Alcohol consumption and liver phenotype of individuals with alpha-1 antitrypsin deficiency

Abstract

Alcohol; Liver cirrhosis; Liver fibrosis

Alcohol; Cirrosis hepática; Fibrosis hepática

Alcohol; Cirrosi hepàtica; Fibrosi hepàtica

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.

This work was supported by the EASL registry grant on alpha-1 antitrypsin-related liver disease, the DFG grants STR1095/6-1 (to P.S.) and SFB 1382 (ID 403224013) (to P.S., N.G. and C.T.), the Interdisciplinary Centre for Clinical Research within the Faculty of Medicine at the RWTH Aachen University (PTD 1-3) (to M.F. and P.S.), the German Liver Foundation (to M.F.) and an unrestricted grant from CSL Behring. The participation of the Vall d'Hebron Research Institute (VHIR) was supported by an unrestricted grant from Grifols to the Catalan Center for Alpha-1 antitrypsin deficiency.