Correlation of Intrahepatic Biliary Cysts and the Time of Liver Failure in Biliary Atresia After Kasai Procedure
Biliary atresia (BA) is a progressive neonatal cholestatic disease characterized by fibro-obliterative changes in the extrahepatic and intrahepatic bile ducts, leading to biliary obstruction and eventual liver failure. Despite advances in surgical management, the Kasai portoenterostomy (KP) procedure—though life-prolonging—often fails to prevent long-term complications. A significant proportion of patients still require liver transplantation (LT) due to progressive fibrosis, recurrent cholangitis, and portal hypertension. Among postoperative complications, intrahepatic biliary cysts (IBC), defined as cystic dilatations of the intrahepatic bile ducts ≥1 cm in diameter, have emerged as a potential prognostic factor. This study investigates the relationship between IBC formation, clinical outcomes, and pathological features in BA patients undergoing LT after KP, aiming to elucidate their role in delaying liver failure.
Study Design and Patient Characteristics
The multicenter retrospective analysis included 179 BA patients who underwent LT between January 2008 and December 2018 across four hospitals in China. All patients had type III BA (involving the porta hepatis) diagnosed within three months of birth and underwent KP. The criteria for LT eligibility included end-stage cirrhosis and hepatic failure. Preoperative imaging, specifically computed tomography (CT) scans performed within one month before LT, identified IBC in 36 patients (20.1%). The cohort was stratified into IBC-positive (n=36) and IBC-negative (n=143) groups. Fifty liver specimens (18 IBC-positive, 32 IBC-negative) were randomly selected for histopathological analysis using hematoxylin and eosin (H&E) staining.
Patient demographics revealed a female predominance (104 females vs. 75 males). Notably, the IBC-positive group had a significantly higher proportion of females (75.0% vs. 53.5% in the IBC-negative group, P = 0.021). The median age at KP was 71.36 days in the IBC-positive group compared to 62.76 days in the IBC-negative group, though this difference was not statistically significant (P = 0.094). Postoperative cholangitis rates were comparable between groups (75.0% vs. 76.2%, P = 0.878), suggesting that IBC formation is not directly linked to infectious complications.
Laboratory and Imaging Findings
Preoperative laboratory tests highlighted distinct differences in liver function markers. The IBC-positive group exhibited lower median levels of alanine transaminase (ALT: 68.95 U/L vs. 108.90 U/L, P = 0.006), aspartate transaminase (AST: 137.15 U/L vs. 207.60 U/L, P = 0.032), total bilirubin (TB: 72.58 mmol/L vs. 210.41 mmol/L, P = 0.021), and direct bilirubin (DB: 59.22 mmol/L vs. 166.29 mmol/L, P = 0.008) compared to the IBC-negative group. Total bile acid (TBA) and lactate dehydrogenase (LDH) levels showed no significant intergroup variation. Renal function and hematological parameters (e.g., platelet count, hemoglobin) were also comparable.
CT imaging in IBC-positive patients demonstrated fusiform or beaded cystic dilatations predominantly in the liver’s middle lobe, distributed along the Glisson’s sheath. These findings suggest that IBCs may arise from segmental bile duct obstruction, with localized compensatory dilation mitigating cholestasis and reducing systemic bilirubin accumulation.
Pathological Analysis of Liver Tissue
Histopathological evaluation focused on liver fibrosis, bile duct hyperplasia, bile plugs, and ductal plate malformation (DPM). Liver fibrosis was staged using the METAVIR system and further subclassified via the Laennec method. Both groups exhibited advanced fibrosis, with no significant difference in the proportion of mild, moderate, or severe cirrhosis. Bile duct hyperplasia, quantified by counting proliferative ducts per high-power field, was graded from 0 to 3. Similarly, DPM—assessed as present (score=2) or absent (score=1)—showed no intergroup variation.
However, bile plug severity, graded from 1 (absent) to 4 (diffuse), was significantly lower in the IBC-positive group (P = 0.013). H&E staining revealed irregular bile lakes surrounded by fibrous tissue in IBC-positive livers, with minimal bile duct epithelial structures. These findings imply that cystic dilatations may act as reservoirs for bile retention, reducing intraductal pressure and subsequent cholestatic injury.
Survival Analysis and Time to Liver Failure
The median time to liver failure (TLF)—defined as the interval between KP and LT—was significantly longer in the IBC-positive group (11.50 months vs. 9.00 months, P = 0.038). Survival curves demonstrated a delayed progression to end-stage liver disease in patients with IBC, suggesting a protective mechanism. This contrasts with prior studies reporting IBC as a risk factor for recurrent cholangitis or accelerated fibrosis. The study posits that IBC formation may temporarily alleviate cholestasis, thereby decelerating hepatocellular damage.
Mechanistic Insights and Clinical Implications
The pathogenesis of IBC remains debated. Prevailing theories attribute cystic dilatations to post-inflammatory strictures, impaired bile drainage, or congenital ductal plate malformations. However, the comparable rates of DPM and cholangitis between groups in this study suggest alternative mechanisms. The observed reduction in bile plug severity and bilirubin levels in IBC-positive patients supports the hypothesis that dilated cysts serve as compensatory reservoirs, facilitating bile excretion into the intestinal lumen via anastomosed jejunal loops.
Clinically, the delayed TLF in IBC-positive patients highlights the need for nuanced prognostic assessment. While IBC may transiently improve bile drainage, their long-term impact remains ambiguous. Some studies associate IBC with recurrent cholangitis or portal hypertension, underscoring the necessity for individualized monitoring.
Limitations and Future Directions
The retrospective design and reliance on preoperative CT scans (which may underestimate small cysts) limit the study’s generalizability. Additionally, the absence of serial imaging data precludes analysis of IBC progression relative to fibrosis. Future prospective studies integrating magnetic resonance cholangiopancreatography (MRCP) and elastography could elucidate temporal relationships between IBC formation, biliary dynamics, and liver stiffness.
Conclusion
This study demonstrates that intrahepatic biliary cysts correlate with prolonged native liver survival in biliary atresia patients after Kasai portoenterostomy. The lower bilirubin levels, reduced bile plug severity, and delayed liver failure in IBC-positive patients suggest a compensatory role for cystic dilatations in mitigating cholestatic injury. However, the long-term benefits remain uncertain, necessitating further research into their pathophysiological mechanisms and therapeutic potential.
doi.org/10.1097/CM9.0000000000001260
Was this helpful?
0 / 0