Neonatal Dubin-Johnson Syndrome and its Differentiation from Biliary Atresia

Abstract

Background and Aims: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). Methods: 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. Results: 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 (p<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, p<0.00001) with an AST cutoff of 87 IU/L. Conclusions: 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.

Differentiating Neonatal Dubin Johnson Syndrome from Biliary Atresia: Start Simply

“…The important caveat is that success or prognosis of the Kasai procedure is negatively impacted by increased age at time of surgery, therefore a timely referral is crucial. 4,6 In this issue of the journal, Liu et al 7 investigate how to make the distinction between BA and nDJS using simple hepatic function tests, which is a noble effort to achieve timely and cost-effective care. The difficulty arises because there can be an overlap in the clinical presentation of both conditions, especially when all of the liver function tests are abnormal in nDJS.…”

“…A hepatobiliary iminodiacetic acid scan can exclude BA when there is excretion into the small bowel, but is often noncontributory. 4 Liu et al 7 found that overall liver chemistries are lower in nDBS compared with BA. Using specific cutoffs for liver tests, they found that an AST level of <87 IU/L had a high sensitivity and specificity for nDBS, and therefore highlight its potential as a sensitive biomarker to differentiate nDBS from BA.…”

“…Using specific cutoffs for liver tests, they found that an AST level of <87 IU/L had a high sensitivity and specificity for nDBS, and therefore highlight its potential as a sensitive biomarker to differentiate nDBS from BA. 7 Given its wide availability, applying this finding is a good starting point to reach a diagnosis in a neonate with jaundice. Complementing this with other tests can help guide the physician for final diagnosis.…”

Clinical characteristics and follow-up of a newborn with Dubin–Johnson Syndrome: A clinical case report

“…[8,9] Early and precise diagnosis not only streamlines clinical management but also avoids potential complications arising from misdiagnosis with other hepatic conditions. [10,11] This study presents a neonatal clinical perspective of the disease. Through this exploration, we may contribute to a better understanding of DJS' infancy presentation and its developmental trajectory.…”