Introduction: Biliary atresia (BA) is the most common cause of obstructive cholestasis in neonates. The primary treatment for BA is surgical palliation via Kasai Portoenterostomy (KPE). Despite KPE, nearly half of patients with BA require a liver transplant (LT) by two years of age, and overall lifetime risk of LT is high. Efforts have been made to identify factors that prognosticate the need for and timing of LT in this population. We performed a retrospective study of individuals with BA & KPE with the goal of identifying genetic predictors of outcome.

Method: Individuals with BA were dichotomized into KPE failure (KF; LT listing prior to age 2 years) and success (KS; LT listing after age 2 years), representing persistent cholestasis post-KPE and non-cholestatic complications, respectively. Genetic evaluation of 77 genes associated with Mendelian cholestatic disorders was performed on liver tissue and blood specimens, previously saved in IRB approved biorepositories. The incidence of pathogenic genetic variants was compared between groups.

Results: 129 individuals were included (KF=71, KS=58). 489 variants were identified in 67 genes, including 40 variants classified as pathogenic/likely pathogenic present in 14 genes. Thirty-six individuals harbored one or more pathogenic/likely pathogenic variant. There was no significant difference in the frequency of pathogenic/likely pathogenic variants between groups (Table 1).

Conclusion: Our study did not identify a genetic risk predictor for KPE outcomes. Additional higher-powered studies are warranted; however, based on our study, families should not be counseled that variants in Mendelian cholestasis genes predict worse KPE outcomes.