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Filipovic B, Marjanovic-Haljilji M, Blagojevic D, Dragovic M, Krsmanovic E, Matovic A, Panic N, Kiurski S, Zagorac Z, Milanovic M, Markovic O, Djokovic A, Glisic T, Dragasevic S, Popovic D. A Closer Look into Autoimmune Liver Diseases. Int J Mol Sci 2025; 26:1863. [PMID: 40076490 PMCID: PMC11899773 DOI: 10.3390/ijms26051863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 02/07/2025] [Accepted: 02/14/2025] [Indexed: 03/14/2025] Open
Abstract
Autoimmune liver diseases involve a heterogeneous group of chronic inflammatory disorders, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Sometimes presented consistently as an overlapping syndrome, their pathogenesis is rather complex and has yet to be fully elucidated, despite extensive research efforts. This review article corroborates the molecular mechanisms of autoimmune liver diseases, as well as existing and potential therapeutic modalities.
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Affiliation(s)
- Branka Filipovic
- Department of Gastroenterology, Clinical and Hospital Center “Dr Dragisa Misovic-Dedinje”, Heroja Milana Tepica 1, 11020 Belgrade, Serbia; (B.F.); (D.B.); (M.D.); (E.K.); (N.P.); (S.K.); (D.P.)
- Faculty of Medicine, University of Belgrade, Dr Subotica Starijeg 8, 11000 Belgrade, Serbia; (M.M.); (O.M.); (A.D.); (T.G.); (S.D.)
| | - Marija Marjanovic-Haljilji
- Department of Gastroenterology, Clinical and Hospital Center “Dr Dragisa Misovic-Dedinje”, Heroja Milana Tepica 1, 11020 Belgrade, Serbia; (B.F.); (D.B.); (M.D.); (E.K.); (N.P.); (S.K.); (D.P.)
| | - Dragana Blagojevic
- Department of Gastroenterology, Clinical and Hospital Center “Dr Dragisa Misovic-Dedinje”, Heroja Milana Tepica 1, 11020 Belgrade, Serbia; (B.F.); (D.B.); (M.D.); (E.K.); (N.P.); (S.K.); (D.P.)
| | - Milica Dragovic
- Department of Gastroenterology, Clinical and Hospital Center “Dr Dragisa Misovic-Dedinje”, Heroja Milana Tepica 1, 11020 Belgrade, Serbia; (B.F.); (D.B.); (M.D.); (E.K.); (N.P.); (S.K.); (D.P.)
| | - Emilija Krsmanovic
- Department of Gastroenterology, Clinical and Hospital Center “Dr Dragisa Misovic-Dedinje”, Heroja Milana Tepica 1, 11020 Belgrade, Serbia; (B.F.); (D.B.); (M.D.); (E.K.); (N.P.); (S.K.); (D.P.)
| | - Ana Matovic
- Department of Cardiology, Clinical and Hospital Center “Dr Dragisa Misovic-Dedinje”, Heroja Milana Tepica 1, 11020 Belgrade, Serbia;
| | - Natasa Panic
- Department of Gastroenterology, Clinical and Hospital Center “Dr Dragisa Misovic-Dedinje”, Heroja Milana Tepica 1, 11020 Belgrade, Serbia; (B.F.); (D.B.); (M.D.); (E.K.); (N.P.); (S.K.); (D.P.)
| | - Stanimir Kiurski
- Department of Gastroenterology, Clinical and Hospital Center “Dr Dragisa Misovic-Dedinje”, Heroja Milana Tepica 1, 11020 Belgrade, Serbia; (B.F.); (D.B.); (M.D.); (E.K.); (N.P.); (S.K.); (D.P.)
| | - Zagor Zagorac
- Clinic for Surgery, Clinical and Hospital Center “Dr Dragisa Misovic-Dedinje”, Heroja Milana Tepica 1, 11020 Belgrade, Serbia;
| | - Miljan Milanovic
- Faculty of Medicine, University of Belgrade, Dr Subotica Starijeg 8, 11000 Belgrade, Serbia; (M.M.); (O.M.); (A.D.); (T.G.); (S.D.)
- Clinic for Surgery, Clinical and Hospital Center “Dr Dragisa Misovic-Dedinje”, Heroja Milana Tepica 1, 11020 Belgrade, Serbia;
| | - Olivera Markovic
- Faculty of Medicine, University of Belgrade, Dr Subotica Starijeg 8, 11000 Belgrade, Serbia; (M.M.); (O.M.); (A.D.); (T.G.); (S.D.)
- Department of Hematology, Clinical and Hospital Center “Bezanijska Kosa”, Dr Zorza Matea s/n, 11080 Belgrade, Serbia
| | - Aleksandra Djokovic
- Faculty of Medicine, University of Belgrade, Dr Subotica Starijeg 8, 11000 Belgrade, Serbia; (M.M.); (O.M.); (A.D.); (T.G.); (S.D.)
- Department of Cardiology, Clinical and Hospital Center “Bezanijska Kosa”, Dr Zorza Matea s/n, 11080 Belgrade, Serbia
| | - Tijana Glisic
- Faculty of Medicine, University of Belgrade, Dr Subotica Starijeg 8, 11000 Belgrade, Serbia; (M.M.); (O.M.); (A.D.); (T.G.); (S.D.)
- Clinic for Gastroenterology and Hepatology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Sanja Dragasevic
- Faculty of Medicine, University of Belgrade, Dr Subotica Starijeg 8, 11000 Belgrade, Serbia; (M.M.); (O.M.); (A.D.); (T.G.); (S.D.)
- Clinic for Gastroenterology and Hepatology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Dusan Popovic
- Department of Gastroenterology, Clinical and Hospital Center “Dr Dragisa Misovic-Dedinje”, Heroja Milana Tepica 1, 11020 Belgrade, Serbia; (B.F.); (D.B.); (M.D.); (E.K.); (N.P.); (S.K.); (D.P.)
- Faculty of Medicine, University of Belgrade, Dr Subotica Starijeg 8, 11000 Belgrade, Serbia; (M.M.); (O.M.); (A.D.); (T.G.); (S.D.)
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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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Vinutha M, Sharma UR, Swamy G, Rohini S, Vada S, Janandri S, Haribabu T, Taj N, Gayathri SV, Jyotsna SK, Mudagal MP. COVID-19-related liver injury: Mechanisms, diagnosis, management; its impact on pre-existing conditions, cancer and liver transplant: A comprehensive review. Life Sci 2024; 356:123022. [PMID: 39214285 DOI: 10.1016/j.lfs.2024.123022] [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: 02/19/2024] [Revised: 08/20/2024] [Accepted: 08/25/2024] [Indexed: 09/04/2024]
Abstract
AIMS This review explores the mechanisms, diagnostic approaches, and management strategies for COVID-19-induced liver injury, with a focus on its impact on patients with pre-existing liver conditions, liver cancer, and those undergoing liver transplantation. MATERIALS AND METHODS A comprehensive literature review included studies on clinical manifestations of liver injury due to COVID-19. Key areas examined were direct viral effects, drug-induced liver injury, cytokine storms, and impacts on individuals with chronic liver diseases, liver transplants, and the role of vaccination. Data were collected from clinical trials, observational studies, case reports, and review literature. KEY FINDINGS COVID-19 can cause a spectrum of liver injuries, from mild enzyme elevations to severe hepatic dysfunction. Injury mechanisms include direct viral invasion, immune response alterations, drug toxicity, and hypoxia-reperfusion injury. Patients with chronic liver conditions (such as alcohol-related liver disease, nonalcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma) face increased risks of severe outcomes. The pandemic has worsened pre-existing liver conditions, disrupted cancer treatments, and complicated liver transplantation. Vaccination remains crucial for reducing severe disease, particularly in chronic liver patients and transplant recipients. Telemedicine has been beneficial in managing patients and reducing cross-infection risks. SIGNIFICANCE This review discusses the importance of improved diagnostic methods and management strategies for liver injury caused by COVID-19. It emphasizes the need for close monitoring and customized treatment for high-risk groups, advocating for future research to explore long-term effects, novel therapies, and evidence-based approaches to improve liver health during and after the pandemic.
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Affiliation(s)
- M Vinutha
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - Uday Raj Sharma
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India.
| | - Gurubasvaraja Swamy
- Department of Pharmaceutical Chemistry, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - S Rohini
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - Surendra Vada
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - Suresh Janandri
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - T Haribabu
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - Nageena Taj
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - S V Gayathri
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - S K Jyotsna
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
| | - Manjunatha P Mudagal
- Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, India
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Nasir N, Khanum I, Habib K, Wagley A, Arshad A, Majeed A. Insight into COVID-19 associated liver injury: Mechanisms, evaluation, and clinical implications. HEPATOLOGY FORUM 2024; 5:139-149. [PMID: 39006140 PMCID: PMC11237249 DOI: 10.14744/hf.2023.2023.0025] [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: 05/27/2023] [Revised: 07/25/2023] [Accepted: 11/02/2023] [Indexed: 07/16/2024]
Abstract
COVID-19 has affected millions worldwide, causing significant morbidity and mortality. While predominantly involving the respiratory tract, SARS-CoV-2 has also caused systemic illnesses involving other sites. Liver injury due to COVID-19 has been variably reported in observational studies. It has been postulated that liver damage may be due to direct damage by the SARS-CoV-2 virus or multifactorial secondary to hepatotoxic therapeutic options, as well as cytokine release syndrome and sepsis-induced multiorgan dysfunction. The approach to a COVID-19 patient with liver injury requires a thorough evaluation of the pattern of hepatocellular injury, along with the presence of underlying chronic liver disease and concurrent medications which may cause drug-induced liver injury. While studies have shown uneventful recovery in the majority of mildly affected patients, severe COVID-19 associated liver injury has been associated with higher mortality, prolonged hospitalization, and greater morbidity in survivors. Furthermore, its impact on long-term outcomes remains to be ascertained as recent studies report an association with metabolic-fatty liver disease. This present review provides insight into the subject by describing the postulated mechanism of liver injury, its impact in the presence of pre-existing liver disease, and its short- and long-term clinical implications.
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Affiliation(s)
- Nosheen Nasir
- Section of Adult Infectious Diseases, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Iffat Khanum
- Section of Adult Infectious Diseases, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Kiren Habib
- Section of Adult Infectious Diseases, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Abdullah Wagley
- Research Facilitation Office, Medical College, Aga Khan University, Karachi, Pakistan
| | - Aleena Arshad
- Section of Adult Infectious Diseases, Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Atif Majeed
- Section of Gastroenterology, Department of Medicine, Aga Khan University, Karachi, Pakistan
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Lenci I, Milana M, Savino L, Signorello A, Baiocchi L. Development of Autoimmune Hepatitis after COVID-19 Infection in Vaccinated Women. Rev Recent Clin Trials 2024; 19:267-272. [PMID: 38797899 DOI: 10.2174/0115748871292641240514114921] [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: 12/19/2023] [Revised: 03/29/2024] [Accepted: 04/04/2024] [Indexed: 05/29/2024]
Abstract
PURPOSE SARS-CoV-2 infection has been associated with the impairment of several organs, including the liver. In addition, cases of autoimmune hepatitis have been described in association with COVID-19 disease. According to some case reports, vaccination has also been suggested to elicit the immune liver disorder. CASE DESCRIPTION We report on the case series of two middle-aged women developing COVID-19 infection despite a completed vaccination schedule. More interestingly, the infection was followed by the onset of acute hepatitis with a significant increase in the values of liver function tests (x 10 normal values). After ruling out the main causes of liver damage (viral, toxic, etc.), a diagnosis of autoimmune hepatitis was made and supported by liver histology in both cases. The clinical picture was quickly reverted with immunosuppressive (steroid) therapy, also confirming the diagnosis. CONCLUSION We observed a possible relationship between COVID-19 infection and the onset of autoimmune hepatitis and also described this occurrence in vaccinated subjects. It remains to be clarified whether repeated exposure to viral antigens (vaccination plus true infection) or specific emerging viral genotype (omicron strain) may facilitate the onset of this immune liver disease.
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Affiliation(s)
- Ilaria Lenci
- Hepatology Unit, Department of Clinical Medicine, Policlinico Universitario Tor Vergata, Rome, Italy
| | - Martina Milana
- Hepatology Unit, Department of Clinical Medicine, Policlinico Universitario Tor Vergata, Rome, Italy
| | - Luca Savino
- Pathological Anatomy, Department for Assistential Process Integration, Policlinico Universitario Tor Vergata, Rome, Italy
| | - Alessandro Signorello
- Hepatology Unit, Department of Clinical Medicine, Policlinico Universitario Tor Vergata, Rome, Italy
| | - Leonardo Baiocchi
- Hepatology Unit, Department of Clinical Medicine, Policlinico Universitario Tor Vergata, Rome, Italy
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Sahin E, Dag A, Eren F. The pleiotropic approach to coronavirus disease-19 pathogenesis: The impact of liver diseases associated host genetic variants. HEPATOLOGY FORUM 2023; 5:93-96. [PMID: 38487739 PMCID: PMC10936119 DOI: 10.14744/hf.2023.2023.0018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 07/06/2023] [Indexed: 03/17/2024]
Abstract
Coronavirus disease-2019 (COVID-19) is a novel multisystemic viral disease caused pandemic. The disease impact involves liver and associated systems. Undoubtedly, host genetic background influences the predisposition and prediction of infection. Variants among human populations might increase susceptibility or protect against severe outcomes. In this manner, rs738409 variant of patatin-like phospholipase domain-containing protein 3 gene appears to be protective in some populations in spite of its aggravating effect on non-alcoholic fatty liver diseases (NAFLDs) and steatohepatitis. DRB1*15:01 allele of human leukocyte antigen is associated with protective effect in European and Japanese populations. DRB1*03:01 contrarily increases the susceptibility of severe COVID-19 infection in European populations. rs1260326 in glucokinase regulatory protein gene, rs112875651 in tribbles homolog 1 gene, rs429358 in apolipoprotein 1, and rs58542926 in transmembrane 6 superfamily 2 alleles are found related with NAFLD and obesity; thus, hypercoagulability and severe COVID-19 outcomes. In chronic or acute liver diseases, comorbid syndromes are the key factors to explain increased severity. There might not be a direct association between the variant and severe COVID-19 infection. As it is concluded, there are genes and variants known and unknown yet to be studied to reveal the association with disease severity.
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Affiliation(s)
- Eren Sahin
- Marmara University School of Medicine, 3 year Pre-Clinical Student, Istanbul, Turkiye
| | - Ali Dag
- Marmara University School of Medicine, 3 year Pre-Clinical Student, Istanbul, Turkiye
| | - Fatih Eren
- Department of Medical Biology, Marmara University School of Medicine, Istanbul, Turkiye
- Department of Medical Biology, Eastern Mediterranean University School of Medicine, Famagusta, Turkish Republic of Northern Cyprus
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Taylor-Robinson SD, Morgan MY. COVID-19 and the Liver: A Complex and Evolving Picture. Hepat Med 2023; 15:209-220. [PMID: 37965296 PMCID: PMC10641025 DOI: 10.2147/hmer.s384172] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 10/28/2023] [Indexed: 11/16/2023] Open
Abstract
Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily attacks the respiratory system, other organs, such as the liver, are also affected. In this overview, the effects of SARS-CoV-2 infection on the liver in both healthy people and in those with pre-existing liver disease are documented; the relationship between coronavirus disease 19 (COVID-19) vaccination and liver injury is examined; the mechanism of SARS-CoV-2-associated liver injury is explored; and the long-term consequences of COVID-19 are delineated, both in people with and without pre-existing liver disease.
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Affiliation(s)
- Simon D Taylor-Robinson
- Department of Surgery and Cancer, Imperial College London, London, UK
- Department of Public Health, Busitema University and Mbale Clinical Research Institute, Mbale, Uganda
| | - Marsha Y Morgan
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
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Liu S, Zhao Y, Feng X, Xu H. SARS-CoV-2 infection threatening intestinal health: A review of potential mechanisms and treatment strategies. Crit Rev Food Sci Nutr 2023; 63:12578-12596. [PMID: 35894645 DOI: 10.1080/10408398.2022.2103090] [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] [Indexed: 01/08/2023]
Abstract
The outbreak of the COVID-19 pandemic has brought great problems to mankind, including economic recession and poor health. COVID-19 patients are frequently reported with gastrointestinal symptoms such as diarrhea and vomiting in clinical diagnosis. Maintaining intestinal health is the key guarantee to maintain the normal function of multiple organs, otherwise it will be a disaster. Therefore, the purpose of this review was deeply understanded the potential mechanism of SARS-CoV-2 infection threatening intestinal health and put forward reasonable treatment strategies. Combined with the existing researches, we summarized the mechanism of SARS-CoV-2 infection threatening intestinal health, including intestinal microbiome disruption, intestinal barrier dysfunction, intestinal oxidative stress and intestinal cytokine storm. These adverse intestinal events may affect other organs through the circulatory system or aggravate the course of the disease. Typically, intestinal disadvantage may promote the progression of SARS-CoV-2 through the gut-lung axis and increase the disease degree of COVID-19 patients. In view of the lack of specific drugs to inhibit SARS-CoV-2 replication, the current review described new strategies of probiotics, prebiotics, postbiotics and nutrients to combat SARS-CoV-2 infection and maintain intestinal health. To provide new insights for the prevention and treatment of gastrointestinal symptoms and pneumonia in patients with COVID-19.
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Affiliation(s)
- Shanji Liu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Yu Zhao
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Xiaoyan Feng
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Hengyi Xu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
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Lim JK, Njei B. Clinical and Histopathological Discoveries in Patients with Hepatic Injury and Cholangiopathy Who Have Died of COVID-19: Insights and Opportunities for Intervention. Hepat Med 2023; 15:151-164. [PMID: 37814605 PMCID: PMC10560482 DOI: 10.2147/hmer.s385133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 09/28/2023] [Indexed: 10/11/2023] Open
Abstract
The COVID-19 pandemic has had a profound impact on global health, necessitating a comprehensive understanding of its diverse manifestations. Cholangiopathy, a condition characterized by biliary dysfunction, has emerged as a significant complication in COVID-19 patients. In this review, we report the epidemiology of COVID-19, describe the hepatotropism of SARS-CoV-2, and present the histopathology of acute liver injury (ALI) in COVID-19. Additionally, we explore the relationship between pre-existing chronic liver disease and COVID-19, shedding light on the increased susceptibility of these individuals to develop cholangiopathy. Through an in-depth analysis of cholangiopathy in COVID-19 patients, we elucidate its clinical manifestations, diagnostic criteria, and underlying pathogenesis involving inflammation, immune dysregulation, and vascular changes. Furthermore, we provide a summary of studies investigating post-COVID-19 cholangiopathy, highlighting the long-term effects and potential management strategies for this condition, and discussing opportunities for intervention, including therapeutic targets, diagnostic advancements, supportive care, and future research needs.
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Affiliation(s)
- Joseph K Lim
- Yale Liver Center and Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
| | - Basile Njei
- Yale Liver Center and Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
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10
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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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11
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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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Imam MT, Almalki ZS, Alzahrani AR, Al-Ghamdi SS, Falemban AH, Alanazi IM, Shahzad N, Muhammad Alrooqi M, Jabeen Q, Shahid I. COVID-19 and severity of liver diseases: Possible crosstalk and clinical implications. Int Immunopharmacol 2023; 121:110439. [PMID: 37315370 PMCID: PMC10247890 DOI: 10.1016/j.intimp.2023.110439] [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: 03/20/2023] [Revised: 05/30/2023] [Accepted: 05/31/2023] [Indexed: 06/16/2023]
Abstract
COVID-19-infected individuals and those who recovered from the infection have been demonstrated to have elevated liver enzymes or abnormal liver biochemistries, particularly with preexisting liver diseases, liver metabolic disorders, viral hepatitis, and other hepatic comorbidities. However, possible crosstalk and intricate interplay between COVID-19 and liver disease severity are still elusive, and the available data are murky and confined. Similarly, the syndemic of other blood-borne infectious diseases, chemical-induced liver injuries, and chronic hepatic diseases continued to take lives while showing signs of worsening due to the COVID-19 crisis. Moreover, the pandemic is not over yet and is transitioning to becoming an epidemic in recent years; hence, monitoring liver function tests (LFTs) and assessing hepatic consequences of COVID-19 in patients with or without liver illnesses would be of paramount interest. This pragmatic review explores the correlations between COVID-19 and liver disease severity based on abnormal liver biochemistries and other possible mechanisms in individuals of all ages from the emergence of the COVID-19 pandemic to the post-pandemic period. The review also alludes to clinical perspectives of such interactions to curb overlapping hepatic diseases in people who recovered from the infection or living with long COVID-19.
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Affiliation(s)
- Mohammad T Imam
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Ziyad S Almalki
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Abdullah R Alzahrani
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Saeed S Al-Ghamdi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Alaa H Falemban
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Ibrahim M Alanazi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Naiyer Shahzad
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | | | - Qaisar Jabeen
- Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Imran Shahid
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia.
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13
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Liatsos GD. SARS-CoV-2 induced liver injury: Incidence, risk factors, impact on COVID-19 severity and prognosis in different population groups. World J Gastroenterol 2023; 29:2397-2432. [PMID: 37179584 PMCID: PMC10167898 DOI: 10.3748/wjg.v29.i16.2397] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 02/17/2023] [Accepted: 04/07/2023] [Indexed: 04/24/2023] Open
Abstract
Liver is unlikely the key organ driving mortality in coronavirus disease 2019 (COVID-19) however, liver function tests (LFTs) abnormalities are widely observed mostly in moderate and severe cases. According to this review, the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5% to 96.8% worldwide. The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West. Multifactorial mechanisms are implicated in COVID-19-induced liver injury. Among them, hypercytokinemia with "bystander hepatitis", cytokine storm syndrome with subsequent oxidative stress and endotheliopathy, hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury. Liver hypoxia may also contribute under specific conditions, while direct hepatocyte injury is an emerging mechanism. Except for initially observed severe acute respiratory distress syndrome corona virus-2 (SARS-CoV-2) tropism for cholangiocytes, more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy (EM). The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA, S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization. New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery, suggesting a post-COVID-19 persistent live injury.
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Affiliation(s)
- George D Liatsos
- Department of Internal Medicine, Hippokration General Hospital, Athens 11527, Attiki, Greece
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14
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Buchynskyi M, Kamyshna I, Oksenych V, Zavidniuk N, Kamyshnyi A. The Intersection of COVID-19 and Metabolic-Associated Fatty Liver Disease: An Overview of the Current Evidence. Viruses 2023; 15:v15051072. [PMID: 37243158 DOI: 10.3390/v15051072] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 04/23/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
The global population is currently experiencing the impact of the SARS-CoV-2 coronavirus, which has caused the Coronavirus Disease 2019 (COVID-19) pandemic. With our profound comprehension of COVID-19, encompassing the involvement sequence of the respiratory tract, gastrointestinal system, and cardiovascular apparatus, the multiorgan symptoms of this infectious disease have been discerned. Metabolic-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a pervasive public health concern intricately linked with metabolic dysregulation and estimated to afflict one-fourth of the global adult population. The burgeoning focus on the association between COVID-19 and MAFLD is justified by the potential role of the latter as a risk factor for both SARS-CoV-2 infection and the subsequent emergence of severe COVID-19 symptoms. Investigations have suggested that changes in both innate and adaptive immune responses among MAFLD patients may play a role in determining the severity of COVID-19. The remarkable similarities observed in the cytokine pathways implicated in both diseases imply the existence of shared mechanisms governing the chronic inflammatory responses characterizing these conditions. The effect of MAFLD on the severity of COVID-19 illness remains uncertain, as indicated by conflicting results in cohort investigations.
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Affiliation(s)
- Mykhailo Buchynskyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Iryna Kamyshna
- Department of Medical Rehabilitation, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Valentyn Oksenych
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway
| | - Nataliia Zavidniuk
- Department of Infectious Diseases with Epidemiology, Dermatology and Venerology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Aleksandr Kamyshnyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
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15
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Roshanshad R, Roshanshad A, Fereidooni R, Hosseini-Bensenjan M. COVID-19 and liver injury: Pathophysiology, risk factors, outcome and management in special populations. World J Hepatol 2023; 15:441-459. [PMID: 37206656 PMCID: PMC10190688 DOI: 10.4254/wjh.v15.i4.441] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 02/05/2023] [Accepted: 03/20/2023] [Indexed: 04/20/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 is an ongoing health concern. In addition to affecting the respiratory system, COVID-19 can potentially damage other systems in the body, leading to extra-pulmonary manifestations. Hepatic manifestations are among the common consequences of COVID-19. Although the precise mechanism of liver injury is still questionable, several mechanisms have been hypothesized, including direct viral effect, cytokine storm, hypoxic-ischemic injury, hypoxia-reperfusion injury, ferroptosis, and hepatotoxic medications. Risk factors of COVID-19-induced liver injury include severe COVID-19 infection, male gender, advanced age, obesity, and underlying diseases. The presentations of liver involvement comprise abnormalities in liver enzymes and radiologic findings, which can be utilized to predict the prognosis. Increased gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase levels with hypoalbuminemia can indicate severe liver injury and anticipate the need for intensive care units’ hospitalization. In imaging, a lower liver-to-spleen ratio and liver computed tomography attenuation may indicate a more severe illness. Furthermore, chronic liver disease patients are at a higher risk for severe disease and death from COVID-19. Nonalcoholic fatty liver disease had the highest risk of advanced COVID-19 disease and death, followed by metabolic-associated fatty liver disease and cirrhosis. In addition to COVID-19-induced liver injury, the pandemic has also altered the epidemiology and pattern of some hepatic diseases, such as alcoholic liver disease and hepatitis B. Therefore, it warrants special vigilance and awareness by healthcare professionals to screen and treat COVID-19-associated liver injury accordingly.
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Affiliation(s)
- Romina Roshanshad
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz 7184731443, Iran
| | | | - Reza Fereidooni
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
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16
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Wang Y, Wang Y, Duan G, Yang H. NAFLD was independently associated with severe COVID-19 among younger patients rather than older patients: A meta-analysis. J Hepatol 2023; 78:e136-e139. [PMID: 36309129 PMCID: PMC9597581 DOI: 10.1016/j.jhep.2022.10.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 10/10/2022] [Accepted: 10/16/2022] [Indexed: 11/06/2022]
Affiliation(s)
- Ying Wang
- Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou 450001, China
| | - Yadong Wang
- Department of Toxicology, Henan Center for Disease Control and Prevention, Zhengzhou 450016, China
| | - Guangcai Duan
- Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou 450001, China
| | - Haiyan Yang
- Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou 450001, China.
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17
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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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18
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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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19
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Brevini T, Maes M, Webb GJ, John BV, Fuchs CD, Buescher G, Wang L, Griffiths C, Brown ML, Scott WE, Pereyra-Gerber P, Gelson WTH, Brown S, Dillon S, Muraro D, Sharp J, Neary M, Box H, Tatham L, Stewart J, Curley P, Pertinez H, Forrest S, Mlcochova P, Varankar SS, Darvish-Damavandi M, Mulcahy VL, Kuc RE, Williams TL, Heslop JA, Rossetti D, Tysoe OC, Galanakis V, Vila-Gonzalez M, Crozier TWM, Bargehr J, Sinha S, Upponi SS, Fear C, Swift L, Saeb-Parsy K, Davies SE, Wester A, Hagström H, Melum E, Clements D, Humphreys P, Herriott J, Kijak E, Cox H, Bramwell C, Valentijn A, Illingworth CJR, Dahman B, Bastaich DR, Ferreira RD, Marjot T, Barnes E, Moon AM, Barritt AS, Gupta RK, Baker S, Davenport AP, Corbett G, Gorgoulis VG, Buczacki SJA, Lee JH, Matheson NJ, Trauner M, Fisher AJ, Gibbs P, Butler AJ, Watson CJE, Mells GF, Dougan G, Owen A, Lohse AW, Vallier L, Sampaziotis F. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature 2023; 615:134-142. [PMID: 36470304 PMCID: PMC9977684 DOI: 10.1038/s41586-022-05594-0] [Citation(s) in RCA: 181] [Impact Index Per Article: 90.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 11/23/2022] [Indexed: 12/12/2022]
Abstract
Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2)1, could represent a new chemoprophylactic approach for COVID-19 that complements vaccination2,3. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials.
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Affiliation(s)
- Teresa Brevini
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK.
| | - Mailis Maes
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK
| | - Gwilym J Webb
- Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Binu V John
- Division of Gastroenterology and Hepatology, University of Miami and Miami VA Health System, Miami, FL, USA
| | - Claudia D Fuchs
- Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Gustav Buescher
- Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Lu Wang
- Transplant and Regenerative Medicine Laboratory, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Chelsea Griffiths
- Transplant and Regenerative Medicine Laboratory, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Marnie L Brown
- Transplant and Regenerative Medicine Laboratory, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - William E Scott
- Transplant and Regenerative Medicine Laboratory, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Pehuén Pereyra-Gerber
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK
| | - William T H Gelson
- Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Department of Medicine, University of Cambridge, Cambridge, UK
| | | | - Scott Dillon
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK
| | | | - Jo Sharp
- Centre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Megan Neary
- Centre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Helen Box
- Centre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Lee Tatham
- Centre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - James Stewart
- Department of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK
| | - Paul Curley
- Centre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Henry Pertinez
- Centre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Sally Forrest
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK
| | - Petra Mlcochova
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK
- Division of Gastroenterology and Hepatology, University of Miami and Miami VA Health System, Miami, FL, USA
| | | | - Mahnaz Darvish-Damavandi
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Victoria L Mulcahy
- Academic Department of Medical Genetics, University of Cambridge, Cambridge, UK
| | - Rhoda E Kuc
- Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
| | - Thomas L Williams
- Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
| | - James A Heslop
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK
| | | | - Olivia C Tysoe
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK
- Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK
| | | | | | - Thomas W M Crozier
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK
| | - Johannes Bargehr
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK
- Department of Medicine, University of Cambridge, Cambridge, UK
- Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK
| | - Sanjay Sinha
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK
- Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK
| | - Sara S Upponi
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Corrina Fear
- Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK
| | - Lisa Swift
- Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK
| | - Kourosh Saeb-Parsy
- Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK
- Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Susan E Davies
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Axel Wester
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Hannes Hagström
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Espen Melum
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Hybrid Technology Hub Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway
| | | | | | - Jo Herriott
- Centre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Edyta Kijak
- Centre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Helen Cox
- Centre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Chloe Bramwell
- Centre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Anthony Valentijn
- Centre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Christopher J R Illingworth
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
- Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, UK
| | - Bassam Dahman
- Department of Health Behavior and Policy, Virginia Commonwealth University, Richmond, VA, USA
| | - Dustin R Bastaich
- Department of Health Behavior and Policy, Virginia Commonwealth University, Richmond, VA, USA
| | - Raphaella D Ferreira
- Division of Gastroenterology and Hepatology, University of Miami and Miami VA Health System, Miami, FL, USA
| | - Thomas Marjot
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - Eleanor Barnes
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - Andrew M Moon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Alfred S Barritt
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Ravindra K Gupta
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - Stephen Baker
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK
| | - Anthony P Davenport
- Experimental Medicine and Immunotherapeutics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
| | - Gareth Corbett
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Vassilis G Gorgoulis
- Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
- Biomedical Research Foundation, Academy of Athens, Athens, Greece
| | - Simon J A Buczacki
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Joo-Hyeon Lee
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK
- Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
| | - Nicholas J Matheson
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK
- Department of Medicine, University of Cambridge, Cambridge, UK
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
- NHS Blood and Transplant, Cambridge, UK
| | - Michael Trauner
- Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Andrew J Fisher
- Transplant and Regenerative Medicine Laboratory, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Paul Gibbs
- Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK
- Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Andrew J Butler
- Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK
- Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Christopher J E Watson
- Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK
- Roy Calne Transplant Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre, and the NIHR Blood and Transplant Research Unit (BTRU) at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT), Cambridge, UK
| | - George F Mells
- Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Academic Department of Medical Genetics, University of Cambridge, Cambridge, UK
| | - Gordon Dougan
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK
| | - Andrew Owen
- Centre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
| | - Ansgar W Lohse
- Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Ludovic Vallier
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK.
- Wellcome Sanger Institute, Hinxton, UK.
- Berlin Institute of Health (BIH), BIH Centre for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Berlin, Germany.
- Max Planck Institute for Molecular Genetics, Berlin, Germany.
| | - Fotios Sampaziotis
- Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK.
- Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
- Department of Medicine, University of Cambridge, Cambridge, UK.
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20
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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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21
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Said ZNA, El Habashy SA, Zaky S. COVID-19-induced transaminitis and hyperbilirubinemia: Presentation and outcomes. World J Gastroenterol 2023; 29:1123-1130. [PMID: 36926664 PMCID: PMC10011958 DOI: 10.3748/wjg.v29.i7.1123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 12/29/2022] [Accepted: 02/13/2023] [Indexed: 02/21/2023] Open
Abstract
The risk of liver injury in patients with coronavirus disease 2019 (COVID-19) infection is quite evident. Furthermore, liver function test abnormalities are still detected in COVID-19 patients despite the development of antivirals and the availability of several types of vaccines. This editorial describes liver involvement during COVID-19 infection in patients with or without preexisting liver injury, such as chronic liver disease, to elucidate COVID-19-induced liver function abnormalities and their severity, pathophysiology, clinical manifestations, and clinical and laboratory outcomes. We also discuss the effect of vaccination against COVID-19 to better understand host factors, such as age, gender, and race, on the incidence and severity of liver dysfunction at initial presentation and during the illness. Finally, we summarize the results of relevant meta-analyses published to date and highlight the importance of adequate liver function monitoring in the current climate of the overwhelming COVID-19 pandemic.
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Affiliation(s)
- Zeinab Nabil Ahmed Said
- Department of Medical Microbiology and Immunology, Faculty of Medicine (For Girls), Al-Azhar University, Cairo 11754, Nasr City, Egypt
| | | | - Samy Zaky
- Department of Hepato-gastroenterology and Infectious Diseases, Faculty of Medicine (For Girls), Al-Azhar University, Cairo 11754, Egypt
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22
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Vujčić I. Outcomes of COVID-19 among patients with liver disease. World J Gastroenterol 2023; 29:815-824. [PMID: 36816621 PMCID: PMC9932431 DOI: 10.3748/wjg.v29.i5.815] [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: 09/17/2022] [Revised: 12/25/2022] [Accepted: 01/20/2023] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is primarily a respiratory disease with multi-organ involvement, including impaired liver function. It has been noticed that a significant proportion of COVID-19 patients have liver dysfunction, especially those with a more severe disease course. The coronavirus causes direct damage to the liver using the angiotensin-converting enzyme 2, a cell-surface receptor for cellular entry, that is expressed in the liver. According to previous research, liver enzyme abnormalities were observed in a considerable proportion of COVID-19 patients, and elevated liver transaminases were found in about 20% of these patients, alkaline phosphatase in 6.1%, and gamma-glutamyl transferase in 21.1%. COVID-19 might trigger a deterioration of liver function in patients with pre-existing chronic liver diseases (CLDs) and also in those without previous liver disorders. The majority of COVID-19 patients who develop liver injury are men, the elderly, and those with a higher body mass index. Compared to the general population, COVID-19 is associated with significant morbidity and mortality in patients with liver disease (cirrhosis and liver transplantation recipients). However, some studies indicate that CLDs have a lesser role in determining patient progression towards higher disease severity.
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Affiliation(s)
- Isidora Vujčić
- Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade 11000, Belgrade, Serbia
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23
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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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Abstract
The coronavirus disease-2019 (COVID-19) pandemic has had a large impact on patients with chronic liver disease (CLD) and liver transplantation (LT) recipients. Patients with advanced CLD are at a significantly increased risk of poor outcomes in the setting of severe acute respiratory syndrome coronavirus 2 infection. The pandemic has also considerably altered the management and care that is provided to patients with CLD, pre-LT patients, and LT recipients. Vaccination against COVID-19 protects patients with CLD and LT recipients from adverse outcomes and is safe in these patients; however, vaccine efficacy may be reduced in LT recipients and other immunosuppressed patients.
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25
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Gupta T, Sharma H. COVID-19 and the liver: Are footprints still there? World J Gastroenterol 2023; 29:656-669. [PMID: 36742164 PMCID: PMC9896610 DOI: 10.3748/wjg.v29.i4.656] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 10/13/2022] [Accepted: 11/21/2022] [Indexed: 01/20/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases. An early trend in higher mortality in patients with acute respiratory distress attracted all researchers to closely monitor patients for the involvement of other systems. It soon became apparent that patients with chronic liver diseases are at increased risk of mortality given their cirrhosis-associated immune dysfunction. Additionally, liver function abnormalities were noted in patients with severe COVID-19. Profound cytokine storm, direct viral infection, drugs and reactivation of viral infections were causes of deranged liver functions. Here, we discuss the relation between COVID-19 and chronic liver disease, specifically cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease (NAFLD), as well as the liver manifestations of COVID-19. The metabolic syndrome, obesity, diabetes mellitus and NAFLD were found to worsen outcome in different studies reported worldwide. Decompensated cirrhosis should be considered a risk factor for death and severe COVID-19. Recently, COVID-19 related cholangiopathy has also been reported with changes of secondary sclerosing cholangitis. The long-term persistence of viral antigens in gut epithelia raises concern regarding the future risk of autoimmune liver diseases.
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Affiliation(s)
- Tarana Gupta
- Department of Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak 124001, Haryana, India
| | - Hemant Sharma
- Department of Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak 124001, Haryana, India
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26
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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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27
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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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28
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Baldelli L, Marjot T, Barnes E, Barritt AS, Webb GJ, Moon AM. SARS-CoV-2 Infection and Liver Disease: A Review of Pathogenesis and Outcomes. Gut Liver 2023; 17:12-23. [PMID: 36457261 PMCID: PMC9840920 DOI: 10.5009/gnl220327] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/31/2022] [Accepted: 09/07/2022] [Indexed: 12/03/2022] Open
Abstract
The impact of the coronavirus disease 2019 (COVID-19) pandemic has been immense, and it continues to have lasting repercussions. While the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus primarily infects the respiratory system, other organ systems are affected, including the liver. Scientific knowledge on the role of SARS-CoV-2 infection and liver injury has evolved rapidly, with recent data suggesting specific hepatotropism of SARS-CoV-2. Moreover, additional concerns have been raised in regard to long-term liver damage, related to emerging cases of post-COVID-19 cholangiopathy and chronic cholestasis. Great effort has also been focused on studying how specific subpopulations with chronic medical conditions might be disproportionately impacted by COVID-19. One such population includes individuals with chronic liver disease (CLD) and cirrhosis, with an expanding body of research indicating these patients being particularly susceptible to adverse outcomes. In this review, we provide an updated summary on the current pathogenesis and mechanism of liver injury in the setting of SARS-CoV-2 infection, the association between health outcomes and SARS-CoV-2 infection in patients with CLD, and the unique consequences of the COVID-19 pandemic on the routine care of patients with CLD.
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Affiliation(s)
- Luke Baldelli
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Thomas Marjot
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - Eleanor Barnes
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - A. Sidney Barritt
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Gwilym J. Webb
- Cambridge Liver Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Andrew M. Moon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
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29
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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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30
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Al-Rawi TSS, Al-Ani RM. Liver dysfunction-related COVID-19: A narrative review. World J Meta-Anal 2023; 11:5-17. [DOI: 10.13105/wjma.v11.i1.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 11/25/2022] [Accepted: 12/14/2022] [Indexed: 01/11/2023] Open
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31
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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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Xu J, Wang Y, Feng H, Liu F, Yang H. HBV/HCV Infection Was Not Significantly Independently Associated with COVID-19 Severity: A Meta-Analysis of Confounding Variables-Adjusted Data. Dig Dis Sci 2022; 68:2161-2163. [PMID: 36562890 PMCID: PMC9782272 DOI: 10.1007/s10620-022-07799-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022]
Affiliation(s)
- Jie Xu
- Department of Epidemiology, School of Public Health, Zhengzhou University, No. 100 of Science Avenue, Zhengzhou, 450001 China
| | - Yujia Wang
- School of Nursing, Hebi Polytechnic, Hebi, 458030 China
| | - Huifen Feng
- Department of Infectious Diseases, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China
| | - Fang Liu
- Department of Epidemiology, School of Public Health, Zhengzhou University, No. 100 of Science Avenue, Zhengzhou, 450001 China
| | - Haiyan Yang
- Department of Epidemiology, School of Public Health, Zhengzhou University, No. 100 of Science Avenue, Zhengzhou, 450001 China
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Schinas G, Polyzou E, Mitropetrou F, Pazionis A, Gogos C, Triantos C, Akinosoglou K. COVID-19 Vaccination in Patients with Chronic Liver Disease. Viruses 2022; 14:v14122778. [PMID: 36560782 PMCID: PMC9785164 DOI: 10.3390/v14122778] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 12/09/2022] [Accepted: 12/13/2022] [Indexed: 12/15/2022] Open
Abstract
Vaccination against SARS-CoV-2 has become a central public health issue, primarily for vulnerable populations such as individuals with Chronic Liver Disease (CLD). Increased COVID-19-related mortality and disease severity has been noted in this subgroup of patients. Severe COVID-19 tends to further deregulate liver function in patients with chronic liver failure or cirrhosis and even reactivate hepatitis in people living with HBV or HCV. In addition, impaired hepatic function leads to several limitations in possible therapeutic interventions. Chronic hepatic dysregulation, along with the underlying cirrhosis-associated immune dysfunction (CAID), leads to a decreased immune response to vaccination that, in turn, may result in reduced efficacy rates and lowered lasting protection. According to current guidelines, timely vaccination and frequent booster shot administration are deemed necessary in this context. Vaccination-related adverse events are mostly mild in nature and similar to those reported in the general population, whereas the incidence of liver injury following vaccination is relatively rare. We aimed to review available evidence and recommendations associated with COVID-19 vaccination in patients with chronic liver disease, and provide insight to current issues and future directions.
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Affiliation(s)
- Georgios Schinas
- Department of Internal Medicine, University General Hospital of Patras, 26504 Rio, Greece
- Department of Medicine, University of Patras, 26504 Rio, Greece
| | - Eleni Polyzou
- Department of Internal Medicine, University General Hospital of Patras, 26504 Rio, Greece
- Department of Medicine, University of Patras, 26504 Rio, Greece
| | | | | | - Charalambos Gogos
- Department of Internal Medicine, University General Hospital of Patras, 26504 Rio, Greece
- Department of Medicine, University of Patras, 26504 Rio, Greece
| | - Christos Triantos
- Department of Medicine, University of Patras, 26504 Rio, Greece
- Division of Gastroenterology, Department of Internal Medicine, University General Hospital of Patras, 26504 Rio, Greece
- Correspondence: or ; Tel.: +30-6972894651
| | - Karolina Akinosoglou
- Department of Internal Medicine, University General Hospital of Patras, 26504 Rio, Greece
- Department of Medicine, University of Patras, 26504 Rio, Greece
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More efforts to explore the association between cirrhosis and COVID-19 mortality, and the association between NAFLD and severe COVID-19. J Hepatol 2022; 78:e178-e180. [PMID: 36503028 PMCID: PMC9744118 DOI: 10.1016/j.jhep.2022.11.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 11/23/2022] [Indexed: 12/13/2022]
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Elghannam MT, Hassanien MH, Ameen YA, ELattar GM, ELRay AA, Turky EA, ELTalkawy MD. COVID-19 and liver diseases. EGYPTIAN LIVER JOURNAL 2022; 12:43. [PMID: 35880136 PMCID: PMC9301896 DOI: 10.1186/s43066-022-00202-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 07/06/2022] [Indexed: 12/15/2022] Open
Abstract
Coronavirus causes an outbreak of viral pneumonia that spread throughout the world. Liver injury is becoming more widely recognized as a component of the clinical picture of COVID-19 infection. Hepatitis with serum ALT elevation has been reported in up to half of patients. Patients with CLD were at a higher risk of decompensation with liver failure, hospitalization, and mortality. The percentage of acute liver injury (ALI) varied from 5 to 28%. COVID-19 hinders HCV elimination by 2030. It is recommended to continue treatment of chronic HCV and chronic HBV if already receiving treatment. Consider using antiviral therapy to prevent viral flare-ups in patients with occult or resolved HBV and COVID-19 who are receiving immunosuppressive agents. Patients with AIH do not have an increased risk of adverse outcomes even in high-risk areas. There is an association between MAFLD and disease progression. Patients with any type of cancer are at a higher risk of infection and are more likely to develop more severe clinical outcomes. Most societies advise against immunosuppressant modifications in patients with mild COVID-19, whereas in rare cases such as severe lymphopenia, worsening pneumonia, or bacterial or fungal superinfection, reduction or discontinuation of antiproliferative agents and lymphocyte-depleting therapies has been suggested.
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36
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Hanif FM, Majid Z, Ahmed S, Luck NH, Mubarak M. Hepatic manifestations of coronavirus disease 2019 infection: Clinical and laboratory perspective. World J Virol 2022; 11:453-466. [PMID: 36483109 PMCID: PMC9724207 DOI: 10.5501/wjv.v11.i6.453] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 10/17/2022] [Accepted: 11/07/2022] [Indexed: 11/23/2022] Open
Abstract
The novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has become a global challenge of unprecedented nature since December 2019. Although most patients with COVID-19 exhibit mild clinical manifestations and upper respiratory tract involvement, in approximately 5%-10% of patients, the disease is severe and involves multiple organs, leading to multi-organ dysfunction and failure. The liver and gastrointestinal tract are also frequently involved in COVID-19. In the context of liver involvement in patients with COVID-19, many key aspects need to be addressed in both native and transplanted organs. This review focuses on the clinical presentations and laboratory abnormalities of liver function tests in patients with COVID-19 with no prior liver disease, patients with pre-existing liver diseases and liver transplant recipients. A brief overview of the history of COVID-19 and etiopathogenesis of the liver injury will also be described as a prelude to better understanding the above aspects.
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Affiliation(s)
- Farina M Hanif
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Zain Majid
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Shoaib Ahmed
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Nasir H Luck
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
| | - Muhammed Mubarak
- Department of Pathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
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Grando M, Balbi M, Zeppieri M. COVID-19-induced liver injury in adult patients: A brief overview. World J Virol 2022; 11:443-452. [PMID: 36483102 PMCID: PMC9724208 DOI: 10.5501/wjv.v11.i6.443] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/07/2022] [Accepted: 10/12/2022] [Indexed: 11/23/2022] Open
Abstract
Coronavirus disease has spread worldwide since 2019, causing important pandemic issues and various social health problems to date. Little is known about the origin of this virus and the effects it has on extra-pulmonary organs. The different mechanisms of the virus and the influence it has on humans are still being studied, with hopes of finding a cure for the disease and the pathologies associated with the infection. Liver damage caused by coronavirus disease 2019 (COVID-19) is sometimes underestimated and has been of important clinical interest in the past few years. Hepatic dysfunctions can manifest in different forms which can sometimes be mild and without specific signs and symptoms or be severe with important clinical implications. There are several studies that have tried to explain the mechanism of entry (hepatotropism) of the virus into hepatocytes and the effects the virus has on this important organ. What clearly emerges from the current literature is that hepatic injury represents an important clinical aspect in the management of patients infected with COVID-19, especially in frail patients and those with comorbidities. The aim of our brief overview is to summarize the current literature regarding the forms of hepatic damage, complications, mechanisms of pathology, clinical features of liver injury, influence of comorbidities and clinical management in patients with COVID-19 infection.
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Affiliation(s)
- Martina Grando
- Department of Internal Medicine, Azienda Sanitaria Friuli Occidentale, San Vito al Tagliamento 33078, Italy
| | - Massimiliano Balbi
- Department of Internal Medicine, Azienda Sanitaria Friuli Occidentale, San Vito al Tagliamento 33078, Italy
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
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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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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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40
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Lee SK, Kwon JH, Yoon N, Lee SH, Sung PS. Immune-mediated liver injury represented as overlap syndrome after SARS-CoV-2 vaccination. J Hepatol 2022; 77:1209-1211. [PMID: 35817223 PMCID: PMC9265239 DOI: 10.1016/j.jhep.2022.06.029] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 06/20/2022] [Accepted: 06/25/2022] [Indexed: 12/22/2022]
Affiliation(s)
- Soon Kyu Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea.
| | - Jung Hyun Kwon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea
| | - Nara Yoon
- Department of Pathology, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea
| | - Sung Hak Lee
- Department of Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea
| | - Pil Soo Sung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea.
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41
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Muacevic A, Adler JR. COVID-19 Vaccination-Induced Cholangiopathy and Autoimmune Hepatitis: A Series of Two Cases. Cureus 2022; 14:e30304. [PMID: 36258805 PMCID: PMC9565316 DOI: 10.7759/cureus.30304] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/14/2022] [Indexed: 12/01/2022] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has been associated with significant morbidity and mortality. Following the introduction of vaccines, various side effects have been reported. Whilst those reported may be attributed to the vaccine itself, at times, it may simply incite an immunological phenomenon. We present a case series of two patients who presented with symptoms of yellowing of the eyes and the skin along with fatigue, and tiredness, following vaccination for COVID-19. The diagnosis of post COVID-19-vaccination related hepatitis is one of the fewer, less understood, yet reported side effects associated with significant morbidity. The diagnosis of COVID-19 vaccination-related cholangitis is an outcome reported here for the first time to the best of our knowledge. It was alarming that both patients did not have any significant past history of medical ailments. A prompt assessment followed by investigations including liver biopsy assisted in a timely understanding of the phenomenon with complete resolution of the symptoms.
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Li P, Liu Y, Cheng Z, Yu X, Li Y. COVID-19-associated liver injury: Clinical characteristics, pathophysiological mechanisms and treatment management. Biomed Pharmacother 2022; 154:113568. [PMID: 36029543 PMCID: PMC9381432 DOI: 10.1016/j.biopha.2022.113568] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/14/2022] [Accepted: 08/15/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global epidemic and poses a major threat to public health. In addition to COVID-19 manifesting as a respiratory disease, patients with severe disease also have complications in extrapulmonary organs, including liver damage. Abnormal liver function is relatively common in COVID-19 patients; its clinical manifestations can range from an asymptomatic elevation of liver enzymes to decompensated hepatic function, and liver injury is more prevalent in severe and critical patients. Liver injury in COVID-19 patients is a comprehensive effect mediated by multiple factors, including liver damage directly caused by SARS-CoV-2, drug-induced liver damage, hypoxia reperfusion dysfunction, immune stress and inflammatory factor storms. Patients with chronic liver disease (especially alcohol-related liver disease, nonalcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma) are at increased risk of severe disease and death after infection with SARS-CoV-2, and COVID-19 aggravates liver damage in patients with chronic liver disease. This article reviews the latest SARS-CoV-2 reports, focusing on the liver damage caused by COVID-19 and the underlying mechanism, and expounds on the risk, treatment and vaccine safety of SARS-CoV-2 in patients with chronic liver disease and liver transplantation.
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Affiliation(s)
- Penghui Li
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Ying Liu
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Ziqi Cheng
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Xiaorui Yu
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Yinxiong Li
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; State Key Laboratory of Respiratory Disease, Guangzhou, China; China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou, China.
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Characteristics of COVID-19 Infection in a Hospitalized Autoimmune Hepatitis Patient. Pathogens 2022; 11:pathogens11091054. [PMID: 36145486 PMCID: PMC9501835 DOI: 10.3390/pathogens11091054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/12/2022] [Accepted: 08/18/2022] [Indexed: 01/08/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a major public health worldwide. Hepatic dysfunction has been seen in patients with COVID-19 and could be related to a viral cytopathic effect, an exacerbated immune reaction, or drug-induced liver damage. Currently, routine modification of immunosuppressive therapy in patients with autoimmune hepatitis (AIH) before and after SARS-CoV-2 infection remains an important topic to be discussed. However, there is little evidence about this thematic to support any recommendation. Here, we described a case report in which the use of an immunosuppressive drug by a patient with diagnosed AIH might have influenced the COVID-19 clinical course with altered laboratory hematological and biochemical parameters during infection.
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Mirza H, Noori MAM, Akbar H, Fichadiya H, Kaur IP, Sachdeva S, Grewal J, Khakwani MZ, Levitt H, Chang W, Wasty N, Patton C, Shah A, Angi P, Mughal MS. Hypertension as an Independent Risk Factor for In-Patient Mortality in Hospitalized COVID-19 Patients: A Multicenter Study. Cureus 2022; 14:e26741. [PMID: 35836713 PMCID: PMC9275529 DOI: 10.7759/cureus.26741] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/20/2022] [Indexed: 01/08/2023] Open
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45
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Chen J, Liu Y, Qin J, Ruan C, Zeng X, Xu A, Yang R, Li J, Cai H, Zhang Z. Hypertension as an independent risk factor for severity and mortality in patients with COVID-19: a retrospective study. Postgrad Med J 2022; 98:515-522. [PMID: 37066501 PMCID: PMC8494531 DOI: 10.1136/postgradmedj-2021-140674] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 08/31/2021] [Indexed: 01/08/2023]
Abstract
PURPOSE OF THE STUDY Hypertension is one of the most common comorbidities in COVID-19 pneumonia. However, whether it is an independent factor on the severity and mortality of COVID-19 has not been studied. STUDY DESIGN In this study, 736 patients with a PCR-confirmed diagnosis of COVID-19 were included from 12 January 2020 to 25 March 2020. All patients were divided into two groups according to whether or not they were hypertensive. After propensity score matching (PSM) to remove the interference of mismatches in the baseline data, the clinical characteristics and outcomes of angiotensin II receptor blocker (ARB)/ACE inhibitors application were analysed. RESULTS A total of 220 (29.9%) patients were hypertensive, and 516 (70.1%) patients were not hypertensive. PSM eliminated demographic and comorbidity differences between the two groups. Of all participants, 32 patients died (4.3% mortality), including 17 out of 220 in the hypertension group (7.7%) and 15 out of 516 in the non-hypertension group (2.9%). The incidence of intensive care unit (ICU) stay in the hypertension group (12.8%) was higher than in the non-hypertension group (5.3%) (p<0.05). Logistic regression analysis showed that hypertension was an independent risk factor for death, not other comorbidities. Kaplan-Meier analysis showed that mortality was higher in the hypertension group than in the non-hypertension group before and after PSM (p<0.05). There was no statistically significant difference in ICU therapy, mortality and hospitalisation time between hypertensive patients with or without ARBs/ACE inhibitors (p>0.05). CONCLUSION Hypertension was an independent risk factor for the severity and mortality of patients with COVID-19. ARBs/ACE inhibitors should not be discontinued in hypertensive patients with COVID-19.
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Affiliation(s)
- Jiankun Chen
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
- Guangzhou Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Emerging Infectious Diseases, Guangzhou, Guangdong, China
| | - Yuntao Liu
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
- Guangzhou Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Emerging Infectious Diseases, Guangzhou, Guangdong, China
| | - Jinying Qin
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Chunyan Ruan
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Xianghui Zeng
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Aiting Xu
- Department of Chinese Medicine, People's Hospital of Yangjiang, Yangjiang, Guangdong, China
| | - Rongyuan Yang
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
- Guangzhou Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Emerging Infectious Diseases, Guangzhou, Guangdong, China
| | - Jiqiang Li
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
- Guangzhou Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Emerging Infectious Diseases, Guangzhou, Guangdong, China
| | - Huayang Cai
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Zhongde Zhang
- The Second Affiliated Hospital (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
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Impact of SARS-CoV-2 Pandemic on Vascular Liver Diseases. Clin Gastroenterol Hepatol 2022; 20:1525-1533.e5. [PMID: 34968728 PMCID: PMC8710430 DOI: 10.1016/j.cgh.2021.12.032] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 12/14/2021] [Accepted: 12/16/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Vascular liver diseases (VLDs) are represented mainly by portosinusoidal vascular disease (PSVD), noncirrhotic splanchnic vein thrombosis (SVT), and Budd Chiari syndrome (BCS). It is unknown whether patients with VLDs constitute a high-risk population for complications and greater coronavirus disease 2019 (COVID-19)-related mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to assess the prevalence and severity of SARS-CoV-2 infection among patients with VLDs, as well as to assess its impact on hepatic decompensation and survival. METHODS This is an observational international study analyzing the prevalence and severity of SARS-CoV-2 infection in VLDs between March 2020 and March 2021, compared with the general population (GP). Patients from Spain (5 centers; n = 493) and France (1 center; n = 475) were included. RESULTS Nine hundred sixty-eight patients were included: 274 with PSVD, 539 with SVT, and 155 with BCS. Among them, 138 (14%) were infected with SARS-CoV-2: 53 with PSVD, 77 with SVT, and 8 with BCS. The prevalence of SARS-CoV-2 infection in patients with PSVD (19%) and SVT (14%) was significantly higher than in the GP (6.5%; P < .05), whereas it was very similar in patients with BCS (5%). In terms of infection severity, patients with VLDs also presented a higher need of hospital admission (14% vs 7.3%; P < .01), intensive care unit admission (2% vs 0.7%; P < .01), and mortality (4% vs 1.5%; P < .05) than the GP. Previous history of ascites (50% vs 8%; P < .05) and post-COVID-19 hepatic decompensation (50% vs 4%; P < .05) were associated with COVID-19 mortality. CONCLUSIONS Patients with PSVD and SVT could be at higher risk of infection by SARS-CoV-2 and at higher risk of severe COVID-19 disease.
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Sahin T, Simsek C, Balaban HY. Practical points that gastrointestinal fellows should know in management of COVID-19. World J Clin Cases 2022; 10:5133-5145. [PMID: 35812670 PMCID: PMC9210885 DOI: 10.12998/wjcc.v10.i16.5133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 07/31/2021] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
Pandemics obligate providers to transform their clinical practice. An extensive effort has been put to find out feasible approaches for gastrointestinal diseases and also to manage coronavirus disease 2019 (COVID-19) related gastrointestinal conditions. Diarrhea, hepatitis, and pancreatitis can be seen in the COVID-19 course. Endoscopic procedures increase the risk of contamination for medical staff and patients despite precautions, therefore indications should be tailored to balance risks vs benefits. Furthermore, whether the immunosupression in inflammatory bowel diseases, liver transplantation, and autoimmune liver diseases increases COVID-19 related risks and how to modify immunosupression are topics of ongoing debate. This review aims to provide most up to date practical approaches that a gastrointestinal fellow should be aware on the problems and management of gastrointestinal and hepatobiliary diseases during the COVID-19 pandemic.
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Affiliation(s)
- Tevhide Sahin
- Department of Gastroenterology, Hacettepe University, Faculty of Medicine, Ankara 06100, Turkey
| | - Cem Simsek
- Department of Gastroenterology, Hacettepe University, Faculty of Medicine, Ankara 06100, Turkey
| | - Hatice Yasemin Balaban
- Department of Gastroenterology, Hacettepe University, Faculty of Medicine, Ankara 06100, Turkey
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Lleo A, Cazzagon N, Rigamonti C, Cabibbo G, Lai Q, Muratori L, Carbone M. Clinical update on risks and efficacy of anti-SARS-CoV-2 vaccines in patients with autoimmune hepatitis and summary of reports on post-vaccination liver injury. Dig Liver Dis 2022; 54:722-726. [PMID: 35410851 PMCID: PMC8958090 DOI: 10.1016/j.dld.2022.03.014] [Citation(s) in RCA: 6] [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: 01/25/2022] [Revised: 03/18/2022] [Accepted: 03/21/2022] [Indexed: 12/12/2022]
Abstract
Patients with liver diseases, especially those with cirrhosis, have an increased mortality risk when infected by SARS-CoV-2 and therefore anti-SARS-CoV-2 vaccine has been recommended by leading Scientific Associations for all patients with chronic liver diseases. However, previous reports have shown a reduced antibody response following the full course of vaccination in immunosuppressed patients, including liver transplant recipients and several rheumatic diseases. This document, drafted by an expert panel of hepatologists appointed by the Italian Association for the Study of the Liver (AISF), aims to present the updated scientific data on the safety and efficacy of anti-SARS-CoV-2 mRNA vaccines in patients with autoimmune hepatitis (AIH). Furthermore, given the recent reports of sporadic cases of AIH-like cases following anti-SARS-CoV-2 mRNA vaccines, we summarize available data. Finally, we provide experts recommendations based on the limited data available.
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Affiliation(s)
- Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Internal Medicine and Hepatology Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
| | - Nora Cazzagon
- Gastroenterology Unit, Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, Italy
| | - Cristina Rigamonti
- Department of Translational Medicine, Università del Piemonte Orientale and Division of Internal Medicine, Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, Italy
| | - Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Quirino Lai
- Unità di Chirurgia Generale e Trapianti d'Organo, Dipartimento di Chirurgia Generale e Specialistica, Sapienza Università di Roma, Azienda Ospedaliero-Universitaria Policlinico Umberto I di Roma, Italy
| | - Luigi Muratori
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Center for the Study and Treatment of Autoimmune Diseases of the Liver and Biliary System, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Marco Carbone
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
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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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Abstract
PURPOSE OF REVIEW The objective of this review is to examine the epidemiology and pathogenesis of liver injury in coronavirus disease 2019 (COVID-19) and the impact of COVID-19 on patients with chronic liver disease (CLD) and liver transplant recipients. RECENT FINDINGS Abnormal liver chemistries occur in up to 60% of COVID-19 patients and are typically mild. COVID-19- associated liver injury may be because of direct viral cytopathic effect, immune-mediated damage, hypoxia, drug-induced liver injury (DILI), or exacerbation of CLD. COVID-19 patients with CLD and who are liver transplant recipients are at risk for severe disease and mortality. COVID-19 precipitated hepatic decompensation in 20-46% of cirrhotic patients. Alcohol consumption and cases of acute alcohol- associated hepatitis increased during the COVID-19 pandemic. Corticosteroids and calcineurin inhibitors are well tolerated to use during COVID-19 but immunomodulators have been associated with mortality. Less than 50% of transplant recipients produce adequate antibody titers after COVID-19 vaccination. SUMMARY COVID-19 patients with CLD should be monitored for liver injury and hepatic decompensation. Patients with CLD and liver transplant recipients should be considered for targeted COVID-19 pharmacotherapeutics and advised vaccination against COVID-19, including a third booster dose. CLD treatments and immunosuppression in liver transplant recipients could generally continue without interruption during COVID-19 infection, with the possible exception of immunomodulators.
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Affiliation(s)
- James Philip Esteban
- Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Lindsay Sobotka
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Colmbus, Ohio
| | - Don C Rockey
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, South Carolina, Charleston, USA
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