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.

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Instituto de Salud Carlos 3 Madrid Spain

Department of Clinical Research Faculty of Health Sciences University of Southern Denmark Odense Denmark

Department of Gastroenterology and Hepatology Odense University Hospital Odense C Denmark

Department of Hepatogastroenterology Institute for Clinical and Experimental Medicine Health Care Provider of the European Reference Network on Rare Liver Disorders Prague Czech Republic

Department of Internal Medicine 1 and Clinical Chemistry Heidelberg University Hospital Heidelberg Germany

Department of Medicine Gastroenterology and Hepatology Unit Sahlgrenska University Hospital Health Care Provider of the European Reference Network on Rare Liver Disorders Gothenburg Sweden

Department of Pneumology Vall d'Hebron University Hospital Vall d'Hebron Research Institute Barcelona Spain

Division of Gastroenterology and Hepatology Department of Internal Medicine 3 Medical University of Vienna Health Care Provider of the European Reference Network on Rare Liver Disorders Vienna Austria

Institute of Applied Health Research University of Birmingham Birmingham UK

Institute of Forensic and Traffic Medicine Heidelberg University Hospital Heidelberg Germany

Liver Unit Hospital Universitari Vall d'Hebron Vall d'Hebron Research Institute Universitat Autonoma de Barcelona Barcelona Spain

Medical Clinic 3 Gastroenterology Metabolic Diseases and Intensive Care University Hospital RWTH Aachen Health Care Provider of the European Reference Network on Rare Liver Disorders Aachen Germany

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