Histologic Features of Liver Injury Associated With SARS-CoV-2 Messenger RNA Vaccines.

Many drugs can induce liver injury; however, vaccine-induced liver injury is a rare phenomenon. SARS-CoV-2 messenger RNA (mRNA) vaccines are now widely administered, and clinical evidence of liver injury has been reported. To characterize the histologic features of SARS-CoV-2 mRNA vaccine-associated liver injury. Thirteen liver biopsies from 12 patients with elevated liver enzymes clinically favored to be secondary to SARS-CoV-2 mRNA vaccine were identified between 2021 and 2022. Demographics, clinical information, and histologic features of liver biopsies were reviewed. All patients (median age, 58 years; M:F = 4:8) received at least 1 dose of SARS-CoV-2 mRNA vaccines (7 Pfizer and 5 Moderna). Four patients had a history of liver disease. Nine patients developed symptoms between 1 day and 2 months after receiving the vaccine dose. Viral serologies were negative. Drug-induced liver injury was thought to be less likely clinically in the 3 patients who had started new medications. Autoimmune antibodies were detected in 9 patients. Moderate to severe active hepatitis was the dominant histologic pattern of injury (9 of 13 biopsies; 69%). Resolving hepatitis, cholestatic hepatitic injury, and bile duct injury were identified in 1 biopsy each. All patients recovered spontaneously or with steroid therapy except one patient who developed autoimmune hepatitis. Moderate to severe active hepatitis is commonly observed in SARS-CoV-2 mRNA vaccine-associated liver injury, and female patients may be more susceptible to injury. Liver injury resolves spontaneously or with steroid treatment. In rare cases, these vaccines may trigger an underlying immune condition.

Obeng RC ，Escobar DJ ，Vadasz B ，Zheng W ，Ju JY ，Booth AL ，Yang GY ，Al Diffalha S ，Dhall D ，Westerhoff M ，Xue Y ... -  《-》

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

Efe C ，Kulkarni AV ，Terziroli Beretta-Piccoli B ，Magro B ，Stättermayer A ，Cengiz M ，Clayton-Chubb D ，Lammert C ，Bernsmeier C ，Gül Ö ，la Tijera FH ，Anders M ，Lytvyak E ，Akın M ，Purnak T ，Liberal R ，Peralta M ，Ebik B ，Duman S ，Demir N ，Balaban Y ，Urzua Á ，Contreras F ，Venturelli MG ，Bilgiç Y ，Medina A ，Girala M ，Günşar F ，Londoño MC ，Androutsakos T ，Kisch A ，Yurci A ，Güzelbulut F ，Çağın YF ，Avcı E ，Akyıldız M ，Dindar-Demiray EK ，Harputluoğlu M ，Kumar R ，Satapathy SK ，Mendizabal M ，Silva M ，Fagiuoli S ，Roberts SK ，Soylu NK ，Idilman R ，Yoshida EM ，Montano-Loza AJ ，Dalekos GN ，Ridruejo E ，Schiano TD ，Wahlin S ... -  《-》

Immunogenicity and safety of a booster dose of a self-amplifying RNA COVID-19 vaccine (ARCT-154) versus BNT162b2 mRNA COVID-19 vaccine: a double-blind, multicentre, randomised, controlled, phase 3, non-inferiority trial.

Oda Y ，Kumagai Y ，Kanai M ，Iwama Y ，Okura I ，Minamida T ，Yagi Y ，Kurosawa T ，Greener B ，Zhang Y ，Walson JL ... -  《-》

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

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. 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. 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. 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. 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.

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 ... -  《-》

Outcomes and factors associated with relapse of vaccine-induced liver injury after SARS CoV-2 immunization: A nationwide study.

Different patterns of liver injury have been reported in association with the SARS-CoV-2 vaccines. The aim of this study was to describe a nationwide cohort of patients with SARS CoV-2 vaccine-induced liver injury, focusing on treatment and the evolution after further booster administration. multicentre, retrospective-prospective study, including subjects who developed abnormal liver tests within 90 days after administration of SARS-CoV-2 vaccination. 47 cases were collected: 17 after prime dose and 30 after booster. Age was 57 years, 30 (63.8 %) were female, and 7 (14.9 %) had a history of prior autoimmune hepatitis (AIH). Most cases were non-severe, though 9 (19.1 %) developed acute liver injury or failure (ALF). Liver injury tended to be more severe in those presenting after a booster (p=0.084). Pattern of liver injury was hepatocellular (80.9 %), mixed (12.8 %) and 3 (6.4 %) cholestatic. Liver biopsy was performed on 33 patients; 29 showed findings of AIH. Forty-one (87.2 %) patients received immunosuppressants, mostly corticosteroids (35/41). One required liver transplantation and another died due to ALF. Immunosuppression was discontinued in 6/41 patients without later rebound. Twenty-five subjects received at least one booster and 7 (28.0 %) relapsed from the liver injury, but all were non-severe. Recurrence was less frequent among patients on immunosuppressants at booster administration (28.6 % vs. 88.9 %, p=0.007). SARS CoV-2 vaccine-induced liver injury is heterogeneous but mostly immune-mediated. Relapse of liver injury after re-exposure to vaccine is frequent (28.0 %) but mild. Immunosuppression at booster administration is associated with a lower risk of liver injury.

Barreira-Díaz A ，Riveiro-Barciela M ，Fernández-Bonilla EM ，Bernal V ，Castiella A ，Casado-Martín M ，Delgado C ，Londoño MC ，Díaz-González Á ，Pérez-Medrano I ，Conthe A ，Sala M ，Mateos B ，Gómez-Camarero J ，Antón-Conejero D ，Pozo-Calzada CD ，Cuenca F ，Villagrasa-Vilella A ，Salcedo M ... -  《Annals of Hepatology》