COVID-19 Vaccination Effectiveness and Clinical Outcomes in Chronic Liver Disease: A Nationwide Retrospective Cohort Study

Abstract

Background/Aims: This study investigated the effectiveness of COVID-19 vaccination in decompensated cirrhosis. Methods: This study comprised a population-based cohort of 1 583 777 patients with chronic liver disease (CLD), including decompensated cirrhosis, from the National Health Insurance Service data in South Korea. The primary outcome was the risk of COVID-19 within 6 months after vaccination between 26 February 2021 and 31 December 2021. Hospitalisation and all-cause mortality rates were also investigated. Target trial specifications with propensity score matching were used to minimise the bias between the unvaccinated and vaccinated groups. Results: The mean age of patients was 54.2 years, and 54.5% were men. In total, 61 765 patients (3.9%) had decompensated cirrhosis. Compared to the unvaccinated group, the vaccinated group exhibited a lower risk of COVID-19 (hazard ratio [HR] = 0.94; 95% confidence interval [CI] = 0.91–0.97), hospitalisation (HR = 0.86; 95% CI = 0.83–0.89), and all-cause mortality (HR = 0.27; 95% CI = 0.20–0.36) in CLD. However, there was no statistical difference in the clinical outcomes among patients with decompensated cirrhosis with respect to COVID-19 vaccination. The multivariable analysis determined that COVID-19 vaccination reduced all-cause mortality in CLD (HR = 0.39; 95% CI = 0.32–0.49) and decompensated cirrhosis increased all-cause mortality in patients with COVID-19 (HR = 2.94; 95% CI = 2.15–4.02). These results were consistent during the pre-Delta and Delta-variant periods. Conclusions: COVID-19 vaccination reduced the risk of COVID-19, hospitalisation, and mortality in CLD. However, patients with decompensated cirrhosis had a poor prognosis independently of COVID-19 vaccination. © 2026 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.