用 4-半乳糖基木糖（Gaxilose）进行乳糖酶缺乏症的无创诊断：一项多中心、开放标签、ⅡB-Ⅲ期非随机试验。

Noninvasive diagnosis of hypolactasia with 4-Galactosylxylose (Gaxilose): a multicentre, open-label, phase IIB-III nonrandomized trial.

机构信息

*Departamento de Bioquímica and Instituto de Investigaciones Biomédicas Alberto Sols Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas, Facultad de Medicina, Universidad Autónoma de Madrid †Venter Pharma SL ‡Departamento de Estadística, Chiltern International Spain SA §Departamento de Medicina Preventiva y Salud Pública y Microbiología, Facultad de Medicina de la Universidad Autónoma de Madrid ∥Servicio de Bioquímica, Sección de Gastroenterología y Nutrición ¶Servicio de Digestivo, Hospital Universitario La Paz #Servicio de Digestivo, Hospital Universitario Ramón y Cajal ††Instituto de Química Orgánica General, Consejo Superior de Investigaciones Científicas ‡‡Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Madrid **Servicio de Digestivo, Hospital San Juan de Dios de Aljarafe, Sevilla, Spain.

出版信息

J Clin Gastroenterol. 2014 Jan;48(1):29-36. doi: 10.1097/MCG.0b013e318297fb10.

DOI:10.1097/MCG.0b013e318297fb10

PMID:23722657

Abstract

GOALS AND BACKGROUND

Hypolactasia affects over half of the world population. Diagnosis remains problematic as currently available tests, such as the hydrogen breath test, have low reliability and lactose intolerance symptoms are unspecific. We evaluated the diagnostic performance and safety of a new noninvasive diagnostic test based on urine or serum measurement of D-xylose after lactase cleavage of orally administered 4-galactosylxylose (gaxilose).

STUDY

In a multicentre, open-label, nonrandomized, phase IIb-III study, consecutive patients with symptoms suggestive of lactose intolerance sequentially underwent intestinal biopsy for direct measurement of lactase activity (reference standard), hydrogen breath test, and blood glucose test after lactose challenge, 4- and 5-hour urine-based gaxilose test, and blood-based gaxilose test. For the gaxilose tests, 0 to 4 and 4 to 5 hours urine samples were taken after a 0.45 g gaxilose dose, whereas serum samples were taken 90 minutes after a 2.7 g dose for D-xylose determination. Genetic testing of hypolactasia was also assessed.

RESULTS

Of the 222 patients enrolled, 203 completed all diagnostic tests; 108 were hypolactasic according to biopsy. The sensitivities and specificities and positive and negative predictive values of the gaxilose tests were all >90% versus 69% to 85% for the hydrogen breath test and the blood glucose test. The area under the ROC curve was significantly higher for the gaxilose tests (>0.9, P≤0.007). These tests also had higher sensitivity than genetic testing for hypolactasia and were well tolerated.

CONCLUSIONS

The diagnostic performance of the gaxilose tests is excellent and can substantially improve the diagnosis of hypolactasia.

摘要

目的和背景

低乳糖酶活性影响了世界上超过一半的人口。由于目前可用的测试（如氢呼气试验）可靠性较低，且乳糖不耐受症状不具有特异性，因此该疾病的诊断仍然存在问题。我们评估了一种新的非侵入性诊断测试的诊断性能和安全性，该测试基于口服 4-半乳糖基木糖（gaxilose）后经乳糖酶切割，对尿液或血清中的 D-木糖进行测量。

研究

在一项多中心、开放标签、非随机、IIb-III 期研究中，连续出现乳糖不耐受症状的患者依次进行肠道活检，以直接测量乳糖酶活性（参考标准）、氢呼气试验和乳糖负荷后血糖试验、4 小时和 5 小时基于尿液的 gaxilose 试验以及基于血液的 gaxilose 试验。对于 gaxilose 试验，在 0.45 g gaxilose 剂量后 0 至 4 小时和 4 至 5 小时采集尿液样本，而在 2.7 g 剂量后 90 分钟采集血清样本以测定 D-木糖。还评估了低乳糖酶活性的基因检测。

结果

在纳入的 222 名患者中，203 名患者完成了所有诊断性测试；根据活检，108 名患者为低乳糖酶活性。gaxilose 试验的敏感性、特异性和阳性预测值和阴性预测值均>90%，而氢呼气试验和血糖试验的敏感性和特异性分别为 69%至 85%。gaxilose 试验的 ROC 曲线下面积明显更高（>0.9，P≤0.007）。这些测试的敏感性也高于基因检测，并且耐受性良好。