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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; 164:491-498. [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] [MESH Headings] [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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Gleeson D, Bornand R, Brownlee A, Dhaliwal H, Dyson JK, Hails J, Henderson P, Kelly D, Mells GF, Miquel R, Oo YH, Sutton A, Yeoman A, Heneghan MA. British Society of Gastroenterology guidelines for diagnosis and management of autoimmune hepatitis. Gut 2025:gutjnl-2024-333171. [PMID: 40169244 DOI: 10.1136/gutjnl-2024-333171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Accepted: 10/22/2024] [Indexed: 04/03/2025]
Abstract
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease which, if untreated, often leads to cirrhosis, liver failure and death. The last British Society of Gastroenterology (BSG) guideline for the management of AIH was published in 2011. Since then, our understanding of AIH has advanced in many areas. This update to the previous guideline was commissioned by the BSG and developed by a multidisciplinary group. The aim of this guideline is to review and summarise the current evidence, in order to inform and guide diagnosis and management of patients with AIH and its variant syndromes. The main focus is on AIH in adults, but the guidelines should also be relevant to older children and adolescents.
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Affiliation(s)
- Dermot Gleeson
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Division of Clinical Medicine, School of Medicine and Population Science, University of Sheffield, Sheffield, UK
| | | | | | - Harpreet Dhaliwal
- Department of Gastroenterology, Manchester Royal Infirmary, Manchester, UK
| | - Jessica K Dyson
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Janeane Hails
- Division of Gastroenterology and Hepatology, Addenbrooke's Hospital, Cambridge, UK
| | - Paul Henderson
- Royal Hospital for Children and Young People, Edinburgh, UK
| | - Deirdre Kelly
- Birmingham Women's & Children's Hospital, Birmingham, UK
- University of Birmingham, Birmingham, UK
| | - George F Mells
- Division of Gastroenterology and Hepatology, Addenbrooke's Hospital, Cambridge, UK
- Academic Department of Medical Genetics, University of Cambridge, Cambridge, UK
| | - Rosa Miquel
- Liver Histopathology Laboratory, Institute of Liver Studies, King's College London, London, UK
| | - Ye H Oo
- Centre for Liver and Gastroenterology research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- NIHR Biomedical Research Centre, University of Birmingham and University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
- Centre for Rare Diseases, European Reference Network on Hepatological Diseases (ERN-RARE-LIVER) centre, Birmingham, UK
| | - Anthea Sutton
- Sheffield Centre for Health and Related Research, The University of Sheffield, Sheffield, UK
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3
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Caponcello MG, Navarro PO, Bonazzetti C, Campoli C, Savoldi A, Gentilotti E, Monforte AD, Lo Caputo S, Otero-Varela L, Castrejón I, Tacconelli E, Rodríguez-Baño J, Palacios-Baena ZR, Mendoza DM, Navarrete VM, Tomelleri A, Ljung L, Rocha TM, Palma P, Palacios-Baena ZR, Salamanca-Rivera E, Paniagua-García M, Fassio A, Bixio R, Tombetti E, Conti F. ORCHESTRA Delphi consensus: diagnostic and therapeutic management of SARS-CoV-2 infection in patients with rheumatological diseases. Clin Microbiol Infect 2025:S1198-743X(25)00091-6. [PMID: 40049395 DOI: 10.1016/j.cmi.2025.02.030] [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: 12/24/2024] [Revised: 02/19/2025] [Accepted: 02/25/2025] [Indexed: 04/01/2025]
Abstract
OBJECTIVES The clinical management of COVID-19 in immunocompromised patients remains a challenge. This work aimed to develop a consensus to establish recommendations for the clinical, diagnostic, and therapeutic management of patients with rheumatic diseases and COVID-19. METHODS A panel of 14 international experts was selected, and Delphi methodology was used for the consensus, after a systematic literature review. Twenty-four questions were formulated and presented to the panel. The experts voted using a 6-point Likert scale (1) 'Strongly disagree' (SD); (2) 'Disagree' (D); (3) 'Somewhat disagree' (SWD); (4) 'Somewhat agree' (SWA); (5) 'Agree' (A); (6) 'Strongly agree' (SA). To establish consensus, simple or cumulative agreement ≥80% was required over a maximum of three rounds. Cumulative agreement was defined as the sum of response percentages on items 1-2 (SD + D); 2-3 (D + SWD); 4-5 (SWA + A); or 5-6 (A + SA), distinguishing a strong degree of agreement (A + SA) or disagreement (SD + D) from a moderate degree of agreement (SWA + A) or disagreement (D + SWD). RESULTS After the three rounds, consensus was reached on 23 of the 24 questions and 10 recommendations were made. DISCUSSION The Delphi methodology allowed consensus on recommendations in areas with insufficient scientific evidence, which can be considered for decision-making in the management of patients with rheumatological diseases while awaiting better evidence.
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Affiliation(s)
- Maria Giulia Caponcello
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena; Departamento de Medicina, Universidad de Sevilla; Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Seville, Spain; CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain
| | - Paula Olivares Navarro
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena; Departamento de Medicina, Universidad de Sevilla; Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Seville, Spain; CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain
| | - Cecilia Bonazzetti
- Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna; Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Caterina Campoli
- Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna
| | - Alessia Savoldi
- Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Italy
| | - Elisa Gentilotti
- Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Italy
| | | | - Sergio Lo Caputo
- Unit of Infectious Diseases, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Lucía Otero-Varela
- Research Unit, Spanish Society of Rheumatology, c/Marqués de Duero, 5 1(a) Planta - 28001 Madrid
| | - Isabel Castrejón
- Servicio de Reumatología, Hospital Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Departamento de Medicina. Universidad Complutense de Madrid
| | - Evelina Tacconelli
- Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Italy
| | - Jesús Rodríguez-Baño
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena; Departamento de Medicina, Universidad de Sevilla; Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Seville, Spain; CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain
| | - Zaira R Palacios-Baena
- Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena; Departamento de Medicina, Universidad de Sevilla; Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Seville, Spain; CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain.
| | | | | | - Alessandro Tomelleri
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy
| | - Lotta Ljung
- Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Centre for Rheumatology, Academic Specialistcenter, Stockholm, Sweden
| | - Teresa Martins Rocha
- Rheumatology Departament, Centro Hospitalar Universitário de S. João, Porto, Portugal; Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Pedro Palma
- Infectious Diseases Department, Tâmega e Sousa Local Health Unit, PBE, Penfaiel, Portugal
| | - Zaira R Palacios-Baena
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Spain; Departamento de Medicina, Universidad de Sevilla, Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Seville, Spain
| | - Elena Salamanca-Rivera
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Spain; Departamento de Medicina, Universidad de Sevilla, Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Seville, Spain
| | - María Paniagua-García
- Department of Infectious Diseases, Microbiology and Parasitology, Virgen del Rocío University Hospital, Seville, Spain; Institute of Biomedicine of Seville (IBiS), Virgen del Rocío and Virgen Macarena University Hospitals/CSIC/University of Seville, Seville, Spain
| | - Angelo Fassio
- Rheumatology Unit, University of Verona, Verona, Italy
| | | | - Enrico Tombetti
- Unit of Medicine and Rheumatology, ASST Fatebenefratelli-Sacco, Milan, Italy; Department of Biomedical and Clinical Sciences, University of Milan. Cristina Garufi, Italy; Lupus Clinic, Rheumatology, Department of Clinical Internal Medicine, Anaesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Fabrizio Conti
- Rheumatology Unit, Department of Internal Clinical Sciences, Anaesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Italy
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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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Ji Y, Fei S, Ji H, OuYang F, Ding R, Sun L, Chen H, Ju X, Tao J, Han Z, Du M, Wang Z, Tan R, Gu M. A Cohort Study of the Long-Term Influences of SARS-CoV-2 on Kidney Allograft Outcomes in Chinese Recipients: 1-Year Follow-Up Experience. KIDNEY DISEASES (BASEL, SWITZERLAND) 2025; 11:128-142. [PMID: 40135199 PMCID: PMC11936455 DOI: 10.1159/000543935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 01/29/2025] [Indexed: 03/27/2025]
Abstract
Introduction The aim of the study was to investigate the long-term effects of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection and novel coronavirus disease (COVID-19) on prognosis of kidney transplant recipients. Methods A 1-year retrospective study was carried out among 362 domestic kidney transplant recipients who were divided into observational (COVID-19) and control groups. Stratification analysis was then carried out to investigate whether repeated infections and infection severity could influence graft prognosis. Kaplan-Meier curves assessed 1-year graft survival, while one-way analysis of variance (ANOVA) compared graft function and laboratory parameters. Generalized estimating equations and repeated-measures ANOVA confirmed the magnitude of the impact of COVID-19 on kidney grafts. Generalized logistic regression and Cox regression established a model for analyzing COVID-19 risk factors. Meta-analysis and subgroup analysis were performed for validation. Results Exposure of COVID-19 had a significant effect on graft function within 1 year (p < 0.001), and this kind of effect was mostly brought by severer infections in the stratification analysis regarding graft survival rate (p < 0.001), estimated glomerular filtration rate (eGFR) level (p < 0.001), and 1-year eGFR slope (p = 0.014). Diagnostic model showed tacrolimus patients are less likely to get severe COVID-19 than cyclosporine (p = 0.004). Hyperglycemia (p = 0.004) and low hemoglobin (p = 0.023) are adverse factors for severe pneumonia. Hemoptysis, hypo-lymphopenia, high procalcitonin and ferritin are linked to poor allograft outcomes with SARS-CoV-2 infection. Conclusions COVID-19 severity is linked to poor kidney allograft prognosis. Hyperglycemia, low hemoglobin, and drug protocols including cyclosporine rather than tacrolimus are correlated with COVID-19 pneumonia. Hemoptysis, low lymphocytes, high procalcitonin or ferritin were concerned with kidney allograft prognosis post-COVID-19.
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Affiliation(s)
- Yisheng Ji
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- The First Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Shuang Fei
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hongsheng Ji
- Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Fan OuYang
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- The Second Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Runmin Ding
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- The Second Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Li Sun
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hao Chen
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaobing Ju
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jun Tao
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhijian Han
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Mulong Du
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zijie Wang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ruoyun Tan
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Min Gu
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Tian Z, Chen Y, Yao Y, Chen L, Zhu X, Shen Z, Yang S, Jin H. Immunogenicity and risk factors for poor humoral immune response to SARS-CoV-2 vaccine in patients with autoimmune hepatitis: a systematic review and meta-analysis. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024; 116:671-679. [PMID: 38235657 DOI: 10.17235/reed.2024.10053/2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2024]
Abstract
BACKGROUND research on the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients with autoimmune hepatitis (AIH) has produced varied results, and the determinants of the immunological response remain largely elusive. METHODS a comprehensive search of three primary databases (PubMed, Embase, and Web of Science) yielded pertinent studies on the topic. The data extraction was a collaborative effort among three independent researchers, who subsequently reconvened to validate the key data that were collated. The primary outcomes were the magnitudes of humoral and cellular immune responses to the vaccines. The secondary outcomes were related to factors affecting the humoral immune response post-vaccination. RESULTS this systematic review incorporated eight studies, and the meta-analysis involved three studies. The average antibody response rates after one, two, and three doses of the SARS-CoV-2 vaccine were 86 %, 82 %, and 91 %, respectively. Unexpectedly, the antibody concentrations of seropositive patients were markedly lower than those of their healthy counterparts. The cellular immune response rates after two and three vaccine doses were 74 % and 56 %, respectively. Treatment with mycophenolate mofetil and corticosteroids was associated with a notable decrease in seropositivity (pooled odds ratio [95 % confidence interval]: 2.62 [2.12-3.25] and 2.4 [1.51-3.82], respectively). In contrast, azathioprine had no discernable impact on the humoral response. CONCLUSION in patients with AIH, the immune response to COVID-19 vaccination is attenuated. Specific immunosuppressive agents, such as steroids and MMF, have been found to reduce antibody responses. Recognizing these determinants is crucial to formulating individualized vaccination strategies for patients with AIH. Further research with an emphasis on post-vaccination cellular immunity will be essential to refine the vaccination approaches for this demographic.
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Affiliation(s)
- Zhaoxu Tian
- Critical Care Medicine, Pingyao Campus of The First People's Hospital of Hangzhou,
| | - Yonghua Chen
- Critical Care Medicine, Pingyao Campus of The First People's Hospital of Hangzhou
| | - Yingxin Yao
- Critical Care Medicine, Pingyao Campus of The First People's Hospital of Hangzhou
| | - Lihua Chen
- Critical Care Medicine , Pingyao Campus of The First People's Hospital of Hangzhou
| | - Xiakai Zhu
- Critical Care Medicine, Pingyao Campus of The First People's Hospital of Hangzhou
| | - Zhaocong Shen
- Critical Care Medicine, Pingyao Campus of The First People's Hospital of Hangzhou
| | - Shanwei Yang
- Critical Care Medicine, Pingyao Campus of The First People's Hospital of Hangzhou
| | - Hangbin Jin
- Critical Care Medicine, Pingyao Campus of The First People's Hospital of Hangzhou
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Woelfel S, Junker D, Bergamin I, Meyer-Herbon P, Stillhard R, Graf N, Leinenkugel G, Dütschler J, König M, Kammerlander L, Häuptle R, Zwyssig S, Krieger C, Truniger S, Koller S, Metzger-Peter K, Frei N, Albrich WC, Friedrich M, Bernsmeier C, Niess JH, Korte W, Bürgi JJ, Dulovic A, Schneiderhan-Marra N, Semela D, Brand S. STAR LIGHT Study: XBB.1.5 COVID-19 mRNA Vaccines Boost Systemic but Not Mucosal Immunity Against the SARS-CoV-2 JN.1 Variant in Patients with Chronic Liver Disease. Vaccines (Basel) 2024; 12:1241. [PMID: 39591144 PMCID: PMC11598625 DOI: 10.3390/vaccines12111241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 10/23/2024] [Accepted: 10/27/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND Patients with chronic liver disease (CLD) have impaired vaccine immunogenicity and an excess risk of severe COVID-19. While variant-adapted COVID-19 mRNA vaccines are recommended for vulnerable individuals, their efficacy in patients with CLD has not been studied. METHODS We present the first evaluation of XBB.1.5 COVID-19 vaccine immunogenicity against the SARS-CoV-2 JN.1 variant in patients with CLD. Serum anti-receptor binding domain (RBD) IgG, neutralization, and saliva anti-RBD IgG and IgA against wild-type SARS-CoV-2 (WT) and the XBB.1.5, EG.5.1, BA.2.86, and JN.1 variants were quantified before and 2-4 weeks following a fourth dose of XBB.1.5 mRNA vaccines. RESULTS Vaccination boosted anti-RBD IgG and neutralization against all tested variants including JN.1 (each p < 0.001). Following immunization, neutralization was lower against JN.1 compared to WT, XBB.1.5, and EG.5.1 (p < 0.001, p < 0.001, and p < 0.01, respectively). Vaccination reduced neutralization failure rates against BA.2.86 and JN.1 (each p < 0.05). The evasion of vaccine-induced antibodies by the tested variants was low, indicated by the positive correlation between anti-RBD IgG and neutralization. At mucosal sites, vaccination boosted anti-RBD IgG (each p < 0.01) but failed to induce infection-blocking IgA (each p > 0.05). CONCLUSION XBB.1.5 vaccines protect CLD patients against recent SARS-CoV-2 variants, but developing vaccines with optimized mucosal immunogenicity is required to prevent SARS-CoV-2 transmission and recurrent seasonal COVID-19 outbreaks.
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Affiliation(s)
- Simon Woelfel
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
- Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Faculty of Medicine, Ludwig Maximilian University (LMU), 80336 Munich, Germany
| | - Daniel Junker
- NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany
| | - Irina Bergamin
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
| | - Pamela Meyer-Herbon
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
| | - Roman Stillhard
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
| | - Nicole Graf
- Clinical Trials Unit, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
| | - Georg Leinenkugel
- University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital of Basel, 4002 Basel, Switzerland
| | - Joel Dütschler
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
- Outpatient Clinic, Ambulatory Services Rorschach, 9400 Rorschach, Switzerland
| | - Marius König
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
| | - Livia Kammerlander
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
| | - Rahel Häuptle
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
| | - Sarah Zwyssig
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
| | - Claudia Krieger
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
| | - Samuel Truniger
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
- Outpatient Clinic, Ambulatory Services Rorschach, 9400 Rorschach, Switzerland
| | - Seraina Koller
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
| | - Katline Metzger-Peter
- University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital of Basel, 4002 Basel, Switzerland
| | - Nicola Frei
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
| | | | - Werner C. Albrich
- Division of Infectious Diseases, Infection Prevention and Travel Medicine, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
| | - Matthias Friedrich
- Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UK
| | - Christine Bernsmeier
- University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital of Basel, 4002 Basel, Switzerland
- Gastroenterology Group, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland
| | - Jan Hendrik Niess
- University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital of Basel, 4002 Basel, Switzerland
- Gastroenterology Group, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland
| | - Wolfgang Korte
- Center for Laboratory Medicine, 9001 St. Gallen, Switzerland
| | - Justus J. Bürgi
- Center for Laboratory Medicine, 9001 St. Gallen, Switzerland
| | - Alex Dulovic
- NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany
| | | | - David Semela
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
| | - Stephan Brand
- Department of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland
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Luxenburger H, Thimme R. SARS-CoV-2 and the liver: clinical and immunological features in chronic liver disease. Gut 2023; 72:1783-1794. [PMID: 37316169 PMCID: PMC10423489 DOI: 10.1136/gutjnl-2023-329623] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 05/24/2023] [Indexed: 06/16/2023]
Abstract
SARS-CoV-2 infection may affect the liver in healthy individuals but also influences the course of COVID-19 in patients with chronic liver disease (CLD). As described in healthy individuals, a strong SARS-CoV-2-specific adaptive immune response is important for the outcome of COVID-19, however, knowledge on the adaptive immune response in CLD is limited.Here, we review the clinical and immunological features of SARS-CoV-2 infection in individuals with CLD. Acute liver injury occurs in many cases of SARS-CoV-2 infection and may be induced by multiple factors, such as cytokines, direct viral infection or toxic effects of COVID-19 drugs. In individuals with CLD, SARS-CoV-2 infection may have a more severe course and promote decompensation and particularly in patients with cirrhosis. Compared with healthy individuals, the SARS-CoV-2-specific adaptive immune responses is impaired in patients with CLD after both, natural infection and vaccination but improves at least partially after booster vaccination.Following SARS-CoV-2 vaccination, rare cases of acute vaccine-induced liver injury and the development of autoimmune-like hepatitis have been reported. However, the concomitant elevation of liver enzymes is reversible under steroid treatment.
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Affiliation(s)
- Hendrik Luxenburger
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Robert Thimme
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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9
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Moriya K, Nakakita T, Nakayama N, Matsuo Y, Komeda Y, Hanatani J, Kaya D, Nagamatsu S, Matsuo H, Uejima M, Nakamura F. SARS-CoV-2 Vaccination Response in Japanese Patients with Autoimmune Hepatitis: Results of Propensity Score-Matched Case-Control Study. J Clin Med 2023; 12:5411. [PMID: 37629453 PMCID: PMC10455609 DOI: 10.3390/jcm12165411] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/18/2023] [Accepted: 08/19/2023] [Indexed: 08/27/2023] Open
Abstract
BACKGROUND/AIMS Although the World Health Organization declared the end of the public health emergency of international concern focusing on COVID-19 in May 2023, this bothersome virus continues to mutate, and the possibility of the emergence of mutant strains with high infectivity and severe disease rates has not disappeared. Thus, medical evidence must be accumulated, which is indispensable for protecting both patients under immunosuppressive treatments and the healthy population. This study examined SARS-CoV-2 vaccination responses in Japanese patients with autoimmune hepatitis (AIH) compared with healthy controls. METHODS This observational study registered 22 patients with histologically diagnosed AIH and 809 healthy controls in our hospital. Their Elecsys anti-SARS-CoV-2 spike antibody concentrations before and after vaccination were evaluated. RESULTS In this study, 72.7% and 18.2% of patients with AIH received steroids and azathioprine, respectively. Significant negative correlations were found between age and anti-SARS-CoV-2 spike antibody concentration in both groups; however, no sex differences were found. Although anti-SARS-CoV-2 spike antibody concentration was drastically augmented after the second vaccination (p < 0.05) in the AIH group, these levels were significantly lower than those in the controls (p < 0.05). In the age- and sex-matched analysis, the population ratio with a minimum response (≤100 binding antibody units (BAU/mL) was higher among patients with AIH than among controls 26 weeks after the second vaccination (44% vs. 7%, p < 0.05). CONCLUSIONS The anti-SARS-CoV-2 spike antibody concentration in AIH patients was significantly lower than that in controls after the second vaccination. Continued and widespread vaccination, particularly for patients requiring medical immunomodulation, is recommended.
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Affiliation(s)
- Kei Moriya
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (Y.M.)
- Department of Gastroenterology, Nara Medical University, Nara 634-8521, Japan
| | - Tomoko Nakakita
- Department of Laboratory Medicine, Nara Prefecture General Medical Center, Nara 630-8581, Japan
| | - Natsuki Nakayama
- Department of Laboratory Medicine, Nara Prefecture General Medical Center, Nara 630-8581, Japan
| | - Yuya Matsuo
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (Y.M.)
| | - Yusuke Komeda
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (Y.M.)
- Department of Gastroenterology, Nara Medical University, Nara 634-8521, Japan
| | - Junichi Hanatani
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (Y.M.)
- Department of Gastroenterology, Nara Medical University, Nara 634-8521, Japan
| | - Daisuke Kaya
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (Y.M.)
- Department of Gastroenterology, Nara Medical University, Nara 634-8521, Japan
| | - Shinsaku Nagamatsu
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (Y.M.)
- Department of Gastroenterology, Nara Medical University, Nara 634-8521, Japan
| | - Hideki Matsuo
- Department of Gastroenterology, Nara Prefecture General Medical Center, Nara 630-8581, Japan; (Y.M.)
- Department of Gastroenterology, Nara Medical University, Nara 634-8521, Japan
| | - Masakazu Uejima
- Department of Gastroenterology, Nara Medical University, Nara 634-8521, Japan
- Department of Diabetes and Endocrinology, Nara Prefecture General Medical Center, Nara 630-8581, Japan
| | - Fumihiko Nakamura
- Department of Laboratory Medicine, Nara Prefecture General Medical Center, Nara 630-8581, Japan
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10
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Zhu K, Tsai O, Chahal D, Hussaini T, Yoshida EM. COVID-19 and Liver Disease: An Evolving Landscape. Semin Liver Dis 2023; 43:351-366. [PMID: 37604206 DOI: 10.1055/a-2157-3318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/23/2023]
Abstract
The COVID-19 pandemic has resulted in significant worldwide morbidity and mortality. In this review, we examine the intricate relationships between COVID-19 and liver diseases. While respiratory manifestations of COVID-19 are well known, its impact and consequences in patients with liver diseases remain an area of ongoing investigation. COVID-19 can induce liver injury through various mechanisms and is associated with higher mortality in individuals with preexisting chronic liver disease. Mortality increases with the severity of chronic liver disease and the level of care required. The outcomes in patients with autoimmune hepatitis remain unclear, whereas liver transplant recipients are more likely to experience symptomatic COVID-19 but have comparable outcomes to the general population. Despite suboptimal immunological response, COVID-19 vaccinations are safe and effective in liver disease, although cases of autoimmune hepatitis-like syndrome have been reported. In conclusion, COVID-19 has significant implications in liver diseases; early recognition and treatments are important for improving patient outcomes.
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Affiliation(s)
- Kai Zhu
- Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Olivia Tsai
- Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Daljeet Chahal
- Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
- BC Liver Transplant Program, Vancouver, British Columbia, Canada
| | - Trana Hussaini
- BC Liver Transplant Program, Vancouver, British Columbia, Canada
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
| | - Eric M Yoshida
- Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada
- BC Liver Transplant Program, Vancouver, British Columbia, Canada
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11
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Wang Y, Li P, Lavrijsen M, Rottier RJ, den Hoed CM, Bruno MJ, Kamar N, Peppelenbosch MP, de Vries AC, Pan Q. Immunosuppressants exert differential effects on pan-coronavirus infection and distinct combinatory antiviral activity with molnupiravir and nirmatrelvir. United European Gastroenterol J 2023; 11:431-447. [PMID: 37226653 PMCID: PMC10256998 DOI: 10.1002/ueg2.12417] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 04/18/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND Immunocompromised populations, such as organ transplant recipients and patients with inflammatory bowel disease (IBD) receiving immunosuppressive/immunomodulatory medications, may be more susceptible to coronavirus infections. However, little is known about how immunosuppressants affect coronavirus replication and their combinational effects with antiviral drugs. OBJECTIVE This study aims to profile the effects of immunosuppressants and the combination of immunosuppressants with oral antiviral drugs molnupiravir and nirmatrelvir on pan-coronavirus infection in cell and human airway organoids (hAOs) culture models. METHODS Different coronaviruses (including wild type, delta and omicron variants of SARS-CoV-2, and NL63, 229E and OC43 seasonal coronaviruses) were used in lung cell lines and hAOs models. The effects of immunosuppressants were tested. RESULTS Dexamethasone and 5-aminosalicylic acid moderately stimulated the replication of different coronaviruses. Mycophenolic acid (MPA), 6-thioguanine (6-TG), tofacitinib and filgotinib treatment dose-dependently inhibited viral replication of all tested coronaviruses in both cell lines and hAOs. The half maximum effective concentration (EC50) of tofacitinib against SARS-CoV-2 was 0.62 μM and the half maximum cytotoxic concentration (CC50) was above 30 μM, which resulted in a selective index (SI) of about 50. The anti-coronavirus effect of the JAK inhibitors tofacitinib and filgotinib is dependent on the inhibition of STAT3 phosphorylation. Combinations of MPA, 6-TG, tofacitinib, and filgotinib with the oral antiviral drugs molnupiravir or nirmatrelvir exerted an additive or synergistic antiviral activity. CONCLUSIONS Different immunosuppressants have distinct effects on coronavirus replication, with 6-TG, MPA, tofacitinib and filgotinib possessing pan-coronavirus antiviral activity. The combinations of MPA, 6-TG, tofacitinib and filgotinib with antiviral drugs exerted an additive or synergistic antiviral activity. Thus, these findings provide an important reference for optimal management of immunocompromised patients infected with coronaviruses.
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Affiliation(s)
- Yining Wang
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Pengfei Li
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Marla Lavrijsen
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Robbert J. Rottier
- Department of Pediatric SurgeryErasmus MC‐Sophia Children's HospitalRotterdamThe Netherlands
- Department of Cell BiologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Caroline M. den Hoed
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
- Erasmus MC Transplant InstituteErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Marco J. Bruno
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Nassim Kamar
- Department of NephrologyDialysis and Organ TransplantationCHU RangueilINSERM UMR 1291Toulouse Institute for Infectious and Inflammatory Disease (Infinity)University Paul SabatierToulouseFrance
| | - Maikel P. Peppelenbosch
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Annemarie C. de Vries
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
| | - Qiuwei Pan
- Department of Gastroenterology and HepatologyErasmus MC‐University Medical CenterRotterdamThe Netherlands
- Erasmus MC Transplant InstituteErasmus MC‐University Medical CenterRotterdamThe Netherlands
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12
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Marginean CM, Cinteza E, Vasile CM, Popescu M, Biciusca V, Docea AO, Mitrut R, Popescu MS, Mitrut P. Features of Liver Injury in COVID-19 Pathophysiological, Biological and Clinical Particularities. GASTROENTEROLOGY INSIGHTS 2023; 14:156-169. [DOI: 10.3390/gastroent14020012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2025] Open
Abstract
The outbreak of the coronavirus pandemic in March 2020 has caused unprecedented pressure on public health and healthcare. The spectrum of COVID-19 onset is large, from mild cases with minor symptoms to severe forms with multi-organ dysfunction and death. In COVID-19, multiple organ damage has been described, including lung damage, acute kidney injury, liver damage, stroke, cardiovascular and digestive tract disorders. The aspects of liver injury are different, sometimes presenting with only a slight increase in liver enzymes, but sometimes with severe liver injury, leading to acute liver failure requiring liver transplantation. In patients with chronic liver disease, especially liver cirrhosis, immune dysfunction can increase the risk of infection. Immune dysfunction has a multifactorial physiopathological mechanism, implying a complement system and macrophage activation, lymphocyte and neutrophil activity dysfunction, and intestinal dysbiosis. This review aims to evaluate the most relevant studies published in the last years related to the etiopathogenetic, biochemical, and histological aspects of liver injury in patients diagnosed with COVID-19. Liver damage is more evident in patients with underlying chronic liver disease, with a significantly higher risk of developing severe outcomes of COVID-19 and death. Systemic inflammation, coagulation disorders, endothelial damage, and immune dysfunction explain the pathogenic mechanisms involved in impaired liver function. Although various mechanisms of action of SARS-CoV-2 on the liver cell have been studied, the impact of the direct viral effect on hepatocytes is not yet established.
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Affiliation(s)
- Cristina Maria Marginean
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Eliza Cinteza
- Pediatrics Department, University of Medicine and Pharmacy “Carol Davila”, 020021 Bucharest, Romania
- Department of Pediatric Cardiology, “Marie Curie” Emergency Children’s Hospital, 041451 Bucharest, Romania
| | - Corina Maria Vasile
- Department of Pediatric Cardiology, “Marie Curie” Emergency Children’s Hospital, 041451 Bucharest, Romania
- Department of Pediatric and Adult Congenital Cardiology, Bordeaux University Hospital, 33600 Pessac, France
| | - Mihaela Popescu
- Department of Endocrinology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Viorel Biciusca
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Radu Mitrut
- Department of Cardiology, University and Emergency Hospital, 050098 Bucharest, Romania
| | - Marian Sorin Popescu
- Ph.D. School Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Paul Mitrut
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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13
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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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14
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Nevola R, Criscuolo L, Beccia D, Delle Femine A, Ruocco R, Imbriani S, Alfano M, Villani A, Russo A, Perillo P, Marfella R, Adinolfi LE, Sasso FC, Marrone A, Rinaldi L. Impact of chronic liver disease on SARS-CoV-2 infection outcomes: Roles of stage, etiology and vaccination. World J Gastroenterol 2023; 29:800-814. [PMID: 36816617 PMCID: PMC9932424 DOI: 10.3748/wjg.v29.i5.800] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/12/2022] [Accepted: 01/18/2023] [Indexed: 02/06/2023] Open
Abstract
Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it has represented a dramatic global public health concern. Though affecting mainly the respiratory system, SARS-CoV-2 disease, defined as coronavirus disease 2019 (COVID-19), may have a systemic involvement leading to multiple organ dysfunction. Experimental evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and SARS-CoV-2. On the other side, patients with chronic liver disease have been demonstrated to have a poor prognosis with COVID-19. In particular, patients with liver cirrhosis appear extremely vulnerable to infection. Moreover, the etiology of liver disease and the vaccination status could affect the COVID-19 outcomes. This review analyzes the impact of the disease stage and the related causes on morbidity and mortality, clinical outcomes during SARS-CoV-2 infection, as well as the efficacy of vaccination in patients with chronic liver disease.
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Affiliation(s)
- Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Livio Criscuolo
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Domenico Beccia
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Augusto Delle Femine
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Rachele Ruocco
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Simona Imbriani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Maria Alfano
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Angela Villani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Antonio Russo
- Department of Mental Health and Public Medicine, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Pasquale Perillo
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Luigi Elio Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
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15
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Hartl J, Rüther DF, Duengelhoef PM, Brehm TT, Steinmann S, Weltzsch JP, Glaser F, Sterneck M, Sebode M, Weiler-Normann C, Lütgehetmann M, Schaub GM, Haag F, Schramm C, Wiesch JSZ, Lohse AW. Analysis of the humoral and cellular response after the third COVID-19 vaccination in patients with autoimmune hepatitis. Liver Int 2023; 43:393-400. [PMID: 35840342 PMCID: PMC9349728 DOI: 10.1111/liv.15368] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 06/23/2022] [Accepted: 07/12/2022] [Indexed: 01/25/2023]
Abstract
BACKGROUND & AIMS To explore the humoral and T-cell response to the third COVID-19 vaccination in autoimmune hepatitis (AIH). METHODS Anti-SARS-CoV-2 antibody titers were prospectively determined in 81 AIH patients and 53 healthy age- and sex-matched controls >7 days (median 35) after the first COVID-19 booster vaccination. The spike-specific T-cell response was assessed using an activation-induced marker assay (AIM) in a subset of patients. RESULTS Median antibody levels were significantly lower in AIH compared to controls (10 908 vs. 25 000 AU/ml, p < .001), especially in AIH patients treated with MMF (N = 14, 4542 AU/ml, p = .004) or steroids (N = 27, 7326 AU/ml, p = .020). Also, 48% of AIH patients had antibody titers below the 10% percentile of the healthy controls (9194 AU/ml, p < .001). AIH patients had a high risk of failing to develop a spike-specific T-cell response (15/34 (44%) vs. 2/16 (12%), p = .05) and showed overall lower frequencies of spike-specific CD4 + T cells (median: 0.074% vs 0.283; p = .01) after the booster vaccination compared to healthy individuals. In 34/81 patients, antibody titers before and after booster vaccination were available. In this subgroup, all patients but especially those without detectable/low antibodies titers (<100 AU/ml) after the second vaccination (N = 11/34) showed a strong, 148-fold increase. CONCLUSION A third COVID-19 vaccination efficiently boosts antibody levels and T-cell responses in AIH patients and even seroconversion in patients with the absent immune response after two vaccinations, but to a lower level compared to controls. Therefore, we suggest routinely assessing antibody levels in AIH patients and offering additional booster vaccinations to those with suboptimal responses.
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Affiliation(s)
- Johannes Hartl
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Darius Ferenc Rüther
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Paul Maria Duengelhoef
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Thomas Theo Brehm
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany
| | - Silja Steinmann
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Jan Philipp Weltzsch
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Fabian Glaser
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Martina Sterneck
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marcial Sebode
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Christina Weiler-Normann
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Marc Lütgehetmann
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.,Department for Clinical Immunology of Infectious Diseases, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.,Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Golda Melina Schaub
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany
| | - Friedrich Haag
- Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Schramm
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.,Martin-Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Hamburg Center for Translational Immunology (HCTI), Hamburg, Germany
| | - Julian Schulze Zur Wiesch
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany
| | - Ansgar Wilhelm Lohse
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.,German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.,Hamburg Center for Translational Immunology (HCTI), Hamburg, Germany
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16
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Krishnan A, Patel RA, Hadi YB, Mukherjee D, Shabih S, Thakkar S, Singh S, Woreta TA, Alqahtani SA. Clinical characteristics and outcomes of COVID-19 in patients with autoimmune hepatitis: A population-based matched cohort study. World J Hepatol 2023; 15:68-78. [PMID: 36744163 PMCID: PMC9896506 DOI: 10.4254/wjh.v15.i1.68] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 10/25/2022] [Accepted: 11/14/2022] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Patients with autoimmune hepatitis (AIH) require life-long immunosuppressive agents that may increase the risk of poor coronavirus disease 2019 (COVID-19) outcomes. There is a paucity of large data at the population level to assess whether patients with AIH have an increased risk of severe diseases. AIM To evaluate the impact of pre-existing AIH on the clinical outcomes of patients with COVID-19. METHODS We conducted a population-based, multicenter, propensity score-matched cohort study with consecutive adult patients (≥ 18 years) diagnosed with COVID-19 using the TriNeTx research network platform. The outcomes of patients with AIH (main group) were compared to a propensity score-matched cohort of patients: (1) Without chronic liver disease (CLD); and (2) Patients with CLD except AIH (non-AIH CLD) control groups. Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects. The primary outcome was all-cause mortality, and secondary outcomes were hospitalization rate, need for critical care, severe disease, mechanical ventilation, and acute kidney injury (AKI). For each outcome, the risk ratio (RR) and confidence intervals (CI) were calculated to compare the association of AIH with the outcome. RESULTS We identified 375 patients with AIH, 1647915 patients with non-CLD, and 15790 patients with non-AIH CLD with COVID-19 infection. Compared to non-CLD patients, the AIH cohort had an increased risk of all-cause mortality (RR = 2.22; 95%CI: 1.07-4.61), hospitalization rate (RR = 1.78; 95%CI: 1.17-2.69), and severe disease (RR = 1.98; 95%CI: 1.19-3.26). The AIH cohort had a lower risk of hospitalization rate (RR = 0.72; 95%CI: 0.56-0.92), critical care (RR = 0.50; 95%CI: 0.32-0.79), and AKI (RR = 0.56; 95%CI: 0.35-0.88) compared to the non-AIH CLD patients. CONCLUSION Patients with AIH are associated with increased hospitalization risk, severe disease, and all-cause mortality compared to patients without pre-existing CLD from the diagnosis of COVID-19. However, patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD.
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Affiliation(s)
- Arunkumar Krishnan
- Section of Gastroenterology and Hepatology, West Virginia University School of Medicine, Morgantown, WV 26505, United States
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
| | - Ruhee A Patel
- Section of Gastroenterology and Hepatology, West Virginia University School of Medicine, Morgantown, WV 26505, United States
| | - Yousaf Bashir Hadi
- Section of Gastroenterology and Hepatology, West Virginia University School of Medicine, Morgantown, WV 26505, United States
| | - Diptasree Mukherjee
- Department of Medicine, Apex Institute of Medical Science, Kolkata 700075, West Bengal, India
| | - Sarah Shabih
- Section of Gastroenterology and Hepatology, West Virginia University School of Medicine, Morgantown, WV 26505, United States
| | - Shyam Thakkar
- Section of Gastroenterology and Hepatology, West Virginia University School of Medicine, Morgantown, WV 26505, United States
| | - Shailendra Singh
- Section of Gastroenterology and Hepatology, West Virginia University School of Medicine, Morgantown, WV 26505, United States
| | - Tinsay A Woreta
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - Saleh A Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
- Liver Transplant Center, King Faisal Specialist Hospital and Research Center, Riyadh 12713, Saudi Arabia
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17
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Walia D, Saraya A, Gunjan D. COVID-19 in patients with pre-existing chronic liver disease - predictors of outcomes. World J Virol 2023; 12:30-43. [PMID: 36743659 PMCID: PMC9896592 DOI: 10.5501/wjv.v12.i1.30] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 10/19/2022] [Accepted: 12/06/2022] [Indexed: 01/18/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) has affected patients with pre-existing chronic liver disease (CLD) in various ways. The maximum impact was seen on patients with underlying cirrhosis who have shown to have poor clinical outcomes in the form of increased risk of hepatic decompensation, acute-on-chronic liver failure, and even mortality. It is of paramount importance to identify various factors which are associated with unfavorable outcomes for prognostication and making informed management strategy. Many factors have been evaluated in different studies in patients with underlying CLD. Some of these factors include the severity of underlying chronic liver disease, comorbid conditions, age, and severity of COVID-19. Overall, the outcomes are not fav-orable in patients with cirrhosis as evidenced by data from various studies. The main purpose of this review is to identify the predictors of adverse clinical outcomes including mortality in patients with CLD for risk stratification, prognostication, and appropriate clinical management.
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Affiliation(s)
- Dinesh Walia
- Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi 110029, New Delhi, India
| | - Anoop Saraya
- Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi 110029, New Delhi, India
| | - Deepak Gunjan
- Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi 110029, New Delhi, India
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18
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Qi RB, Wu ZH. Association between COVID-19 and chronic liver disease: Mechanism, diagnosis, damage, and treatment. World J Virol 2023; 12:22-29. [PMID: 36743657 PMCID: PMC9896589 DOI: 10.5501/wjv.v12.i1.22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/03/2022] [Accepted: 11/21/2022] [Indexed: 01/18/2023] Open
Abstract
As the outbreak evolves, our understanding of the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) on the liver has grown. In this review, we discussed the hepatotropic nature of SARS-CoV-2 and described the distribution of receptors for SARS-CoV-2 (e.g., angiotensin-converting enzyme 2) in the vascular endothelium and cholangiocytes of the liver. Also, we proposed mechanisms for possible viral entry that mediate liver injury, such as liver fibrosis. Due to SARS-CoV-2-induced liver damage, many COVID-19 patients develop liver dysfunction, mainly characterized by moderately elevated serum aminotransferase levels. Patients with chronic liver disease (CLD), such as cirrhosis, hepatocellular carcinoma, nonalcoholic fatty liver disease, and viral hepatitis, are also sensitive to SARS-CoV-2 infection. We discussed the longer disease duration and higher mortality following SARS-CoV-2 infection in CLD patients. Correspondingly, relevant risk factors and possible mechanisms were proposed, including cirrhosis-related immune dysfunction and liver deco-mpensation. Finally, we discussed the potential hepatotoxicity of COVID-19-related vaccines and drugs, which influence the treatment of CLD patients with SARS-CoV-2 infection. In addition, we suggested that COVID-19 vaccines in terms of immunogenicity, duration of protection, and long-term safety for CLD patients need to be further researched. The diagnosis and treatment for liver injury caused by COVID-19 were also analyzed in this review.
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Affiliation(s)
- Ruo-Bing Qi
- Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Zheng-Hao Wu
- Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
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19
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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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20
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Philips CA, Madhu D, Augustine P. Investigating the correlation between COVID-19 and the progression of chronic liver disease. Expert Rev Gastroenterol Hepatol 2023; 17:603-613. [PMID: 37086388 DOI: 10.1080/17474124.2023.2206564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 04/20/2023] [Indexed: 04/23/2023]
Abstract
INTRODUCTION The novel coronavirus disease 2019 has thrown light on various heterogeneous afflictions of newly emerging viruses on the human body. Early reports demonstrated direct effect of novel coronavirus on the liver, but subsequently, this did not stand up to validation. The SARS-CoV-2 virus affects the liver differentially; in healthy compared to those with preexisting liver disease. AREAS COVERED This exhaustive paper reviews the current, literature on mechanisms by which COVID-19 affects the healthy liver and those with preexisting liver disease such as alcohol-related and nonalcoholic fatty liver, autoimmune liver disease, chronic liver disease and cirrhosis, hepatocellular carcinoma, viral hepatitis, and liver transplant recipients, with special mention on drug-and herb-induced liver injury with COVID-19 therapies. Search methodology: the review (Dec. 2022 - Jan. 2023) is based on PubMed (NLM) search using the keyword 'COVID' with supplementary searches using 'fibrosis;' 'liver;' 'cirrhosis;' 'CLD;' 'NAFLD;' 'NASH;' 'hepatocellular carcinoma;' 'hepatitis;' 'fatty liver;' 'alcohol;' 'viral;' 'transplant;' and 'liver failure.' EXPERT OPINION Direct liver tropism of SARS-CoV-2 does not cause liver damage. Adverse events following infection depend on the severity of liver disease, the severity of COVID-19, and other risk factors such as metabolic syndrome and older age. Alcohol-related liver disease independently predicts adverse outcomes.
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Affiliation(s)
- Cyriac Abby Philips
- Clinical and Translational Hepatology and The Monarch Liver Laboratory, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, Kerala, India
| | - Deepak Madhu
- Department of Gastroenterology, Lisie Hospital, Ernakulam, Kerala, India
| | - Philip Augustine
- Department of Gastroenterology and Advanced GI Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, Kerala, India
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21
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Peshevska-Sekulovska M, Bakalova P, Snegarova V, Lazova S, Velikova T. COVID-19 Vaccines for Adults and Children with Autoimmune Gut or Liver Disease. Vaccines (Basel) 2022; 10:2075. [PMID: 36560485 PMCID: PMC9781431 DOI: 10.3390/vaccines10122075] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 12/01/2022] [Accepted: 12/02/2022] [Indexed: 12/07/2022] Open
Abstract
The SARS-CoV-2 pandemic raised many challenges for all patients with chronic conditions and those with autoimmune diseases, both adults and children. Special attention is paid to their immunological status, concomitant diseases, and the need for immunosuppressive therapy. All of these factors may impact their COVID-19 course and outcome. COVID-19 vaccination is accepted as one of the most successful strategies for pandemic control. However, individuals with immune-mediated chronic diseases, including autoimmune liver and gut diseases, have been excluded from the vaccine clinical trials. Therefore, we rely on real-world data from vaccination after vaccine approval for these patients to fill the evidence gap for the long-term safety and efficacy of COVID-19 vaccines in patients with autoimmune gut and liver diseases. Current recommendations from inflammatory bowel disease (IBD) societies suggest COVID-19 vaccination in children older than 5 years old, adults and even pregnant females with IBD. The same recommendations are applied to patients with autoimmune liver diseases. Nevertheless, autoimmune disease patients still experience high levels of COVID-19 vaccine hesitancy, and more studies have to be conducted to clarify this issue.
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Affiliation(s)
- Monika Peshevska-Sekulovska
- Department of Gastroenterology, University Hospital Lozenetz, 1407 Sofia, Bulgaria
- Medical Faculty, Sofia University St. Kliment Ohridski, 1407 Sofia, Bulgaria
| | - Plamena Bakalova
- Department of Gastroenterology, University Hospital Lozenetz, 1407 Sofia, Bulgaria
| | - Violeta Snegarova
- Clinic of Internal Diseases, Naval Hospital—Varna, Military Medical Academy, Medical Faculty, Medical University, 9000 Varna, Bulgaria
| | - Snezhina Lazova
- Pediatric Department, University Hospital “N. I. Pirogov”,“General Eduard I. Totleben” Blvd 21, Health Care Department, 1606 Sofia, Bulgaria
- Faculty of Public Health, Medical University Sofia, Bialo More 8 Str., 1527 Sofia, Bulgaria
| | - Tsvetelina Velikova
- Medical Faculty, Sofia University St. Kliment Ohridski, 1407 Sofia, Bulgaria
- Department of Clinical Immunology, University Hospital Lozenetz, Medical Faculty, Sofia University St. Kliment Ohridski, 1407 Sofia, Bulgaria
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22
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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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23
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Impact of COVID-19 on the liver and on the care of patients with chronic liver disease, hepatobiliary cancer, and liver transplantation: An updated EASL position paper. J Hepatol 2022; 77:1161-1197. [PMID: 35868584 PMCID: PMC9296253 DOI: 10.1016/j.jhep.2022.07.008] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 07/06/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023]
Abstract
The COVID-19 pandemic has presented a serious challenge to the hepatology community, particularly healthcare professionals and patients. While the rapid development of safe and effective vaccines and treatments has improved the clinical landscape, the emergence of the omicron variant has presented new challenges. Thus, it is timely that the European Association for the Study of the Liver provides a summary of the latest data on the impact of COVID-19 on the liver and issues guidance on the care of patients with chronic liver disease, hepatobiliary cancer, and previous liver transplantation, as the world continues to deal with the consequences of the COVID-19 pandemic.
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24
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Efe C, Taşçılar K, Gerussi A, Bolis F, Lammert C, Ebik B, Stättermayer AF, Cengiz M, Gökçe DT, Cristoferi L, Peralta M, Massoumi H, Montes P, Cerda E, Rigamonti C, Yapalı S, Adali G, Çalışkan AR, Balaban Y, Eren F, Eşkazan T, Barutçu S, Lytvyak E, Zazueta GM, Kayhan MA, Heurgue-Berlot A, De Martin E, Yavuz A, Bıyık M, Narro GC, Duman S, Hernandez N, Gatselis NK, Aguirre J, Idilman R, Silva M, Mendizabal M, Atay K, Güzelbulut F, Dhanasekaran R, Montano-Loza AJ, Dalekos GN, Ridruejo E, Invernizzi P, Wahlin S. SARS-CoV-2 vaccination and risk of severe COVID-19 outcomes in patients with autoimmune hepatitis. J Autoimmun 2022; 132:102906. [PMID: 36088883 PMCID: PMC9448709 DOI: 10.1016/j.jaut.2022.102906] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 08/24/2022] [Accepted: 08/26/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Data regarding outcome of Coronavirus disease 2019 (COVID-19) in vaccinated patients with autoimmune hepatitis (AIH) are lacking. We evaluated the outcome of COVID-19 in AIH patients who received at least one dose of Pfizer- BioNTech (BNT162b2), Moderna (mRNA-1273) or AstraZeneca (ChAdOx1-S) vaccine. PATIENTS AND METHODS We performed a retrospective study on AIH patients with COVID-19. The outcomes of AIH patients who had acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection after at least one dose of COVID-19 vaccine were compared to unvaccinated patients with AIH. COVID-19 outcome was classified according to clinical state during the disease course as: (i) no hospitalization, (ii) hospitalization without oxygen supplementation, (iii) hospitalization with oxygen supplementation by nasal cannula or mask, (iv) intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v) ICU admission with invasive mechanical ventilation or (vi) death, and data was analyzed using ordinal logistic regression. RESULTS We included 413 (258 unvaccinated and 155 vaccinated) patients (81%, female) with a median age of 52 (range: 17-85) years at COVID-19 diagnosis. The rates of hospitalization were (36.4% vs. 14.2%), need for any supplemental oxygen (29.5% vs. 9%) and mortality (7% vs. 0.6%) in unvaccinated and vaccinated AIH patients with COVID-19. Having received at least one dose of SARS-CoV-2 vaccine was associated with a significantly lower risk of worse COVID-19 severity, after adjusting for age, sex, comorbidities and presence of cirrhosis (adjusted odds ratio [aOR] 0.18, 95% confidence interval [CI], 0.10-0.31). Overall, vaccination against SARS-CoV-2 was associated with a significantly lower risk of mortality from COVID-19 (aOR 0.20, 95% CI 0.11-0.35). CONCLUSIONS SARS-CoV-2 vaccination significantly reduced the risk of COVID-19 severity and mortality in patients with AIH.
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Affiliation(s)
- Cumali Efe
- Department of Gastroenterology, Harran University Hospital, Şanlıurfa, Turkey.
| | - Koray Taşçılar
- Department of Medicine 3-Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
| | - Alessio Gerussi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Francesca Bolis
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Craig Lammert
- Department of Medicine Indiana, University School of Medicine, Indianapolis, IN, USA
| | - Berat Ebik
- Department of Gastroenterology, Gazi Yaşargil Education and Research Hospital, Diyarbakir, Turkey
| | - Albert Friedrich Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mustafa Cengiz
- Department of Gastroenterology, Gülhane Training and Research Hospital, Ankara, Turkey
| | | | - Laura Cristoferi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Mirta Peralta
- Hepatology Section, Hospital Francisco J Muñiz, Ciudad Autónoma de Buenos Aires, Argentina; Latin American Liver Research Educational and Awareness Network (LALREAN), Pilar, Argentina
| | - Hatef Massoumi
- Department of Medicine, Montefiore Medical Center, Bronx, NY, USA
| | - Pedro Montes
- Gastroenterology and Hepatology Unit, Hospital Nacional Daniel A. Carrión, Callao, Peru
| | - Eira Cerda
- Hepatology Unit, Hospital Militar Central de México, Ciudad de México, Mexico
| | - Cristina Rigamonti
- Department of Translational Medicine, Università del Piemonte Orientale UPO, Novara, Italy; Division of Internal Medicine, "AOU Maggiore della Carità", Novara, Italy
| | - Suna Yapalı
- Department of Gastroenterology, Acıbadem University School of Medicine, İstanbul, Turkey
| | - Gupse Adali
- Department of Gastroenterology, Umraniye Education and Research Hospital, Istanbul, Turkey
| | - Ali Rıza Çalışkan
- Department of Gastroenterology, Adıyaman University, Adıyaman, Turkey
| | - Yasemin Balaban
- Department of Gastroenterology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Fatih Eren
- Department of Gastroenterology, Medical Faculty, Uludag University, Bursa, Turkey
| | - Tuğçe Eşkazan
- Department of Gastroenterology, Cerrahpaşa School of Medicine, İstanbul, Turkey
| | - Sezgin Barutçu
- Department of Gastroenterology, University of Gaziantep Medical Faculty, Gaziantep, Turkey
| | - Ellina Lytvyak
- University of Alberta Division of Gastroenterology and Liver Unit, Edmonton, AB, Canada
| | - Godolfino Miranda Zazueta
- Gastroenterology Unit, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, Mexico
| | - Meral Akdogan Kayhan
- Department of Gastroenterology, Gülhane Training and Research Hospital, Ankara, Turkey
| | | | - Eleonora De Martin
- Centre Hepato-Biliaire, Hôpital Paul-Brousse, FHU Hepatinov, INSERM Unit UMR 1193, Univ Paris-Saclay, France
| | - Ahmet Yavuz
- Division of Gastroenterology, Necmettin Erbakan University, Meram School of Medicine, Konya, Turkey
| | - Murat Bıyık
- Division of Gastroenterology, Necmettin Erbakan University, Meram School of Medicine, Konya, Turkey
| | - Graciela Castro Narro
- Gastroenterology Unit, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, Mexico
| | - Serkan Duman
- Department of Gastroenterology, Ankara University Medical Faculty, Ankara, Turkey
| | - Nelia Hernandez
- Gastroenterology and Hepatology Unit, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
| | - Nikolaos K Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Greece; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
| | - Jonathan Aguirre
- Hepatology Unit, Hospital Ángeles Pedregal, Ciudad de México, Mexico
| | - Ramazan Idilman
- Department of Gastroenterology, Ankara University Medical Faculty, Ankara, Turkey
| | - Marcelo Silva
- Latin American Liver Research Educational and Awareness Network (LALREAN), Pilar, Argentina; Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Argentina
| | - Manuel Mendizabal
- Latin American Liver Research Educational and Awareness Network (LALREAN), Pilar, Argentina; Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Argentina
| | - Kadri Atay
- Department of Gastroenterology, Mardin State Hospital, Mardin, Turkey
| | - Fatih Güzelbulut
- Department of Gastroenterology, Haydarpaşa Numune Education and Research Hospital, İstanbul, Turkey
| | | | - Aldo J Montano-Loza
- University of Alberta Division of Gastroenterology and Liver Unit, Edmonton, AB, Canada
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Greece; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece
| | - Ezequiel Ridruejo
- Latin American Liver Research Educational and Awareness Network (LALREAN), Pilar, Argentina; Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Argentina; Hepatology Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas, CEMIC, Ciudad Autónoma de Buenos Aires, Argentina
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy
| | - Staffan Wahlin
- Hepatology Division, Department of Upper GI Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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Schneider L, Schubert L, Winkler F, Munda P, Winkler S, Tobudic S. SARS-CoV-2 Vaccine Response in Patients With Autoimmune Hepatitis. Clin Gastroenterol Hepatol 2022; 20:2145-2147.e2. [PMID: 35487452 PMCID: PMC9040499 DOI: 10.1016/j.cgh.2022.04.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 04/04/2022] [Accepted: 04/06/2022] [Indexed: 02/07/2023]
Abstract
Patients suffering from autoimmune hepatitis, a chronic immune-mediated liver disease with an incidence of 0.9 to 2 per 100,000 population per year in Europe, are considered to have a particularly increased risk for coronavirus disease 2019 (Covid-19)-associated hospitalization and death.1,2 Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination provides an essential tool to reduce morbidity and mortality in this cohort. However, a large multicenter study in China has shown a lower immunogenic response to inactivated whole-virion SARS-CoV-2 vaccines of chronic liver disease patients in comparison with the healthy population.3 Furthermore, reports from inflammatory bowel diseases or rheumatic disorders showed a reduced serologic response in patients taking glucocorticoids or thiopurine.4,5 The decrease in vaccine-induced antibodies over time, as well as the emergence of variants of concern, led to the recommendation of an additional vaccination in immunocompromised patients.
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Affiliation(s)
- Lisa Schneider
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
| | - Lorenz Schubert
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
| | - Florian Winkler
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Petra Munda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Stefan Winkler
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
| | - Selma Tobudic
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
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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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Terziroli Beretta-Piccoli B, Lleo A. Is immunosuppression truly associated with worse outcomes in autoimmune hepatitis patients with COVID-19? Liver Int 2022; 42:274-276. [PMID: 35092335 DOI: 10.1111/liv.15138] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 12/14/2021] [Indexed: 12/14/2022]
Affiliation(s)
- Benedetta Terziroli Beretta-Piccoli
- Epatocentro Ticino, Lugano, Switzerland
- King's College London Faculty of Life Sciences & Medicine, Institute of Liver Studies, MowatLabs, London, UK
- Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
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