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Nayak D, Bhalla R, Kaur L, Bansal D, Singh S, Bagdi N, Michael J, Chaudhuri A, Tyagi L, Makhija B, Madaan S, Das D, Shukla I, Sanyal S, Saleem KS, Yadav A. Impact of Homeoprophylactic Arsenicum album 30c on COVID-19 Vaccine-related Adverse Events: A Combined Retrospective-Prospective Cohort Study. HOMEOPATHY 2025. [PMID: 40355111 DOI: 10.1055/a-2512-9763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
OBJECTIVE Arsenicum album 30C (AA30) was recommended by the Government of India for the prevention of coronavirus infection. In the wake of the reporting of COVID-19 vaccine-related adverse events (AEs) and consequent vaccine hesitancy, this study was undertaken to assess the impact of homeo-prophylactic AA30 on COVID-19 vaccine-related AEs. METHODS This was a combined retrospective-prospective cohort study that included participants who had been enrolled in an ongoing prospective, parallel cohort study being conducted in urban slums of New Delhi and who had received either or both doses of the COVID-19 vaccine. The reporting of COVID-19 vaccine-related AEs was compared between a cohort that had been receiving homeopathic AA30 as a prophylactic for influenza-like/COVID-like illness with one in which no homeopathic intervention was provided. RESULTS A total of 1,737 participants who received either or both doses of vaccination for COVID-19 were included in the study, out of whom 436 participants were from the medicine cohort (MC) and 1,301 were from the control cohort (CC). Overall odds of developing AEs after either dose of COVID-19 vaccine in MC as compared with CC was found to be statistically significantly lower (overall crude OR = 0.29, 95% confidence interval [CI] = 0.23 to 0.37; p = 0.0001). The adjusted OR after accounting for age, sex, co-morbidities and vaccine type was 0.30 (95% CI = 0.24 to 0.39; p = 0.0001). The protective effect of the medicine against post-vaccination AEs was evident after the first dose as well as after the second dose, with overall crude OR being 0.37 (95% CI = 0.29 to 0.48; p = 0.0001) and 0.28 (95% CI = 0.19 to 0.41; p = 0.0001) respectively. CONCLUSION Prior use of the homeopathic medicine AA30 was able to significantly reduce COVID-19 vaccine-related AEs.
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Affiliation(s)
- Debadatta Nayak
- Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
| | - Ruchika Bhalla
- Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
| | - Lovepreet Kaur
- Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
| | - Divya Bansal
- Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
| | - Smita Singh
- Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
| | - Navita Bagdi
- Department of Clinical Research, Central Council for Research in Homoeopathy, New Delhi, India
| | - James Michael
- Clinical Research Unit for Homoeopathy, Under the Central Council for Research in Homoeopathy, Civil Hospital, Aizawl, Mizoram, India
| | - Abhishek Chaudhuri
- Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
| | - Lalit Tyagi
- Department of Clinical Research, Clinical Research Unit for Homoeopathy, Sri Vijaya Puram, Andaman & Nicobar Islands, India
| | - Bhavna Makhija
- Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
| | - Shikha Madaan
- Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
| | - Deblina Das
- Department of Health & Family Welfare (AYUSH), Government of West Bengal, Kolkata, West Bengal, India
| | - Indu Shukla
- Department of Practice of Medicine, State K.G.K. Homoeopathic Medical College and Hospital, Moradabad, Uttar Pradesh, India
| | - Srimonti Sanyal
- Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
| | - Khan Sheeba Saleem
- Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
| | - Ajay Yadav
- Department of Epidemic Cell, Central Council for Research in Homoeopathy, New Delhi, India
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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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Björnsson ES. The Epidemiology of Newly Recognized Causes of Drug-Induced Liver Injury: An Update. Pharmaceuticals (Basel) 2024; 17:520. [PMID: 38675480 PMCID: PMC11053599 DOI: 10.3390/ph17040520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 04/12/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
The incidence and prevalence of drug-induced liver injury appear to be increasing globally, for example, with the introduction of checkpoint inhibitors. Several reviews have been published in the last decade on the epidemiology of DILI, both among hospitalized patients and in the general population, as well as from retrospective and prospective studies on DILI. Most of these reviews have not focused on newly recognized agents that have recently changed the landscape of DILI. Apart from liver injury associated with antibiotics, oncological agents, particularly checkpoint inhibitors, are increasingly being recognized as causing liver injury. The type of liver injury associated with these agents is not idiosyncratic but rather an indirect type of injury. Furthermore, recently, COVID-19 vaccines and green tea extract have been found to lead to liver injury. Checkpoint inhibitors have revolutionized the treatment of many malignancies, such as malignant melanoma, lung cancer, and renal cancer. Via the activation of T cells, they can increase immune activity against malignant cells, but at the same time, they can decrease immune tolerance and therefore lead to immune-related adverse effects in many organs. The most common adverse effect in clinical practice is liver injury. A recent prospective study demonstrated an 8% frequency of DILI due to the use of checkpoint inhibitors among patients with malignant melanoma and renal cancer. This rate is much higher than observed with drugs, leading to idiosyncratic liver injury. Shortly after the implementation of the worldwide vaccination program against COVID-19, several case reports were published on suspected vaccination-induced autoimmune-like hepatitis occurring shortly after the vaccination. At first, these reports were met with skepticism, but currently, around 100 reports have been published, and cases of positive recurrence have been reported. The clinical, biochemical, immunological, and histological features are indistinguishable from classic autoimmune hepatitis (AIH). These reactions are very similar to drug-induced autoimmune-like hepatitis (DI-ALH) due to drugs such as nitrofurantoin, minocycline, and infliximab, which do not relapse after a short course of corticosteroids, which is the general rule in classic autoimmune hepatitis (AIH). Green tea extract has been found to be a well-documented cause of acute hepatocellular liver injury with jaundice. A strong HLA association has been reported, showing a high prevalence of HLA-B*35:01 among patients suffering from green tea-induced liver injury. Overall, 3% of patients recruited in the DILIN study were supplemented with green tea extract as one of the ingredients. In a prospective population-based study from Iceland, green tea was implicated in approximately 8% of patients with DILI.
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Affiliation(s)
- Einar Stefan Björnsson
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The National University Hospital of Iceland, Faculty of Medicine, University of Iceland, Hringbraut, 101 Reykjavik, Iceland
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Masuta Y, Minaga K, Otsuka Y, Okai N, Hara A, Masaki S, Nagai T, Honjo H, Kudo M, Watanabe T. Cytokine and chemokine profiles in ulcerative colitis relapse after coronavirus disease 2019 vaccination. J Clin Biochem Nutr 2024; 74:127-135. [PMID: 38510687 PMCID: PMC10948343 DOI: 10.3164/jcbn.23-26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 07/12/2023] [Indexed: 03/22/2024] Open
Abstract
Coronavirus disease 2019 (COVID-19) vaccines are highly effective; however, vaccine-related adverse events, including autoimmunity, have been reported. Case reports describing relapse or new-onset of ulcerative colitis (UC) after COVID-19 mRNA vaccination are available. However, the molecular mechanisms underlying the development of colonic inflammation associated with COVID-19 mRNA vaccination are poorly understood. Furthermore, it is unclear whether the relapse of UC after COVID-19 vaccination is driven by unique cytokine responses that differ from those of UC not associated with vaccination. mRNAs derived from COVID-19 vaccines are potent inducers of type I IFN response. We encountered three cases of UC relapse after COVID-19 vaccination. mRNA expressions of IFN-α, IFN-β, IL-1β, and IL-12/23p40 showed higher tendency in the colonic mucosa of patients with UC associated with vaccination compared with those not associated with vaccination. In contrast, the expressions of C-X-C motif chemokine ligand 9 (CXCL9) and CXCL10 were comparable. Immunofluorescence analyses also showed higher expression of IFN-α in the colonic mucosa of patients with UC associated with COVID-19 vaccination than in those not associated with vaccination. Taken together, these data suggest that the colonic mucosa of patients with UC who relapsed after COVID-19 vaccination was characterized by enhanced type I IFN responses.
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Affiliation(s)
- Yasuhiro Masuta
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Kosuke Minaga
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Yasuo Otsuka
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Natsuki Okai
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Akane Hara
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Sho Masaki
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Tomoyuki Nagai
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Hajime Honjo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
| | - Tomohiro Watanabe
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
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Chen Z, Wang Y, He T, Li H, Ao L, Pan Q, Zhou Y, Zhu Q, Xiang D, Zhang G, Ling N, Chen M, Hu P, Peng M, Cai D, Zhang D, Ren H. Safety and Immunogenicity After Primary and Booster Inactivated SARS-Cov-2 Vaccination in Patients with Autoimmune Liver Diseases. J Clin Transl Hepatol 2024; 12:162-171. [PMID: 38343613 PMCID: PMC10851071 DOI: 10.14218/jcth.2023.00049] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 08/11/2023] [Accepted: 08/29/2023] [Indexed: 01/05/2025] Open
Abstract
BACKGROUND AND AIMS SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports. However, the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases (AILD) is still unknown. METHODS Eighty-four patients with AILD were prospectively followed up after the second dose (primary) of inactivated SARS-CoV-2 vaccine. Some of them received the third dose (booster) of inactivated vaccine. Adverse events (AEs), autoimmune activation, and liver inflammation exacerbation after primary and booster vaccination were recorded. Meanwhile, dynamics of antireceptor-binding-domain IgG (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD-specific B cells responses were evaluated. RESULTS The overall AEs in AILD patients after primary and booster vaccination were 26.2% and 13.3%, respectively. The decrease of C3 level and increase of immunoglobulin light chain κ and λ levels were observed in AILD patients after primary vaccination, however, liver inflammation was not exacerbated, even after booster vaccination. Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination. Notably, the antibody titers were significantly elevated after booster vaccination (10-fold in anti-RBD-IgG and 7.4-fold in NAbs, respectively), which was as high as in healthy controls. Unfortunately, the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants. Changes of atypical memory B cells were inversely related to antibody levels, which indicate that the impaired immune memory was partially restored partly by the booster vaccination. CONCLUSIONS The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants.
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Affiliation(s)
- Zhiwei Chen
- Department of Infectious Diseases, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yuting Wang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Taiyu He
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hu Li
- Department of Infectious Diseases, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ling Ao
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qingbo Pan
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yingzhi Zhou
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qian Zhu
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dejuan Xiang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Gaoli Zhang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ning Ling
- Department of Infectious Diseases, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Min Chen
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Peng Hu
- Department of Infectious Diseases, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Mingli Peng
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dachuan Cai
- Department of Infectious Diseases, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dazhi Zhang
- Department of Infectious Diseases, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hong Ren
- Department of Infectious Diseases, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Wu HY, Su TH, Liu CJ, Yang HC, Tsai JH, Wei MH, Chen CC, Tung CC, Kao JH, Chen PJ. Hepatitis B reactivation: A possible cause of coronavirus disease 2019 vaccine induced hepatitis. J Formos Med Assoc 2024; 123:88-97. [PMID: 37349170 PMCID: PMC10281508 DOI: 10.1016/j.jfma.2023.06.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 05/08/2023] [Accepted: 06/08/2023] [Indexed: 06/24/2023] Open
Abstract
BACKGROUND AND AIMS Coronavirus disease 2019 (COVID-19) vaccines were rapidly implemented globally and vaccine-associated immune-related hepatitis was recently reported. We aim to investigate its impact in regions endemic of chronic hepatitis B (CHB). METHODS We retrospectively collected patients who developed hepatitis within 90 days after COVID-19 vaccination in Taiwan. The mechanisms of hepatitis included vaccine induced liver injury (VILI) and immune-related hepatitis, which are direct liver injuries defined as aspartate or alanine aminotransferase (AST or ALT) increased ≥ 5-fold upper limit of normal (ULN) and/or AST or ALT ≥ 3-fold of ULN with concurrent total bilirubin ≥ 2-fold of ULN. Indirect liver injury due to HBV reactivation was defined as HBsAg reverse seroconversion or significant rise in HBV DNA level. The demographics, clinical data, and course of hepatitis were compared statistically. RESULTS Twenty-five patients were included with a median age of 54. The culprit vaccines were ChAdOx1 nCoV-19 (n = 9), mRNA-1273 (n = 12), and BNT162b2 (n = 4). The characteristics of hepatitis were comparable regardless of vaccine subtypes. The median onset of hepatitis was 25 days post vaccination, with a peak of 10-fold ALT-increase. The etiologies included HBV reactivation (n = 10), VILI (n = 10), and immune-related hepatitis (n = 5). HBV reactivation accounts for 90% of vaccine-induced hepatitis in patients of CHB (n = 10), and two patients died. Patients with initial AST levels >500 U/L increased 27-fold risks of liver injury greater than moderate severity compared with those without. CONCLUSION COVID-19 vaccine induced hepatitis is a clinical significant complication, and HBV reactivation may account for a possible mechanism.
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Affiliation(s)
- Hsin-Yun Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Huei Tsai
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Han Wei
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, BioMedical Park Hospital, HsinChu, Taiwan
| | - Chieh-Chang Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Chih Tung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
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Xie X, Zhong L, Gan X, Liu Y, Zhu Y, Chen B, Yu H. Autoimmune hepatitis collapsed after the COVID-19 vaccination. Clin Res Hepatol Gastroenterol 2023; 47:102226. [PMID: 37844776 DOI: 10.1016/j.clinre.2023.102226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 10/11/2023] [Accepted: 10/12/2023] [Indexed: 10/18/2023]
Affiliation(s)
- XiaoYue Xie
- Department of Gastroenterology, The Second Affifiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, China
| | - Li Zhong
- Department of Gastroenterology, The Second Affifiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, China
| | - XiaYu Gan
- Department of Gastroenterology, The Second Affifiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, China
| | - Yi Liu
- Department of Gastroenterology, The Second Affifiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, China
| | - YuLan Zhu
- Department of Gastroenterology, The Second Affifiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, China
| | - BoShi Chen
- Department of Gastroenterology, The Second Affifiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, China
| | - HuiHong Yu
- Department of Gastroenterology, The Second Affifiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, China.
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Liu Y, Lu J, Zhan H, Yuan W, Li X, Kang H, Li H, Chen Y, Cheng L, Sun X, Zheng H, Wang W, Dai E, Li Y. Inactivated SARS-CoV-2 booster vaccine enhanced immune responses in patients with chronic liver diseases. Virol Sin 2023; 38:723-734. [PMID: 37487943 PMCID: PMC10590695 DOI: 10.1016/j.virs.2023.07.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/26/2023] Open
Abstract
Chronic liver disease (CLD) entails elevated risk of COVID-19 severity and mortality. The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear. Therefore, we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls (HC) to analyze neutralizing antibodies (NAbs) against SARS-CoV-2 prototype and BA.4/5 variant, anti-receptor binding domain (RBD) IgG, and total anti-SARS-CoV-2 antibodies. Serum levels of the total anti-SARS-CoV-2 antibodies, anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose, but were relatively lower than those of HCs. Induced humoral responses decreased over time after booster vaccination. The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold. All four SARS-CoV-2 antibodies, including total anti-SARS-CoV-2 antibodies, anti-RBD IgG and NAbs against prototype and BA.4/5, were lower in patients with severe CLD than those with non-severe CLD. After booster shot, age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients. Additionally, white blood cell counts and hepatitis B core antibodies were the protective factors, and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies. Overall, our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines. All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak. CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5, which hindered the protective effect of the booster shot against Omicron prevalence. Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.
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Affiliation(s)
- Yongmei Liu
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Jianhua Lu
- Department of Clinical Laboratory, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, 050021, China
| | - Haoting Zhan
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Wenfang Yuan
- Division of Liver Diseases, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, 050021, China
| | - Xiaomeng Li
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China; Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100035, China
| | - Haiyan Kang
- Division of Liver Diseases, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, 050021, China
| | - Haolong Li
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Yongliang Chen
- Division of Liver Diseases, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, 050021, China
| | - Linlin Cheng
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xingli Sun
- Division of Liver Diseases, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, 050021, China
| | - Haojie Zheng
- Division of Liver Diseases, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, 050021, China
| | - Wei Wang
- Division of Liver Diseases, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, 050021, China
| | - Erhei Dai
- Division of Liver Diseases, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, 050021, China.
| | - Yongzhe Li
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
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9
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Kondo R, Iwakiri Y, Kage M, Yano H. Endotheliopathy of liver sinusoidal endothelial cells in liver disease. Pathol Int 2023; 73:381-393. [PMID: 37589433 DOI: 10.1111/pin.13361] [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: 07/21/2023] [Accepted: 07/27/2023] [Indexed: 08/18/2023]
Abstract
Liver is the largest solid organ in the abdominal cavity, with sinusoid occupying about half of its volume. Under liver disease, hemodynamics in the liver tissue dynamically change, resulting in injury to liver sinusoidal endothelial cells (LSECs). We discuss the injury of LSECs in liver diseases in this article. Generally, in noninflamed tissues, vascular endothelial cells maintain quiescence of circulating leukocytes, and unnecessary blood clotting is inhibited by multiple antithrombotic factors produced by the endothelial cells. In the setting of inflammation, injured endothelial cells lose these functions, defined as inflammatory endotheliopathy. In chronic hepatitis C, inflammatory endotheliopathy in LSECs contributes to platelet accumulation in the liver tissue, and the improvement of thrombocytopenia by splenectomy is attenuated in cases with severe hepatic inflammation. In COVID-19, LSEC endotheliopathy induced by interleukin (IL)-6 trans-signaling promotes neutrophil accumulation and platelet microthrombosis in the liver sinusoids, resulting in liver injury. IL-6 trans-signaling promotes the expression of intercellular adhesion molecule-1, chemokine (C-X-C motif) ligand (CXCL1), and CXCL2, which are the neutrophil chemotactic mediators, and P-selectin, E-selectin, and von Willebrand factor, which are involved in platelet adhesion to endothelial cells, in LSECs. Restoring LSECs function is important for ameliorating liver injury. Prevention of endotheliopathy is a potential therapeutic strategy in liver disease.
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Affiliation(s)
- Reiichiro Kondo
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Yasuko Iwakiri
- Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Masayoshi Kage
- Department of Medical Engineering, Junshin Gakuen University, Fukuoka, Japan
| | - Hirohisa Yano
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
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10
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Aghamohamadi N, Shahba F, Zarezadeh Mehrabadi A, Khorramdelazad H, Karimi M, Falak R, Emameh RZ. Age-dependent immune responses in COVID-19-mediated liver injury: focus on cytokines. Front Endocrinol (Lausanne) 2023; 14:1139692. [PMID: 37654571 PMCID: PMC10465349 DOI: 10.3389/fendo.2023.1139692] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 07/21/2023] [Indexed: 09/02/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is potentially pathogenic and causes severe symptoms; in addition to respiratory syndromes, patients might experience other severe conditions such as digestive complications and liver complications injury. The abnormality in the liver is manifested by hepatobiliary dysfunction and enzymatic elevation, which is associated with morbidity and mortality. The direct cytopathic effect, immune dysfunction, cytokine storm, and adverse effects of therapeutic regimens have a crucial role in the severity of liver injury. According to aging and immune system alterations, cytokine patterns may also change in the elderly. Moreover, hyperproduction of cytokines in the inflammatory response to SARS-CoV-2 can lead to multi-organ dysfunction. The mortality rate in elderly patients, particularly those with other comorbidities, is also higher than in adults. Although the pathogenic effect of SARS-CoV-2 on the liver has been widely studied, the impact of age and immune-mediated responses at different ages remain unclear. This review discusses the association between immune system responses in coronavirus disease 2019 (COVID-19) patients of different ages and liver injury, focusing on cytokine alterations.
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Affiliation(s)
- Nazanin Aghamohamadi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Faezeh Shahba
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Zarezadeh Mehrabadi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Khorramdelazad
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Milad Karimi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Falak
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Reza Zolfaghari Emameh
- Department of Energy and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
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11
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Dass L, Pacia AMM, Hamidi M. Acute hepatitis of unknown etiology in an adult female: A case report. World J Clin Cases 2023; 11:5282-5289. [DOI: 10.12998/wjcc.v11.i22.5282] [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: 04/04/2023] [Revised: 06/07/2023] [Accepted: 06/30/2023] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND Acute liver injury (ALI) refers to inflammation of the hepatic parenchyma without hepatic encephalopathy that lasts less than 6 mo. When the etiology is unknown, Acute Hepatitis of Unknown Origin (AHUO) can present as a diagnostic and treatment challenge. AHUO in the adult population is unusual and poorly documented. It has an incidence between 11% and 75%. Currently, no treatment guidelines exist. With no identified cause, treatment is often blind, and the wrong treatment plan may have unintended consequences.
CASE SUMMARY We present the case of a 58-year-old woman who presented to the emergency room for elevated liver function tests (LFTs). Her symptoms started 10 d prior to admission and included nausea, vomiting, jaundice, decreased appetite, weight loss of 10 lbs, and dark urine. She denied drinking alcohol or taking any hepatotoxic agents, including acetaminophen, statins, vitamins, or supplements. She was admitted to the hospital, and an etiologic work-up was carried out. Her initial bloodwork revealed elevated liver enzymes (alanine aminotransferase 2500 U/L, aspartate aminotransferase 3159 U/L, and alkaline phosphatase 714 U/L) and elevated total bilirubin of 6.4 mg/dL. She tested negative for common infectious etiologies such as hepatotropic viruses A, B, C, and E. Further infective work-up revealed negative serology for cytomegalovirus, Epstein-Barr virus, herpes simplex virus 1 & 2, and human immunodeficiency virus. Her autoantibody test results were negative, including anti-smooth muscle antibody, anti-mitochondrial antibody, and anti-liver kidney microsome 1 antibody. Magnetic resonance cholangiopancreatography ruled out biliary causes of elevated LFTs, and her core liver biopsy proved inconclusive. Over the course of her hospital stay, the patient's LFTs improved with supportive care and without steroids.
CONCLUSION Idiopathic hepatitis makes treatment challenging. It can leave patients feeling confused and unfulfilled. Thus, educating the patient thoroughly for shared decision-making and management becomes essential.
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Affiliation(s)
- Lucinda Dass
- Department of Clinical Studies, St. George's University, True Blue 00000, Grenada
| | | | - Mahgol Hamidi
- Department of Clinical Studies, St. George's University, True Blue 00000, Grenada
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12
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Dass L, Pacia AMM, Hamidi M. Acute hepatitis of unknown etiology in an adult female: A case report. World J Clin Cases 2023; 11:5288-5295. [PMID: 37621598 PMCID: PMC10445075 DOI: 10.12998/wjcc.v11.i22.5288] [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: 04/04/2023] [Revised: 06/07/2023] [Accepted: 06/30/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Acute liver injury (ALI) refers to inflammation of the hepatic parenchyma without hepatic encephalopathy that lasts less than 6 mo. When the etiology is unknown, Acute Hepatitis of Unknown Origin (AHUO) can present as a diagnostic and treatment challenge. AHUO in the adult population is unusual and poorly documented. It has an incidence between 11% and 75%. Currently, no treatment guidelines exist. With no identified cause, treatment is often blind, and the wrong treatment plan may have unintended consequences. CASE SUMMARY We present the case of a 58-year-old woman who presented to the emergency room for elevated liver function tests (LFTs). Her symptoms started 10 d prior to admission and included nausea, vomiting, jaundice, decreased appetite, weight loss of 10 lbs, and dark urine. She denied drinking alcohol or taking any hepatotoxic agents, including acetaminophen, statins, vitamins, or supplements. She was admitted to the hospital, and an etiologic work-up was carried out. Her initial bloodwork revealed elevated liver enzymes (alanine aminotransferase 2500 U/L, aspartate aminotransferase 3159 U/L, and alkaline phosphatase 714 U/L) and elevated total bilirubin of 6.4 mg/dL. She tested negative for common infectious etiologies such as hepatotropic viruses A, B, C, and E. Further infective work-up revealed negative serology for cytomegalovirus, Epstein-Barr virus, herpes simplex virus 1 & 2, and human immunodeficiency virus. Her autoantibody test results were negative, including anti-smooth muscle antibody, anti-mitochondrial antibody, and anti-liver kidney microsome 1 antibody. Magnetic resonance cholangiopancreatography ruled out biliary causes of elevated LFTs, and her core liver biopsy proved inconclusive. Over the course of her hospital stay, the patient's LFTs improved with supportive care and without steroids. CONCLUSION Idiopathic hepatitis makes treatment challenging. It can leave patients feeling confused and unfulfilled. Thus, educating the patient thoroughly for shared decision-making and management becomes essential.
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Affiliation(s)
- Lucinda Dass
- Department of Clinical Studies, St. George's University, True Blue 00000, Grenada
| | | | - Mahgol Hamidi
- Department of Clinical Studies, St. George's University, True Blue 00000, Grenada
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13
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Cheung CKM, Law KWT, Law AWH, Law MF, Ho R, Wong SH. Efficacy of Vaccine Protection Against COVID-19 Virus Infection in Patients with Chronic Liver Diseases. J Clin Transl Hepatol 2023; 11:718-735. [PMID: 36969905 PMCID: PMC10037513 DOI: 10.14218/jcth.2022.00339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 10/22/2022] [Accepted: 11/14/2022] [Indexed: 01/19/2023] Open
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a useful weapon to combat the virus. Patients with chronic liver diseases (CLDs), including compensated or decompensated liver cirrhosis and noncirrhotic diseases, have a decreased immunologic response to coronavirus disease 2019 vaccines. At the same time, they have increased mortality if infected. Current data show a reduction in mortality when patients with chronic liver diseases are vaccinated. A suboptimal vaccine response has been observed in liver transplant recipients, especially those receiving immunosuppressive therapy, so an early booster dose is recommended to achieve a better protective effect. Currently, there are no clinical data comparing the protective efficacy of different vaccines in patients with chronic liver diseases. Patient preference, availability of the vaccine in the country or area, and adverse effect profiles are factors to consider when choosing a vaccine. There have been reports of immune-mediated hepatitis after coronavirus disease 2019 vaccination, and clinicians should be aware of that potential side effect. Most patients who developed hepatitis after vaccination responded well to treatment with prednisolone, but an alternative type of vaccine should be considered for subsequent booster doses. Further prospective studies are required to investigate the duration of immunity and protection against different viral variants in patients with chronic liver diseases or liver transplant recipients, as well as the effect of heterologous vaccination.
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Affiliation(s)
- Carmen Ka Man Cheung
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China
| | | | | | - Man Fai Law
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China
| | - Rita Ho
- Department of Medicine, North District Hospital, Hong Kong, China
| | - Sunny Hei Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
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14
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Wang M, Qi J, Liu Y. Autoimmune hepatitis following COVID-19 vaccination: Clinical characteristics of 35 reported cases. Drug Discov Ther 2023:2023.01022. [PMID: 37331808 DOI: 10.5582/ddt.2023.01022] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/20/2023]
Abstract
The coronavirus disease 2019 (COVID-19) vaccines have been shown to be effective in protecting people from severe disease progression, hospitalisation and death. However, a wide range of side effects have been reported worldwide. New onset or flare-up of autoimmune hepatitis (AIH) is an extremely rare adverse event following COVID-19 vaccination, with the majority of cases presenting with mild symptoms. Unfortunately, there have been cases of fatal complications. In this mini-review, we have summarised the clinical characteristics of a total of 35 currently reported cases of AIH after COVID-19 vaccination and suggest that patients with autoimmune diseases may be at higher risk of developing AIH after vaccination.
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Affiliation(s)
| | - Juan Qi
- Qingdao Municipal Hospital, Qingdao, China
| | - Yujuan Liu
- Qingdao Women and Children's Hospital, Qingdao, China
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15
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Zhou H, Ye Q. Clinical Features of COVID-19 Vaccine-Associated Autoimmune Hepatitis: A Systematic Review. Diseases 2023; 11:80. [PMID: 37366868 DOI: 10.3390/diseases11020080] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 05/17/2023] [Accepted: 05/24/2023] [Indexed: 06/28/2023] Open
Abstract
Autoimmune hepatitis (AIH) is an inflammatory liver disease wherein the body's immune system instigates an attack on the liver, causing inflammation and hepatic impairment. This disease usually manifests in genetically predisposed individuals and is triggered by stimuli or environments such as viral infections, environmental toxins, and drugs. The causal role of COVID-19 vaccination in AIH remains uncertain. This review of 39 cases of vaccine-related AIH indicates that female patients above the age of 50 years or those with potential AIH risk factors may be susceptible to vaccine-related AIH, and the clinical features of vaccine-associated AIH are similar to those of idiopathic AIH. These features commonly manifest in patients after the first dose of vaccination, with symptom onset typically delayed by 10-14 days. The incidence of underlying liver disease in patients with potential health conditions associated to liver disease is similar to that of patients without preexisting illnesses. Steroid administration is effective in treating vaccine-related AIH-susceptible patients, with most patients experiencing improvement in their clinical symptoms. However, care should be taken to prevent bacterial infections during drug administration. Furthermore, the possible pathogenic mechanisms of vaccine-associated AIH are discussed to offer potential ideas for vaccine development and enhancement. Although the incidence of vaccine-related AIH is rare, individuals should not be deterred from receiving the COVID-19 vaccine, as the benefits of vaccination significantly outweigh the risks.
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Affiliation(s)
- Hao Zhou
- Department of Laboratory Medicine, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310000, China
| | - Qing Ye
- Department of Laboratory Medicine, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310000, China
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16
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Czaja AJ. Incorporating the Molecular Mimicry of Environmental Antigens into the Causality of Autoimmune Hepatitis. Dig Dis Sci 2023:10.1007/s10620-023-07967-5. [PMID: 37160542 PMCID: PMC10169207 DOI: 10.1007/s10620-023-07967-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 05/01/2023] [Indexed: 05/11/2023]
Abstract
Molecular mimicry between foreign and self-antigens has been implicated as a cause of autoimmune hepatitis in experimental models and cross-reacting antibodies in patients. This review describes the experimental and clinical evidence for molecular mimicry as a cause of autoimmune hepatitis, indicates the limitations and uncertainties of this premise, and encourages investigations that assess diverse environmental antigens as sources of disease-relevant molecular mimics. Pertinent articles were identified in PubMed using multiple search phrases. Several pathogens have linear or conformational epitopes that mimic the self-antigens of autoimmune hepatitis. The occurrence of an acute immune-mediated hepatitis after vaccination for severe acute respiratory syndrome (SARS)-associated coronavirus 2 (SARS-CoV-2) has suggested that vaccine-induced peptides may mimic disease-relevant tissue antigens. The intestinal microbiome is an under-evaluated source of gut-derived antigens that could also engage in molecular mimicry. Chaperone molecules may enhance the pathogenicity of molecular mimics, and they warrant investigation. Molecular mimics of immune dominant epitopes within cytochrome P450 IID6, the autoantigen most closely associated with autoimmune hepatitis, should be sought in diverse environmental antigens and assessed for pathogenicity. Avoidance strategies, dietary adjustments, vaccine improvement, and targeted manipulation of the intestinal microbiota may emerge as therapeutic possibilities. In conclusion, molecular mimicry may be a missing causality of autoimmune hepatitis. Molecular mimics of key immune dominant epitopes of disease-specific antigens must be sought in diverse environmental antigens. The ubiquity of molecular mimicry compels rigorous assessments of peptide mimics for immunogenicity and pathogenicity in experimental models. Molecular mimicry may complement epigenetic modifications as causative mechanisms of autoimmune hepatitis.
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Affiliation(s)
- Albert J Czaja
- Professor Emeritus of Medicine, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN, 55905, USA.
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17
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Guo M, Liu X, Chen X, Li Q. Insights into new-onset autoimmune diseases after COVID-19 vaccination. Autoimmun Rev 2023; 22:103340. [PMID: 37075917 PMCID: PMC10108562 DOI: 10.1016/j.autrev.2023.103340] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 04/13/2023] [Indexed: 04/21/2023]
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in more than 670 million infections and almost 7 million deaths globally. The emergence of numerous SARS-CoV-2 has heightened public concern regarding the future course of the epidemic. Currently, the SARS-CoV-2 Omicron variant has rapidly become globally dominant in the COVID-19 pandemic due to its high infectivity and immune evasion. Consequently, vaccination implementation is critically significant. However, growing evidence suggests that COVID-19 vaccination may cause new-onset autoimmune diseases, including autoimmune glomerulonephritis, autoimmune rheumatic diseases, and autoimmune hepatitis. Nevertheless, the causal relationship between COVID-19 vaccines and these autoimmune diseases remains to be demonstrated. In this review, we provide evidence that vaccination induces autoimmunity and summarize possible mechanisms of action, such as molecular mimicry, activation by bystanders, and adjuvants. Our objective is not to refute the importance of vaccines, but to raise awareness about the potential risks of COVID-19 vaccination. In fact, we believe that the benefits of vaccination far outweigh the possible risks and encourage people to get vaccinated.
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Affiliation(s)
- Ming Guo
- Hebei General Hosptial, Shijiazhuang, China; Hebei Medical University, Shijiazhuang, China
| | - Xiaoxiao Liu
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China
| | - Xiangmei Chen
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China
| | - Qinggang Li
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China.
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18
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Ueno M, Takabatake H, Itakura J, Fujita R, Kayahara T, Morimoto Y, Notohara K, Mizuno M. Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review. Clin J Gastroenterol 2023:10.1007/s12328-023-01794-x. [PMID: 37029249 PMCID: PMC10081821 DOI: 10.1007/s12328-023-01794-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 03/27/2023] [Indexed: 04/09/2023]
Abstract
Several vaccines have been developed for coronavirus disease 2019 (COVID-19) and are used worldwide. Here we report a case of severe acute hepatitis induced by COVID-19 vaccination. A 54-year-old woman received two doses of the Pfizer-BioNTech COVID-19 mRNA vaccine and an additional dose of the Moderna COVID-19 mRNA vaccine. Seven days after the third dose, she noticed fatigue, appetite loss and dark urine. Laboratory tests were consistent with severe liver injury and jaundice. Anti-smooth muscle antibody and HLA-DR4 were positive; thus, we suspected that she had autoimmune hepatitis (AIH). Intravenous methylprednisolone followed by oral prednisolone were administered. Because remission was not achieved, we performed percutaneous liver biopsy. Histologically, pan-lobular inflammation with moderate infiltration of lymphocytes and macrophages, interface hepatitis, and rosette formation were present. We regarded these findings as confirmation of the diagnosis of AIH. As she had not responded to corticosteroids, we added azathioprine. Liver biochemistry tests gradually improved, and prednisolone could be tapered without relapse of AIH. Dozens of cases of AIH after COVID-19 vaccination have been reported. Corticosteroids were effective in most cases, but some patients have died from liver failure after vaccination. This case illustrates the efficacy of azathioprine for steroid-refractory AIH induced by COVID-19 vaccination.
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Affiliation(s)
- Masayuki Ueno
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan.
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
| | - Hiroyuki Takabatake
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan
| | - Junya Itakura
- Department of Anatomic Pathology, Kurashiki Central Hospital, Okayama, Japan
| | - Rio Fujita
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Takahisa Kayahara
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan
| | - Youichi Morimoto
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Okayama, Japan
| | - Motowo Mizuno
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan
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19
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Sgamato C, Rocco A, Compare D, Minieri S, Marchitto SA, Maurea S, Nardone G. Autoimmune liver diseases and SARS-CoV-2. World J Gastroenterol 2023; 29:1838-1851. [PMID: 37032727 PMCID: PMC10080695 DOI: 10.3748/wjg.v29.i12.1838] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 01/12/2023] [Accepted: 03/14/2023] [Indexed: 03/28/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry. Here we summarise the current knowledge about auto-immune liver diseases (AILDs) and SARS-CoV-2, focusing on: (1) The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs; (2) the role of SARS-CoV-2 in inducing liver damage and triggering AILDs; and (3) the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver. Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine. Although SARS-CoV-2 infection can lead to the development of several autoimmune diseases, few reports correlate it to the appearance of de novo manifestation of immune-mediated liver diseases such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) or AIH/PBC overlap syndrome. Different case series of an AIH-like syndrome with a good prognosis after SARS-CoV-2 vaccination have been described. Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established, these reports suggest that this association could be more than coincidental.
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Affiliation(s)
- Costantino Sgamato
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Alba Rocco
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Debora Compare
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Stefano Minieri
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Stefano Andrea Marchitto
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
| | - Simone Maurea
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples 80131, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy
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20
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Schinas G, Polyzou E, Dimakopoulou V, Tsoupra S, Gogos C, Akinosoglou K. Immune-mediated liver injury following COVID-19 vaccination. World J Virol 2023; 12:100-108. [PMID: 37033146 PMCID: PMC10075055 DOI: 10.5501/wjv.v12.i2.100] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/23/2022] [Accepted: 01/23/2023] [Indexed: 03/21/2023] Open
Abstract
Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019 (COVID-19) vaccination protocols. All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations, e.g., BNT162b2, mRNA-1273, and ChAdOx1-S, can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration. Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination. The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies. Novel vaccine delivery platforms, e.g., mRNA-containing lipid nanoparticles and adenoviral vectors, contribute to the inflammatory background that leads to an exaggerated immune response, while patterns of molecular mimicry between the spike (S) protein and prominent liver antigens may account for the autoimmune presentation. Immune mediators triggered by vaccination or vaccine ingredients per se, including autoreactive antibodies, cytokines, and cytotoxic T-cell populations, may inflict hepatocellular damage through well-established pathways. We aim to review available data associated with immune-mediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.
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Affiliation(s)
- Georgios Schinas
- Department of Medicine, University of Patras, Patras 26504, Greece
| | - Eleni Polyzou
- Department of Internal Medicine, University of Patras, Patras 26504, Greece
| | | | - Stamatia Tsoupra
- Department of Internal Medicine, University of Patras, Patras 26504, Greece
| | - Charalambos Gogos
- Department of Internal Medicine, University of Patras, Patras 26504, Greece
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21
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COVID-19 Vaccine Booster Hesitancy in Malaysia: A Web-Based Cross-Sectional Study. Vaccines (Basel) 2023; 11:vaccines11030638. [PMID: 36992222 DOI: 10.3390/vaccines11030638] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 03/06/2023] [Accepted: 03/08/2023] [Indexed: 03/18/2023] Open
Abstract
Vaccination is a key public health strategy that is known to be effective in mitigating the risk of infection and severe disease. However, in the context of the COVID-19 pandemic, the percentage (<50%) of Malaysians who have received a booster for the COVID-19 vaccine has remained stagnant over a year. This study aimed to determine the prevalence of and the factors associated with hesitancy toward the second dose of booster for the COVID-19 vaccine. A web-based cross-sectional study was conducted from August to November 2022. The Oxford Vaccine Hesitancy Scale was used to assess the hesitancy toward the second dose of booster for the COVID-19 vaccine. Simple and multiple factors logistic regressions were used to determine the predictors of hesitancy. A p-value less than 0.05 was considered to be statistically significant. Data from 798 respondents were included in the analysis. The prevalence of hesitancy toward the second booster of the COVID-19 vaccine was 26.7%. The predictors of second-booster hesitancy were older age (AOR = 1.040, 95 CI = 1.022, 1.058), having received the third dose (first booster) because of instruction by the government (AOR = 2.125, 95% CI = 1.380, 3.274), concern about serious long term side effects of the vaccine (AOR = 4.010, 95% CI = 2.218, 7.250), and opinions of close friends and immediate family members that the booster is harmful (AOR = 2.201, 95% CI = 1.280, 3.785). Conversely, factors that appear to reduce vaccine booster hesitancy were acceptance of the third dose due to the high number of cases and the increasing rate of infection (AOR = 0.548, 95% CI = 0.317, 0.947), the belief that the vaccine will decrease the risk of getting the infection (AOR = 0.491, 95% CI = 0.277, 0.870), and opinions of close friends and immediate family members that the booster is helpful (AOR = 0.479, 95% CI = 0.273, 0.840). In conclusion, more than one-fifth of Malaysians were hesitant to take the second booster of the COVID-19 vaccine. This suggests that appropriate steps that increase vaccine acceptance, taking into consideration the findings of the present study, are needed to address this issue and to foster more positive attitudes toward vaccination. The survey was available in three main languages but limited to people with internet access; hence, it would likely be biased toward younger adults and social media users and exclude those with limited or no internet access, in particular older people. Therefore, the results are not representative of the Malaysian population at large and caution should be exercised when interpreting the findings.
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22
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Efficacy, Safety and Immunogenicity of Anti-SARS-CoV-2 Vaccines in Patients with Cirrhosis: A Narrative Review. Vaccines (Basel) 2023; 11:vaccines11020452. [PMID: 36851329 PMCID: PMC9966438 DOI: 10.3390/vaccines11020452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 02/08/2023] [Accepted: 02/13/2023] [Indexed: 02/18/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19), has led to a pandemic with more than 6.5 million deaths worldwide. Patients with liver cirrhosis (PWLC) are regarded as prone to severe COVID-19. Vaccination against SARS-CoV-2 has been proven to be the most effective measure against COVID-19 and a variety of different vaccines have been approved for use; namely mRNA and vector-based, inactivated, whole virion, and protein subunit vaccines. Unfortunately, only a small number of PWLC were included in phase I-III vaccine trials, raising concerns regarding their efficacy and safety in this population. The authors, in this review, present available data regarding safety and efficacy of anti-SARS-CoV-2 vaccination in PWLC and discuss post-vaccination antibody responses. Overall, all vaccines seem to be extremely safe, with only a few and insignificant adverse events, and efficient, leading to lower rates of hospitalization and COVID-19-related mortality. T- and B-cell responses, on the other hand, remain an enigma, especially in patients with decompensated disease, since these patients show lower titers of anti-SARS-CoV-2 antibodies in some studies, with a more rapid waning. However, this finding is not consistent, and its clinical impact is still undetermined.
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Abstract
SARS-CoV-2 is the viral agent of COVID-19, a pandemic that surfaced in 2019. Although predominantly a respiratory ailment, patients with COVID-19 can have gastrointestinal (GI) and hepatobiliary manifestations. These manifestations are often mild and transient, but they can be severe and consequential. In the GI tract, ischemic enterocolitis is the most common and significant consequence of COVID-19. In the liver, the reported pathologic findings may often be related to consequences of severe systemic viral infection, but reports of hepatitis presumed to be due to SARS-CoV-2 suggest that direct viral infection of the liver may be a rare complication of COVID-19. In both the GI tract and liver, lingering symptoms of GI or hepatic injury after resolution of pulmonary infection may be part of the evolving spectrum of long COVID.
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Affiliation(s)
- Angela R Shih
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
| | - Joseph Misdraji
- Department of Pathology, Yale New Haven Hospital, Yale University, New Haven, CT, 06510, USA.
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24
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Ozaka S, Kobayashi T, Mizukami K, Murakami K. COVID-19 vaccination and liver disease. World J Gastroenterol 2022; 28:6791-6810. [PMID: 36632314 PMCID: PMC9827578 DOI: 10.3748/wjg.v28.i48.6791] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 11/07/2022] [Accepted: 12/06/2022] [Indexed: 12/26/2022] Open
Abstract
Various vaccines against severe acute respiratory syndrome coronavirus 2 have been developed in response to the coronavirus disease 2019 (COVID-19) global pandemic, several of which are highly effective in preventing COVID-19 in the general population. Patients with chronic liver diseases (CLDs), particularly those with liver cirrhosis, are considered to be at a high risk for severe COVID-19 and death. Given the increased rates of disease severity and mortality in patients with liver disease, there is an urgent need to understand the efficacy of vaccination in this population. However, the data regarding efficacy and safety of COVID-19 vaccination in patients with CLDs is limited. Indeed, several organ-specific or systemic immune-mediated side effects following COVID-19 vaccination, including liver injury similar to autoimmune hepatitis, have been recently reported. Although the number of cases of vaccine-related liver injury is increasing, its frequency, clinical course, and mechanism remain unclear. Here, we review the current findings on COVID-19 vaccination and liver disease, focusing on: (1) The impact of COVID-19 in patients with CLD; (2) The efficacy, safety, and risk-benefit profiles of COVID-19 vaccines in patients with CLD; and (3) Liver injury following COVID-19 vaccination.
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Affiliation(s)
- Sotaro Ozaka
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan
| | - Takashi Kobayashi
- Department of Infectious Disease Control, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan
| | - Kazuhiro Mizukami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan
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25
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De Novo Autoimmune Hepatitis after COVID-19 Infection in an Unvaccinated Patient. Case Reports Hepatol 2022; 2022:8409269. [PMID: 36590671 PMCID: PMC9800079 DOI: 10.1155/2022/8409269] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 10/03/2022] [Accepted: 11/12/2022] [Indexed: 12/24/2022] Open
Abstract
Liver test abnormalities have been described during severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection causing coronavirus disease 2019. Most of them consist of elevation of the aminotransferases that resolve once the infection subsides. There are several reports of autoimmune hepatitis developing after vaccination against COVID-19 and one case of autoimmune hepatitis following COVID-19 infection. We present a patient that was not vaccinated against COVID-19 and developed resistant de novo autoimmune hepatitis following COVID-19 infection requiring aggressive immunosuppression.
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Vaccine-Related Autoimmune Hepatitis: Emerging Association with SARS-CoV-2 Vaccination or Coincidence? Vaccines (Basel) 2022; 10:vaccines10122073. [PMID: 36560483 PMCID: PMC9783100 DOI: 10.3390/vaccines10122073] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 11/30/2022] [Accepted: 12/01/2022] [Indexed: 12/09/2022] Open
Abstract
BACKGROUND There is an increasing number of liver injury cases resembling autoimmune hepatitis (AIH) following SARS-CoV-2 vaccination; however, an association has not yet been established. METHODS/MATERIALS A literature review was performed to identify articles regarding the association of AIH with vaccination, emphasizing on SARS-CoV-2 vaccines, and the proposed mechanisms. We then performed a literature search for AIH-like cases following SARS-CoV-2 vaccination, and we evaluated the included cases for AIH diagnosis using simplified diagnostic criteria (SDC), and for vaccination causality using the Naranjo score for adverse drug reactions. RESULTS We identified 51 AIH-like cases following SARS-CoV-2 vaccination. Forty cases (80%) were characterized as "probable", "at least probable", or "definite" for AIH diagnosis according to SDC. Forty cases (78.4%) were characterized as "probable", four (7.8%) as "possible", and three (5.8%) as "definite" for vaccine-related AIH according to the Naranjo score. CONCLUSION SARS-CoV-2 vaccine-related AIH carries several phenotypes and, although most cases resolve, immunosuppressive therapy seems to be necessary. Early diagnosis is mandatory and should be considered in any patient with acute or chronic hepatitis after SARS-CoV-2 vaccination, especially in those with pre-existing liver disease.
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27
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Efe C, Kulkarni AV, Terziroli Beretta‐Piccoli B, Magro B, Stättermayer A, Cengiz M, Clayton‐Chubb D, Lammert C, Bernsmeier C, Gül Ö, la Tijera FH, Anders M, Lytvyak E, Akın M, Purnak T, Liberal R, Peralta M, Ebik B, Duman S, Demir N, Balaban Y, Urzua Á, Contreras F, Venturelli MG, Bilgiç Y, Medina A, Girala M, Günşar F, Londoño M, Androutsakos T, Kisch A, Yurci A, Güzelbulut F, Çağın YF, Avcı E, Akyıldız M, Dindar‐Demiray EK, Harputluoğlu M, Kumar R, Satapathy SK, Mendizabal M, Silva M, Fagiuoli S, Roberts SK, Soylu NK, Idilman R, Yoshida EM, Montano‐Loza AJ, Dalekos GN, Ridruejo E, Schiano TD, Wahlin S. Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome. Hepatology 2022; 76:1576-1586. [PMID: 35567545 PMCID: PMC9348326 DOI: 10.1002/hep.32572] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/04/2022] [Accepted: 05/05/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series. APPROACH AND RESULTS We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18-79) years at presentation. Liver injury was diagnosed a median 15 (range: 3-65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3-4 liver injury than for grade 1-2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up. CONCLUSIONS SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.
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28
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Shimizu S, Sato K, Ito K, Kita A, Aihara K, Tateyama Y, Abe T, Shibasaki M, Yamazaki S, Fukai Y, Iizuka K, Takizawa D, Arai H, Ide M, Uraoka T. A case of possible drug-induced liver injury due to COVID-19 vaccine. KANZO 2022; 63:530-537. [DOI: 10.2957/kanzo.63.530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/24/2024]
Affiliation(s)
- Soichiro Shimizu
- Department of Gastroenterology and Hepatology, Japanese Red Cross Maebashi Hospital
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine
| | - Ken Sato
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine
| | - Kenta Ito
- Department of Gastroenterology and Hepatology, Japanese Red Cross Maebashi Hospital
| | - Aoi Kita
- Department of Gastroenterology and Hepatology, Japanese Red Cross Maebashi Hospital
| | - Kousuke Aihara
- Department of Gastroenterology and Hepatology, Japanese Red Cross Maebashi Hospital
| | - Yumeo Tateyama
- Department of Gastroenterology and Hepatology, Japanese Red Cross Maebashi Hospital
| | - Takahiro Abe
- Department of Gastroenterology and Hepatology, Japanese Red Cross Maebashi Hospital
| | - Mitsuhiko Shibasaki
- Department of Gastroenterology and Hepatology, Japanese Red Cross Maebashi Hospital
| | - Setsuo Yamazaki
- Department of Gastroenterology and Hepatology, Japanese Red Cross Maebashi Hospital
| | - Yasumori Fukai
- Department of Gastroenterology and Hepatology, Japanese Red Cross Maebashi Hospital
| | - Kenichi Iizuka
- Department of Gastroenterology and Hepatology, Japanese Red Cross Maebashi Hospital
| | - Daichi Takizawa
- Department of Gastroenterology and Hepatology, Japanese Red Cross Maebashi Hospital
| | - Hirotaka Arai
- Department of Gastroenterology and Hepatology, Japanese Red Cross Maebashi Hospital
| | - Munenori Ide
- Department of Pathology Diagnosis, Japanese Red Cross Maebashi Hospital
| | - Toshio Uraoka
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine
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29
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Zheng H, Zhang T, Xu Y, Lu X, Sang X. Autoimmune hepatitis after COVID-19 vaccination. Front Immunol 2022; 13:1035073. [PMID: 36505482 PMCID: PMC9732229 DOI: 10.3389/fimmu.2022.1035073] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 11/04/2022] [Indexed: 11/27/2022] Open
Abstract
Vaccination is one of the most vigorous ways to intervene in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Cases of autoimmune hepatitis (AIH) after coronavirus disease (COVID-19) vaccination have been increasingly reported. Twenty-seven cases of AIH are summarized in this study, providing emerging evidence of autoimmune reactions in response to various COVID-19 vaccines, including in patients with special disease backgrounds such as primary sclerosing cholangitis (PSC), liver transplantation, and previous hepatitis C virus (HCV) treatment. Molecular mimicry, adjuvants, epitope spreading, bystander activation, X chromosome, and sceptical hepatotropism of SARS-CoV-2 may account for, to some extent, such autoimmune phenomena. Immunosuppressive corticosteroids perform well with or without azathioprine in such post-COVID-19-vaccination AIH. However, determination of the exact mechanism and establishment of causality require further confirmation.
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30
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Alhumaid S, Al Mutair A, Rabaan AA, ALShakhs FM, Choudhary OP, Yong SJ, Nainu F, Khan A, Muhammad J, Alhelal F, Al Khamees MH, Alsouaib HA, Al Majhad AS, Al-Tarfi HR, ALyasin AH, Alatiyyah YY, Alsultan AA, Alessa ME, Alessa ME, Alissa MA, Alsayegh EH, Alshakhs HN, Al Samaeel HA, AlShayeb RA, Alnami DA, Alhassan HA, Alabdullah AA, Alhmed AH, AlDera FH, Hajissa K, Al-Tawfiq JA, Al-Omari A. New-onset and relapsed liver diseases following COVID-19 vaccination: a systematic review. BMC Gastroenterol 2022; 22:433. [PMID: 36229799 PMCID: PMC9559550 DOI: 10.1186/s12876-022-02507-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Accepted: 09/07/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Liver diseases post-COVID-19 vaccination is extremely rare but can occur. A growing body of evidence has indicated that portal vein thrombosis, autoimmune hepatitis, raised liver enzymes and liver injuries, etc., may be potential consequence of COVID-19 vaccines. OBJECTIVES To describe the results of a systematic review for new-onset and relapsed liver disease following COVID-19 vaccination. METHODS For this systematic review, we searched Proquest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses PRISMA guideline for studies on the incidence of new onset or relapsed liver diseases post-COVID-19 vaccination, published from December 1, 2020 to July 31, 2022, with English language restriction. RESULTS Two hundred seventy-five cases from one hundred and eighteen articles were included in the qualitative synthesis of this systematic review. Autoimmune hepatitis (138 cases) was the most frequent pathology observed post-COVID-19 vaccination, followed by portal vein thrombosis (52 cases), raised liver enzymes (26 cases) and liver injury (21 cases). Other cases include splanchnic vein thrombosis, acute cellular rejection of the liver, jaundice, hepatomegaly, acute hepatic failure and hepatic porphyria. Mortality was reported in any of the included cases for acute hepatic failure (n = 4, 50%), portal vein thrombosis (n = 25, 48.1%), splanchnic vein thrombosis (n = 6, 42.8%), jaundice (n = 1, 12.5%), raised liver enzymes (n = 2, 7.7%), and autoimmune hepatitis (n = 3, 2.2%). Most patients were easily treated without any serious complications, recovered and did not require long-term hepatic therapy. CONCLUSION Reported evidence of liver diseases post-COIVD-19 vaccination should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively very small in relation to the hundreds of millions of vaccinations that have occurred and the protective benefits offered by COVID-19 vaccination far outweigh the risks.
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Affiliation(s)
- Saad Alhumaid
- Administration of Pharmaceutical Care, Al-Ahsa Health Cluster, Ministry of Health, Rashdiah Street, P. O. Box 12944, Al-Ahsa, 31982, Saudi Arabia.
| | - Abbas Al Mutair
- Research Center, Almoosa Specialist Hospital, Al-Ahsa, Saudi Arabia.,College of Nursing, Princess Norah Bint Abdul Rahman University, Riyadh, Saudi Arabia.,School of Nursing, University of Wollongong, Wollongong, Australia
| | - Ali A Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia.,College of Medicine, Alfaisal University, Riyadh, 11533, Saudi Arabia.,Department of Public Health and Nutrition, The University of Haripur, Haripur, Pakistan
| | - Fatemah M ALShakhs
- Respiratory Therapy Department, Prince Saud Bin Jalawi Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Om Prakash Choudhary
- Department of Veterinary Anatomy and Histology, College of Veterinary Sciences and Animal Husbandry, Central Agricultural University (I), Selesih, Aizawl, Mizoram, 796015, India
| | - Shin Jie Yong
- Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Subang Jaya, Malaysia
| | - Firzan Nainu
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar, 90245, Indonesia
| | - Amjad Khan
- Department of Public Health and Nutrition, The University of Haripur, Haripur, Pakistan
| | - Javed Muhammad
- Department of Microbiology, The University of Haripur, Haripur, 22620, Khyber Pakhtunkhwa, Pakistan
| | - Fadil Alhelal
- Optometry Department, Dhahran Eye Specialist Hospital, Ministry of Health, Dhahran, Saudi Arabia
| | | | - Hussain Ahmed Alsouaib
- Medical Store Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Ahmed Salman Al Majhad
- Medical Store Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Hassan Redha Al-Tarfi
- Medical Store Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Ali Hussain ALyasin
- Medical Store Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | | | - Ali Ahmed Alsultan
- Medical Supply Store, Aloyoon General Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Mohammed Essa Alessa
- Inventory Control Unit, Aloyoon General Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Mustafa Essa Alessa
- Pharmacy Department, Aloyoon General Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Mohammed Ahmed Alissa
- Pharmacy Department, Aloyoon General Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Emad Hassan Alsayegh
- Pharmacy Department, Aloyoon General Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Hassan N Alshakhs
- Pharmacy Department, Aloyoon General Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | | | - Rugayah Ahmed AlShayeb
- Pharmacy Department, King Fahad Hofuf Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Dalal Ahmed Alnami
- Pharmacy Department, King Fahad Hofuf Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Hussain Ali Alhassan
- Pharmacy Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | | | - Ayat Hussain Alhmed
- Administration of Nursing Care, Maternity and Children Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Faisal Hussain AlDera
- General Surgery Department, King Fahad Hofuf Hospital, Ministry of Health, Al-Ahsa, Saudi Arabia
| | - Khalid Hajissa
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Jaffar A Al-Tawfiq
- Infectious Disease Unit, Specialty Internal Medicine, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia.,Infectious Disease Division, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.,Infectious Disease Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Awad Al-Omari
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.,Research Center, Dr. Sulaiman Al Habib Medical Group, Riyadh, Saudi Arabia
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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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32
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Awan MH, Samreen S, Salim B, Gul H, Perveen S, Nasim A. Corona Virus Disease-19 Vaccine-associated Autoimmune Disorders. RHEUMATOLOGY AND IMMUNOLOGY RESEARCH 2022; 3:111-119. [PMID: 36788969 PMCID: PMC9895874 DOI: 10.2478/rir-2022-0019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 07/21/2022] [Indexed: 02/16/2023]
Abstract
Coronavirus disease is a highly infectious viral disease caused by severe acute respiratory syndrome virus (SARS nCoV2). It was declared a pandemic within a few months of identification of its index case. The spread of COVID-19 across the globe was rampant, overwhelming healthcare systems and crippling global economies. Since the world was caught off guard by the pandemic, vaccine programs had to be rolled out in emergency to curb its spread. Ten vaccines have been granted Emergency Use Authorization thus far. Much of the side effects we know today are post-marketing adverse effects. Most of them are mild like myalgia and injection-site reactions, but a few of them such as post-vaccination autoimmune diseases have alerted the medical community. These include vaccine-induced thrombotic thrombocytopenia, autoimmune hepatitis, myocarditis, and Graves' disease. We attempt to summarize the diverse autoimmune phenomena reported after COVID-19 vaccination, with an aim to sensitize the medical community so that they can be better equipped in management when confronted with these diseases. This review by no means refutes the potential benefit of COVID-19 vaccination which has consolidated its place in preventing infections and substantially reducing severity and mortality.
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Affiliation(s)
- Marriam Hussain Awan
- Postgraduate Resident in Rheumatology, Fauji Foundation Hospital, Rawalpindi, Pakistan
| | - Saba Samreen
- Postgraduate Resident in Rheumatology, Fauji Foundation Hospital, Rawalpindi, Pakistan
| | - Babur Salim
- Postgraduate Resident in Rheumatology, Fauji Foundation Hospital, Rawalpindi, Pakistan
| | - Haris Gul
- Postgraduate Resident in Rheumatology, Fauji Foundation Hospital, Rawalpindi, Pakistan
| | - Shahida Perveen
- Postgraduate Resident in Rheumatology, Fauji Foundation Hospital, Rawalpindi, Pakistan
| | - Amjad Nasim
- Postgraduate Resident in Rheumatology, Fauji Foundation Hospital, Rawalpindi, Pakistan
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Izagirre A, Arzallus T, Garmendia M, Torrente S, Castiella A, Zapata EM. Autoimmune hepatitis following COVID-19 vaccination. J Autoimmun 2022; 132:102874. [PMID: 35985054 PMCID: PMC9353598 DOI: 10.1016/j.jaut.2022.102874] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 07/16/2022] [Accepted: 07/16/2022] [Indexed: 11/25/2022]
Affiliation(s)
- Arantzazu Izagirre
- Gastroenterology Department, Donostia University Hospital, San Sebastian, Spain.
| | - Teresa Arzallus
- Gastroenterology Department, Donostia University Hospital, San Sebastian, Spain
| | - Maddi Garmendia
- Pathology Department, Donostia University Hospital, San Sebastian, Spain
| | - Silvia Torrente
- Gastroenterology Department, Donostia University Hospital, San Sebastian, Spain
| | - Agustin Castiella
- Gastroenterology Department, Donostia University Hospital, San Sebastian, Spain
| | - Eva María Zapata
- Gastroenterology Department, Donostia University Hospital, San Sebastian, Spain
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34
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Shahrani S, Sooi CY, Hilmi IN, Mahadeva S. Autoimmune hepatitis (AIH) following coronavirus (COVID-19) vaccine-No longer exclusive to mRNA vaccine? Liver Int 2022; 42:2344-2345. [PMID: 35762286 PMCID: PMC9349898 DOI: 10.1111/liv.15350] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 05/15/2022] [Indexed: 12/28/2022]
Affiliation(s)
- Shahreedhan Shahrani
- Department of Internal Medicine, Gastroenterology and Hepatology UnitUniversity Malaya Medical CentreKuala LumpurMalaysia
| | - Choong Yeong Sooi
- Department of Internal MedicineHospital Tengku Ampuan AfzanKuantanMalaysia
| | - Ida Normiha Hilmi
- Division of Gastroenterology, Department of Medicine, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
| | - Sanjiv Mahadeva
- Division of Gastroenterology, Department of Medicine, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
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Rodríguez Y, Rojas M, Beltrán S, Polo F, Camacho-Domínguez L, Morales SD, Gershwin ME, Anaya JM. Autoimmune and autoinflammatory conditions after COVID-19 vaccination. New case reports and updated literature review. J Autoimmun 2022; 132:102898. [PMID: 36041291 PMCID: PMC9399140 DOI: 10.1016/j.jaut.2022.102898] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 08/11/2022] [Accepted: 08/14/2022] [Indexed: 11/20/2022]
Abstract
Autoimmunity linked to COVID-19 immunization has been recorded throughout the pandemic. Herein we present six new patients who experienced relapses of previous autoimmune disease (AD) or developed a new autoimmune or autoinflammatory condition following vaccination. In addition, we documented additional cases through a systematic review of the literature up to August 1st, 2022, in which 464 studies (928 cases) were included. The majority of patients (53.6%) were women, with a median age of 48 years (IQR: 34 to 66). The median period between immunization and the start of symptoms was eight days (IQR: 3 to 14). New-onset conditions were observed in 81.5% (n: 756) of the cases. The most common diseases associated with new-onset events following vaccination were immune thrombocytopenia, myocarditis, and Guillain-Barré syndrome. In contrast, immune thrombocytopenia, psoriasis, IgA nephropathy, and systemic lupus erythematosus were the most common illnesses associated with relapsing episodes (18.5%, n: 172). The first dosage was linked with new-onset events (69.8% vs. 59.3%, P = 0.0100), whereas the second dose was related to relapsing disease (29.5% vs. 59.3%, P = 0.0159). New-onset conditions and relapsing diseases were more common in women (51.5% and 62.9%, respectively; P = 0.0081). The groups were evenly balanced in age. No deaths were recorded after the disease relapsed, while 4.7% of patients with new-onset conditions died (P = 0.0013). In conclusion, there may be an association between COVID-19 vaccination and autoimmune and inflammatory diseases. Some ADs seem to be more common than others. Vaccines and SARS-CoV-2 may induce autoimmunity through similar mechanisms. Large, well-controlled studies are warranted to validate this relationship and assess additional variables such as genetic and other environmental factors.
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Affiliation(s)
- Yhojan Rodríguez
- Clínica del Occidente, Bogota, Colombia; Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia
| | - Manuel Rojas
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia
| | - Santiago Beltrán
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia
| | - Fernando Polo
- Hospital Infantil de San José, Fundación Universitaria de Ciencias de la Salud. Department of Pathology, Bogota, Colombia
| | - Laura Camacho-Domínguez
- Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia
| | - Samuel David Morales
- Hospital Infantil de San José, Fundación Universitaria de Ciencias de la Salud. Department of Pathology, Bogota, Colombia
| | - M Eric Gershwin
- Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, Davis, CA, United States
| | - Juan-Manuel Anaya
- Clínica del Occidente, Bogota, Colombia; LifeFactors, Rionegro, Colombia.
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Boettler T, Csernalabics B, Salié H, Luxenburger H, Wischer L, Salimi Alizei E, Zoldan K, Krimmel L, Bronsert P, Schwabenland M, Prinz M, Mogler C, Neumann-Haefelin C, Thimme R, Hofmann M, Bengsch B. SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis. J Hepatol 2022; 77:653-659. [PMID: 35461912 PMCID: PMC9021033 DOI: 10.1016/j.jhep.2022.03.040] [Citation(s) in RCA: 86] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 03/29/2022] [Accepted: 03/31/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Autoimmune hepatitis episodes have been described following SARS-CoV-2 infection and vaccination but their pathophysiology remains unclear. Herein, we report the case of a 52-year-old male, presenting with bimodal episodes of acute hepatitis, each occurring 2-3 weeks after BNT162b2 mRNA vaccination. We sought to identify the underlying immune correlates. The patient received oral budesonide, relapsed, but achieved remission under systemic steroids. METHODS Imaging mass cytometry for spatial immune profiling was performed on liver biopsy tissue. Flow cytometry was performed to dissect CD8 T-cell phenotypes and identify SARS-CoV-2-specific and EBV-specific T cells longitudinally. Vaccine-induced antibodies were determined by ELISA. Data were correlated with clinical laboratory results. RESULTS Analysis of the hepatic tissue revealed an immune infiltrate quantitatively dominated by activated cytotoxic CD8 T cells with panlobular distribution. An enrichment of CD4 T cells, B cells, plasma cells and myeloid cells was also observed compared to controls. The intrahepatic infiltrate showed enrichment for CD8 T cells with SARS-CoV-2-specificity compared to the peripheral blood. Notably, hepatitis severity correlated longitudinally with an activated cytotoxic phenotype of peripheral SARS-CoV-2-specific, but not EBV-specific, CD8+ T cells or vaccine-induced immunoglobulins. CONCLUSIONS COVID-19 vaccination can elicit a distinct T cell-dominant immune-mediated hepatitis with a unique pathomechanism associated with vaccination-induced antigen-specific tissue-resident immunity requiring systemic immunosuppression. LAY SUMMARY Liver inflammation is observed during SARS-CoV-2 infection but can also occur in some individuals after vaccination and shares some typical features with autoimmune liver disease. In this report, we show that highly activated T cells accumulate and are evenly distributed in the different areas of the liver in a patient with liver inflammation following SARS-CoV-2 vaccination. Moreover, within the population of these liver-infiltrating T cells, we observed an enrichment of T cells that are reactive to SARS-CoV-2, suggesting that these vaccine-induced cells can contribute to liver inflammation in this context.
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Affiliation(s)
- Tobias Boettler
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Benedikt Csernalabics
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Henrike Salié
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Hendrik Luxenburger
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Lara Wischer
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Elahe Salimi Alizei
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Faculty of Chemistry and Pharmacy, University of Freiburg, Freiburg, Germany
| | - Katharina Zoldan
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Laurenz Krimmel
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Peter Bronsert
- Institute for Surgical Pathology, Freiburg University Medical Center, University of Freiburg, Freiburg, Germany
| | - Marius Schwabenland
- Institute of Neuropathology and Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Marco Prinz
- Institute of Neuropathology and Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany
| | - Carolin Mogler
- Institute of Pathology, TUM School of Medicine, Technical University of Munich, Munich, Germany
| | - Christoph Neumann-Haefelin
- 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
| | - Maike Hofmann
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Bertram Bengsch
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), partner site Freiburg, Germany.
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Zhao Y, Zhao Y, Li M, Zhou Y, Zhang Y, Su X, Zhang Z, Jin L. Association of COVID-19 vaccination before conception with maternal liver function during early pregnancy: a cohort study of 7745 Chinese pregnant women. Emerg Microbes Infect 2022; 11:2222-2228. [PMID: 36000197 PMCID: PMC9542934 DOI: 10.1080/22221751.2022.2117100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Multicenter case series has reported patients with hepatic injury following COVID-19 vaccination, which raised concern for the possibility of vaccine-induced liver dysfunction. We aimed to assess the impact of COVID-19 vaccination on liver function of pregnant women, who may be uniquely susceptible to vaccine-induced liver dysfunction. We conducted a retrospective cohort study at a tertiary hospital in Shanghai, China. Vaccine administration was obtained from the electronic vaccination record. Serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total bile acid (TBA) and total bilirubin (TBIL) in early pregnancy were determined by enzymatic methods. Among the 7745 included pregnant women, 3832 (49.5%) received at least two doses of an inactivated vaccine. COVID-19 vaccination was significantly associated with higher levels of maternal serum TBA. Compared with unvaccinated pregnant women, the mean TBA levels increased by 0.17 μmol/L (β = 0.17, 95% CI, 0.04, 0.31) for women who had been vaccinated within 3 months before the date of conception. Moreover, COVID-19 vaccination was significantly associated with an increased risk of maternal hyperbileacidemia. The risk of hyperbileacidemia increased by 113% (RR = 2.13; 95% CI, 1.17-3.87) for pregnant women who had been vaccinated within 3 months before conception compared with unvaccinated pregnant women. However, when the interval from complete vaccination to conception was prolonged to more than 3 months, COVID-19 vaccination was not associated with serum TBA levels or maternal hyperbileacidemia. Our findings suggest that vaccination with inactivated COVID-19 vaccines more than 3 months before conception have no detrimental effects on maternal liver function in early pregnancy.
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Affiliation(s)
- Yan Zhao
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yongbo Zhao
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Mengyuan Li
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yicheng Zhou
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yijun Zhang
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xin Su
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ziyi Zhang
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Liping Jin
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
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Esmaeilzadeh A, Maleki AJ, Moradi A, Siahmansouri A, Yavari MJ, Karami P, Elahi R. Major severe acute respiratory coronavirus-2 (SARS-CoV-2) vaccine-associated adverse effects; benefits outweigh the risks. Expert Rev Vaccines 2022; 21:1377-1394. [DOI: 10.1080/14760584.2022.2116008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Abdolreza Esmaeilzadeh
- Department of Immunology, Zanjan University of Medical Sciences, Zanjan, Iran
- Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran
| | - Armin Jahani Maleki
- M.D., School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Amirhosein Moradi
- M.D., School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Amir Siahmansouri
- M.D., School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | | | - Parsa Karami
- M.D., School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Reza Elahi
- M.D., School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
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39
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Lasagna A, Lenti MV, Cassaniti I, Sacchi P. Development of hepatitis triggered by SARS-CoV-2 vaccination in patient with cancer during immunotherapy: a case report. Immunotherapy 2022; 14:915-925. [PMID: 35694999 PMCID: PMC9196259 DOI: 10.2217/imt-2021-0342] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 05/12/2022] [Indexed: 12/18/2022] Open
Abstract
Patients with cancer have a higher risk of severe COVID-19, and expert consensus advocates for COVID-19 vaccination in this population. Some cases of autoimmune hepatitis have been described after the administration of COVID-19 vaccine in the people in apparently good health. Immune checkpoint inhibitors (ICIs) are responsible for a wide spectrum of immune-related adverse events (irAEs). This article reports a case of hepatitis and colitis in a 52-year-old woman who was undergoing immunotherapy and was HBV positive 10 days after receiving the first Pfizer-BioNTech COVID-19 vaccine dose. Because both ICIs and the COVID-19 vaccines stimulate the immune response, the authors hypothesize that these vaccines may increase the incidence of irAEs during ICI treatment. There is a complex interplay between the immune-mediated reaction triggered by the vaccination and PD-L1 co-administration.
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Affiliation(s)
- Angioletta Lasagna
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, 27100, Italy
| | - Marco Vincenzo Lenti
- Department of Internal Medicine, Clinica Medica, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, 27100, Italy
| | - Irene Cassaniti
- Department of Microbiology & Virology, Molecular Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, 27100, Italy
| | - Paolo Sacchi
- Division of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Pavia, 27100, Italy
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40
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Hasegawa N, Matsuoka R, Ishikawa N, Endo M, Terasaki M, Seo E, Tsuchiya K. Autoimmune hepatitis with history of HCV treatment triggered by COVID-19 vaccination: case report and literature review. Clin J Gastroenterol 2022; 15:791-795. [PMID: 35716255 PMCID: PMC9206395 DOI: 10.1007/s12328-022-01654-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 05/30/2022] [Indexed: 01/06/2023]
Abstract
Although vaccines have been effective against the worldwide pandemic of Coronavirus Disease 19 (COVID-19), some case reports have described autoimmune hepatitis triggered by COVID-19 vaccination. Meanwhile, hepatitis C virus (HCV) is known to be related to autoimmune diseases. Here, we report a case of autoimmune hepatitis with history of HCV treatment triggered by COVID-19 vaccination. An 82-year-old woman was referred to our hospital for severe liver injury. She had received a COVID-19 vaccination 7 days prior. She had a history of HCV treatment with direct-acting antivirals 7 years previously. In her blood data, despite HCV antibody positivity, she was negative for HCV RNA by real-time RT-PCR. Anti-nuclear antibody was positive and IgG was elevated. Interface hepatitis and plasma cell infiltration were confirmed pathologically. She was diagnosed as autoimmune hepatitis and her liver injury quickly improved after initiation of steroid administration. This is a first case report of autoimmune hepatitis with history of HCV treatment triggered by COVID-19 vaccination.
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Affiliation(s)
- Naoyuki Hasegawa
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan.
| | - Ryota Matsuoka
- Department of Pathology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Naoki Ishikawa
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Masato Endo
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Masahiko Terasaki
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Emiko Seo
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Kiichiro Tsuchiya
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan
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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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42
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Efe C, Harputluoğlu M, Soylu NK, Yilmaz S. Letter to the editor: Liver transplantation following severe acute respiratory syndrome-coronavirus-2 vaccination-induced liver failure. Hepatology 2022; 75:1669-1671. [PMID: 35175635 PMCID: PMC9087410 DOI: 10.1002/hep.32409] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 02/07/2022] [Indexed: 01/05/2023]
Affiliation(s)
- Cumali Efe
- Department of GastroenterologyHarran University HospitalŞanlıurfaTurkey
| | - Murat Harputluoğlu
- Department of GastroenterologyInönü University School of MedicineMalatyaTurkey
| | - Neşe Karadağ Soylu
- Department of PathologyInonu University Faculty of MedicineMalatyaTurkey
| | - Sezai Yilmaz
- Department of SurgeryLiver Transplantation InstituteInonu UniversityMalatyaTurkey
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Sergi CM. Acute Hepatitis of Unknown Origin (AHUO)-The Puzzle Ahead. Diagnostics (Basel) 2022; 12:1215. [PMID: 35626370 PMCID: PMC9140145 DOI: 10.3390/diagnostics12051215] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 05/10/2022] [Indexed: 02/06/2023] Open
Abstract
An intriguing form of hepatitis has been detected in more than a hundred children worldwide [...].
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Affiliation(s)
- Consolato M Sergi
- Division of Anatomic Pathology, Children's Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada
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44
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Cao Z, Gui H, Sheng Z, Xin H, Xie Q. Letter to the editor: Exacerbation of autoimmune hepatitis after COVID-19 vaccination. Hepatology 2022; 75:757-759. [PMID: 34862637 PMCID: PMC9015495 DOI: 10.1002/hep.32269] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 11/30/2021] [Accepted: 12/01/2021] [Indexed: 02/06/2023]
Affiliation(s)
- Zhujun Cao
- Department of Infectious DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Honglian Gui
- Department of Infectious DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Zike Sheng
- Department of Infectious DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Haiguang Xin
- Department of Infectious DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Qing Xie
- Department of Infectious DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
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45
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Mungmunpuntipantip R, Wiwanitkit V. Letter to the editor: "Autoimmune hepatitis after COVID-19 vaccination". Hepatology 2022; 75:756. [PMID: 34797931 PMCID: PMC8652931 DOI: 10.1002/hep.32249] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 11/02/2021] [Indexed: 01/05/2023]
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46
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Palla P, Vergadis C, Sakellariou S, Androutsakos T. Reply. Hepatology 2022; 75:756-757. [PMID: 34797940 PMCID: PMC9011454 DOI: 10.1002/hep.32248] [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: 11/12/2021] [Accepted: 11/12/2021] [Indexed: 12/08/2022]
Affiliation(s)
- Panagiota Palla
- Department of PathophysiologyNational and Kapodistrian University of Athens, Medical SchoolAthensGreece
| | | | - Stratigoula Sakellariou
- First Department of PathologyNational and Kapodistrian University of Athens, Medical SchoolAthensGreece
| | - Theodoros Androutsakos
- Department of PathophysiologyNational and Kapodistrian University of Athens, Medical SchoolAthensGreece
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Suzuki Y, Kakisaka K, Takikawa Y. Letter to the editor: Autoimmune hepatitis after COVID-19 vaccination: Need for population-based epidemiological study. Hepatology 2022; 75:759-760. [PMID: 34904265 DOI: 10.1002/hep.32280] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 12/03/2021] [Indexed: 12/28/2022]
Affiliation(s)
- Yuji Suzuki
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba-cho, Japan
| | - Keisuke Kakisaka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba-cho, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba-cho, Japan
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Kountouras J, Gialamprinou D, Kotronis G, Papaefthymiou A, Economidou E, Soteriades ES, Vardaka E, Chatzopoulos D, Tzitiridou-Chatzopoulou M, Papazoglou DD, Doulberis M. Ofeleein i mi Vlaptin-Volume II: Immunity Following Infection or mRNA Vaccination, Drug Therapies and Non-Pharmacological Management at Post-Two Years SARS-CoV-2 Pandemic. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:309. [PMID: 35208631 PMCID: PMC8874934 DOI: 10.3390/medicina58020309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 01/06/2022] [Accepted: 02/14/2022] [Indexed: 12/15/2022]
Abstract
The persistence of the coronavirus disease 2019 (COVID-19) pandemic has triggered research into limiting transmission, morbidity and mortality, thus warranting a comprehensive approach to guide balanced healthcare policies with respect to people's physical and mental health. The mainstay priority during COVID-19 is to achieve widespread immunity, which could be established through natural contact or vaccination. Deep knowledge of the immune response combined with recent specific data indicates the potential inferiority of induced immunity against infection. Moreover, the prevention of transmission has been founded on general non-pharmacological measures of protection, albeit debate exists considering their efficacy and, among other issues, their socio-psychological burden. The second line of defense is engaged after infection and is supported by a plethora of studied agents, such as antibiotics, steroids and non-steroid anti-inflammatory drugs, antiviral medications and other biological agents that have been proposed, though variability in terms of benefits and adverse events has not allowed distinct solutions, albeit certain treatments might have a role in prevention and/or treatment of the disease. This narrative review summarizes the existing literature on the advantages and weaknesses of current COVID-19 management measures, thus underlining the necessity of acting based on the classical principle of "ofeleein i mi vlaptin", that is, to help or not to harm.
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Affiliation(s)
- Jannis Kountouras
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54652 Thessaloniki, Central Macedonia, Greece; (A.P.); (E.V.); (D.C.); (M.T.-C.); (M.D.)
| | - Dimitra Gialamprinou
- Second Neonatal Department and NICU, Papageorgiou General Hospital, Aristotle University of Thessaloniki, 56403 Thessaloniki, Central Macedonia, Greece;
| | - Georgios Kotronis
- Department of Internal Medicine, General Hospital Aghios Pavlos of Thessaloniki, 55134 Thessaloniki, Central Macedonia, Greece;
| | - Apostolis Papaefthymiou
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54652 Thessaloniki, Central Macedonia, Greece; (A.P.); (E.V.); (D.C.); (M.T.-C.); (M.D.)
- Department of Gastroenterology, University Hospital of Larisa, Mezourlo, 41110 Larisa, Thessaly, Greece
| | - Eleftheria Economidou
- School of Economics and Management, Healthcare Management Program, Open University of Cyprus, Nicosia 12794, Cyprus; (E.E.); (E.S.S.)
| | - Elpidoforos S. Soteriades
- School of Economics and Management, Healthcare Management Program, Open University of Cyprus, Nicosia 12794, Cyprus; (E.E.); (E.S.S.)
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Environmental and Occupational Medicine and Epidemiology (EOME), Boston, MA 02115, USA
| | - Elisabeth Vardaka
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54652 Thessaloniki, Central Macedonia, Greece; (A.P.); (E.V.); (D.C.); (M.T.-C.); (M.D.)
- Department of Nutritional Sciences and Dietetics, School of Health Sciences, International Hellenic University, 57400 Thessaloniki, Central Macedonia, Greece
| | - Dimitrios Chatzopoulos
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54652 Thessaloniki, Central Macedonia, Greece; (A.P.); (E.V.); (D.C.); (M.T.-C.); (M.D.)
| | - Maria Tzitiridou-Chatzopoulou
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54652 Thessaloniki, Central Macedonia, Greece; (A.P.); (E.V.); (D.C.); (M.T.-C.); (M.D.)
- Midwifery Department, School of Healthcare Sciences, University of West Macedonia, Koila, 50100 Kozani, Central Macedonia, Greece
| | - Dimitrios David Papazoglou
- Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland;
| | - Michael Doulberis
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54652 Thessaloniki, Central Macedonia, Greece; (A.P.); (E.V.); (D.C.); (M.T.-C.); (M.D.)
- Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, 5001 Aarau, Switzerland
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COVID-19 vaccine and autoimmunity. A new case of autoimmune hepatitis and review of the literature. J Transl Autoimmun 2022; 5:100140. [PMID: 35013724 PMCID: PMC8730708 DOI: 10.1016/j.jtauto.2022.100140] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 01/02/2022] [Indexed: 12/19/2022] Open
Abstract
Autoimmunity following COVID-19 vaccination has been reported. Herein, a 79-year-old man with clinical and immunological features of autoimmune hepatitis type 1 after ChAdOx1 nCoV-19 vaccination is presented. Clinical manifestations rapidly remitted after the instauration of immunomodulatory management. This case, together with a comprehensive review of the literature, illustrates the association between COVID-19 vaccines and the development of autoimmune conditions.
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Chow KW, Pham NV, Ibrahim BM, Hong K, Saab S. Autoimmune Hepatitis-Like Syndrome Following COVID-19 Vaccination: A Systematic Review of the Literature. Dig Dis Sci 2022; 67:4574-4580. [PMID: 35486203 PMCID: PMC9052185 DOI: 10.1007/s10620-022-07504-w] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 01/15/2022] [Indexed: 12/19/2022]
Abstract
OBJECTIVES During the summer of 2021, case reports began to emerge documenting a small number of individuals who developed autoimmune hepatitis (AIH) following COVID-19 vaccination. These cases are rare and novel, and very little is known. In our systematic review, we analyzed every published case of AIH and reviewed their characteristic findings, treatment, and outcomes. METHODS We searched PubMed, Embase, and Web of Science from December 1, 2019, to November 1, 2021. Two researchers independently extracted information from the articles about vaccine type, patient history, laboratory values, histology results, treatment regimens, and disease course. RESULTS Thirty-two patients developed AIH-like syndromes after receiving a COVID-19 vaccine. Jaundice was the most frequently reported symptom (81%), and 19% of patients were initially asymptomatic and presented with elevated liver enzymes found during routine bloodwork. Mean alanine transaminase, aspartate transaminase, and total bilirubin were 1231 U/L, 921 U/L, and 14 mg/dL, respectively. Anti-nuclear antibody was positive in 56%, and anti-smooth muscle antibody in 28% of patients. Steroids were used in 75% of patients. Improvement or complete resolution was seen in 97% of patients. One patient died despite aggressive steroid treatment. CONCLUSION COVID-19 vaccine-induced AIH is an uncommon association with just 32 documented cases in the literature. Clinicians should be vigilant for AIH in patients who present with liver injury following vaccination. These new findings should under not deter individuals from getting vaccinated, as the benefits of vaccination far outweigh the risks. Fortunately, COVID-19 vaccine-induced AIH appears amendable to corticosteroid therapy and appears to have a favorable outcome.
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Affiliation(s)
- Kenneth W. Chow
- Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA USA
| | - Nguyen V. Pham
- Departments of Surgery, UCLA Medical Center, Pfleger Liver Institute, University of California at Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095 USA
| | - Britney M. Ibrahim
- Departments of Surgery, UCLA Medical Center, Pfleger Liver Institute, University of California at Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095 USA
| | - Kimberly Hong
- Departments of Surgery, UCLA Medical Center, Pfleger Liver Institute, University of California at Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095 USA
| | - Sammy Saab
- Departments of Surgery, UCLA Medical Center, Pfleger Liver Institute, University of California at Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095 USA ,Departments of Medicine, UCLA Medical Center, Pfleger Liver Institute, University of California at Los Angeles, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095 USA
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