Université de Lyon, université Lyon 1, INRAE, EPHE, UMR754, IVPC, F-69007 Lyon, France; Centre de référence des maladies pulmonaires rares, Orphalung, RESPIFIL, ERN-LUNG, F-69500 Bron, France; Hospices civils de Lyon, hôpital Louis-Pradel, service de pneumologie, F-69500 Bron, France; Inserm, hospices civils de Lyon, CIC 1407, F-69500 Bron, France.
Centre de référence des maladies pulmonaires rares, Orphalung, RESPIFIL, ERN-LUNG, F-69500 Bron, France; Hospices civils de Lyon, hôpital Louis-Pradel, service de pneumologie, F-69500 Bron, France.
Presse Med. 2023 Sep;52(3):104170. doi: 10.1016/j.lpm.2023.104170. Epub 2023 Jul 29.
Alpha1-antitrypsin deficiency (AATD) is a rare autosomal recessive disease associated with the homozygous Z variant of the SERPINA1 gene. Clinical expression of AATD, reported 60 years ago associate a severe deficiency, pulmonary emphysema and/or liver fibrosis. Pulmonary emphysema is due to the severe alpha1-antitrypsin deficiency of the ZZ homozygous status and is favored by smoking. Liver fibrosis is due to the ZZ homozygous status and is favored by obesity and excessive chronic alcohol intake, with a risk of liver cancer. Diagnosis is based on serum level and either isoelectric focusing determination of the biochemical phenotype or PCR detection of some variants. SERPINA1 gene sequencing is necessary in case of discrepancies between the results of these tests. No treatment is available for the liver disease in AATD. Although no specific trial has been performed, COPD in AATD should be treated as per COPD recommendations. Based on a randomized clinical trial, augmentation therapy is indicated in non-smoking adults less than 70 years of age with emphysema at chest CT, confirmed homozygous AATD, and FEV1 between 35% and 70% of predicted. In contrast Z heterozygosis (MZ or SZ) brings a risk of lung or liver disease only in association with further risk factors. Early detection, in all patients with COPD and chronic liver disease, is critical for the correct information of Z variant carriers. News ways of correcting the liver production of alpha1-antitrypsin will modify the care of AATD patients.
α1-抗胰蛋白酶缺乏症（AATD）是一种罕见的常染色体隐性遗传病，与 SERPINA1 基因的纯合 Z 变体有关。AATD 的临床表现于 60 年前被报道，与严重缺乏、肺气肿和/或肝纤维化有关。肺气肿是由于 ZZ 纯合状态导致的严重α1-抗胰蛋白酶缺乏，并受吸烟的影响。肝纤维化是由于 ZZ 纯合状态，并受肥胖和过量慢性酒精摄入的影响，伴有肝癌风险。诊断基于血清水平和等电聚焦测定的生化表型或某些变体的 PCR 检测。如果这些测试的结果存在差异，则需要对 SERPINA1 基因进行测序。AATD 中的肝病没有有效的治疗方法。尽管没有进行专门的试验，但应根据 COPD 建议治疗 AATD 中的 COPD。基于一项随机临床试验，对于胸部 CT 显示肺气肿、确诊为纯合 AATD、FEV1 占预计值的 35%至 70%的非吸烟成年人，小于 70 岁的患者可进行增敏治疗。相比之下，Z 杂合性（MZ 或 SZ）仅在与其他危险因素相关时才会导致肺部或肝脏疾病的风险。对于所有 COPD 和慢性肝病患者，早期检测对于正确告知 Z 变体携带者至关重要。纠正肝脏产生α1-抗胰蛋白酶的新方法将改变 AATD 患者的护理方式。
