α-1抗胰蛋白酶缺乏症成人的肝胆表型
Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency.
作者信息
Fromme Malin, Schneider Carolin V, Pereira Vitor, Hamesch Karim, Pons Monica, Reichert Matthias C, Benini Federica, Ellis Paul, H Thorhauge Katrine, Mandorfer Mattias, Burbaum Barbara, Woditsch Vivien, Chorostowska-Wynimko Joanna, Verbeek Jef, Nevens Frederik, Genesca Joan, Miravitlles Marc, Nuñez Alexa, Schaefer Benedikt, Zoller Heinz, Janciauskiene Sabina, Abreu Nélia, Jasmins Luís, Gaspar Rui, Liberal Rodrigo, Macedo Guilherme, Mahadeva Ravi, Gomes Catarina, Schneider Kai Markus, Trauner Michael, Krag Aleksander, Gooptu Bibek, Thorburn Douglas, Marshall Aileen, Hurst John R, Lomas David A, Lammert Frank, Gaisa Nadine T, Clark Virginia, Griffiths William, Trautwein Christian, Turner Alice M, McElvaney Noel G, Strnad Pavel
机构信息
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.
Department of Gastroenterology, Centro Hospitalar do Funchal, Madeira, Portugal.
出版信息
Gut. 2022 Feb;71(2):415-423. doi: 10.1136/gutjnl-2020-323729. Epub 2021 Feb 25.
OBJECTIVE
Alpha-1 antitrypsin deficiency (AATD) is a common, potentially lethal inborn disorder caused by mutations in alpha-1 antitrypsin (AAT). Homozygosity for the 'PiZ' variant of AAT (PiZZ genotype) causes lung and liver disease, whereas heterozygous 'PiZ' carriage (PiMZ genotype) predisposes to gallstones and liver fibrosis. The clinical significance of the more common 'Pi*S' variant remains largely undefined and no robust data exist on the prevalence of liver tumours in AATD.
DESIGN
Baseline phenotypes of AATD individuals and non-carriers were analysed in 482 380 participants in the UK Biobank. 1104 participants of a multinational cohort (586 PiZZ, 239 PiSZ, 279 non-carriers) underwent a comprehensive clinical assessment. Associations were adjusted for age, sex, body mass index, diabetes and alcohol consumption.
RESULTS
Among UK Biobank participants, PiZZ individuals displayed the highest liver enzyme values, the highest occurrence of liver fibrosis/cirrhosis (adjusted OR (aOR)=21.7 (8.8-53.7)) and primary liver cancer (aOR=44.5 (10.8-183.6)). Subjects with PiMZ genotype had slightly elevated liver enzymes and moderately increased odds for liver fibrosis/cirrhosis (aOR=1.7 (1.2-2.2)) and cholelithiasis (aOR=1.3 (1.2-1.4)). Individuals with homozygous PiS mutation (PiSS genotype) harboured minimally elevated alanine aminotransferase values, but no other hepatobiliary abnormalities. Pi*SZ participants displayed higher liver enzymes, more frequent liver fibrosis/cirrhosis (aOR=3.1 (1.1-8.2)) and primary liver cancer (aOR=6.6 (1.6-26.9)). The higher fibrosis burden was confirmed in a multinational cohort. Male sex, age ≥50 years, obesity and the presence of diabetes were associated with significant liver fibrosis.
CONCLUSION
Our study defines the hepatobiliary phenotype of individuals with the most relevant AATD genotypes including their predisposition to liver tumours, thereby allowing evidence-based advice and individualised hepatological surveillance.
目的
α-1抗胰蛋白酶缺乏症（AATD）是一种常见的、潜在致命的先天性疾病，由α-1抗胰蛋白酶（AAT）基因突变引起。AAT的“PiZ”变异型纯合子（PiZZ基因型）会导致肺部和肝脏疾病，而杂合子携带“PiZ”（PiMZ基因型）易患胆结石和肝纤维化。更为常见的“Pi*S”变异型的临床意义在很大程度上仍不明确，且关于AATD患者肝肿瘤患病率尚无可靠数据。
设计
在英国生物银行的482380名参与者中分析了AATD个体和非携带者的基线表型。一个跨国队列的1104名参与者（586名PiZZ、239名PiSZ、279名非携带者）接受了全面的临床评估。对年龄、性别、体重指数、糖尿病和饮酒情况进行了关联调整。
结果
在英国生物银行参与者中，PiZZ个体的肝酶值最高，肝纤维化/肝硬化发生率最高（调整后的比值比（aOR）=21.7（8.8 - 53.7））以及原发性肝癌发生率最高（aOR = 44.5（10.8 - 183.6））。PiMZ基因型的受试者肝酶略有升高且肝纤维化/肝硬化的几率适度增加（aOR = 1.7（1.2 - 2.2））以及胆结石几率增加（aOR = 1.3（1.2 - 1.4））。纯合子PiS突变个体（PiSS基因型）的丙氨酸转氨酶值略有升高，但无其他肝胆异常。Pi*SZ参与者的肝酶更高，肝纤维化/肝硬化更频繁（aOR = 3.1（1.1 - 8.2））以及原发性肝癌（aOR = 6.6（1.6 - 26.9））。在一个跨国队列中证实了更高的纤维化负担。男性、年龄≥50岁、肥胖和糖尿病的存在与显著的肝纤维化相关。
结论
我们的研究明确了具有最相关AATD基因型个体的肝胆表型，包括他们患肝肿瘤的易感性，从而能够提供循证建议和个体化的肝病监测。
Zotero 插件