Liu Teng, Zhao Jing, Feng Jia-Yan, Lu Yi, Sheps Jonathan A, Wang Ren-Xue, Han Jun, Ling Victor, Wang Jian-She
The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China.
The Department of Pathology, Children's Hospital of Fudan University, Shanghai, China.
J Clin Transl Hepatol. 2023 Feb 28;11(1):163-173. doi: 10.14218/JCTH.2021.00460. Epub 2022 Mar 11.
The aim was to determine if liver biochemistry indices can be used as biomarkers to help differentiate patients with neonatal Dubin-Johnson syndrome (nDJS) from those with biliary atresia (BA).
Patients with genetically-confirmed nDJS or cholangiographically confirmed BA were retrospectively enrolled and randomly assigned to discovery or verification cohorts. Their liver chemistries, measured during the neonatal period, were compared. Predictive values were calculated by receiver operating characteristic curve analysis.
A cohort of 53 nDJS patients was recruited, of whom 13 presented with acholic stools, and 14 underwent diagnostic cholangiography or needle liver biopsy to differentiate from BA. Thirty-five patients in the cohort, with complete biochemical information measured during the neonatal period, were compared with 133 infants with cholangiographically confirmed BA. Total and direct bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acids, alkaline phosphatase, and gamma-glutamyl transferase were significantly lower in nDJS than in BA. In the discovery cohort, the areas under the curve for ALT and AST were 0.908 and 0.943, respectively. In the validation cohort, 13/15 patients in the nDJS group were classified as nDJS, and 10/53 in the BA control group were positive (<0.00001) with an ALT biomarker cutoff value of 75 IU/L. Thirteen of 15 patients were classified as nDJS and none were classified positive in the BA group (13/15 vs. 0/53, <0.00001) with an AST cutoff of 87 IU/L.
Having assembled and investigated the largest cohort of nDJS patients reported to date, we found that nDJS patients could be distinguished from BA patients using the serum AST level as a biomarker. The finding may be clinically useful to spare cholestatic nDJS patients unnecessary invasive procedures.
本研究旨在确定肝脏生化指标是否可作为生物标志物，以帮助鉴别新生儿杜宾-约翰逊综合征（nDJS）患者与胆道闭锁（BA）患者。
对基因确诊的nDJS患者或经胆管造影确诊的BA患者进行回顾性纳入，并随机分配至发现队列或验证队列。比较他们在新生儿期测量的肝脏生化指标。通过受试者工作特征曲线分析计算预测值。
招募了53例nDJS患者，其中13例出现无胆汁粪便，14例接受了诊断性胆管造影或经皮肝穿刺活检以与BA进行鉴别。将该队列中35例在新生儿期有完整生化指标信息的患者与133例经胆管造影确诊的BA婴儿进行比较。nDJS患者的总胆红素、直接胆红素、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆汁酸、碱性磷酸酶和γ-谷氨酰转移酶均显著低于BA患者。在发现队列中，ALT和AST的曲线下面积分别为0.908和0.943。在验证队列中，nDJS组15例患者中有13例被分类为nDJS，BA对照组53例中有10例为阳性（<0.00001），ALT生物标志物临界值为75 IU/L。15例患者中有13例被分类为nDJS，BA组无1例被分类为阳性（13/15 vs. 0/53，<0.00001），AST临界值为87 IU/L。
在汇集并研究了迄今为止报告的最大规模的nDJS患者队列后，我们发现可将血清AST水平作为生物标志物来区分nDJS患者与BA患者。这一发现可能在临床上有助于避免胆汁淤积性nDJS患者接受不必要的侵入性检查。
