Approaches to Biliary Atresia Care at Cincinnati Children's Full Event

BA pathogenesis involves four primary defective cell types: epithelial cells (virus, toxin, genetic variants causing loss of cellular polarity), immune cells (abnormal response to common viruses), mesenchymal cells (defects in peribiliary gland niche maintenance), and vascular cells (abnormal peribiliary plexus perfusion causing ischemic injury)

CMV is recognized as a modifier in BA, not a direct cause, with emerging evidence that active CMV at time of Kasai may warrant antiviral treatment and affects clinical trial eligibility

Ciliopathy-type BA represents a distinct genetic subgroup with specific clinical features including hepatopulmonary syndrome and multiple bile lakes, requiring different clinical approach and follow-up

Cincinnati's 1700-gene panel for BA workup (in development) includes cholestasis genes and ciliopathy genes, representing expansion beyond standard cholestasis panels to capture genetic modifiers and ciliopathy variants

42% of BA patients undergoing liver transplant at Cincinnati Children's over 10-year period were unpalliated (no prior Kasai attempt), which is described as 'scandalous' for 2000s North America

Liver biopsy performed too early (<30 days) can show incomplete pathologic picture with absent bile plugs or only stromal edema, making diagnosis more difficult and requiring expert pathologist review

Alagille syndrome is the diagnosis that causes most anxiety when considering Kasai, as performing Kasai on Alagille patient precipitates higher likelihood of transplant need. Hypoplastic ducts on cholangiogram can be difficult to differentiate from BA

Non-white infants with BA referred to Cincinnati Children's at median 67 days versus 37 days for white infants, with only 53% of non-white infants receiving Kasai versus 84% of white infants (odds ratio 4.8)

Neighborhood deprivation index independently predicts BA outcomes: infants in most economically distressed areas 50% less likely to receive Kasai or survive to age 2 with native liver, even after controlling for race

Biliary atresia splenic malformation (BASM) patients with preduodenal portal vein often have no hilar plate, requiring abandonment of Kasai attempt. BASM patients have worse outcomes than isolated BA

Kasai revision is indicated for patients with initially successful drainage (bilirubin <2 at 90 days) who develop recurrent cholangitis and acolic stools, not for patients with failed primary Kasai. Cincinnati data shows revision patients lived longer with native liver

Pre-operative indicators suggesting primary transplant over Kasai: significant ascites on ultrasound, bridging fibrosis on liver biopsy, micronodular cirrhosis, and hilar varices. Age is relative—Cincinnati has performed successful Kasai up to 120 days and unsuccessful at 50 days based on these findings

Performing Kasai in 24-25 day old infant is 'very different experience' than 5-7 week old due to smaller bowel caliber, requiring single-layer rather than two-layer anastomosis and increasing technical risk of jejunojejunostomy complications

Cincinnati's selective steroid protocol (implemented 2017) for post-Kasai patients with acolic stools, targeting infants <45 days or those with liver inflammation, increased successful bile drainage from 40% to 84%, with recent two-year data showing 89% drainage rate