Plasma alpha-fetoprotein and other biochemical indicators for constructing early diagnosis models of potential biliary atresia in children

doi:10.3969/j.issn.2095-4344.1426

Abstract

Abstract:

BACKGROUND: Biliary atresia is not suitable as a method for early diagnosis because it mainly depends on intraoperative diagnosis, and the operation is complicated, and there is a great injury to the child. Therefore, finding simple and effective blood biochemical diagnostic indicators will improve early diagnosis efficiency.
OBJECTIVE: To measure the plasma alpha-fetoprotein level in children with biliary atresia and to investigate the application value of plasma alpha-fetoprotein level and blood biochemical indicators.
METHODS: Blood samples were harvested from 48 infants with biliary atresia, 20 infants with neonatal hepatitis, and 9 healthy controls. Plasma alpha-fetoprotein level was measured by enzyme-linked immunosorbent assay. The correlation between plasma alpha-fetoprotein level and blood biochemical indicators was analyzed to establish a potential diagnosis model. This study was approved by the Ethics Committee of Xinhua Hospital, China (approval No. XHEC-D-2013-026).
RESULTS AND CONCLUSION: Plasma alpha-fetoprotein level in infants with biliary atresia and neonatal hepatitis was significantly higher than that in the healthy controls (P < 0.001), but no significant difference in plasma alpha-fetoprotein level was observed between infants with biliary atresia and neonatal hepatitis (P > 0.05). There was no significant difference in plasma alpha-fetoprotein level between infants with different stages of cirrhosis (P > 0.05). Blood biochemical indexes indicated severe liver injury in infants with biliary atresia and neonatal hepatitis. There were significant differences in plasma prealbumin (P < 0.05) and γ-glutaminyl transpeptidase levels between infants with biliary atresia and neonatal hepatitis (P < 0.01). Plasma alpha-fetoprotein level was negatively correlated with γ-glutaminyl transpeptidase level (r =-0.516, P < 0.01). A potential diagnosis model was established based on plasma alpha-fetoprotein, prealbumin, γ-glutaminyl transpeptidase levels, age and sex of infant patients, with a sensitivity of 81.82%, specificity of 91.67%, and area under the curve of 0.939. Results suggest that plasma alpha-fetoprotein level increased in infants with biliary atresia. Establishing a diagnosis model based on blood biochemical indicators such as plasma alpha-fetoprotein is of certain reference value for clinical diagnosis of biliary atresia.

Key words: alpha-fetoprotein, biliary atresia, neonatal hepatitis, γ-glutaminyl transpeptidase, prealbumin, blood biochemical indicators, diagnostic model, biomarker

CLC Number:

Yang Tianqi1, Hu Xiaowen1, Zhou Kejun2, Wan Chunling1. Plasma alpha-fetoprotein and other biochemical indicators for constructing early diagnosis models of potential biliary atresia in children[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(31): 5046-5051.

Figures/Tables 5

2.4 胆道闭锁患儿肝纤维化水平与甲胎蛋白浓度无关胆道闭锁患儿一般伴发不同程度的肝纤维化，并呈渐进性发展趋势。肝纤维化水平可反映胆道闭锁患儿肝脏损伤的严重程度。研究中的48例胆道闭锁患儿均伴发肝纤维化，纤维化水平由临床医生通过METAVIR标准进行分级，分级标准：0为无纤维化；1为汇管区纤维性扩大，但无纤维间隔形成；2为汇管区纤维性扩大，少数纤维间隔形成；3为多数纤维间隔形成，无硬化结节；4为肝硬化。依据肝纤维化水平对胆道闭锁患儿进行分组，比较了组间甲胎蛋白水平，发现不同肝纤维化水平的患儿血浆甲胎蛋白无显著差异，见图2B。 2.5 胆道闭锁患儿血生化指标总体情况收集了患儿一系列血生化检查的指标，包括血细胞统计指标、肝功能指标和凝血功能指标等。但由于各个患者所接受的检查差别较大，一些指标缺失值较多。此次研究中保留了缺失值小于50%的生化指标纳入后续分析。在这些指标中，有9项指标在胆道闭锁组或肝炎组中出现异常，分别是前白蛋白、总胆汁酸、谷丙转氨酶、谷草转氨酶、碱性磷酸酶、γ-谷氨酰转肽酶、总胆红素、直接胆红素和白球比。异常指标均与肝功能相关，提示胆道闭锁和肝炎患儿肝脏均受到严重损伤。在这些异常指标中，有2项指标在胆道闭锁和肝炎组之间表现出显著的差异，见图3A，B，分别是前白蛋白和γ-谷氨酰转肽酶，提示这2种物质有作为鉴别两种疾病的潜力。 2.6 γ-谷氨酰转肽酶水平与甲胎蛋白浓度负相关通过Spearman检验方法研究了胆道闭锁和肝炎患儿各项血生化指标与甲胎蛋白水平之间的相关性。发现在所有纳入分析的血生化指标中，仅有γ-谷氨酰转肽酶一项与甲胎蛋白值显著相关，见图3C。甲胎蛋白和γ-谷氨酰转肽酶水平呈现负相关，Spearman相关系关系数为r=-0.516，P < 0.01。不仅如此，当胆道闭锁和肝炎分别进行计算时， γ-谷氨酰转肽酶和甲胎蛋白仍然都呈现出显著的相关性及相似的相关系数(胆道闭锁组：r=-0.513；肝炎组：r=-0.446)。 2.7 通过血生化指标构建诊断模型研究中联合了年龄、性别、甲胎蛋白、前白蛋白、γ-谷氨酰转肽酶5项指标，通过二元Logistic回归方法构建了用于鉴别胆道闭锁和新生儿肝炎的诊断模型。通过该模型，可以将胆道闭锁患者和新生儿肝炎患者很好的区分开。图3D的ROC曲线显示该模型的曲线下面积AUC可达0.939，该模型的敏感性为81.92%，精确性为91.67%。"

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