背景:在胆汁淤积患者中,及时准确的鉴别诊断胆道闭锁(BA)非常重要。基质金属蛋白酶-7(MMP-7)作为BA的诊断标记物有很大的希望。本研究旨在探讨年龄特异性血清MMP-7区分BA与其他胆汁淤积性儿科患者的准确性。
方法:这是一项单中心诊断准确性和验证性研究,包括回顾性和前瞻性队列。使用ELISA试剂盒测量血清MMP-7浓度,在一个年龄为0~365日且无肝胆疾病的健康婴儿队列中调查了其随年龄变化的轨迹(n=284).临床BA诊断基于术中胆道造影和随后的组织学检查。在胆汁淤积患者的回顾性队列(n=318,172BA)中评估了血清MMP-7的年龄特异性截止值的诊断准确性,并在前瞻性队列(n=687,包括395BA)中进行了验证。
结果:MMP-7浓度随年龄呈非线性下降,在健康新生儿中显示较高的水平,在新生儿胆汁淤积中显示较高的临界值。回顾性队列的ROC曲线下面积(AUROC)为0.967(95%置信区间[CI]:0.946-0.988),18ng/mL的截止值产生93.0%(95CI:88.1-96.3%),93.8%(95CI:88.6-97.1%),94.7%(95CI:90.1-97.5%),灵敏度为91.9%(95CI:86.4-95.8%),特异性,阳性预测值(PPV),和负预测值(NPV),分别。MMP-7的性能在更大的前瞻性队列中成功验证,诊断灵敏度为95.9%(379/395;95%CI:93.5-97.7%),特异性为87.3%(255/292;95%CI:83.0-90.9%),PPV为91.1%(379/416;95%CI:87.9-93.7%),净现值为94.1%(255/271;95%CI:90.6-96.6%),分别。此外,28.1ng/mL的较高截止值达到最佳灵敏度,特异性,PPV,0-30天婴儿的净现值,这是86.4%(95%CI:75.0-94.0%),95.5%(95%CI:77.2-99.9%),98.1%(95%CI:89.7-100%),和72.4%(95%CI:52.8-87.3%),分别。
结论:血清MMP-7在鉴别BA和非BA胆汁淤积中是准确可靠的,显示了其在BA诊断算法中的潜在应用,并在未来有关BA发病机制的研究中发挥了重要作用。
BACKGROUND: Prompt and precise differential diagnosis of biliary atresia (BA) among cholestatic patients is of great importance. Matrix metalloproteinase-7 (MMP-7) holds great promise as a diagnostic marker for BA. This
study aimed to investigate the accuracy of age-specific serum MMP-7 for discriminating BA from other cholestatic pediatric patients.
METHODS: This was a single center diagnostic accuracy and validation
study including both retrospective and prospective cohorts. Serum MMP-7 concentrations were measured using an ELISA kit, the trajectory of which with age was investigated in a healthy infants cohort aged 0 to 365 days without hepatobiliary diseases (n = 284). Clinical BA diagnosis was based on intraoperative cholangiography and subsequent histological examinations. The diagnostic accuracy of age-specific cutoffs of serum MMP-7 were assessed in a retrospective cohort of cholestatic patients (n = 318, with 172 BA) and validated in a prospective cohort (n = 687, including 395 BA).
RESULTS: The MMP-7 concentration declines non-linearly with age, showing higher levels in healthy neonates as well as higher cutoff value in neonatal
cholestasis. The area under the ROC curve (AUROC) was 0.967 (95% confidence interval [CI]: 0.946-0.988) for the retrospective cohort, and the cutoff of 18 ng/mL yielded 93.0% (95%CI: 88.1-96.3%), 93.8% (95%CI: 88.6-97.1%), 94.7% (95%CI: 90.1-97.5%), and 91.9% (95%CI: 86.4-95.8%) for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), respectively. The performance of MMP-7 was successfully validated in the larger prospective cohort, resulting in a diagnostic sensitivity of 95.9% (379/395; 95% CI: 93.5-97.7%), a specificity of 87.3% (255/292; 95% CI: 83.0-90.9%), a PPV of 91.1% (379/416; 95% CI: 87.9-93.7%), and a NPV of 94.1% (255/271; 95% CI: 90.6-96.6%), respectively. Besides, higher cutoff value of 28.1 ng/mL achieved the best sensitivity, specificity, PPV, and NPV for infants aged 0-30 days, which was 86.4% (95% CI: 75.0-94.0%), 95.5% (95% CI: 77.2-99.9%), 98.1% (95% CI: 89.7-100%), and 72.4% (95% CI: 52.8-87.3%), respectively.
CONCLUSIONS: The serum MMP-7 is accurate and reliable in differentiating BA from non-BA
cholestasis, showing its potential application in the diagnostic algorithm for BA and significant role in the future research regarding pathogenesis of BA.