P2D323: Indocyanine Green Clearance Can Be Used to Exclude the Diagnosis of Biliary Atresia

Background: Biliary atresia (BA) is the most common cause of pathological jaundice in infants. No single diagnostic study can confirm the diagnosis of BA outside of conventional intra-operative cholangiography. Notably, indocyanine green (IC-Green) cholangiography is commonly used by surgeons to enhance visualization of the biliary tree. By taking IC-Green cholangiography one step further, we aim to evaluate the timing of IC-Green clearance from the biliary tree into the intestine of infants and to determine if IC-Green clearance into stool could differentiate between BA and other causes of neonatal jaundice. We hypothesize that visualization of IC-Green clearance into stool could be a safe, rapid, inexpensive, and noninvasive way to confirm extrahepatic biliary tree patency.

Methods: A prospective single center cohort study was performed on infants with jaundice after obtaining IRB approval. Inclusion criteria included age less than or equal to twelve months plus one of the following: clinical jaundice, direct bilirubin >1 mg/dL, acholic stools, liver imaging for cholestasis evaluation, genetic testing for cholestasis evaluation, or suspected BA by pediatric hepatologist. Exclusion criteria included iodine or shellfish allergy, formal liver resection, and/or liver transplantation. Infants undergoing laparoscopic pyloromyotomy for hypertrophic pyloric stenosis (HPS) formed the age-matched control group. Infants were given IC-Green (0.1mg/kg) via peripheral IV and soiled diapers for up to 96 hours post-injection were analyzed for fluorescence using the AMI-HTX in vivo imaging system (Spectral imaging). Intra-operative images were also obtained using the 1688 AIM 4K Platform (Stryker). At the time of analysis, nine subjects were enrolled in the experimental group and four in the control group.

Results: The mean age of control HPS subjects was 6.25 weeks compared to 7.46 weeks for the experimental jaundice group (P=0.63). IC-Green delivery ranged between 30 minutes and 12 hours prior to incision for HPS subjects undergoing laparoscopic pyloromyotomy. Fluorescence of the gallbladder was visualized intra-operatively in all subjects with HPS. All subjects with HPS cleared IC-Green into stool within 24 hours of delivery. In the jaundice group, three subjects were found to have BA, none of which cleared IC-Green into stool within 24 hours of delivery. The remaining six subjects with jaundice did not have BA and all had detectable IC-Green fluorescence in stool within 24 hours of delivery.

Conclusion: Assessment of IC-Green clearance into stool in an innovative approach to evaluate biliary drainage non-invasively. Despite our small sample size, clearance of IC-Green into stool appears to be a highly accurate tool to exclude the diagnosis of BA and has the potential to facilitate earlier diagnosis and treatment of BA. Further investigation will be directed toward increasing sample size to determine sensitivity, specificity, positive predictive value, and negative predicative value of this new screening tool.