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      Liver injury after SARS‐CoV ‐2 vaccination: Features of immune‐mediated hepatitis, role of corticosteroid therapy and outcome

      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 26 , 34 , 35 , 36 , 26 , 37 , 38 , 18 , 39 , 18 , 39 , 4 , 40 , 41 , 20 , 42 , 13 , 43 , 44 , 18 , 39 , 45 , 46 , 47
      Hepatology
      Wiley

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          Abstract

          <div class="section"> <a class="named-anchor" id="hep32572-sec-0001"> <!-- named anchor --> </a> <h5 class="section-title" id="d8022396e1845">Background and Aims</h5> <p id="d8022396e1847">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. </p> </div><div class="section"> <a class="named-anchor" id="hep32572-sec-0002"> <!-- named anchor --> </a> <h5 class="section-title" id="d8022396e1850">Approach and Results</h5> <p id="d8022396e1852">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%, <i>p</i> = 0.001) and more often for patients with than without immune‐mediated hepatitis (71.1% vs. 38.2%, <i>p</i> = 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 Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution.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. </p> </div><div class="section"> <a class="named-anchor" id="hep32572-sec-0003"> <!-- named anchor --> </a> <h5 class="section-title" id="d8022396e1861">Conclusions</h5> <p id="d8022396e1863">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. </p> </div><p class="first" id="d8022396e1866">SARS‐COV‐2 vaccination and liver injury. <div class="boxed-text panel" id="hep32572-blkfxd-0001"> <a class="named-anchor" id="hep32572-blkfxd-0001"> <!-- named anchor --> </a> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/07c29ec9-19b3-4ea7-98ad-d55db20cf3b1/PubMedCentral/image/HEP-9999-0-g001.jpg"/> </div> <div class="panel-content"/> </div> </p>

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          Most cited references36

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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              COVID-19 vaccines: modes of immune activation and future challenges

              The new vaccines against SARS-CoV-2 are novel in terms of specificity, their wide dissemination across the global population and the inclusion of newly licensed mRNA platforms. We discuss here how the approved vaccines trigger innate immunity to promote durable immunological memory and consider the future implications of protecting populations with these vaccines.
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                Author and article information

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                Journal
                Hepatology
                Hepatology
                Wiley
                0270-9139
                1527-3350
                May 14 2022
                Affiliations
                [1 ]Department of Gastroenterology Harran University Hospital Şanlıurfa Turkey
                [2 ]Department of Hepatology and Liver Transplantation Asian Institute of Gastroenterology Hospitals. Gachibowli India, 500032 Hyderabad
                [3 ]Faculty of Biomedical Sciences, Università Della Svizzera Italiana, 6900, Lugano Switzerland. Epatocentro Ticino, Via Soldino 5, 6900 Lugano
                [4 ]Gastroenterology Hepatology and Transplantation, ASST Papa Giovanni XXIII‐Bergamo Bergamo Italy
                [5 ]Division of Gastroenterology and Hepatology, Department of Internal Medicine III Medical University of Vienna Vienna Austria
                [6 ]Department of Gastroenterology, Gülhane Training and Research Hospital Ankara Turkey
                [7 ]Department of Gastroenterology, Alfred Health Melbourne Victoria Australia
                [8 ]Department of Medicine Indiana University School of Medicine Indianapolis IN USA
                [9 ]Department of Biomedicine University of Basel Switzerland; University Centre for Gastrointestinal and Liver Diseases Basel Switzerland
                [10 ]Department of Gastroenterology Kırıkkale University Kırıkkale Turkey
                [11 ]Gastroenterology and Hepatology Unit. Hospital General de México Ciudad de México México
                [12 ]Hepatology and Liver Transplant Unit, Hospital Alemán Ciudad Autónoma de Buenos Aires Argentina
                [13 ]University of Alberta Division of Gastroenterology and Liver Unit Edmonton Alberta Canada
                [14 ]Department of Gastroenterology Akdeniz University Faculty of Medicine Antalya Turkey
                [15 ]Division of Gastroenterology, Hepatology and Nutrition McGovern Medical School 6431 Fannin, MSB1.150, Houston, TX, 77030 USA
                [16 ]Gastroenterology and Hepatology Department, Centro Hospitalar e Universitário de São João, Porto, Portugal; World Gastroenterology Organization (WGO) Porto Training Center Porto Portugal
                [17 ]Hepatology Section, Hospital Francisco J Muñiz Ciudad Autónoma de Buenos Aires Argentina
                [18 ]Latin American Liver Research Educational and Awareness Network (LALREAN), Pilar Argentina
                [19 ]Department of Gastroenterology, Gazi Yaşargil Education and Research Hospital Diyarbakir Turkey
                [20 ]Department of Gastroenterology Ankara University Medical Faculty Ankara Turkey
                [21 ]Haseki Training and Research Hospital, Department of Gastroenterology Istanbul Turkey
                [22 ]Department of Gastroenterology, Faculty of Medicine Hacettepe University Ankara Turkey
                [23 ]Gastroenterology and Hepatology Unit. Hospital Clínico Universidad de Chile Santiago de Chile Chile
                [24 ]Centro de Gastroenterología Avanzada. Dominican Republic
                [25 ]Clinica Stella Maris, Gastroenterology and Hepatology Unit Lima Peru
                [26 ]Department of Gastroenterology Inönü University School of Medicine Malatya Turkey
                [27 ]Gastroenterology and Hepatology Unit, Hospital de Clínicas, Universidad Nacional de Asunción. Paraguay
                [28 ]Department of Gastroenterology Ege University School of Medicine İzmir Turkey
                [29 ]Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd Barcelona Spain
                [30 ]Department of Pathophysiology National and Kapodistrian University of Athens Medical School Athens Greece
                [31 ]Hepatology Section, Hospital Bonorino Udaondo Ciudad Autónoma de Buenos Aires Argentina
                [32 ]Department of Gastroenterology Erciyes University School of Medicine Kayseri Turkey
                [33 ]Department of Gastroenterology, Haydarpaşa Numune Education and Research Hospital İstanbul Turkey
                [34 ]Department of Gastroenterology KTO Karatay University Medical School Affiliated Konya Medicana Hospital Konya Turkey
                [35 ]Department of Gastroenterology Koc University School of Medicine Istanbul Turkey
                [36 ]Department of Infectious Diseases and Clinical Microbiology Bitlis Tatvan State Hospital Bitlis Turkey
                [37 ]Department of Gastroenterology and Hepatology, Changi General Hospital, Medicine Academic Clinical Programme, Sing Health Duke‐NUS Academic Medical Centre Singapore
                [38 ]Department of Internal Medicine Donald and Barbara Zucker School of Medicine Northwell Health, Manhasset, NY 11030 USA
                [39 ]Hepatology and Liver Transplant Unit, Hospital Universitario Austral Pilar Argentina
                [40 ]Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia; Central Clinical School, Department of Medicine Monash University Melbourne Victoria Australia
                [41 ]Department of Pathology Inonu University Faculty of Medicine Malatya 44280 Turkey
                [42 ]Division of Gastroenterology University of British Columbia and Vancouver General Hospital Vancouver Canada
                [43 ]Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases General University Hospital of Larissa Greece
                [44 ]European Reference Network on Hepatological Diseases (ERN RARE‐LIVER) General University Hospital of Larissa Larissa Greece
                [45 ]Hepatology Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas, CEMIC Ciudad Autónoma de Buenos Aires Argentina
                [46 ]Division of Liver Diseases, the Mount Sinai Medical Center New York USA
                [47 ]Hepatology Division, Department of Upper GI Diseases Karolinska Institutet and Karolinska University Hospital Stockholm Sweden
                Article
                10.1002/hep.32572
                c7c3abbc-eb9d-494d-b66b-ea89d109bd2e
                © 2022

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                http://doi.wiley.com/10.1002/tdm_license_1.1

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