Objectives: 

Timely diagnosis is a critical challenge and is associated with improved survival of biliary atresia (BA) patients. We aimed to measure matrix metalloproteinase-7 (MMP-7) levels in BA patients within 3 days of birth using the dried blood spot (DBS) method and evaluate its potential as a screening tool.

Methods: 

The study enrolled 132 patients, including 25 patients diagnosed with BA and 107 non-BA patients with other congenital or perinatal conditions from the National Taiwan University Children Hospital. The stored DBS samples collected from 48 to 72 hours of life were retrieved from newborn screening centers. MMP-7 on the DBS was quantified using a sensitive sandwich enzyme-linked immunosorbent assay (ELISA).

Results: 

The MMP-7 levels of BA patients on the DBS were significantly higher than those of non-BA patients (19.2 ± 10.4 vs 5.6 ± 2.7 ng/mL, P value < 0.0001). MMP-7 levels in non-BA patients, including 5 patients with hepatobiliary structural anomaly, 9 patients with intrahepatic cholestasis, and 93 patients with other perinatal diseases, were 11.6 ± 4.2 ng/mL, 6.9 ± 3.0 ng/mL, and 5.2 ± 2.1 ng/mL, respectively. The DBS MMP-7 level showed good accuracy for identifying BA, with an area under the curve of 93.7% [95% confidence interval (CI): 87.7%–99.7%]. The MMP-7 cutoff at 8.0 ng/mL showed a sensitivity of 92.0% (95% CI: 75.0%–98.6%) and specificity of 92.5% (95% CI: 85.9%–96.1%) for detecting BA from other congenital or perinatal diseases.

Conclusions: 

MMP-7 DBS analysis can be used to distinguish BA from other conditions as early as 3 days of age.

中文翻译：

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使用干血斑基质金属蛋白酶 7 筛查新生儿胆道闭锁的初步研究

目标： 

及时诊断是一项关键挑战，并且与胆道闭锁 (BA) 患者的生存率提高有关。我们旨在使用干血斑 (DBS) 方法测量出生后 3 天内 BA 患者的基质金属蛋白酶 7 (MMP-7) 水平，并评估其作为筛查工具的潜力。

方法： 

该研究招募了 132 名患者，包括 25 名诊断为 BA 的患者和 107 名来自台大儿童医院的其他先天性或围产期疾病的非 BA 患者。从新生儿筛查中心检索从出生后 48 至 72 小时收集的存储的 DBS 样本。使用灵敏的夹心酶联免疫吸附测定 (ELISA) 对 DBS 上的 MMP-7 进行量化。

结果： 

DBS 上 BA 患者的 MMP-7 水平显着高于非 BA 患者（19.2 ± 10.4 vs 5.6 ± 2.7 ng/mL，P值 < 0.0001）。非 BA 患者（包括 5 例肝胆结构异常患者、9 例肝内胆汁淤积患者和 93 例其他围产期疾病患者）的 MMP-7 水平分别为 11.6 ± 4.2 ng/mL、6.9 ± 3.0 ng/mL 和 5.2 ±分别为 2.1 纳克/毫升。DBS MMP-7 水平显示出识别 BA 的良好准确性，曲线下面积为 93.7% [95% 置信区间 (CI)：87.7%–99.7%]。8.0 ng/mL 的 MMP-7 截止值对检测来自其他先天性或围产期疾病。

结论： 

MMP-7 DBS 分析可用于在 3 日龄时将 BA 与其他病症区分开来。