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Morphologic and molecular analysis of liver injury after SARS-CoV-2 vaccination reveals distinct characteristics.
Uzun, Sarp; Zinner, Carl P; Beenen, Amke C; Alborelli, Ilaria; Bartoszek, Ewelina M; Yeung, Jason; Calgua, Byron; Reinscheid, Matthias; Bronsert, Peter; Stalder, Anna K; Haslbauer, Jasmin D; Vosbeck, Juerg; Mazzucchelli, Luca; Hoffmann, Tobias; Terracciano, Luigi M; Hutter, Gregor; Manz, Michael; Panne, Isabelle; Boettler, Tobias; Hofmann, Maike; Bengsch, Bertram; Heim, Markus H; Bernsmeier, Christine; Jiang, Sizun; Tzankov, Alexandar; Terziroli Beretta-Piccoli, Benedetta; Matter, Matthias S.
Afiliación
  • Uzun S; Institute of Pathology, University Hospital Basel, Basel, Switzerland.
  • Zinner CP; Institute of Pathology, University Hospital Basel, Basel, Switzerland.
  • Beenen AC; Institute of Pathology, University Hospital Basel, Basel, Switzerland.
  • Alborelli I; Institute of Pathology, University Hospital Basel, Basel, Switzerland.
  • Bartoszek EM; Microscopy Core Facility, Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Yeung J; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Calgua B; Institute of Pathology, University Hospital Basel, Basel, Switzerland.
  • Reinscheid M; Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany.
  • Bronsert P; Institute for Surgical Pathology, Freiburg University Medical Center, University of Freiburg, Freiburg, Germany; Core Facility for Histopathology and Digital Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Stalder AK; Institute of Pathology, University Hospital Basel, Basel, Switzerland.
  • Haslbauer JD; Institute of Pathology, University Hospital Basel, Basel, Switzerland.
  • Vosbeck J; Institute of Pathology, University Hospital Basel, Basel, Switzerland.
  • Mazzucchelli L; Istituto Cantonale di Patologia, Locarno, Switzerland.
  • Hoffmann T; Innere Medizin, Spital Dornach, Dornach, Switzerland.
  • Terracciano LM; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
  • Hutter G; Brain Tumor Immunotherapy Lab, Department of Biomedicine, University of Basel, Basel, Switzerland; Department of Neurosurgery, University Hospital Basel, Basel, Switzerland.
  • Manz M; Gastroenterology and Hepatology, University Centre for Gastrointestinal and Liver Diseases Basel, Switzerland.
  • Panne I; Gastroenterology and Hepatology, University Centre for Gastrointestinal and Liver Diseases Basel, Switzerland.
  • Boettler T; Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Hofmann M; Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Bengsch B; 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; Partner Site Fr
  • Heim MH; Gastroenterology and Hepatology, University Centre for Gastrointestinal and Liver Diseases Basel, Switzerland; Department of Biomedicine, University of Basel, Switzerland.
  • Bernsmeier C; Gastroenterology and Hepatology, University Centre for Gastrointestinal and Liver Diseases Basel, Switzerland; Department of Biomedicine, University of Basel, Switzerland.
  • Jiang S; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Pathology, Dana Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Tzankov A; Institute of Pathology, University Hospital Basel, Basel, Switzerland.
  • Terziroli Beretta-Piccoli B; Faculty of Biomedical Sciences, Università Della Svizzera Italiana, Lugano, Switzerland; Epatocentro Ticino, Lugano, Switzerland; MowatLabs, Faculty of Life Sciences and Medicine, King's College London, King's College Hospital, London, UK.
  • Matter MS; Institute of Pathology, University Hospital Basel, Basel, Switzerland. Electronic address: matthias.matter@usb.ch.
J Hepatol ; 79(3): 666-676, 2023 09.
Article en En | MEDLINE | ID: mdl-37290592
BACKGROUND & AIMS: Liver injury after COVID-19 vaccination is very rare and shows clinical and histomorphological similarities with autoimmune hepatitis (AIH). Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury (VILI) and its relationship to AIH. Therefore, we compared VILI with AIH. METHODS: Formalin-fixed and paraffin-embedded liver biopsy samples from patients with VILI (n = 6) and from patients with an initial diagnosis of AIH (n = 9) were included. Both cohorts were compared by histomorphological evaluation, whole-transcriptome and spatial transcriptome sequencing, multiplex immunofluorescence, and immune repertoire sequencing. RESULTS: Histomorphology was similar in both cohorts but showed more pronounced centrilobular necrosis in VILI. Gene expression profiling showed that mitochondrial metabolism and oxidative stress-related pathways were more and interferon response pathways were less enriched in VILI. Multiplex analysis revealed that inflammation in VILI was dominated by CD8+ effector T cells, similar to drug-induced autoimmune-like hepatitis. In contrast, AIH showed a dominance of CD4+ effector T cells and CD79a+ B and plasma cells. T-cell receptor (TCR) and B-cell receptor sequencing showed that T and B cell clones were more dominant in VILI than in AIH. In addition, many T cell clones detected in the liver were also found in the blood. Interestingly, analysis of TCR beta chain and Ig heavy chain variable-joining gene usage further showed that TRBV6-1, TRBV5-1, TRBV7-6, and IgHV1-24 genes are used differently in VILI than in AIH. CONCLUSIONS: Our analyses support that SARS-CoV-2 VILI is related to AIH but also shows distinct differences from AIH in histomorphology, pathway activation, cellular immune infiltrates, and TCR usage. Therefore, VILI may be a separate entity, which is distinct from AIH and more closely related to drug-induced autoimmune-like hepatitis. IMPACT AND IMPLICATIONS: Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury (VILI). Our analysis shows that COVID-19 VILI shares some similarities with autoimmune hepatitis, but also has distinct differences such as increased activation of metabolic pathways, a more prominent CD8+ T cell infiltrate, and an oligoclonal T and B cell response. Our findings suggest that VILI is a distinct disease entity. Therefore, there is a good chance that many patients with COVID-19 VILI will recover completely and will not develop long-term autoimmune hepatitis.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Hepatitis Autoinmune / Enfermedad Hepática Crónica Inducida por Sustancias y Drogas / COVID-19 Idioma: En Revista: J Hepatol Asunto de la revista: GASTROENTEROLOGIA Año: 2023 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Hepatitis Autoinmune / Enfermedad Hepática Crónica Inducida por Sustancias y Drogas / COVID-19 Idioma: En Revista: J Hepatol Asunto de la revista: GASTROENTEROLOGIA Año: 2023 Tipo del documento: Article