Abstract：
BACKGROUND: Biliary atresia (BA), a progressive condition affecting canalicular-bile duct function/anatomy, requires prompt surgical intervention for favorable outcomes. Therefore, we conducted a network meta-analysis of common diagnostic methods to assess their performance and provide evidence-based support for clinical decision-making.
METHODS: We reviewed literature in PubMed, EMBASE, and Cochrane for BA diagnostics. The search included gamma-glutamyl transferase (GGT), direct/combined bilirubin, matrix metalloproteinase 7 (MMP-7), ultrasonic triangular cord sign (TCS), hepatic scintigraphy (HS), and percutaneous cholangiocholangiography/percutaneous transhepatic cholecysto-cholangiography (PCC/PTCC). QUADAS-2 assessed study quality. Heterogeneity and threshold effect were evaluated using I2 and Spearman\'s correlation. We combined effect estimates, constructed SROC models, and conducted a network meta-analysis based on the ANOVA model, along with meta-regression and subgroup analysis, to obtain precise diagnostic performance assessments for BA.
RESULTS: A total of 40 studies were included in our analysis. GGT demonstrated high diagnostic accuracy for BA with a sensitivity of 81.5% (95% CI 0.792-0.836) and specificity of 72.1% (95% CI 0.693-0.748). Direct bilirubin/conjugated bilirubin showed a sensitivity of 87.6% (95% CI 0.833-0.911) but lower specificity of 59.4% (95% CI 0.549-0.638). MMP-7 exhibited a total sensitivity of 91.5% (95% CI 0.893-0.934) and a specificity of 84.3% (95% CI 0.820-0.863). TCS exhibited a sensitivity of 58.1% (95% CI 0.549-0.613) and high specificity of 92.9% (95% CI 0.911-0.944). HS had a high sensitivity of 98.4% (95% CI 0.968-0.994) and moderate specificity of 79.0% (95% CI 0.762-0.816). PCC/PTCC exhibited excellent diagnostic performance with a sensitivity of 100% (95% CI 0.900-1.000) and specificity of 87.0% (95% CI 0.767-0.939). Based on the ANOVA model, the network meta-analysis revealed that MMP-7 ranked second overall, with PCC/PTCC ranking first, both exhibiting superior diagnostic accuracy compared to other techniques. Our analysis showed no significant bias in most methodologies, but MMP-7 and hepatobiliary scintigraphy exhibited biases, with p values of 0.023 and 0.002, respectively.
CONCLUSIONS: MMP-7 and ultrasound-guided PCC/PTCC show diagnostic potential in the early diagnosis of BA, but their clinical application is restricted due to practical limitations. Currently, the cutoff value of MMP-7 is unclear, and further evidence-based medical research is needed to firmly establish its diagnostic value. Until more evidence is available, MMP-7 is not suitable for widespread diagnostic use. Therefore, considering cost and operational simplicity, liver function tests combined with ultrasound remain the most clinically valuable non-invasive diagnostic methods for BA.
METHODS: We reviewed literature in PubMed, EMBASE, and Cochrane for BA diagnostics. The search included gamma-glutamyl transferase (GGT), direct/combined bilirubin, matrix metalloproteinase 7 (MMP-7), ultrasonic triangular cord sign (TCS), hepatic scintigraphy (HS), and percutaneous cholangiocholangiography/percutaneous transhepatic cholecysto-cholangiography (PCC/PTCC). QUADAS-2 assessed study quality. Heterogeneity and threshold effect were evaluated using I2 and Spearman\'s correlation. We combined effect estimates, constructed SROC models, and conducted a network meta-analysis based on the ANOVA model, along with meta-regression and subgroup analysis, to obtain precise diagnostic performance assessments for BA.
RESULTS: A total of 40 studies were included in our analysis. GGT demonstrated high diagnostic accuracy for BA with a sensitivity of 81.5% (95% CI 0.792-0.836) and specificity of 72.1% (95% CI 0.693-0.748). Direct bilirubin/conjugated bilirubin showed a sensitivity of 87.6% (95% CI 0.833-0.911) but lower specificity of 59.4% (95% CI 0.549-0.638). MMP-7 exhibited a total sensitivity of 91.5% (95% CI 0.893-0.934) and a specificity of 84.3% (95% CI 0.820-0.863). TCS exhibited a sensitivity of 58.1% (95% CI 0.549-0.613) and high specificity of 92.9% (95% CI 0.911-0.944). HS had a high sensitivity of 98.4% (95% CI 0.968-0.994) and moderate specificity of 79.0% (95% CI 0.762-0.816). PCC/PTCC exhibited excellent diagnostic performance with a sensitivity of 100% (95% CI 0.900-1.000) and specificity of 87.0% (95% CI 0.767-0.939). Based on the ANOVA model, the network meta-analysis revealed that MMP-7 ranked second overall, with PCC/PTCC ranking first, both exhibiting superior diagnostic accuracy compared to other techniques. Our analysis showed no significant bias in most methodologies, but MMP-7 and hepatobiliary scintigraphy exhibited biases, with p values of 0.023 and 0.002, respectively.
CONCLUSIONS: MMP-7 and ultrasound-guided PCC/PTCC show diagnostic potential in the early diagnosis of BA, but their clinical application is restricted due to practical limitations. Currently, the cutoff value of MMP-7 is unclear, and further evidence-based medical research is needed to firmly establish its diagnostic value. Until more evidence is available, MMP-7 is not suitable for widespread diagnostic use. Therefore, considering cost and operational simplicity, liver function tests combined with ultrasound remain the most clinically valuable non-invasive diagnostic methods for BA.
摘要：
背景：胆道闭锁（BA），影响小管-胆管功能/解剖的进行性疾病，需要及时的手术干预以获得良好的结果。因此,我们对常用诊断方法进行了网络荟萃分析,以评估其性能,并为临床决策提供循证支持.
方法：我们回顾了PubMed，EMBASE,和Cochrane用于BA诊断。搜索包括γ-谷氨酰转移酶（GGT），直接/联合胆红素，基质金属蛋白酶7（MMP-7），超声波三角线标志（TCS），肝闪烁显像（HS），和经皮胆管造影/经皮经肝胆囊胆管造影（PCC/PTCC）。QUADAS-2评估研究质量。使用I2和Spearman相关性评估异质性和阈值效应。我们结合了效应估计，构建的SROC模型，并基于方差分析模型进行了网络荟萃分析，连同荟萃回归和亚组分析，获得BA的精确诊断性能评估。
结果：共有40项研究纳入我们的分析。GGT对BA具有较高的诊断准确性，敏感性为81.5%（95%CI0.792-0.836），特异性为72.1%（95%CI0.693-0.748）。直接胆红素/结合胆红素的敏感性为87.6%（95%CI0.833-0.911），但特异性较低，为59.4%（95%CI0.549-0.638）。MMP-7的总敏感性为91.5%（95%CI0.893-0.934），特异性为84.3%（95%CI0.820-0.863）。TCS的敏感性为58.1%（95%CI0.549-0.613），高特异性为92.9%（95%CI0.911-0.944）。HS的敏感性为98.4%（95%CI0.968-0.994），特异性为79.0%（95%CI0.762-0.816）。PCC/PTCC表现出优异的诊断性能，灵敏度为100％（95％CI0.900-1.000），特异性为87.0％（95％CI0.767-0.939）。基于方差分析模型，网络荟萃分析显示，MMP-7总体排名第二，PCC/PTCC排名第一，与其他技术相比，两者都表现出更高的诊断准确性。我们的分析表明，在大多数方法中没有明显的偏差，但是MMP-7和肝胆闪烁显像显示出偏差，p值分别为0.023和0.002。
结论：MMP-7和超声引导下的PCC/PTCC在BA的早期诊断中显示出诊断潜力，但由于实际应用的局限性，其临床应用受到限制。目前,MMP-7的临界值不清楚，需要进一步的循证医学研究来牢固确立其诊断价值。在有更多证据之前,MMP-7不适合广泛的诊断用途。因此,考虑到成本和操作简单性，肝功能检查联合超声检查仍是临床上最有价值的非侵入性BA诊断方法.
方法：我们回顾了PubMed，EMBASE,和Cochrane用于BA诊断。搜索包括γ-谷氨酰转移酶（GGT），直接/联合胆红素，基质金属蛋白酶7（MMP-7），超声波三角线标志（TCS），肝闪烁显像（HS），和经皮胆管造影/经皮经肝胆囊胆管造影（PCC/PTCC）。QUADAS-2评估研究质量。使用I2和Spearman相关性评估异质性和阈值效应。我们结合了效应估计，构建的SROC模型，并基于方差分析模型进行了网络荟萃分析，连同荟萃回归和亚组分析，获得BA的精确诊断性能评估。
结果：共有40项研究纳入我们的分析。GGT对BA具有较高的诊断准确性，敏感性为81.5%（95%CI0.792-0.836），特异性为72.1%（95%CI0.693-0.748）。直接胆红素/结合胆红素的敏感性为87.6%（95%CI0.833-0.911），但特异性较低，为59.4%（95%CI0.549-0.638）。MMP-7的总敏感性为91.5%（95%CI0.893-0.934），特异性为84.3%（95%CI0.820-0.863）。TCS的敏感性为58.1%（95%CI0.549-0.613），高特异性为92.9%（95%CI0.911-0.944）。HS的敏感性为98.4%（95%CI0.968-0.994），特异性为79.0%（95%CI0.762-0.816）。PCC/PTCC表现出优异的诊断性能，灵敏度为100％（95％CI0.900-1.000），特异性为87.0％（95％CI0.767-0.939）。基于方差分析模型，网络荟萃分析显示，MMP-7总体排名第二，PCC/PTCC排名第一，与其他技术相比，两者都表现出更高的诊断准确性。我们的分析表明，在大多数方法中没有明显的偏差，但是MMP-7和肝胆闪烁显像显示出偏差，p值分别为0.023和0.002。
结论：MMP-7和超声引导下的PCC/PTCC在BA的早期诊断中显示出诊断潜力，但由于实际应用的局限性，其临床应用受到限制。目前,MMP-7的临界值不清楚，需要进一步的循证医学研究来牢固确立其诊断价值。在有更多证据之前,MMP-7不适合广泛的诊断用途。因此,考虑到成本和操作简单性，肝功能检查联合超声检查仍是临床上最有价值的非侵入性BA诊断方法.
