背景:α-1抗胰蛋白酶缺乏症(AATD)是一种显性常染色体遗传性疾病,使患者易于发展为肺和/或肝脏疾病,和Pi*Z等位基因是最临床相关的突变。
目的:为了评估临床参数和AATD表型的影响,特别是Pi*Z等位基因,肝纤维化。
方法:横断面队列研究,包括连续的AATD患者,随访肺科或肝病会诊。
结果:包括69名患者,49.3%的人具有Pi*MZ表型,10.1%的人具有Pi*ZZ表型。年龄≥55岁,诊断年龄≥41岁,诊断AAT<77mg/dL预测非酒精性脂肪性肝病纤维化评分(NFS),不排除晚期纤维化[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岁和诊断年龄≥41岁预测中度至晚期纤维化的纤维化-4指数(AUC=0.831,P<0.001;AUC=0.795,P<0.001)。高血压患者,2型糖尿病(DM),血脂异常,代谢综合征,定期饮酒更可能发生NFS,但不排除晚期纤维化(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033)。具有至少一个Pi*Z等位基因和2型DM的患者肝脏硬度测量值≥7.1kPa的可能性增加了8倍(P=0.040)。
结论:AATD患者肝病的危险因素包括年龄≥50岁,诊断年龄≥41岁,代谢危险因素,经常饮酒,至少一个Pi*Z等位基因,诊断时的AAT值<77mg/dL。我们创建了一种用于AATD患者肝脏疾病筛查的算法,用于初级保健,选择那些转诊到肝病咨询。
BACKGROUND: 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.
OBJECTIVE: To evaluate the impact of clinical parameters and AATD phenotypes, particularly the Pi*Z allele, in liver fibrosis.
METHODS: Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation.
RESULTS: Included 69 patients, 49.3% had Pi*MZ phenotype and 10.1% Pi*ZZ. 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, P < 0.001; AUC = 0.836, P < 0.001; AUC = 0.681, P = 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, P < 0.001; AUC = 0.795, P < 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 (P < 0.001, P = 0.002, P = 0.008, P < 0.001, P = 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 (P = 0.040).
CONCLUSIONS: 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.