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. © 2022 The Author(s)
ABSTRACT
Background: Vaccines provide effective protection against COVID-19. Nevertheless, concerns about their efficacy and safety have been reported.1-2 The term vaccine hesitancy refers to delay in the acceptance of vaccines (or total refusal) despite their availability.3 COVID-19 vaccination was strongly recommended for Liver Transplant (LT) recipients by the AASLD. The aim of our study was to assess COVID-19 vaccine hesitancy among LT patients, its reasons and possible determinants. Methods: Between January and February 2021, a web-based questionnaire was sent to LT patients followed at our liver transplant out-patient clinic in Milan, Italy. The questionnaire was adapted from a previous validated questionnaire.4 Patients were classified as willing, hesitant and refusing (totally opposing) to accept COVID-19 vaccination, and the reasons and possible factors influencing vaccine hesitancy were investigated. When the COVID-19 vaccines became available for LT candidates and recipients in Italy (March 2021), the entire cohort of LT recipients was contacted by phone and called for vaccination, and the rate of refusals recorded. Results: The web-based survey was sent to 583 patients, of whom 190 responded (response rate of 32.6%). Among the respondents, 157 (82.7%) were willing to be vaccinated against COVID-19, while 27 (14.2%) were hesitant and 6 (3.1%) did not answer this specific question. Among the hesitant, 3 were refusing, for a refusal rate of 1.5%. The reasons most frequently given by hesitant patients to justify their refusal (more than one could be indicated) was the fear of adverse events in 22/27 and concerns about the rapid development of COVID-19 vaccines in 17/27 (Figure). Thirteen hesitant patients (48.1%) answered that their COVID-19 vaccine hesitancy was influenced by being a transplant recipient. None of the possible determinants were significantly associated with vaccination hesitancy/refusal in multivariate analysis. Of the 667 patients followed at our Centre 628 were called by phone to be vaccinated and asked about their COVID-19 willingness and the 6.5% (41) of the patients refused the scheduled vaccination. Conclusion: Since it is crucial to achieve adequate vaccinations of LT patients, it is very important to identify the reasons influencing hesitancy so that appropriate patient-doctor communication can be established and specific vaccinations campaigns further implemented.
ABSTRACT
Background: Despite the dominance of respiratory disease, acute-on-chronic liver failure (ACLF) and acute decompensation (AD) have been reported in patients with COVID-19 and preexisting liver disease, in particular cirrhosis. Moreover, COVID-19 has been associated with increased mortality in patients with end-stage liver disease (ESLD). Aim our study is to evaluate the impact of SARS-CoV-2 infection in patients with ESLD listed for liver transplant (LT). Methods: Data from adults listed for LT with laboratory-confirmed SARS-CoV-2 infection were collected from 7 LT centers across Italy. Results: From March 1st to October 31st 2020, 29 patients listed for LT were tested positive for SARS-CoV-2 infection. Twenty-one patients (72%) were male, median age was 59 years (20-71). The most common indication (70%) for LT was ESLD. The mean MELD score was 18 (8-32). At diagnosis, twenty patients (69%) presented at least one symptom: 38% fever, 28% dry cough, and 31% respiratory distress. Notably, 25% of patients presented hepatic encephalopathy as first presenting symptom. The remaining 9 patients (31%) were completely asymptomatic: nasopharyngeal swab was performed according to surveillance protocols. Twenty-one patients (70%) required hospitalization for the management of COVID-19. Respiratory support was necessary in 13 patients (45%): 5 (17%) required O2-supply, 4 (14%) non-invasive ventilation and 4 (14%) mechanical ventilation. Only five patients (17%) received at least one drug for infection treatment (see table). Heparin was administrated in 7 patients (28%). No bleeding episodes were reported. Eight (%) patients died after a median time of 6 days (2-29) from Covid-19 diagnosis, with a 30-day-mortality rate of 30%. Three patients died of liver failure, while the remaining of multiple organ failures. In the univariate analysis, factors associated with 30-days mortality were respectively presence of comorbidities (0.07), severity of liver disease according to MELD score (0.05) and severity of respiratory failure (0.011). In the cox-regression analysis, only the severity of respiratory failure was significantly associated with the mortality (HR 3.13, IC 1.53-6.3). Conclusions: COVID-19 is associated with elevated mortality in LT candidates, listed for ESLD.