Histological and serological features of acute liver injury after SARS-CoV-2 vaccination

Greta Codoni; Theresa Kirchner; Bastian Engel; Alejandra Maria Villamil; Cumali Efe; Albert Friedrich Stättermayer; Jan Philipp Weltzsch; Marcial Sebode; Christine Bernsmeier; Ana Lleo; Tom Jg Gevers; Limas Kupčinskas; Agustin Castiella; Jose Pinazo; Eleonora De Martin; Ingrid Bobis; Thomas Damgaard Sandahl; Federica Pedica; Federica Invernizzi; Paolo Del Poggio; Tony Bruns; Mirjam Kolev; Nasser Semmo; Fernando Bessone; Baptiste Giguet; Guido Poggi; Masayuki Ueno; Helena Jang; Gülsüm Özlem Elpek; Neşe Karadağ Soylu; Andreas Cerny; Heiner Wedemeyer; Diego Vergani; Giorgina Mieli-Vergani; M Isabel Lucena; Raul J Andrade; Yoh Zen; Richard Taubert; Benedetta Terziroli Beretta-Piccoli

doi:10.1016/j.jhepr.2022.100605

Histological and serological features of acute liver injury after SARS-CoV-2 vaccination

Greta Codoni, Theresa Kirchner, Bastian Engel, Alejandra Maria Villamil, Cumali Efe, Albert Friedrich Stättermayer, Jan Philipp Weltzsch, Marcial Sebode, Christine Bernsmeier, Ana Lleo, Tom Jg Gevers, Limas Kupčinskas, Agustin Castiella, Jose Pinazo, Eleonora De Martin, Ingrid Bobis, Thomas Damgaard Sandahl, Federica Pedica, Federica Invernizzi, Paolo Del PoggioTony Bruns, Mirjam Kolev, Nasser Semmo, Fernando Bessone, Baptiste Giguet, Guido Poggi, Masayuki Ueno, Helena Jang, Gülsüm Özlem Elpek, Neşe Karadağ Soylu, Andreas Cerny, Heiner Wedemeyer, Diego Vergani, Giorgina Mieli-Vergani, M Isabel Lucena, Raul J Andrade, Yoh Zen, Richard Taubert, Benedetta Terziroli Beretta-Piccoli^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND & AIMS: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features.

METHODS: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited; 35 females; median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines.

RESULTS: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases; seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed.

CONCLUSION: Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition.

IMPACT AND IMPLICATIONS: Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition.

Original language	English
Article number	100605
Number of pages	13
Journal	JHEP Reports
Volume	5
Issue number	1
DOIs	https://doi.org/10.1016/j.jhepr.2022.100605
Publication status	Published - Jan 2023

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Codoni, G., Kirchner, T., Engel, B., Villamil, A. M., Efe, C., Stättermayer, A. F., Weltzsch, J. P., Sebode, M., Bernsmeier, C., Lleo, A., Gevers, T. J., Kupčinskas, L., Castiella, A., Pinazo, J., De Martin, E., Bobis, I., Sandahl, T. D., Pedica, F., Invernizzi, F., ... Terziroli Beretta-Piccoli, B. (2023). Histological and serological features of acute liver injury after SARS-CoV-2 vaccination. JHEP Reports, 5(1), Article 100605. https://doi.org/10.1016/j.jhepr.2022.100605

@article{d3d1e63c1d184b3da20f261afed01757,

title = "Histological and serological features of acute liver injury after SARS-CoV-2 vaccination",

abstract = "BACKGROUND & AIMS: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features.METHODS: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited; 35 females; median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines.RESULTS: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases; seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed.CONCLUSION: Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition.IMPACT AND IMPLICATIONS: Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition.",

author = "Greta Codoni and Theresa Kirchner and Bastian Engel and Villamil, {Alejandra Maria} and Cumali Efe and St{\"a}ttermayer, {Albert Friedrich} and Weltzsch, {Jan Philipp} and Marcial Sebode and Christine Bernsmeier and Ana Lleo and Gevers, {Tom Jg} and Limas Kup{\v c}inskas and Agustin Castiella and Jose Pinazo and {De Martin}, Eleonora and Ingrid Bobis and Sandahl, {Thomas Damgaard} and Federica Pedica and Federica Invernizzi and {Del Poggio}, Paolo and Tony Bruns and Mirjam Kolev and Nasser Semmo and Fernando Bessone and Baptiste Giguet and Guido Poggi and Masayuki Ueno and Helena Jang and Elpek, {G{\"u}ls{\"u}m {\"O}zlem} and Soylu, {Ne{\c s}e Karadağ} and Andreas Cerny and Heiner Wedemeyer and Diego Vergani and Giorgina Mieli-Vergani and Lucena, {M Isabel} and Andrade, {Raul J} and Yoh Zen and Richard Taubert and {Terziroli Beretta-Piccoli}, Benedetta",

note = "{\textcopyright} 2022 The Author(s).",

year = "2023",

month = jan,

doi = "10.1016/j.jhepr.2022.100605",

language = "English",

volume = "5",

journal = "JHEP Reports",

issn = "2589-5559",

publisher = "Elsevier BV",

number = "1",

}

Codoni, G, Kirchner, T, Engel, B, Villamil, AM, Efe, C, Stättermayer, AF, Weltzsch, JP, Sebode, M, Bernsmeier, C, Lleo, A, Gevers, TJ, Kupčinskas, L, Castiella, A, Pinazo, J, De Martin, E, Bobis, I, Sandahl, TD, Pedica, F, Invernizzi, F, Del Poggio, P, Bruns, T, Kolev, M, Semmo, N, Bessone, F, Giguet, B, Poggi, G, Ueno, M, Jang, H, Elpek, GÖ, Soylu, NK, Cerny, A, Wedemeyer, H, Vergani, D, Mieli-Vergani, G, Lucena, MI, Andrade, RJ, Zen, Y, Taubert, R & Terziroli Beretta-Piccoli, B 2023, 'Histological and serological features of acute liver injury after SARS-CoV-2 vaccination', JHEP Reports, vol. 5, no. 1, 100605. https://doi.org/10.1016/j.jhepr.2022.100605

TY - JOUR

T1 - Histological and serological features of acute liver injury after SARS-CoV-2 vaccination

AU - Codoni, Greta

AU - Kirchner, Theresa

AU - Engel, Bastian

AU - Villamil, Alejandra Maria

AU - Efe, Cumali

AU - Stättermayer, Albert Friedrich

AU - Weltzsch, Jan Philipp

AU - Sebode, Marcial

AU - Bernsmeier, Christine

AU - Lleo, Ana

AU - Gevers, Tom Jg

AU - Kupčinskas, Limas

AU - Castiella, Agustin

AU - Pinazo, Jose

AU - De Martin, Eleonora

AU - Bobis, Ingrid

AU - Sandahl, Thomas Damgaard

AU - Pedica, Federica

AU - Invernizzi, Federica

AU - Del Poggio, Paolo

AU - Bruns, Tony

AU - Kolev, Mirjam

AU - Semmo, Nasser

AU - Bessone, Fernando

AU - Giguet, Baptiste

AU - Poggi, Guido

AU - Ueno, Masayuki

AU - Jang, Helena

AU - Elpek, Gülsüm Özlem

AU - Soylu, Neşe Karadağ

AU - Cerny, Andreas

AU - Wedemeyer, Heiner

AU - Vergani, Diego

AU - Mieli-Vergani, Giorgina

AU - Lucena, M Isabel

AU - Andrade, Raul J

AU - Zen, Yoh

AU - Taubert, Richard

AU - Terziroli Beretta-Piccoli, Benedetta

PY - 2023/1

Y1 - 2023/1

N2 - BACKGROUND & AIMS: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features.METHODS: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited; 35 females; median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines.RESULTS: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases; seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed.CONCLUSION: Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition.IMPACT AND IMPLICATIONS: Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition.

AB - BACKGROUND & AIMS: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features.METHODS: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited; 35 females; median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines.RESULTS: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases; seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed.CONCLUSION: Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition.IMPACT AND IMPLICATIONS: Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition.

U2 - 10.1016/j.jhepr.2022.100605

DO - 10.1016/j.jhepr.2022.100605

M3 - Article

C2 - 36440259

SN - 2589-5559

VL - 5

JO - JHEP Reports

JF - JHEP Reports

IS - 1

M1 - 100605

ER -

Histological and serological features of acute liver injury after SARS-CoV-2 vaccination

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