tetano
Editor, Senior Moderator
JHEP Rep
. 2022 Oct 13;5(1):100605.
doi: 10.1016/j.jhepr.2022.100605. eCollection 2023 Jan.
Histological and serological features of acute liver injury after SARS-CoV-2 vaccination
Greta Codoni[SUP] 1 [/SUP], Theresa Kirchner[SUP] 2 3 [/SUP], Bastian Engel[SUP] 2 3 [/SUP], Alejandra Maria Villamil[SUP] 4 [/SUP], Cumali Efe[SUP] 5 [/SUP], Albert Friedrich Stättermayer[SUP] 6 [/SUP], Jan Philipp Weltzsch[SUP] 7 3 [/SUP], Marcial Sebode[SUP] 7 3 [/SUP], Christine Bernsmeier[SUP] 8 [/SUP], Ana Lleo[SUP] 9 10 [/SUP], Tom Jg Gevers[SUP] 3 11 [/SUP], Limas Kupčinskas[SUP] 3 12 [/SUP], Agustin Castiella[SUP] 13 [/SUP], Jose Pinazo[SUP] 14 [/SUP], Eleonora De Martin[SUP] 15 [/SUP], Ingrid Bobis[SUP] 16 [/SUP], Thomas Damgaard Sandahl[SUP] 17 [/SUP], Federica Pedica[SUP] 18 [/SUP], Federica Invernizzi[SUP] 18 [/SUP], Paolo Del Poggio[SUP] 19 [/SUP], Tony Bruns[SUP] 3 20 [/SUP], Mirjam Kolev[SUP] 21 [/SUP], Nasser Semmo[SUP] 21 [/SUP], Fernando Bessone[SUP] 22 [/SUP], Baptiste Giguet[SUP] 23 [/SUP], Guido Poggi[SUP] 24 [/SUP], Masayuki Ueno[SUP] 25 26 [/SUP], Helena Jang[SUP] 27 [/SUP], Gülsüm Özlem Elpek[SUP] 28 [/SUP], Neşe Karadağ Soylu[SUP] 29 [/SUP], Andreas Cerny[SUP] 30 [/SUP], Heiner Wedemeyer[SUP] 2 3 [/SUP], Diego Vergani[SUP] 31 [/SUP], Giorgina Mieli-Vergani[SUP] 31 [/SUP], M Isabel Lucena[SUP] 14 32 [/SUP], Raul J Andrade[SUP] 14 32 [/SUP], Yoh Zen[SUP] 31 [/SUP], Richard Taubert[SUP] 2 3 [/SUP], Benedetta Terziroli Beretta-Piccoli[SUP] 1 30 31 [/SUP]
Affiliations
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.
Keywords: AIH, autoimmune hepatitis; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AMA, anti-mitochondrial antibody; ANA, anti-nuclear antibody; AST, aspartate aminotransferase; COVID-19, coronavirus disease 2019; DILI, drug-induced liver injury; IAIHG, International Autoimmune Hepatitis Group; IFT, indirect immunofluorescence; LKM, liver kidney microsomal; LT, liver transplantation; PCA, parietal cell antigen; SARS-CoV-2 vaccines; SARS-CoV-2, severe acute respiratory syndrome coronavirus type 2; SLA, soluble liver antigen; SMA, anti-smooth muscle antibody; ULN, upper limit of normal; acute liver injury; autoimmune liver serology; liver histology; pIgG, polyreactive IgG.
. 2022 Oct 13;5(1):100605.
doi: 10.1016/j.jhepr.2022.100605. eCollection 2023 Jan.
Histological and serological features of acute liver injury after SARS-CoV-2 vaccination
Greta Codoni[SUP] 1 [/SUP], Theresa Kirchner[SUP] 2 3 [/SUP], Bastian Engel[SUP] 2 3 [/SUP], Alejandra Maria Villamil[SUP] 4 [/SUP], Cumali Efe[SUP] 5 [/SUP], Albert Friedrich Stättermayer[SUP] 6 [/SUP], Jan Philipp Weltzsch[SUP] 7 3 [/SUP], Marcial Sebode[SUP] 7 3 [/SUP], Christine Bernsmeier[SUP] 8 [/SUP], Ana Lleo[SUP] 9 10 [/SUP], Tom Jg Gevers[SUP] 3 11 [/SUP], Limas Kupčinskas[SUP] 3 12 [/SUP], Agustin Castiella[SUP] 13 [/SUP], Jose Pinazo[SUP] 14 [/SUP], Eleonora De Martin[SUP] 15 [/SUP], Ingrid Bobis[SUP] 16 [/SUP], Thomas Damgaard Sandahl[SUP] 17 [/SUP], Federica Pedica[SUP] 18 [/SUP], Federica Invernizzi[SUP] 18 [/SUP], Paolo Del Poggio[SUP] 19 [/SUP], Tony Bruns[SUP] 3 20 [/SUP], Mirjam Kolev[SUP] 21 [/SUP], Nasser Semmo[SUP] 21 [/SUP], Fernando Bessone[SUP] 22 [/SUP], Baptiste Giguet[SUP] 23 [/SUP], Guido Poggi[SUP] 24 [/SUP], Masayuki Ueno[SUP] 25 26 [/SUP], Helena Jang[SUP] 27 [/SUP], Gülsüm Özlem Elpek[SUP] 28 [/SUP], Neşe Karadağ Soylu[SUP] 29 [/SUP], Andreas Cerny[SUP] 30 [/SUP], Heiner Wedemeyer[SUP] 2 3 [/SUP], Diego Vergani[SUP] 31 [/SUP], Giorgina Mieli-Vergani[SUP] 31 [/SUP], M Isabel Lucena[SUP] 14 32 [/SUP], Raul J Andrade[SUP] 14 32 [/SUP], Yoh Zen[SUP] 31 [/SUP], Richard Taubert[SUP] 2 3 [/SUP], Benedetta Terziroli Beretta-Piccoli[SUP] 1 30 31 [/SUP]
Affiliations
- PMID: 36440259
- PMCID: PMC9691430
- DOI: 10.1016/j.jhepr.2022.100605
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.
Keywords: AIH, autoimmune hepatitis; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AMA, anti-mitochondrial antibody; ANA, anti-nuclear antibody; AST, aspartate aminotransferase; COVID-19, coronavirus disease 2019; DILI, drug-induced liver injury; IAIHG, International Autoimmune Hepatitis Group; IFT, indirect immunofluorescence; LKM, liver kidney microsomal; LT, liver transplantation; PCA, parietal cell antigen; SARS-CoV-2 vaccines; SARS-CoV-2, severe acute respiratory syndrome coronavirus type 2; SLA, soluble liver antigen; SMA, anti-smooth muscle antibody; ULN, upper limit of normal; acute liver injury; autoimmune liver serology; liver histology; pIgG, polyreactive IgG.