Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany.
Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain.
Liver Int. 2024 Oct;44(10):2660-2671. doi: 10.1111/liv.16044. Epub 2024 Jul 19.
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 PiZ AAT variant (PiMZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium.
Reported alcohol consumption was evaluated in two cohorts: (i) the community-based United Kingdom Biobank (17 145 PiMZ, 141 PiZZ subjects, and 425 002 non-carriers [PiMM]); and (ii) the European Alpha1 liver consortium (561 PiZZ individuals). Cohort (ii) included measurements of carbohydrate-deficient transferrin (CDT).
In both cohorts, no/low alcohol intake was reported by >80% of individuals, while harmful consumption was rare (~1%). Among PiMM and PiMZ 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 PiZZ individuals from both cohorts, moderate alcohol consumption had no marked impact on serum transaminase levels. Among PiZZ subjects from cohort (ii) who reported no/low alcohol consumption, those with increased CDT levels more often had signs of advanced liver disease.
PiMZ/PiZZ 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.
α-1 抗胰蛋白酶缺乏症是一种由 α-1 抗胰蛋白酶 (AAT) 突变引起的遗传性疾病。我们分析了英国生物库和欧洲 Alpha1 肝脏联合会中发现的杂合子/纯合子 PiZ AAT 变异体（PiMZ/Pi*ZZ 基因型）个体的饮酒与肝脏相关参数之间的关系。
在两个队列中评估了报告的饮酒量：（i）基于社区的英国生物库（17145 名 PiMZ、141 名 PiZZ 受试者和 425002 名非携带者[PiMM]）；和（ii）欧洲 Alpha1 肝脏联合会（561 名 PiZZ 个体）。队列（ii）包括对碳水化合物缺乏转铁蛋白 (CDT) 的测量。
在两个队列中，>80%的个体报告无/低酒精摄入，而有害饮酒则很少见（~1%）。在队列（i）的 PiMM 和 PiMZ 个体中，适度饮酒导致转氨酶升高的速度增加<30%，γ-谷氨酰转移酶值增加约 50%，而有害饮酒导致异常水平增加至少两倍。在来自两个队列的 PiZZ 个体中，适度饮酒对血清转氨酶水平没有明显影响。在队列（ii）中报告无/低酒精摄入的 PiZZ 受试者中，那些 CDT 水平升高的人更常出现晚期肝病的迹象。
PiMZ/PiZZ 基因型似乎不会显著加重中度饮酒引起的肝毒性。CDT 值可能有助于检测那些有晚期纤维化的人饮酒情况。需要更多的数据来评估有害饮酒的影响。
