Boeckmans Joost, Schattenberg Jörn M, Fromme Malin, Strnad Pavel, Hagström Hannes
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
In Vitro Liver Disease Modelling Team, In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Liver Int. 2025 Jul;45(7):e70165. doi: 10.1111/liv.70165.
Severe alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition characterised by low systemic levels of alpha-1 antitrypsin due to its retention in the liver. Consequently, it predisposes individuals to the development of chronic obstructive pulmonary disease and liver cirrhosis. Much progress has been made to non-invasively monitor liver fibrosis and cirrhosis in individuals with other liver diseases, but it remains unclear how to assess liver disease in people with AATD. This narrative review examined the available evidence on non-invasive tests (NITs) to stage liver fibrosis and predict incident major adverse liver outcomes in people with AATD. Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE), blood-based NITs, and serum liver enzymes are generally normal or mildly elevated in individuals with AATD. Further, VCTE-LSM and blood-based NITs, including the AST to platelet ratio index and fibrosis-4 score, have diagnostic utility for predicting F2 and F3 fibrosis and hold excellent (AUROC ≥ 0.90) prognostic value for incident major adverse liver outcomes. Gamma-glutamyl transferase also exhibits diagnostic and prognostic utility but is subject to multiple non-AATD-related fluctuations. A potential strategy to non-invasively assess liver disease stage and estimate the risk of major adverse liver outcomes in people with AATD could consist of a combination of VCTE-LSM with blood-based biomarker panels. Future studies should explore if liver stiffness naturally fluctuates over time in people with AATD, assess the ideal frequency of follow-up, and evaluate if NITs can guide the treatment of AATD-related liver disease.
严重的α-1抗胰蛋白酶缺乏症（AATD）是一种罕见的遗传疾病，其特征是由于α-1抗胰蛋白酶在肝脏中潴留，导致全身水平较低。因此，它使个体易患慢性阻塞性肺疾病和肝硬化。在非侵入性监测其他肝脏疾病患者的肝纤维化和肝硬化方面已经取得了很大进展，但目前尚不清楚如何评估AATD患者的肝脏疾病。这篇叙述性综述研究了关于非侵入性检测（NITs）用于对AATD患者的肝纤维化进行分期和预测主要不良肝脏事件发生风险的现有证据。在AATD患者中，使用振动控制瞬时弹性成像（VCTE）进行的肝脏硬度测量（LSM）、基于血液的NITs和血清肝酶通常正常或轻度升高。此外，VCTE-LSM和基于血液的NITs，包括AST与血小板比值指数和纤维化-4评分，对预测F2和F3纤维化具有诊断价值，并且对主要不良肝脏事件的发生具有出色的（AUROC≥0.90）预后价值。γ-谷氨酰转移酶也具有诊断和预后价值，但会受到多种与AATD无关的波动影响。一种非侵入性评估AATD患者肝脏疾病分期和估计主要不良肝脏事件风险的潜在策略可能包括将VCTE-LSM与基于血液的生物标志物组合使用。未来的研究应探讨AATD患者的肝脏硬度是否会随时间自然波动，评估理想的随访频率，并评估NITs是否可以指导AATD相关肝脏疾病的治疗。
