Alpha-1 antitrypsin deficiency (AATD) arises from mutations in the SERPINA1 gene encoding alpha-1 antitrypsin (AAT) that lead to AAT retention in the endoplasmic reticulum of hepatocytes, causing proteotoxic liver injury and loss-of-function lung disease. The homozygous Pi∗Z mutation (Pi∗ZZ genotype) is responsible for the majority of severe AATD cases and can precipitate both paediatric and adult liver diseases, while the heterozygous Pi∗Z mutation (Pi∗MZ genotype) is an established genetic modifier of liver disease. We review genotype-related hepatic phenotypes/disease predispositions. We also describe the mechanisms and factors promoting the development of liver disease, as well as approaches to evaluate the extent of liver fibrosis. Finally, we discuss emerging diagnostic and therapeutic approaches for the clinical management of this often neglected disorder.

Alpha-1 抗胰蛋白酶缺乏症 (AATD) 由SERPINA1突变引起编码 α-1 抗胰蛋白酶 (AAT) 的基因导致 AAT 滞留在肝细胞的内质网中，从而导致蛋白质毒性肝损伤和功能丧失性肺病。纯合子 Pi∗Z 突变（Pi∗ZZ 基因型）是大多数严重 AATD 病例的原因，可诱发儿童和成人肝病，而杂合子 Pi∗Z 突变（Pi∗MZ 基因型）是已确定的遗传修饰因子肝病。我们回顾了基因型相关的肝脏表型/疾病易感性。我们还描述了促进肝病发展的机制和因素，以及评估肝纤维化程度的方法。最后，我们讨论了用于临床管理这种经常被忽视的疾病的新兴诊断和治疗方法。