliation(s)
- Ju-Yeon Cho
- Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
| | - Young-Sun Lee
- Department of Internal Medicine, Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Soon Sun Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Do Seon Song
- Department of Gastroenterology, St. Vincent’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Guro Hospital, Korea University College of Medicine, Seoul, Korea,Corresponding author : Ji Hoon Kim Department of Internal Medicine, Korea University Medical Center, 148 Gurodong-ro, Guro-gu, Seoul 08308, Korea Tel: +82-2-2626-3011, Fax: +82-2-2626-1038, E-mail:
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16
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Abstract
OBJECTIVES Severe acute respiratory syndrome coronavirus 2, the novel coronavirus responsible for coronavirus disease (COVID-19), has been a major cause of morbidity and mortality worldwide. Gastrointestinal and hepatic manifestations during acute disease have been reported extensively in the literature. Post-COVID-19 cholangiopathy has been increasingly reported in adults. In children, data are sparse. Our aim was to describe pediatric patients who recovered from COVID-19 and later presented with liver injury. METHODS This is a retrospective case series study of pediatric patients with post-COVID-19 liver manifestations. We collected data on demographics, medical history, clinical presentation, laboratory results, imaging, histology, treatment, and outcome. RESULTS We report 5 pediatric patients who recovered from COVID-19 and later presented with liver injury. Two types of clinical presentation were distinguishable. Two infants aged 3 and 5 months, previously healthy, presented with acute liver failure that rapidly progressed to liver transplantation. Their liver explant showed massive necrosis with cholangiolar proliferation and lymphocytic infiltrate. Three children, 2 aged 8 years and 1 aged 13 years, presented with hepatitis with cholestasis. Two children had a liver biopsy significant for lymphocytic portal and parenchyma inflammation, along with bile duct proliferations. All 3 were started on steroid treatment; liver enzymes improved, and they were weaned successfully from treatment. For all 5 patients, extensive etiology workup for infectious and metabolic etiologies was negative. CONCLUSIONS We report 2 distinct patterns of potentially long COVID-19 liver manifestations in children with common clinical, radiological, and histopathological characteristics after a thorough workup excluded other known etiologies.
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17
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COVID-19 and Autoimmune Liver Diseases. J Clin Med 2022; 11:jcm11102681. [PMID: 35628807 PMCID: PMC9143939 DOI: 10.3390/jcm11102681] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 05/06/2022] [Accepted: 05/09/2022] [Indexed: 02/06/2023] Open
Abstract
SARS-CoV-2 infection can trigger autoimmune responses, either by a systemic hyperstimulation of the immune system or molecular mimicry (or both). We here summarize the current knowledges about autoimmune liver diseases (AILDs) and COVID-19, focusing on (a) the risk of SARS-CoV-2 infection in patients affected by AILDs and/or under pharmacological treatment with immunosuppressants; (b) the capability of vaccination against SARS-CoV-2 to trigger autoimmune responses in the liver; and (c) the efficacy of vaccines against SARS-CoV-2 in patients with AILDs. Although unconclusive results have been obtained regarding the risk of being infected by SARS-CoV-2, generally indicating that all patients with chronic liver diseases have the same risk, irrespective of the etiology, the use of immunosuppressants in patients with AILDs seems to be correlated to COVID-19 severity. Few cases of autoimmune hepatitis (AIH) after SARS-CoV-2 vaccination have been reported, all characterized by a complete remission upon steroid treatment, but further evidence is needed to demonstrate the causality assessment. Humoral responses have been observed in patients with AILDs upon vaccination. In conclusion, the link between SARS-CoV-2 infection and AILDs is far to be completely elucidated. In these patients, the use of immunosuppressants has been correlated to an increase of disease severity and lower levels of antibodies upon vaccination.
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18
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Abstract
PURPOSE OF REVIEW SARS-CoV2 is a β-coronavirus, isolated for the first time in Wuhan in December 2019. Bilateral interstitial pneumonia is the hallmark of this disease. Liver is the second viral target for frequency and AST and ALT elevation is a common finding. From February 2020, two different cholangiopathies have been reported in COVID-19 patients. The aim of this article is to review the cases so far described in order to share information and awareness about these new clinical entities. RECENT FINDINGS SARS-CoV2 seems to trigger autoimmunity and two cases of primary biliary cholangitis (PBC) have been developed after viral infection while more than 30 patients have showed a rapidly progressing cholangiopathy with features of secondary sclerosing cholangitis (SSC). For what concerns SSC pathogenesis, a theory combining multiple hits is the most recognized. SUMMARY Two different cholangiopathies have been reported in patients after severe-COVID-19. Attention should be paid to the development of cholestasis in ICU setting but above all after discharge and liver function tests should be, therefore, periodically performed. No treatment strategies are available and liver transplantation remains the last option in individuals with liver failure because of SSC. Other efforts are necessary to better understand the pathogenesis and to expand therapeutic options.
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19
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COVID-19 vaccine and autoimmunity. A new case of autoimmune hepatitis and review of the literature. J Transl Autoimmun 2022; 5:100140. [PMID: 35013724 PMCID: PMC8730708 DOI: 10.1016/j.jtauto.2022.100140] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 01/02/2022] [Indexed: 12/19/2022] Open
Abstract
Autoimmunity following COVID-19 vaccination has been reported. Herein, a 79-year-old man with clinical and immunological features of autoimmune hepatitis type 1 after ChAdOx1 nCoV-19 vaccination is presented. Clinical manifestations rapidly remitted after the instauration of immunomodulatory management. This case, together with a comprehensive review of the literature, illustrates the association between COVID-19 vaccines and the development of autoimmune conditions.
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20
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Colapietro F, Lleo A, Generali E. Antimitochondrial Antibodies: from Bench to Bedside. Clin Rev Allergy Immunol 2022; 63:166-177. [PMID: 34586589 PMCID: PMC8480115 DOI: 10.1007/s12016-021-08904-y] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2021] [Indexed: 01/13/2023]
Abstract
Anti-mitochondrial antibodies (AMA) are directed against the E2 subunits of the 2-oxo acid dehydrogenase complexes (PDC-E2) and are the typical biomarkers of primary biliary cholangitis (PBC), being present in 90-95% of patients, with increasing sensitivity at increasing titers. Albeit being highly specific for PBC diagnosis, AMA can be detected in less than 1% of healthy subjects, and thus the management subjects with no sign or symptom of liver disease is still a challenge and data concerning clinical risk of developing PBC in this subgroup of patients are controversial. Moreover, AMA can also be detected in patients affected by overlap syndrome, as well as hepatic diseases (i.e., NASH and viral hepatitis), while the association with autoimmune diseases, in particular Sjögren's syndrome, systemic sclerosis, and systemic lupus erythematosus, is well established. Furthermore, new associations are being identified with inflammatory myositis and heart disease. AMA are directed towards the pyruvate dehydrogenase multi enzyme complex (PDC-E2) subunit, which represents an epithelial specific autoantigen for PBC. This review focuses on the main characteristics of AMA, their association with autoimmune diseases and liver diseases.
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Affiliation(s)
- Francesca Colapietro
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Rozzano, Milan, Italy
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Rozzano, Milan, Italy.
| | - Elena Generali
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Rozzano, Milan, Italy
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21
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McShane C, Kiat C, Rigby J, Crosbie Ó. The mRNA COVID-19 vaccine - A rare trigger of autoimmune hepatitis? J Hepatol 2021; 75:1252-1254. [PMID: 34245804 PMCID: PMC8264276 DOI: 10.1016/j.jhep.2021.06.044] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 06/23/2021] [Accepted: 06/29/2021] [Indexed: 12/28/2022]
Affiliation(s)
- Cathy McShane
- Department of Hepatology, Cork University Hospital, Cork, Ireland.
| | - Clifford Kiat
- Department of Hepatology, Cork University Hospital, Cork, Ireland
| | - Jonathan Rigby
- Department of Histopathology, Cork University Hospital, Cork, Ireland
| | - Órla Crosbie
- Department of Hepatology, Cork University Hospital, Cork, Ireland
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22
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Gaspar R, Castelo Branco C, Macedo G. Liver and COVID-19: From care of patients with liver diseases to liver injury. World J Hepatol 2021; 13:1367-1377. [PMID: 34786172 PMCID: PMC8568576 DOI: 10.4254/wjh.v13.i10.1367] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 07/11/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
The global pandemic of coronavirus disease 2019 (COVID-19) changed dramatically all priorities on medical society and created several challenges for clinicians caring for patients with liver diseases. We performed a comprehensive review about how COVID-19 can affect the liver, the influence of liver diseases on the risk of developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 severity and also some strategies to overcome all the challenges clinicians have to face in the management of patients with liver diseases in a period of time when all the focus turned on COVID-19. We analyze the relationship between COVID-19 and non-alcoholic fatty liver disease, alcoholic liver disease, viral hepatitis, autoimmune liver disease, cirrhosis, hepatocellular carcinoma and liver transplantation, as well as the approach to SARS-CoV-2 vaccination.
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Affiliation(s)
- Rui Gaspar
- Department of Gastroenterology and Hepatology, Centro Hospitalar de São João, Porto 4200, Portugal
| | - Catarina Castelo Branco
- Department of Internal Medicine, Centro Hospitalar e Universitário do Porto, Porto 4100, Portugal
| | - Guilherme Macedo
- Department of Gastroenterology and Hepatology, Centro Hospitalar de São João, Porto 4200, Portugal
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23
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Trivedi PJ, Hirschfield GM. Recent advances in clinical practice: epidemiology of autoimmune liver diseases. Gut 2021; 70:1989-2003. [PMID: 34266966 DOI: 10.1136/gutjnl-2020-322362] [Citation(s) in RCA: 117] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 06/24/2021] [Indexed: 12/13/2022]
Abstract
Autoimmune liver diseases are chronic inflammatory hepatobiliary disorders that when classically defined encompass three distinctive clinical presentations; primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Meaningful changes in disease epidemiology are reported, with increasing incidence and prevalence of AIH and PSC in Europe, and rising prevalence of PBC across Europe, North America and the Asia-Pacific region. However, there appears to be very significant global variation with contemporary incidence rates of disease per 100 000 ranging from 0.84 to 2.75 for PBC, 0.1 to 4.39 for PSC and 0.4 to 2.39 for AIH. Prevalence corresponds, and per 100 000 estimates for PBC range from 1.91 to 40.2, for PSC between 0.78 and 31.7 and for AIH from 4.8 to 42.9. Population-based studies and multicentre observational cohort series provide improved understanding of the clinical course that patients experience, highlighting variations in presenting phenotypes geographically and temporally. Collectively, while autoimmune liver diseases are rare, the clinical burden is disproportionately high relative to population incidence and prevalence. Age, sex and race also impact clinical outcomes, and patient morbidity and mortality are reflected by high need for gastroenterology, hepatology and organ transplant services.
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Affiliation(s)
- Palak J Trivedi
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Centre, University of Birmingham College of Medical and Dental Sciences, Birmingham, Birmingham, UK
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- Liver Unit, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, UK
| | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University of Toronto, Toronto, Ontario, Canada
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24
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Rojas M, Rodríguez Y, Zapata E, Hernández JC, Anaya JM. Cholangiopathy as part of post-COVID syndrome. J Transl Autoimmun 2021; 4:100116. [PMID: 34485887 PMCID: PMC8406516 DOI: 10.1016/j.jtauto.2021.100116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 08/30/2021] [Indexed: 02/07/2023] Open
Abstract
Liver compromise in critically ill patients with coronavirus disease 2019 (COVID-19) is common but usually transient and self-limited. However, liver tests on some patients continue to show abnormal results. Herein, a 29-year-old patient with clinical and histological features of cholangiopathy is presented. Despite treatment with ursodeoxycholic acid and cholestyramine, bilirubin and transaminase levels remained elevated. This case report raises awareness of the difficulty of managing this condition in patients with COVID-19.
Liver compromise in coronavirus disease 2019 (COVID-19) is common. Cholangiopathy must be consider as a clinical manifestation of post-COVID syndrome. Autoimmune liver compromise should be suspected in patients with transaminitis and hyperbilirubinemia.
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Affiliation(s)
- Manuel Rojas
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia
| | - Yhojan Rodríguez
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia.,Clinica del Occidente, Bogota, Colombia
| | - Elizabeth Zapata
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia
| | | | - Juan-Manuel Anaya
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia.,Clinica del Occidente, Bogota, Colombia
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Tan X, Guo J, Chen Z, Königsrainer A, Wichmann D. Systematic review and meta-analysis of clinical outcomes of COVID-19 patients undergoing gastrointestinal endoscopy. Therap Adv Gastroenterol 2021; 14:17562848211042185. [PMID: 34484425 PMCID: PMC8408897 DOI: 10.1177/17562848211042185] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 08/06/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The impact of gastrointestinal endoscopy on COVID-19 infection remains poorly investigated. We herein performed a systematic review and meta-analysis to evaluate the outcomes of COVID-19 in patients undergoing gastrointestinal endoscopy. METHOD Ovid Medline, Ovid EMBASE, Ovid the Cochrane Library, and other electronic databases were searched until 30 November 2020 to identify publications with confirmed COVID-19 infection in patients undergoing gastrointestinal endoscopy. The primary outcomes were SARS-CoV-2 transmission, personal protective equipment use, rates of case fatality, complications, and procedural success. RESULTS A total of 18 articles involving 329 patients were included in this systematic review and meta-analysis. The overall basic reproduction rate is 0.37, while the subgroup results from Asia, Europe, and North America are 0.13, 0.44, and 0.33, respectively. The differences in personal protective equipment use between the positive transmission and non-transmission group are mainly in isolation gowns, N95 or equivalent masks, and goggles or face-shields. The rate of case fatality, complication, and procedural success are 0.17 (95% confidence interval = 0.02-0.38), 0.00 (95% confidence interval = 0.00-0.02), and 0.89 (95% confidence interval = 0.50-1.00), respectively. The fatality rate in Europe was the highest (0.23, 95% confidence interval = 0.04-0.50), which is significantly different from other continents (p = 0.034). CONCLUSION The risk of SARS-CoV-2 transmission within gastrointestinal endoscopy units is considerably low if proper use of personal protective equipment is applied. Similarly, a low fatality and complication rate, as well as a high procedural success rate, indicated that a full recovery of endoscopic units should be considered.
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Affiliation(s)
- Xiangzhou Tan
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China,Department of General, Visceral and Transplantation Surgery, Interdisciplinary Endoscopy Unit, University Hospital Tübingen, Tübingen, Germany
| | - Jianping Guo
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Zihua Chen
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Alfred Königsrainer
- Department of General, Visceral and Transplantation Surgery, Interdisciplinary Endoscopy Unit, University Hospital Tübingen, Tübingen, Germany
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