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1
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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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2
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Li M, Cao W, Jiang T, Deng W, Wang S, Wu S, Zhang L, Lu Y, Chang M, Liu R, Ding X, Shen G, Gao Y, Hao H, Chen X, Hu L, Xu M, Jiang Y, Yi W, Xie Y, Song R. Impact of ursodeoxycholic acid therapy in autoimmune liver disease patients with COVID-19 and its clinical prognosis. BIOSAFETY AND HEALTH 2024; 6:165-170. [PMID: 40078729 PMCID: PMC11895010 DOI: 10.1016/j.bsheal.2024.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 04/27/2024] [Accepted: 04/29/2024] [Indexed: 03/14/2025] Open
Abstract
To explore the impact of ursodeoxycholic acid (UDCA) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and clinical outcomes in patients with autoimmune liver disease (AILD). Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment. Relevant data were collected regarding AILD diagnosis, treatment, biochemical indicators, and imaging examination. The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed. A total of 1,138 patients completed follow-up. The usage rate of hormone (P = 0.003) and immunosuppressant (P = 0.001) used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group. The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients (P = 0.003). The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group (P = 0.018). Logistic regression analysis showed that UDCA use (P = 0.003) was correlated to a lower incidence of SARS-CoV-2, while immunosuppressant use (P = 0.017) increased the incidence. Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group (P = 0.018). UDCA is associated with low SARS-CoV-2 incidence in AILD patients, while immunosuppressant increases its incidence instead. Patients receiving UDCA treatment have a longer recovery time after being infected.
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Affiliation(s)
- Minghui Li
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing 100015, China
| | - Weihua Cao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Tingting Jiang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Wen Deng
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Shiyu Wang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Shuling Wu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Lu Zhang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Yao Lu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Min Chang
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Ruyu Liu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xiaoyan Ding
- Department of Medical Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Ge Shen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Yuanjiao Gao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Hongxiao Hao
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xiaoxue Chen
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Leiping Hu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Mengjiao Xu
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Yuyong Jiang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Wei Yi
- Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Yao Xie
- Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
- Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing 100015, China
| | - Rui Song
- Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
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3
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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: 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: 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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4
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Gerussi A, Halliday N, Carbone M, Invernizzi P, Thorburn D. Open challenges in the management of autoimmune hepatitis. Minerva Gastroenterol (Torino) 2023; 69:61-83. [PMID: 33267568 DOI: 10.23736/s2724-5895.20.02805-6] [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: 03/02/2023]
Abstract
Autoimmune hepatitis (AIH) is a rare autoimmune disease of the liver with many open questions as regards its etiopathogenesis, natural history and clinical management. The classical picture of AIH is chronic hepatitis with fluctuating elevation of serum transaminases and Immunoglobulin G levels, the presence of circulating autoantibodies and typical histological features. However, atypical presentations do occur and are not well captured by current diagnostic scores, with important consequences in terms of missed diagnoses and delayed treatments. AIH is treated with corticosteroids and immunosuppressive drugs but up to 40% of patients do not achieve full biochemical response and are at risk of progressing to cirrhosis and liver failure. Moreover, standard therapies are associated by significant side-effects which may impair the quality of life of patients living with AIH. However, advances in the understanding of the underlying immunology of AIH is raising the prospect of novel therapies and optimization of existing therapeutic approaches to reduce side-effect burdens and potentially restore immunological tolerance. In this review we outlined the clinical characteristics, etiopathogenesis and management of AIH and current challenges in the diagnosis and management of AIH and provided evidence underlying the evolution of diagnostic and clinical management protocols.
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Affiliation(s)
- Alessio Gerussi
- Division of Gastroenterology, Department of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milano-Bicocca, Monza, Monza-Brianza, Italy - .,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Monza-Brianza, Italy - .,Ancient DNA Lab Dan David Center for Human Evolution and Biohistory Research, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel -
| | - Neil Halliday
- Institute for Liver and Digestive Health, University College London, London, UK
| | - Marco Carbone
- Division of Gastroenterology, Department of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milano-Bicocca, Monza, Monza-Brianza, Italy.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Monza-Brianza, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology, Department of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milano-Bicocca, Monza, Monza-Brianza, Italy.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Monza-Brianza, Italy
| | - Douglas Thorburn
- Institute for Liver and Digestive Health, University College London, London, UK
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5
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Ekpanyapong S, Reddy KR. Liver and Biliary Tract Disease in Patients with Coronavirus disease-2019 Infection. Gastroenterol Clin North Am 2023; 52:13-36. [PMID: 36813421 PMCID: PMC9531659 DOI: 10.1016/j.gtc.2022.09.001] [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] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Coronavirus disease-2019 (COVID-19) had become a global pandemic since March 2020. Although, the most common presentation is of pulmonary involvement, hepatic abnormalities can be encountered in up to 50% of infected individuals, which may be associated with disease severity, and the mechanism of liver injury is thought to be multifactorial. Guidelines for management in patients with chronic liver disease during COVID-19 era are being regularly updated. Patients with chronic liver disease and cirrhosis, including liver transplant candidates and liver transplant recipients are strongly recommended to receive SARS-CoV-2 vaccination because it can reduce rate of COVID-19 infection, COVID-19-related hospitalization, and mortality.
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Affiliation(s)
- Sirina Ekpanyapong
- Division of Gastroenterology and Hepatology, Department of Medicine, Huachiew General Hospital, 665 Bumroongmueang Road, Khlong Mahanak, Bangkok 10100, Thailand; Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, 2 Dulles, Liver Transplant Office, HUP3400 Spruce Street, Philadelphia, PA 19104, USA
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, 2 Dulles, Liver Transplant Office, HUP3400 Spruce Street, Philadelphia, PA 19104, USA.
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6
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Brandi N, Spinelli D, Granito A, Tovoli F, Piscaglia F, Golfieri R, Renzulli M. COVID-19: Has the Liver Been Spared? Int J Mol Sci 2023; 24:1091. [PMID: 36674607 PMCID: PMC9866733 DOI: 10.3390/ijms24021091] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 01/09/2023] Open
Abstract
The liver is a secondary and often collateral target of COVID-19 disease but can lead to important consequences. COVID-19 might directly cause a high number of complications in patients with pre-existing chronic liver disease, increasing their risk of hepatic decompensation. Moreover, it also determines indirect consequences in the management of patients with liver disease, especially in those suffering from decompensated cirrhosis and HCC, as well as in the execution of their follow-up and the availability of all therapeutic possibilities. Liver imaging in COVID-19 patients proved to be highly nonspecific, but it can still be useful for identifying the complications that derive from the infection. Moreover, the recent implementation of telemedicine constitutes a possible solution to both the physical distancing and the re-organizational difficulties arising from the pandemic. The present review aims to encompass the currently hypothesized pathophysiological mechanisms of liver injury in patients with COVID-19 mediated by both the direct invasion of the virus and its indirect effects and analyze the consequence of the pandemic in patients with chronic liver disease and liver tumors, with particular regard to the management strategies that have been implemented to face this worldwide emergency and that can be further improved.
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Affiliation(s)
- Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Daniele Spinelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
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7
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Sagnelli C, Macera M, Camaioni C, Salvati A, Coppola N, Sagnelli E. SARS-CoV-2 infection: a hurricane that does not ignore chronic hepatitis. Infection 2022; 50:849-858. [PMID: 35316530 PMCID: PMC8938965 DOI: 10.1007/s15010-022-01804-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 03/09/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND The COVID-19 pandemic significantly compromised screening, laboratory controls, clinical surveillance and treatment of chronic hepatitis patients and worsened their outcome, as evidenced by its significant correlation with advanced cirrhosis, liver decompensation and mortality. RESULTS This pandemic significantly impaired also the sector of liver transplantation, whose wards, operating rooms, outpatients' facilities, and healthcare personnel have been dedicated to patients with COVID-19. In addition, screening and treatment for HBV infection have been delayed or suspended in in most countries, with an increased risk of viral reactivation. Similar delay or suspension have also occurred for universal hepatitis B vaccination programs in many countries. Likewise, COVID-19 pandemic has made unreachable the goal of elimination of HCV infection as a worldwide public-health issue predicted for 2030 by the WHO. CONCLUSION This review article demonstrates how COVID-19 pandemic is causing serious damage to the sector of liver disease, which has quickly lost the beneficial effects of years of study, research, and clinical and technological application, as well as considerable financial investments.
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Affiliation(s)
- Caterina Sagnelli
- Department of Mental Health and Public Medicine, University of Campania "Luigi Vanvitelli", Via Luciano Armanni 5, 80101, Naples, Italy
| | - Margherita Macera
- Department of Mental Health and Public Medicine, University of Campania "Luigi Vanvitelli", Via Luciano Armanni 5, 80101, Naples, Italy
| | - Clarissa Camaioni
- Department of Mental Health and Public Medicine, University of Campania "Luigi Vanvitelli", Via Luciano Armanni 5, 80101, Naples, Italy
| | - Annabella Salvati
- Department of Mental Health and Public Medicine, University of Campania "Luigi Vanvitelli", Via Luciano Armanni 5, 80101, Naples, Italy
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, University of Campania "Luigi Vanvitelli", Via Luciano Armanni 5, 80101, Naples, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Public Medicine, University of Campania "Luigi Vanvitelli", Via Luciano Armanni 5, 80101, Naples, Italy.
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8
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Luo M, Ballester MP, Soffientini U, Jalan R, Mehta G. SARS-CoV-2 infection and liver involvement. Hepatol Int 2022; 16:755-774. [PMID: 35767172 PMCID: PMC9243815 DOI: 10.1007/s12072-022-10364-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 05/07/2022] [Indexed: 02/06/2023]
Abstract
The COVID-19 pandemic is the largest public health challenge in living memory. Patients with underlying liver disease have been disproportionately affected, experiencing high morbidity and mortality. In addition, elevated liver enzymes appear to be a risk factor for disease progression, even in the absence of underlying liver disease. Nevertheless, the mechanism of liver injury in SARS-CoV-2 infection remains largely unknown. This review aims to provide an overview of the mechanisms by which SARS-CoV-2 induces liver injury, and the impact of COVID-19 on cirrhosis, alcohol-related liver disease, autoimmune liver disease, non-alcoholic fatty liver disease, hepatitis B and C virus infection, liver-transplant recipients and patients with hepatocellular carcinoma. Finally, emerging data on vaccination in liver diseases is discussed, to help inform public health policy.
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Affiliation(s)
- Mingjia Luo
- Division of Medicine, University College London, London, UK
| | - Maria Pilar Ballester
- Digestive Disease Department, Hospital Clínic, Universitario de Valencia, Valencia, Spain.,INCLIVA-Biomedical Research Institute, Valencia, Spain
| | - Ugo Soffientini
- The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK.,Liver Failure Group, UCL Medical School, Institute for Liver and Disease Health, University College London, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK
| | - Rajiv Jalan
- Liver Failure Group, UCL Medical School, Institute for Liver and Disease Health, University College London, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK
| | - Gautam Mehta
- The Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK. .,Liver Failure Group, UCL Medical School, Institute for Liver and Disease Health, University College London, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK.
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9
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Ekpanyapong S, Bunchorntavakul C, Reddy KR. COVID-19 and the Liver: Lessons Learnt from the EAST and the WEST, A Year Later. J Viral Hepat 2022; 29:4-20. [PMID: 34352133 PMCID: PMC8446947 DOI: 10.1111/jvh.13590] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023]
Abstract
Globally, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) has been a major cause for significant morbidity and mortality. Since the start of the pandemic, several hepato-biliary manifestations in coronavirus disease 2019 (COVID-19) have been described and unique considerations raised. The review aims to summarize the pathogenesis and hepato-biliary manifestations in COVID-19 and discuss the similarities, contrasting features and disease-specific management across a range of hepato-biliary diseases from the EAST and the WEST. Published studies and regional society guidelines from the EAST and the WEST were comprehensively reviewed and summarized. A wide range of hepato-biliary manifestations, including the infrequent and chronic manifestation of cholangiopathy, has been observed in COVID-19. The pathogenesis of liver injury is multifactorial and with scant evidence for a direct SARS-CoV-2 infection of the liver. Patients with non-alcoholic fatty liver disease, cirrhosis, and liver cancer are potentially at increased risk for severe COVID-19, and there are unique considerations in chronic hepatitis B or C, hepatocellular carcinoma, and in those immunosuppressed such as autoimmune hepatitis or liver transplant recipients. With the surges in SARS-CoV-2 infection, liver transplant activity has variably been impacted. Preliminarily, SARS-CoV-2 vaccines appear to be safe in those with chronic liver disease and in transplant recipients, while emerging data suggest the need for a third dose in immunosuppressed patients. In conclusion, patients with chronic liver disease, particularly cirrhosis, and liver transplant recipients, are vulnerable to severe COVID-19. Over the past year, several unique considerations have been highlighted across a spectrum of hepato-biliary diseases. Vaccination is strongly recommended for those with chronic liver disease and liver transplant recipients.
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Affiliation(s)
- Sirina Ekpanyapong
- Division of Gastroenterology and HepatologyDepartment of MedicineRajavithi HospitalBangkokThailand
| | | | - K. Rajender Reddy
- Division of Gastroenterology and HepatologyDepartment of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
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10
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Gato S, Lucena-Valera A, Muñoz-Hernández R, Sousa JM, Romero-Gómez M, Ampuero J. Impact of COVID-19 on liver disease: From the experimental to the clinic perspective. World J Virol 2021; 10:301-311. [PMID: 34909404 PMCID: PMC8641041 DOI: 10.5501/wjv.v10.i6.301] [Citation(s) in RCA: 4] [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: 03/24/2021] [Revised: 05/18/2021] [Accepted: 08/13/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) has caused a global pandemic unprecedented in over a century. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a predominantly respiratory infection, various degrees of liver function abnormalities have been reported. Pre-existing liver disease in patients with SARS-CoV-2 infection has not been comprehensively evaluated in most studies, but it can critically compromise survival and trigger hepatic decompensation. The collapse of the healthcare services has negatively impacted the diagnosis, monitoring, and treatment of liver diseases in non-COVID-19 patients. In this review, we aim to discuss the impact of COVID-19 on liver disease from the experimental to the clinic perspective.
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Affiliation(s)
- Sheila Gato
- SeLiver Group, Instituto de Biomedicina de Sevilla, Sevilla 41013, Spain
| | - Ana Lucena-Valera
- Digestive Department, Hospital Universitario Virgen del Rocio, Sevilla 41013, Spain
| | - Rocío Muñoz-Hernández
- SeLiver Group, Instituto de Biomedicina de Sevilla, Sevilla 41013, Spain
- University of Seville, Sevilla 41013, Spain
| | - José Manuel Sousa
- Digestive Department, Hospital Universitario Virgen del Rocio, Sevilla 41013, Spain
| | - Manuel Romero-Gómez
- SeLiver Group, Instituto de Biomedicina de Sevilla, Sevilla 41013, Spain
- Digestive Department, Hospital Universitario Virgen del Rocio, Sevilla 41013, Spain
- University of Seville, Sevilla 41013, Spain
| | - Javier Ampuero
- SeLiver Group, Instituto de Biomedicina de Sevilla, Sevilla 41013, Spain
- Digestive Department, Hospital Universitario Virgen del Rocio, Sevilla 41013, Spain
- University of Seville, Sevilla 41013, Spain
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11
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Madhu D, Sharma S, Agarwal A, Saraya A. Special Considerations in the Management of Autoimmune Hepatitis in COVID-19 Hotspots: A Review. J Clin Transl Hepatol 2021; 9:568-575. [PMID: 34447687 PMCID: PMC8369025 DOI: 10.14218/jcth.2021.00001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 04/22/2021] [Accepted: 04/27/2021] [Indexed: 02/06/2023] Open
Abstract
The ongoing coronavirus disease-2019 (COVID-19) pandemic has necessitated special considerations in the management of diseases. The way presence of pre-existing diseases or treatment for it predisposes to, alters course of, and changes the management of COVID-19, is of relevance and is being extensively studied. Autoimmune hepatitis (AIH) is unique in that it is an autoimmune disease mandating treatment with immunosuppressive drugs, as well as a liver disease with potential for varying degrees of underlying fibrosis. The use of immunosuppressive drugs could alter the risk of acquiring COVID-19, the clinical course and severity of COVID-19 and the degree of underlying liver fibrosis could alter the clinical outcomes of patients with COVID-19. In this review, we try to summarize key areas relevant in understanding and improving the clinical care of patients with AIH in the current pandemic. Special considerations required in the management of patients with AIH in COVID-19 hotspots have been outlined based on the current evidence.
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Affiliation(s)
- Deepak Madhu
- Department of Gastroenterology, Aster MIMS Calicut, Kerala, India
- Department of Gastroenterology, Caritas Hospital, Kottayam, Kerala, India
| | - Sanchit Sharma
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ashish Agarwal
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
- Department of Gastroenterology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
- Correspondence to: Anoop Saraya, Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar; New Delhi 110029, India. ORCID: https://orcid.org/0000-0002-3921-6752. Tel: +91-9868397203, E-mail:
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Zecher BF, Buescher G, Willemse J, Walmsley M, Taylor A, Leburgue A, Schramm C, Lohse AW, Sebode M. Prevalence of COVID-19 in patients with autoimmune liver disease in Europe: A patient-oriented online survey. United European Gastroenterol J 2021; 9:797-808. [PMID: 34105883 PMCID: PMC8242670 DOI: 10.1002/ueg2.12100] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 03/29/2021] [Indexed: 02/06/2023] Open
Abstract
Background During the current SARS‐CoV‐2 pandemic it is important to identify risk factors for COVID‐19. Registry studies are providing growing evidence on the elevated risk of mortality from COVID‐19 in patients with chronic liver disease, especially in advanced stages. Results may, however, have a selection bias towards severe cases. Limited data is available on COVID‐19 in patients with autoimmune liver disease (AILD). Aim To perform an online survey to capture the prevalence of COVID‐19 and the state of medical care of patients with AILD in Europe during the pandemic. Methods Data was collected via an anonymous patient‐oriented, online survey, which was available on the EUSurvey platform in nine European languages between 24th June 2020 and 14th October 2020. Of 1834 contributions, 51 were excluded because participants did not name an underlying AILD, and four were excluded because of duplicate data entry. Results Of 1,779 participants, 1,752 resided in 20 different countries of the European Union and the United Kingdom (UK). The five countries with the highest numbers of contributions were France (n = 450), Germany (n = 318), the Netherlands (n = 267), Spain (n = 225), and the UK (n = 183). 2.2% of participants (39/1779) had been diagnosed with COVID‐19. There were no differences regarding age, sex, AILD, the status of liver cirrhosis, or status post liver transplantation between COVID‐19 and non‐COVID‐19 cases. Of the 39 COVID‐19 cases, five patients were admitted to a regular ward, one patient was admitted to ICU and required ventilation. Conclusion In our Europe‐wide, patient‐oriented survey on COVID‐19 in patients with AILD, we detected a low rate of COVID‐19, comparable to the period prevalence of the general population. These results suggest that patients with AILD are not at elevated risk of COVID‐19. Summarize the established knowledge on this subject
Registry studies show that patients with advanced stages of liver disease are at risk of mortality caused by COVID‐19. But since data is entered by the treating physicians, there may be a bias towards reporting severe cases. Limited data is available on COVID‐19 in patients with autoimmune liver disease (AILD). Immunosuppressive treatment required in patients with AIH and AILD patients after liver transplantation might represent an additional risk factor. What are the significant and/or new findings of this study?
In our patient‐oriented survey we did not detect a higher frequency of COVID‐19 cases in patients with AILD compared to the general population. These results suggest that patients with AILD are not at elevated risk of COVID‐19. Our study is therefore an important addition to existing registry studies evaluating the risk of COVID‐19 in patients with AILD.
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Affiliation(s)
- Britta Franziska Zecher
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Gustav Buescher
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - José Willemse
- Dutch Liver Patients Association, Hoogland, The Netherlands
| | | | | | - Angela Leburgue
- Association Pour la Lutte Contre les Maladies Inflammatoires du Foie et des Vois Biliaires (ALBI), Versailles, France
| | - Christoph Schramm
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.,Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Ansgar W Lohse
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
| | - Marcial Sebode
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.,European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany
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Abstract
Liver involvement, indicated by elevated liver function test results, is common in hospitalized patients with coronavirus disease 2019 (COVID-19) and has been linked to disease severity and outcome. A dual pattern of elevated liver function tests can be observed especially in patients with severe or critical COVID-19, characterized by an increase in aminotransferases early in the course of this disease, followed by an increase in cholestasis-associated biochemistry markers at later stages. This dual pattern is associated with inflammatory response markers and poor outcome. Current notions on the mechanisms of liver injury in COVID-19 include direct cytopathic effects of the virus on hepatocytes and cholangiocytes, ischemic and hypoxic liver damage, drug-induced liver injury, activation of hepatic immune cells by excess cytokine production and exacerbation of pre-existing liver disease. Patients with obesity-related non-alcoholic fatty liver disease and, in particular, patients with cirrhosis are at high risk of liver injury and a fatal outcome from COVID-19. In contrast, individuals receiving stable immunosuppressive medication for autoimmune liver diseases or during long-term follow-up after liver transplantation do not have a higher case-to-infection ratio and have a fairly favourable outcome. The present review describes the epidemiology, characteristics and potential pathological mechanisms of COVID-19-related liver injury. Moreover, the influence of pre-existing liver disease on the susceptibility and severity of liver injury in COVID-19 are discussed.
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Affiliation(s)
- Toni Herta
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany,Department of Gastroenterology and HepatologyTytgat Institute for Liver and Intestinal ResearchAGEMAmsterdam University Medical CentersAmsterdamthe Netherlands
| | - Thomas Berg
- Division of HepatologyDepartment of Medicine IILeipzig University Medical CenterLeipzigGermany
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14
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Abstract
The coronavirus disease 2019 (COVID-19) pandemic has brought challenges to clinicians caring for patients with chronic liver disease. In the past 6 months, COVID-19 has led to over 150,000 deaths in the United States and over 660,000 deaths around the world. Mounting evidence suggests that chronic liver diseases can have an adverse effect on the clinical outcomes of patients with COVID-19. We present a comprehensive review of the latest literature on preexisting liver diseases and its interrelationship with COVID-19 infection in cirrhosis, hepatocellular carcinoma, nonalcoholic fatty liver disease, autoimmune hepatitis, and viral hepatitis B. As social distancing and telemedicine gain new footing, we synthesize recommendations from 3 major hepatology societies [American Association for the Study of Liver Disease (AASLD), the European Association for the Study of Liver (EASL), and the Asian Pacific Association for the Study of Liver (APASL)] to present the best approaches for caring for patients with liver diseases as well as those requiring liver transplantation.
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Affiliation(s)
- Abdul Mohammed
- Department of Hospital Medicine, Cleveland Clinic Foundation
| | - Neethi Paranji
- Division of Gastroenterology and Hepatology, Case Western Reserve University School of Medicine, The MetroHealth System, Cleveland, OH
| | - Po-Hung Chen
- Johns Hopkins School of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, MD
| | - Bolin Niu
- Division of Gastroenterology and Hepatology, Case Western Reserve University School of Medicine, The MetroHealth System, Cleveland, OH
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15
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Abstract
The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health crisis causing major challenges for clinical care in patients with gastrointestinal diseases. Although triggering of anti-viral immune responses is essential for clearance of infection, some patients have severe lung inflammation and multiorgan failure due to marked immune cell dysregulation and cytokine storm syndrome. Importantly, the activation of cytotoxic follicular helper T cells and a reduction of regulatory T cells have a crucial, negative prognostic role. These findings lead to the question of whether immunosuppressive and biologic therapies for gastrointestinal diseases affect the incidence or prognosis of COVID-19 and, thus, whether they should be adjusted to prevent or affect the course of the disease. In this Review, data on the use of such therapies are discussed with a primary focus on inflammatory bowel disease, autoimmune hepatitis and liver transplantation. In particular, the roles of corticosteroids, classic immunosuppressive agents (such as thiopurines and mycophenolate mofetil), small molecules (such as Janus kinase (JAK) inhibitors), and biologic agents (such as tumour necrosis factor (TNF) blockers, vedolizumab and ustekinumab) are reviewed. Finally, the use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines for the prevention of infection in patients with gastrointestinal diseases and concomitant immunosuppressive or biologic therapy will be discussed.
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