TY  - JOUR
AU  - Uzun, Sarp
AU  - Zinner, Carl
AU  - Beenen, Amke C
AU  - Alborelli, Ilaria
AU  - Bartoszek, Ewelina M
AU  - Yeung, Jason
AU  - Calgua, Byron
AU  - Reinscheid, Matthias
AU  - Bonsert, Peter
AU  - Stalder, Anna K
AU  - Haslbauer, Jasmine
AU  - Vosbeck, Jürg
AU  - Mazzucchelli, Luca
AU  - Hoffmann, Tobias
AU  - Terracciano, Luigi M
AU  - Hutter, Gregor
AU  - Manz, Michael
AU  - Panne, Isabelle
AU  - Böttler, Tobias
AU  - Hofmann, Maike
AU  - Bengsch, Bertram
AU  - Heim, Markus H
AU  - Bernsmeier, Christine
AU  - Jiang, Sizun
AU  - Tzankov, Alexandar
AU  - Beretta-Piccoli, Benedetta Terziroli
AU  - Matter, Matthias S
TI  - Morphologic and molecular analysis of liver injury after SARS-CoV-2 vaccination reveals distinct characteristics.
JO  - Journal of hepatology
VL  - 79
IS  - 3
SN  - 0168-8278
CY  - [Erscheinungsort nicht ermittelbar]
PB  - Wiley-Blackwell
M1  - DKFZ-2023-01138
SP  - 666-676
PY  - 2023
N1  - 2023 Sep;79(3):666-676
AB  - 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.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.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 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 (DI-AILH). 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 (BCR) 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.Our analyses support that SARS-CoV-2 vaccination-induced liver injury is related to AIH but also shows distinct differences from AIH in histomorphology, pathway activation, cellular immune infiltrates, and TCR usage. VILI may be a separate entity, which is distinct from AIH and more closely related to DI-AILH.Little is known about the pathophysiology of COVID-19 vaccine-induced liver injury. Our analysis shows that COVID-19 vaccine-induced liver injury 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 vaccine-induced liver injury is a distinct disease entity. Therefore, there is a good chance that many patients with COVID-19 vaccine-induced liver injury will recover completely and do not develop long-term autoimmune hepatitis.
KW  - Autoimmune hepatitis (Other)
KW  - COVID-19 (Other)
KW  - Drug Induced Liver Injury (Other)
KW  - SARS-CoV-2 (Other)
KW  - vaccination (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37290592
DO  - DOI:10.1016/j.jhep.2023.05.020
UR  - https://inrepo02.dkfz.de/record/276757
ER  -