Since the onset of the COVID-19 pandemic, SARS-CoV-2 vaccine development has progressed at an unprecedented rate, with recent phase 3 trial data offering the tantalising prospect of achieving herd immunity.1, 2, 3 Until now, researchers have focused on the contribution of specific liver disease phenotypes, including transplantation and immunosuppression, to COVID-19 susceptibility and outcome. However, the hepatology community must now urgently turn its attention to characterising SARS-CoV-2 vaccine responses in these vulnerable patient groups. The Pfizer/BioNTech BNT162b2 mRNA, Moderna mRNA-1273, and the AstraZeneca/University of Oxford ChAdOx1-nCoV-19 chimpanzee adenovirus (ChAd) vector vaccines have each reported excellent safety profiles, marked efficacy in preventing symptomatic COVID-19 (62–95%), and have all gained rapid regulatory approval.1, 2, 3 Currently, it remains unclear why a significant minority of those vaccinated appear susceptible to SARS-CoV-2, although both host factors (eg, underlying chronic diseases or genetic susceptibility) and viral factors (eg, high viral load exposure, specific viral variants) are likely to have a contributory role. Despite the inclusion of nearly 100 000 participants in these trials, data for patients with liver disease are extremely limited (panel ). In the Pfizer vaccination study, 217 (0·6%) of 37 706 participants had liver disease, and only three (<0·1%) had moderate to severe liver disease. A similarly low proportion of patients with liver disease were included in the Moderna trial (196 [0·6%] of 30 351). The ChAdOx1-nCoV-19 vaccine trial explicitly omitted patients with pre-existing liver pathology. Notably, in each study the criteria used to classify liver disease and its severity remain unclear. In addition, all trials listed systemic immunosuppression as an exclusion criterion, thus preventing extrapolation of the data to immunosuppressed liver transplant recipients or patients with autoimmune liver disease. Furthermore, granular detail regarding liver safety profiles remains largely unpublished, although abnormal liver biochemistry was reported in only one of 12 021 participants receiving ChAdOx1-nCoV-19. ChAd vaccines for hepatitis C virus (HCV) have previously been safely given to a small number of patients with non-cirrhotic chronic HCV infection.4 However, a detailed understanding of SARS-CoV-2 vaccine safety and the immunological response in patients with liver disease will almost exclusively come from post-licensing, real-world investigation.