Naomi N Kappe, Malin Fromme, Jan Stolk, Ilaria Ferrarotti, Pavel Strnad, Bart van Hoek
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Aim was to determine performance of serum markers to exclude significant or advanced fibrosis in Pi*ZZ patients.</p><p><strong>Methods: </strong>In two cohorts of total 362 Pi*ZZ patients with sera and TE from Leiden and Aachen 2015-2023 enhanced liver fibrosis test (ELF), Aspartate aminotransferase to Platelet Ratio Index (APRI), and fibrosis-4 index (FIB-4) were determined retrospectively, and performance for the evaluation of fibrosis status was assessed using TE as gold standard, calculating area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) for excluding significant or advanced fibrosis.</p><p><strong>Results: </strong>AUROC of APRI was highest for significant and advanced fibrosis in both cohorts (Leiden: 0.854 (95 % CI 0.749-0.958), Aachen: 0.684 (95 % CI 0.605-0.763)), followed by FIB-4. ELF had the lowest AUROC for significant fibrosis. For advanced fibrosis AUROC for ELF was slightly higher than for FIB-4. APRI <0.41 demonstrated the best overall diagnostic performance in excluding advanced fibrosis with NPV of 97 %. The limited number of liver-related clinical endpoints within 4 years were predicted by APRI and FIB-4.</p><p><strong>Conclusion: </strong>In Pi*ZZ AATD patients APRI below 0.41 or FIB-4 below 1.79 excludes advanced fibrosis/cirrhosis if TE in unavailable, ELF had no additional value. TE remains the preferred method for staging fibrosis in AATD.</p>","PeriodicalId":50485,"journal":{"name":"European Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":6.1000,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Performance of enhanced liver fibrosis test and indirect serum fibrosis markers for exclusion of advanced liver fibrosis in alpha-1 antitrypsin deficiency.\",\"authors\":\"Naomi N Kappe, Malin Fromme, Jan Stolk, Ilaria Ferrarotti, Pavel Strnad, Bart van Hoek\",\"doi\":\"10.1016/j.ejim.2025.07.019\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Alpha-1 antitrypsin deficiency (AATD) (Pi*ZZ) can cause advanced liver fibrosis and cirrhosis in a subset of patients. Transient elastography (TE) to determine degree of fibrosis has been validated in AATD, but is sometimes unavailable. Serum markers of liver fibrosis have not been tested extensively in AATD. Aim was to determine performance of serum markers to exclude significant or advanced fibrosis in Pi*ZZ patients.</p><p><strong>Methods: </strong>In two cohorts of total 362 Pi*ZZ patients with sera and TE from Leiden and Aachen 2015-2023 enhanced liver fibrosis test (ELF), Aspartate aminotransferase to Platelet Ratio Index (APRI), and fibrosis-4 index (FIB-4) were determined retrospectively, and performance for the evaluation of fibrosis status was assessed using TE as gold standard, calculating area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) for excluding significant or advanced fibrosis.</p><p><strong>Results: </strong>AUROC of APRI was highest for significant and advanced fibrosis in both cohorts (Leiden: 0.854 (95 % CI 0.749-0.958), Aachen: 0.684 (95 % CI 0.605-0.763)), followed by FIB-4. ELF had the lowest AUROC for significant fibrosis. For advanced fibrosis AUROC for ELF was slightly higher than for FIB-4. APRI <0.41 demonstrated the best overall diagnostic performance in excluding advanced fibrosis with NPV of 97 %. The limited number of liver-related clinical endpoints within 4 years were predicted by APRI and FIB-4.</p><p><strong>Conclusion: </strong>In Pi*ZZ AATD patients APRI below 0.41 or FIB-4 below 1.79 excludes advanced fibrosis/cirrhosis if TE in unavailable, ELF had no additional value. 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引用次数: 0
摘要
α -1抗胰蛋白酶缺乏症(AATD) (Pi*ZZ)可引起部分患者的晚期肝纤维化和肝硬化。瞬时弹性成像(TE)测定纤维化程度已在AATD中得到验证,但有时不可用。肝纤维化的血清标志物尚未在AATD中广泛检测。目的是确定血清标志物的性能,以排除Pi*ZZ患者的显著或晚期纤维化。方法:在两组共362例来自莱顿和亚琛的Pi*ZZ患者的血清和TE 2015-2023增强肝纤维化试验(ELF)中,回顾性测定了天冬氨酸转氨酶与血小板比值指数(APRI)和纤维化-4指数(FIB-4),并以TE为金标准评估了评估纤维化状态的性能。计算受试者工作特征曲线下面积(AUROC)和阴性预测值(NPV),用于排除显著或晚期纤维化。结果:在两个队列中,APRI的AUROC在显著和晚期纤维化中最高(莱顿:0.854 (95% CI 0.749-0.958),亚琛:0.684 (95% CI 0.605-0.763)),其次是FIB-4。ELF对于显著纤维化的AUROC最低。对于晚期纤维化,ELF的AUROC略高于FIB-4。结论:在Pi*ZZ AATD患者中,APRI低于0.41或FIB-4低于1.79,如果TE不可用,则排除晚期纤维化/肝硬化,ELF无附加价值。TE仍然是AATD中纤维化分期的首选方法。
Performance of enhanced liver fibrosis test and indirect serum fibrosis markers for exclusion of advanced liver fibrosis in alpha-1 antitrypsin deficiency.
Introduction: Alpha-1 antitrypsin deficiency (AATD) (Pi*ZZ) can cause advanced liver fibrosis and cirrhosis in a subset of patients. Transient elastography (TE) to determine degree of fibrosis has been validated in AATD, but is sometimes unavailable. Serum markers of liver fibrosis have not been tested extensively in AATD. Aim was to determine performance of serum markers to exclude significant or advanced fibrosis in Pi*ZZ patients.
Methods: In two cohorts of total 362 Pi*ZZ patients with sera and TE from Leiden and Aachen 2015-2023 enhanced liver fibrosis test (ELF), Aspartate aminotransferase to Platelet Ratio Index (APRI), and fibrosis-4 index (FIB-4) were determined retrospectively, and performance for the evaluation of fibrosis status was assessed using TE as gold standard, calculating area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) for excluding significant or advanced fibrosis.
Results: AUROC of APRI was highest for significant and advanced fibrosis in both cohorts (Leiden: 0.854 (95 % CI 0.749-0.958), Aachen: 0.684 (95 % CI 0.605-0.763)), followed by FIB-4. ELF had the lowest AUROC for significant fibrosis. For advanced fibrosis AUROC for ELF was slightly higher than for FIB-4. APRI <0.41 demonstrated the best overall diagnostic performance in excluding advanced fibrosis with NPV of 97 %. The limited number of liver-related clinical endpoints within 4 years were predicted by APRI and FIB-4.
Conclusion: In Pi*ZZ AATD patients APRI below 0.41 or FIB-4 below 1.79 excludes advanced fibrosis/cirrhosis if TE in unavailable, ELF had no additional value. TE remains the preferred method for staging fibrosis in AATD.
期刊介绍:
The European Journal of Internal Medicine serves as the official journal of the European Federation of Internal Medicine and is the primary scientific reference for European academic and non-academic internists. It is dedicated to advancing science and practice in internal medicine across Europe. The journal publishes original articles, editorials, reviews, internal medicine flashcards, and other relevant information in the field. Both translational medicine and clinical studies are emphasized. EJIM aspires to be a leading platform for excellent clinical studies, with a focus on enhancing the quality of healthcare in European hospitals.