丙氨酸转氨酶正常上限定义的变异性影响了APRI作为慢性丙型肝炎患者纤维化生物标志物的性能：“APRI 就此终结？”

Variability in definitions of transaminase upper limit of the normal impacts the APRI performance as a biomarker of fibrosis in patients with chronic hepatitis C: "APRI c'est fini ?".

作者信息

Perazzo Hugo, Pais Raluca, Munteanu Mona, Ngo Yen, Monneret Denis, Imbert-Bismut Françoise, Moussalli Joseph, Lebray Pascal, Benhamou Yves, Thabut Dominique, Ratziu Vlad, de Ledhingen Victor, Poynard Thierry

机构信息

Hepatology Department, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France.

Hepatology Department, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France; UMR_S 938, INSERM, Université Pierre et Marie Curie, Université Paris 06, Institute of Cardiometabolism and Nutrition (ICAN), Centre de Recherche Saint-Antoine & Paris, France.

出版信息

Clin Res Hepatol Gastroenterol. 2014 Sep;38(4):432-9. doi: 10.1016/j.clinre.2014.04.006. Epub 2014 Jun 9.

DOI:10.1016/j.clinre.2014.04.006

PMID:24924901

Abstract

BACKGROUND

The aspartate aminotransferase platelet ratio index (APRI) is a validated, non-patented blood test for diagnosing fibrosis or cirrhosis in patients with chronic hepatitis C. We assess the impact of two limitations, the variability of the upper limit of normal for aspartate aminotransferase (AST-ULN) and the risk of overestimating fibrosis stage due to necroinflammatory activity.

METHODS

The variability of AST-ULN was assessed by an overview of the literature and an assessment of AST-ULN in 2 control populations 7521 healthy volunteers and 393 blood donors. We assessed the impact of AST-ULN variability on APRI performance for estimating fibrosis prevalence and on the Obuchowski measure using individual data of 1651 patients with APRI, FibroTest and biopsy.

RESULTS

The overview, and the analysis of the control populations found that ULN-AST ranged from 26 to 49 IU/L according to gender, body mass index and serum cholesterol. When this AST-ULN variability was applied to the chronic hepatitis group, the prevalence of advanced fibrosis and cirrhosis as presumed by APRI varied (P<0.001) from 34.7% to 68.5%, and from 11.4% to 32.3%, respectively. This spectrum effect induced variability in APRI performance, which could be similar 0.862 (if AST-ULN=26 IU/L) or lower 0.820 (AST-ULN≥30IU/L) than the stable FibroTest performance (0.867; P=0.35 and P<0.0001 respectively). When applied to 18 acute hepatitis C patients, the rate of false positives of APRI varied from 0% to 61% due to AST-ULN.

CONCLUSION

The AST-ULN variability is high highly associated with the variability of metabolic risk factors between the different control groups. This variability induces a spectrum effect, which could cause misleading interpretations of APRI performance for the staging of fibrosis, comparisons of APRI with other non-invasive tests, and estimates of false positive rate.

摘要

背景

天冬氨酸氨基转移酶与血小板比值指数（APRI）是一种经验证的、无专利的血液检测方法，用于诊断慢性丙型肝炎患者的纤维化或肝硬化。我们评估了两个局限性的影响，即天冬氨酸氨基转移酶正常上限（AST-ULN）的变异性以及由于坏死性炎症活动导致纤维化阶段高估的风险。

方法

通过文献综述和对7521名健康志愿者和393名献血者这两个对照人群的AST-ULN评估，来评估AST-ULN的变异性。我们使用1651名有APRI、FibroTest检测结果及活检数据的患者的个体数据，评估AST-ULN变异性对APRI评估纤维化患病率的性能以及对奥布霍夫斯基测量法的影响。

结果

文献综述及对对照人群的分析发现，根据性别、体重指数和血清胆固醇，AST-ULN范围为26至49 IU/L。当将这种AST-ULN变异性应用于慢性肝炎组时，APRI推测的晚期纤维化和肝硬化患病率分别从34.7%变化至68.5%以及从11.4%变化至32.3%（P<0.001）。这种谱效应导致APRI性能出现变异性，其可能与稳定的FibroTest性能相似（若AST-ULN = 26 IU/L时为0.862）或更低（AST-ULN≥30IU/L时为0.820）（FibroTest性能为0.867；P分别为0.35和P<0.0001）。当应用于18例急性丙型肝炎患者时，由于AST-ULN，APRI的假阳性率从0%变化至61%。