ABSTRACT
Background: Patients with advanced liver disease have well recognized deficiencies in innate and humoral immunity. Phase 3 trials on both BNT162b2 and mRNA-1273 included an extremely limited number of patients with liver disease, and ChAdOx1-nCoV-19 vaccine completely omitted patients with pre-existing liver diseases. Real life data on vaccine response in cirrhotic patients are lacking. To characterize the vaccine response in patients with liver cirrhosis (LC) considered possibly susceptible to SARS-CoV-2 after vaccination. Methods: Levels of binding antibodies and antigen specific B cells against a recombinant GFP tagged SARS-CoV-2 vaccine S protein and total T and NK in patients with established diagnosis of cirrhosis were evaluated by a combined approach based on serological anti-SARS-CoV-2 QuantiVac ELISA (EUROIMMUN) for IgG to the receptor binding domain (RBD) of viral spike protein (S-protein) and flow cytometry analyses. Both assays were performed at baseline before the first BNT162b2 dose, 7 days after the first dose and 10 days after the second dose. Results were compared with those of a group of healthcare workers (HW) comparable for age and gender. The study is ongoing. Further samples will be collected 60 and 180 days after the second dose. Results: Levels of circulating antibodies, antigen specific B cells and total T and NK-T cells were evaluated in 30 LC mostly of HCV- or HBV- related etiology, naive to COVID-19 infection, vaccinated with BNT162b2 mRNA. The majority of patients were male (58%), mean age was 64.36 ± 5.1 yrs. In 30% of LC, as compared to 40% of HW, antiS1 spike IgG antibodies at day 7 were above the positivity threshold. Mean titers were not different from those observed in HW at the same time-point (154.79±10.9 BAU/ml vs 153.5±29.0 BAU/ml). Levels of antigen specific B cells were increased as compared to healthcare workers (p=0.05). B cell response is shown in the Figure. In addition, helper T-cells and cytotoxic T-cells response was increased in LC as compared to HW (p=0.06). These differences were age-independent. Ten days after the second dose mean anti S1 antibody levels were significantly lower than those observed in HW: 836.60± 657.7 vs 1001±705.7 (p<0.0001). Conclusion: Patients with liver cirrhosis showed an initial cellular immune response to SARS-CoV-2 vaccination stronger than that of HW. This ongoing study will shed light on a possible clonal exhaustion phenomenon occurring in LC patients of viral etiology.