Malin Fromme, Laura Rademacher, Samira Amzou, Christi D Cook, Isabel Zacharias, Lanju Zhang, John E Ripollone, Pavel Strnad
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Cox proportional hazard models were used to describe the association between binary circulating Z-polymer levels and adverse clinical outcomes. Correlations between baseline circulating Z-polymer levels and baseline liver fibrosis (liver stiffness measurement [LSM] determined by transient elastography [FibroScan®]) were evaluated. The analyses were stratified by augmentation therapy status.</p><p><strong>Results: </strong>Of 324 adults with the PiZZ genotype and longitudinal follow-up data, 28 reported adverse clinical outcomes. Higher baseline circulating Z-polymer levels were associated with an increased risk of adverse clinical outcomes in both crude (hazard ratio [95% confidence interval, CI], 2.88 [1.21, 6.87]) and age-adjusted (1.96 [0.78, 4.94]) analyses. In adults with the PiZZ genotype, circulating Z-polymer levels were weakly positively correlated with baseline LSM (Spearman's rho [95% CI]: 0.21 [0.11, 0.31]). Similar results were observed after stratification by augmentation therapy status.</p><p><strong>Conclusions: </strong>In adults with the PiZZ genotype, higher circulating Z-polymer levels were associated with a shorter time to adverse clinical outcome, and positively correlated with baseline LSM. 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引用次数: 0
摘要
背景：循环聚合突变型 Z-α-1抗胰蛋白酶（Z-聚合体）是α-1抗胰蛋白酶缺乏症（AATD）的一个特征，但人们对其与不良临床结果和肝纤维化的关系了解有限。我们利用一个大型成人α-1抗胰蛋白酶缺乏症患者队列中的数据探讨了这种关联：方法：我们纳入了欧洲阿尔法-1 肝队列（2015-2020 年）中的 836 名（431 名 PiZZ，405 名 PiMZ）成人 AATD 患者和 312 名对照者（PiMM）。对具有 PiZZ 基因型的成人进行了不良临床结局（最早发生肝脏相关住院、肝移植或全因死亡）的时间到事件分析。采用 Cox 比例危险模型来描述二元循环 Z 聚合物水平与不良临床结果之间的关系。评估了基线循环 Z 聚合物水平与基线肝纤维化（通过瞬态弹性成像法 [FibroScan®] 确定的肝硬度测量值 [LSM]）之间的相关性。分析结果按增强治疗状态进行了分层：结果：在324名具有PiZZ基因型和纵向随访数据的成人中，28人报告了不良临床结果。在粗略（危险比[95% 置信区间，CI]，2.88 [1.21, 6.87]）和年龄调整（1.96 [0.78, 4.94]）分析中，较高的基线循环 Z 聚合物水平与不良临床结果的风险增加有关。在具有 PiZZ 基因型的成年人中，循环 Z 聚合物水平与基线 LSM 呈弱正相关（Spearman's rho [95% CI]：0.21 [0.11, 0.31]）。根据增强治疗状态进行分层后也观察到了类似的结果：结论：在具有 PiZZ 基因型的成人中，较高的循环 Z 聚合物水平与较短的不良临床结局时间相关，并与基线 LSM 呈正相关。循环中的 Z 聚合物水平可能是 AATD 临床相关疾病的预后生物标志物。
Association of circulating Z-polymer with adverse clinical outcomes and liver fibrosis in adults with alpha-1 antitrypsin deficiency.
Background: Circulating polymerized mutant Z-alpha-1 antitrypsin (Z-polymer) constitutes a characteristic feature in alpha-1 antitrypsin deficiency (AATD), but there is limited knowledge about its association with adverse clinical outcomes and liver fibrosis. We explored this association using data from a large cohort of adults with AATD.
Methods: A total of 836 (431 PiZZ, 405 PiMZ) adults with AATD and 312 controls (PiMM) from the European Alpha-1 Liver Cohort (2015-2020) were included. Time-to-event analyses were conducted for adults with the PiZZ genotype followed for adverse clinical outcomes (earliest occurrence of liver-related hospitalization, liver transplant or all-cause mortality). Cox proportional hazard models were used to describe the association between binary circulating Z-polymer levels and adverse clinical outcomes. Correlations between baseline circulating Z-polymer levels and baseline liver fibrosis (liver stiffness measurement [LSM] determined by transient elastography [FibroScan®]) were evaluated. The analyses were stratified by augmentation therapy status.
Results: Of 324 adults with the PiZZ genotype and longitudinal follow-up data, 28 reported adverse clinical outcomes. Higher baseline circulating Z-polymer levels were associated with an increased risk of adverse clinical outcomes in both crude (hazard ratio [95% confidence interval, CI], 2.88 [1.21, 6.87]) and age-adjusted (1.96 [0.78, 4.94]) analyses. In adults with the PiZZ genotype, circulating Z-polymer levels were weakly positively correlated with baseline LSM (Spearman's rho [95% CI]: 0.21 [0.11, 0.31]). Similar results were observed after stratification by augmentation therapy status.
Conclusions: In adults with the PiZZ genotype, higher circulating Z-polymer levels were associated with a shorter time to adverse clinical outcome, and positively correlated with baseline LSM. Circulating Z-polymer levels may be a prognostic biomarker of clinically relevant disease in AATD.
期刊介绍：
United European Gastroenterology Journal (UEG Journal) is the official Journal of the United European Gastroenterology (UEG), a professional non-profit organisation combining all the leading European societies concerned with digestive disease. UEG’s member societies represent over 22,000 specialists working across medicine, surgery, paediatrics, GI oncology and endoscopy, which makes UEG a unique platform for collaboration and the exchange of knowledge.
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