Clinical and histologic features of adults with alpha-1 antitrypsin deficiency in a non-cirrhotic cohort
Clinical and histologic features of adults with alpha-1 antitrypsin deficiency in a non-cirrhotic cohort
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DOI：
10.1016/j.jhep.2018.08.005
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发表时间：
2018-12-01
影响因子：
25.7
通讯作者：
Brantly, Mark
中科院分区：
文献类型：
--
作者：
Clark, Virginia C.;Marek, George;Brantly, Mark
背景和目标：α-1抗胰蛋白酶缺乏症（AATD）是成人肝脏疾病的一种不常见的原因，其自然史的描述仅限于病例系列和疾病登记处的患者报告数据。肝脏病理学仅限于选定的患者或不可用。因此，我们的目的是确定在成人AATD人群谁不知道有肝硬化，同时定义纤维化的危险因素和测试非侵入性markers的diseases.Methods：共94名成人与经典基因型'PI*ZZ' AATD招募来自北美和前瞻性参加了这项研究。结果：临床显著肝纤维化（F >= 2）的患病率为35.1%。F >= 2组的丙氨酸氨基转移酶、天冬氨酸氨基转移酶和γ-谷氨酰转移酶值较高。代谢综合征与临床显著纤维化的存在相关（OR 14.2; 95% CI 3.7-55; p < 0.001）。此外，肝细胞中异常AAT累积、门静脉炎症和肝细胞变性与临床显著纤维化相关。瞬时弹性成像检测F >= 2纤维化的准确性是公平的，AUC为0.70（95%CI 0.58-0.82）。结论：超过三分之一的患有“PI*ZZ”AATD的无症状和肺部受累的成人具有显著的潜在肝纤维化。肝活检显示不同量的积累ZAAT。肝纤维化的风险在存在代谢综合征、肝细胞中AAT蓄积和基线活检时的门静脉炎症的情况下增加。结果支持这一假设，即在这种遗传条件下的肝脏疾病可能与AAT在hepatocyte.Lay中积累的“毒性功能增益”有关：诊断为经典α-1抗胰蛋白酶缺乏症（ZZ）的个体有肝损伤和瘢痕形成的风险，因为肝脏中异常α-1抗胰蛋白酶的积累。ZZ个体的肝活检可以证明肝脏内α-1抗胰蛋白酶的积累，并确定是否存在任何相关的肝脏瘢痕。活检中大量α-1抗胰蛋白酶的individuals可能有肝损伤和纤维化的风险。糖尿病、肥胖症、高胆固醇和高血压（称为代谢综合征）等其他常见疾病与更大程度的肝损伤相关。(C)2018年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background & Aims: Alpha-1 antitrypsin deficiency (AATD) is an uncommonly recognized cause of liver disease in adults, with descriptions of its natural history limited to case series and patient-reported data from disease registries. Liver pathology is limited to selected patients or unavailable. Therefore, we aimed to determine the prevalence and severity of liver fibrosis in an adult AATD population who were not known to have cirrhosis, while defining risk factors for fibrosis and testing non-invasive markers of disease.Methods: A total of 94 adults with classic genotype 'PI*ZZ' AATD were recruited from North America and prospectively enrolled in the study. Liver aminotransferases and markers of synthetic function, transient elastography, and liver biopsy were performed.Results: The prevalence of clinically significant liver fibrosis (F >= 2) was 35.1%. Alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase values were higher in the F >= 2 group. Metabolic syndrome was associated with the presence of clinically significant fibrosis (OR 14.2; 95% CI 3.7-55; p < 0.001). Additionally, the presence of accumulated abnormal AAT in hepatocytes, portal inflammation, and hepatocellular degeneration were associated with clinically significant fibrosis. The accuracy of transient elastography to detect F >= 2 fibrosis was fair, with an AUC of 0.70 (95% CI 0.58-0.82).Conclusions: Over one-third of asymptomatic and lung affected adults with 'PI*ZZ' AATD have significant underlying liver fibrosis. Liver biopsies demonstrated variable amounts of accumulated Z AAT. The risk of liver fibrosis increases in the presence of metabolic syndrome, accumulation of AAT in hepatocytes, and portal inflammation on baseline biopsy. The results support the hypothesis that liver disease in this genetic condition may be related to a "toxic gain of function" from accumulation of AAT in hepatocytes.Lay summary: Individuals diagnosed with classic alpha-1 antitrypsin deficiency (ZZ) are at risk of liver injury and scarring, because of the accumulation of abnormal alpha-1 antitrypsin in the liver. A liver biopsy in ZZ individuals can demonstrate the accumulation of alpha-1 antitrypsin within the liver and identify if any associated liver scarring is present. Indviduals with large amounts of alpha-1 antitrypsin on biopsy may be at risk of liver injury and fibrosis. Additional common medical conditions of diabetes, obesity, high cholesterol, and hypertension (known as metabolic syndrome) are associated with a greater degree of liver injury. (C) 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.