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Background and Aims: Alpha‐1 antitrypsin deficiency is an inherited disorder caused by alpha‐1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver‐related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium. Methods: Reported alcohol consumption was evaluated in two cohorts: (i) the community‐based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non‐carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals). Cohort (ii) included measurements of carbohydrate‐deficient transferrin (CDT). Results: In both cohorts, no/low alcohol intake was reported by >80% of individuals, while harmful consumption was rare (~1%). Among Pi*MM and Pi*MZ individuals from cohort (i), moderate alcohol consumption resulted in a <30% increased rate of elevated transaminases and ~50% increase in elevated gamma‐glutamyl transferase values, while harmful alcohol intake led to an at least twofold increase in the abnormal levels. In Pi*ZZ individuals from both cohorts, moderate alcohol consumption had no marked impact on serum transaminase levels. Among Pi*ZZ subjects from cohort (ii) who reported no/low alcohol consumption, those with increased CDT levels more often had signs of advanced liver disease. Conclusions: Pi*MZ/Pi*ZZ genotype does not seem to markedly aggravate the hepatic toxicity of moderate alcohol consumption. CDT values might be helpful to detect alcohol consumption in those with advanced fibrosis. More data are needed to evaluate the impact of harmful alcohol consumption. [ABSTRACT FROM AUTHOR]

The immunogenicity of repeated vaccination and hybrid immunity in vulnerable patients remains unclear. We studied the impact of iterative Covid-19 mRNA vaccination and hybrid immunity on antibody levels in immunosuppressed subjects. Patients with liver cirrhosis (n = 38), survivors of allogeneic haematopoietic stem cell transplantation (allo-HSCT) (n = 36) and patients with autoimmune liver disease (n = 14) along with healthy controls (n = 20) were monitored for SARS-CoV-2-S1 IgG after their 1st–3rd vaccine doses, 31 of whom became infected with the Omicron variant after the 2nd dose. Ten uninfected allo-HSCT recipients received an additional 4th vaccine dose. Unexpectedly, immunosuppressed patients achieved antibody levels in parity with controls after the 3rd vaccine dose. In all study cohorts, hybrid immunity (effect of vaccination and natural infection) resulted in approximately 10-fold higher antibody levels than vaccine-induced immunity alone. Three doses of the Covid-19 mRNA vaccine entailed high antibody concentrations even in immunocompromised individuals, and hybrid-immunity resulted further augmented levels than vaccination alone. Clinical trial registration: EudraCT 2021-000349-42 [ABSTRACT FROM AUTHOR]