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Background & Aims: Cirrhosis is associated with immune dysregulation and hyporesponsiveness to several vaccines including those against COVID-19. Our aim was to compare outcomes between patients with cirrhosis who received 3 doses of either the Pfizer BNT162b2 mRNA or Moderna mRNA-1273 vaccines to a propensity-matched control group of patients at similar risk of infection who received 2 doses.
Methods: This was a retrospective cohort study of patients with cirrhosis who received 2 or 3 doses of a COVID-19 mRNA vaccine at the Veterans Health Administration. Participants who received 3 doses of the vaccine (n = 13,041) were propensity score matched with 13,041 controls who received 2 doses, and studied between July 18, 2021 and February 11, 2022, when B.1.617.2 (delta) and B.1.1.529 (omicron) were the predominant variants. Outcomes were aggregated as all cases with COVID-19, symptomatic COVD-19, with at least moderate COVID-19, or severe or critical COVID-19.
Results: Receipt of the third dose of a COVID-19 mRNA vaccine was associated with an 80.7% reduction in COVID-19 (95% CI 39.2-89.1, p <0.001), an 80.4% reduction in symptomatic COVID-19, an 80% reduction in moderate, severe or critical COVID-19, (95% CI 34.5-87.6%, p = 0.005), a 100% reduction in severe or critical COVID-19 (95% CI 99.2-100.0, p = 0.01), and a 100% reduction in COVID-19-related death (95% CI 99.8-100.0, p = 0.007). The magnitude of reduction in COVID-19 was greater with the third dose of BNT 162b2 than mRNA-1273 and among participants with compensated rather than decompensated cirrhosis.
Conclusions: Administration of a third dose of a COVID-19 mRNA vaccine was associated with a more significant reduction in COVID-19 in patients with cirrhosis than in the general population, suggesting that the third dose can overcome vaccine hyporesponsiveness in this population.
Lay Summary: Cirrhosis is associated with decreased responsiveness to several vaccines, including those against COVID-19. In this study of 26,082 participants with cirrhosis during the delta and omicron surge, receipt of the third dose of the vaccine was associated with an 80% reduction in COVID-19, a 100% reduction in severe/critical COVID-19, and a 100% reduction in COVID-19-related death. These findings support the importance of a third dose of mRNA vaccine among patients with cirrhosis.
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http://dx.doi.org/10.1016/j.jhep.2022.07.036 | DOI Listing |
Br J Haematol
September 2025
Department of Hematology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Refractory cytomegalovirus (CMV) infection is a severe complication following umbilical cord blood transplantation (UCBT). Antiviral agents, the standard first-line therapy, are limited by toxicity and resistance without robust T-cell immunity. We evaluated third-party donor (TPD)-derived CMV-specific T cells (CMVSTs) as a treatment option.
View Article and Find Full Text PDFBiom J
October 2025
Novella Clinical Full Service, IQVIA, Melbourne, Australia.
Phase I dose escalation trials in oncology generally aim to find the maximum tolerated dose. However, with the advent of molecular-targeted therapies and antibody drug conjugates, dose-limiting toxicities are less frequently observed, giving rise to the concept of optimal biological dose (OBD), which considers both efficacy and toxicity. The estimand framework presented in the addendum of the ICH E9(R1) guidelines strengthens the dialogue between different stakeholders by bringing in greater clarity in the clinical trial objectives and by providing alignment between the targeted estimand under consideration and the statistical analysis methods.
View Article and Find Full Text PDFCell Commun Signal
September 2025
Department of Cytology, Institute of Anatomy, Medical Faculty, Ruhr-University Bochum, Universitätsstr. 150, Building MA 5/52, Bochum, 44801, Germany.
Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by oxidative stress and progressive motor neuron degeneration. This study evaluates the potential neuroprotective effects of caffeine in the Wobbler mouse, an established model of ALS.
Methods: Wobbler mice received caffeine supplementation (60 mg/kg/day) via drinking water, and key parameters, including muscle strength, NAD metabolism, oxidative stress, and motor neuron morphology, were assessed at critical disease stages.
Thorax
September 2025
Usher Institute, The University of Edinburgh, Edinburgh, UK
Background: The long-acting monoclonal antibody nirsevimab and respiratory syncytial virus (RSV) vaccines became available for prevention of severe RSV-associated disease in 2023. While clinical trials showed good efficacy and safety, their restrictive inclusion criteria, small sample sizes and short follow-up limit generalisability. We aimed to summarise real-world evidence on the effectiveness and safety of nirsevimab, RSV maternal vaccine and RSV vaccines for older adults.
View Article and Find Full Text PDFTransplant Cell Ther
September 2025
Department of Hematology, Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
Background: Umbilical cord blood transplantation (UCBT) is a valuable treatment option with the potential for curative outcomes in patients with myeloid malignancies in non-remission status, but relapse and early non-relapse mortality (NRM) remain significant barriers. Tacrolimus and mycophenolate mofetil (MMF) are widely used as graft-versus-host disease (GVHD) prophylaxis in UCBT, but there is no consensus on the appropriate MMF dose for GVHD prophylaxis.
Objectives: We conducted a retrospective analysis to investigate the impact of MMF dose on outcomes in patients undergoing UCBT at our institution.