Ferreira Ana Isabel, Guimarães Catarina, Macedo Silva Vitor, Xavier Sofia, Magalhães Joana, Cotter José
Department of Gastroenterology, Hospital da Senhora da Oliveira - Guimarães, Guimarães 4835-044, Portugal.
Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga 4710-057, Portugal.
World J Hepatol. 2024 Aug 27;16(8):1099-1110. doi: 10.4254/wjh.v16.i8.1099.
Alpha-1 antitrypsin deficiency (AATD) is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease, and Pi*Z allele is the most clinically relevant mutation.
To evaluate the impact of clinical parameters and AATD phenotypes, particularly the Pi*Z allele, in liver fibrosis.
Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation.
Included 69 patients, 49.3% had PiMZ phenotype and 10.1% PiZZ. An age ≥ 55 years, age at diagnosis ≥ 41 years and AAT at diagnosis < 77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score (NFS) not excluding advanced fibrosis [area under the curve (AUC) = 0.840, < 0.001; AUC = 0.836, < 0.001; AUC = 0.681, = 0.025]. An age ≥ 50 years and age at diagnosis ≥ 41 years predicted a fibrosis-4 index of moderate to advanced fibrosis (AUC = 0.831, < 0.001; AUC = 0.795, < 0.001). Patients with hypertension, type 2 diabetes mellitus (DM), dyslipidaemia, metabolic syndrome, and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis ( < 0.001, = 0.002, = 0.008, < 0.001, = 0.033). Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement ≥ 7.1 kPa ( = 0.040).
Risk factors for liver disease in AATD included an age ≥ 50 years, age at diagnosis ≥ 41 years, metabolic risk factors, regular alcohol consumption, at least one Pi*Z allele, and AAT value at diagnosis < 77 mg/dL. We created an algorithm for liver disease screening in AATD patients to use in primary care, selecting those to be referred to Hepatology consultation.
α-1抗胰蛋白酶缺乏症（AATD）是一种共显性常染色体遗传性疾病，使患者易患肺部和/或肝脏疾病，Pi*Z等位基因是最具临床相关性的突变。
评估临床参数和AATD表型，特别是Pi*Z等位基因对肝纤维化的影响。
横断面队列研究，纳入在呼吸科或肝病科门诊连续就诊的AATD患者。
共纳入69例患者，49.3%为PiMZ表型，10.1%为PiZZ表型。年龄≥55岁、诊断时年龄≥41岁以及诊断时AAT<77mg/dL预测非酒精性脂肪性肝病纤维化评分（NFS）不排除存在晚期纤维化[曲线下面积（AUC）=0.840，P<0.001；AUC=0.836，P<0.001；AUC=0.681，P=0.025]。年龄≥50岁和诊断时年龄≥41岁预测纤维化-4指数为中度至重度纤维化（AUC=0.831，P<0.001；AUC=0.795，P<0.001）。患有高血压、2型糖尿病（DM）、血脂异常、代谢综合征以及经常饮酒的患者更有可能出现NFS不排除晚期纤维化（P<0.001，P=0.002，P=0.008，P<0.001，P=0.033）。至少携带一个Pi*Z等位基因且患有2型糖尿病的患者肝脏硬度测量值≥7.1kPa的可能性高8倍（P=0.040）。
AATD患者肝病的危险因素包括年龄≥50岁、诊断时年龄≥41岁、代谢危险因素、经常饮酒、至少一个Pi*Z等位基因以及诊断时AAT值<77mg/dL。我们创建了一种用于AATD患者肝病筛查的算法，以便在初级保健中使用，筛选出需要转诊至肝病科门诊的患者。
