Kasai Procedure in Patients Older Than 90 Days: Worth a Cut

Introduction Age at Kasai portoenterostomy (KPE) has been identified as a predictive factor for native-liver survival in patients with biliary atresia (BA). Outcomes of pediatric liver transplantation (LT) have improved over recent years. It has been proposed to consider primary LT as a treatment option for late-presenting BA infants instead of attempting KPE. We present our experience with patients older than 90 days undergoing KPE. Materials and Methods A retrospective chart review of patients with BA undergoing KPE at our institution between January 2010 and December 2020 was performed. Patients 90 days and older at the time of surgery were included. Patients' characteristics, perioperative data, and follow-up results were collected. Eleven patients matched the inclusion criteria. Mean age at KPE was 108 days (range: 90–133 days). Results Postoperative jaundice clearance (bilirubin < 2 mg/dL) at 2-year follow-up was achieved in three patients (27%). Eight patients (73%) received a liver transplant at a mean of 626 days (range: 57–2,109 days) after KPE. Four patients (36%) were transplanted within 12 months post-KPE. Two patients died 237 and 139 days after KPE due to disease-related complications. One patient is still alive with his native liver, currently 10 years old. Conclusion Even when performed at an advanced age, KPE can help prolong native-liver survival in BA patients and offers an important bridge to transplant. In our opinion, it continues to represent a viable primary treatment option for late-presenting infants with BA.

Adjuvant Therapy with Budesonide Post-Kasai Reduces the Need for Liver Transplantation in Biliary Atresia

Based on the hypothesis that autoimmunological factors coregulate the pathomechanism in biliary atresia (BA), adjuvant therapy with steroids has become routine, although its efficacy has never been proven. In 2010, a study on the advantages of budesonide compared to prednisolone in autoimmune hepatitis gave rise to experimental therapy using budesonide as an adjuvant BA treatment. Ninety-five BA patients prospectively received a budesonide 2 mg/dose rectal foam daily for three months (SG). A case-matched control group (CG: 81) was retrospectively recruited. The outcome measures were survival with native liver (SNL), determined at six months and two years after the Kasai procedure. The follow-up rate was 100%. At six months, SNL was statistically not different but became so after two years (SG: 54%; CG: 32%; p < 0.001). No steroid-related side effects were observed, except for eight patients with finally caught-up growth retardation. This study demonstrates for the first time a significantly longer survival with native liver in patients with BA after adjuvant therapy. However, indication, dosage, and duration of any budesonide application is not given in neonates with BA. Hence, we suggest extending the postoperative use of budesonide in a multicenter observational study with a clearly defined follow-up protocol, particularly in terms of potentially underestimated side effects.

Characteristics of the Gut Microbiome and IL-13/TGF-β1 Mediated Fibrosis in Post-Kasai Cholangitis of Biliary Atresia

Aims: Cholangitis in biliary atresia (BA), which accelerates liver fibrosis progression, is among the most common serious complications after Kasai surgery; however, its etiology remains elusive. Gut microbiome migration may contribute to post-Kasai cholangitis. Further, there is no appropriate model of BA post-Kasai cholangitis for use in investigation of its pathogenesis.Methods: We explored the characteristics of gut microbiome in patients with BA before and after Kasai procedure based on 16S rDNA sequencing. We isolated the dominant strain from patient stool samples and established an in vitro model by infecting patient-derived liver organoids. Bulk RNA-seq was performed, and we conducted qPCR, ELISA, and western blot to explore the mechanism of fibrosis.Results: Gut microbiome diversity was lower in patients after, relative to before, Kasai procedure, while the relative abundance of Klebsiella was higher. Patients who developed cholangitis within 1 month after discharge tended to have simpler gut microbiome composition, dominated by Klebsiella. Klebsiella pneumoniae (KPN) was isolated and used for modeling. RNA-seq showed that BA liver organoids expressed markers of hepatic progenitor cells (KRT19, KRT7, EPCAM, etc.) and that organoids were more stable and less heterogeneous among individuals than liver tissues. After infection with KPN, gene expression patterns in BA liver organoids were enriched in pathways related to infection, apoptosis, and fibrosis. Preliminary experiments indicated the presence of IL-13/TGF-β1-mediated fibrosis in post-Kasai cholangitis.Conclusions: Our findings using a newly-developed model, demonstrate a key role for Klebsiella, and a potential mechanism underlying fibrosis in post-Kasai cholangitis, mediated by the IL-13/TGF-β1 pathway.

Outcomes of late Kasai portoenterostomy in biliary atresia: a single-center experience

Objectives To describe the clinical, histopathologic, and outcomes data for a cohort of patients with biliary atresia (BA), and to identify the factors affecting survival. Methods This was a cross-sectional study of all BA patients diagnosed between 1999 and 2017. Clinical, biochemical, imaging, and histopathologic data were analyzed, and Kaplan–Meier survival rates were compared to identify potential prognostic factors. Results We evaluated 23 patients. The median age at the Kasai procedure was 77 ± 34 days, and the median overall survival was 12.5 ± 65 months. Thirteen (56%) patients survived with their native livers, 3 (13%) received a transplant, and 6 died (26%) while awaiting a transplant. Cholangitis and the use of ursodeoxycholic acid were associated with longer survival, while impaired synthetic function was associated with shorter survival. Conclusions Most patients presented late for the Kasai procedure. The survival rate with the native liver was comparable to other cohorts. Therefore, clinicians are encouraged to refer for the Kasai procedure even with late presentation (between 60 and 90 days), provided there is no hepatic decompensation.