1. Etiological classification and mechanisms of biliary stricture after liver transplantation
Common causes of biliary stricture include postoperative anastomotic stricture, such as choledochojejunostomy stricture following liver transplantation; iatrogenic bile duct injury, such as accidental injury during laparoscopic cholecystectomy; chronic inflammatory disorders, including primary sclerosing cholangitis (PSC) and IgG4-related sclerosing cholangitis; radiation cholangitis; strictures secondary to bile duct stones; trauma; and congenital abnormalities.
Postoperative anastomotic stricture is particularly common in liver transplant recipients. Important differences between anastomotic strictures (AS) and non-anastomotic strictures (NAS) have been documented in terms of pathogenesis, timing of onset, response to endoscopic treatment, recurrence, long-term prognosis, and retransplantation risk. AS originates from focal perianastomotic injury. Early AS, defined as onset within < 1 month, is primarily attributed to surgical mechanical factors such as anastomotic tension and donor-recipient duct-size mismatch, whereas late AS, defined as onset > 1 month, is largely associated with focal ischemia-induced perianastomotic fibrosis9.
In contrast, NAS is associated with diffuse impairment of the biliary microcirculation. Contributing factors include cold ischemia-associated cholangiocyte injury, ischemia-reperfusion injury, ABO-incompatible transplantation, and immune-mediated injury, which may collectively produce multifocal fibrotic lesions extending beyond the anastomotic site4,10,11,12. Most AS develops within the first year after liver transplantation7. By contrast, NAS may occur early following severe ischemic injury or may develop years after transplantation in association with persistent immune-mediated injury8.
Endoscopic balloon dilation and stenting have been associated with high stricture-resolution rates, approximately 90%–97%, in selected patients with localized AS13. For diffuse NAS, endoscopic treatment is often less durable, with reported long-term therapeutic success rates of 25%–50%14. Following successful endoscopic treatment, recurrence of AS has been reported in approximately 21%–33% of cases13,15, whereas recurrence appears to be more frequent in NAS despite repeated interventions. AS generally has a more favorable clinical course when successfully treated. In contrast, NAS may be associated with recurrent cholangitis, progressive biliary injury, graft dysfunction, and, in refractory cases, retransplantation; some series have reported retransplantation in approximately 30% of affected patients12.
2. Clinical manifestations and diagnosis of biliary stricture after liver transplantation
- Clinical manifestations
Biliary strictures following liver transplantation may present with diverse and often nonspecific symptoms, primarily including cholangitis and signs of biliary obstruction such as jaundice, fever, and right upper quadrant pain. In cases of complete biliary obstruction, patients may develop worsening jaundice, pruritus, or clay-colored stools. Some patients experience recurrent cholangitis, and severe cases may progress to liver failure, compromising graft function and patient survival16.
Laboratory findings commonly include elevated serum transaminases, bilirubin, and total bile acids. Gamma-glutamyl transferase (GGT) and/or alkaline phosphatase (ALP) levels exceeding twice the upper limit of normal may have diagnostic significance7.
- Diagnosis
Ultrasonography is commonly used for the initial evaluation of biliary dilation and liver dysfunction because of its accessibility and cost-effectiveness. Magnetic resonance cholangiopancreatography (MRCP) is an important noninvasive modality for diagnosing post-transplant biliary strictures, with reported sensitivity of 93%–97% and specificity of 92%–98%. Gadoxetic acid-enhanced biliary imaging may further improve diagnostic performance12,14,17.
Computed tomography (CT) and ultrasonography may provide complementary assessment of peribiliary structures and associated abnormalities, including bile duct stones, hepatic parenchymal changes, and postoperative vascular status18. Three-dimensional imaging techniques may improve visualization of intrahepatic ductal anatomy by addressing some of the spatial limitations of conventional two-dimensional CT and magnetic resonance imaging. Reported advantages include multi-angle visualization, more precise surgical planning, and improved interdisciplinary collaboration.
Endoscopic retrograde cholangiopancreatography (ERCP) remains the diagnostic reference standard for post-transplant biliary strictures because it allows direct assessment of stricture location, length, and severity while guiding therapeutic decision-making5. Endoscopic ultrasound (EUS) may provide additional information when ERCP findings are inconclusive by allowing high-resolution assessment of the bile duct wall and adjacent lymph nodes. Digital cholangioscopy provides direct intraluminal visualization and may improve the evaluation of epithelial lesions, bile duct stones, and stent-related complications19.
3. Advances in endoscopic treatment techniques
- Endoscopic retrograde cholangiopancreatography
ERCP is the cornerstone of endoscopic therapy for biliary strictures after liver transplantation. Direct endoscopic access and contrast imaging allow assessment of stricture length, location, and severity, and guide subsequent intervention. Therapeutic options include balloon dilation to restore biliary patency and placement of plastic or metal stents to maintain drainage and reduce recurrence.
Recent refinements in ERCP include high-resolution endoscopes and advanced guidewire techniques intended to improve stricture cannulation and procedural safety. Three-dimensional printed silicone models may also support operator training by simulating complex anatomy and procedural maneuvers20. Techniques such as precutting and double-guidewire, or pancreatic duct-assisted, biliary cannulation may improve access, although their technical complexity and learning curve may limit widespread use21.
Beyond standard fluoroscopy-guided ERCP, several newer endoscopic modalities have expanded treatment options for complex post-transplant biliary strictures, particularly in patients with difficult cannulation or surgically altered upper gastrointestinal anatomy. Digital single-operator cholangioscopy permits direct intraluminal visualization of the biliary mucosa and may assist in differentiating inflammatory, fibrotic, or ischemic stricture morphology. It may also identify associated sludge, stones, or loose sutures and facilitate visually guided guidewire passage when fluoroscopic cannulation is unsuccessful22. However, cholangioscopy is limited by higher procedural costs, longer procedure times, the risk of procedure-related cholangitis, and operator-dependent learning curves. Much of the supporting evidence is derived from small, single-center case series rather than large comparative studies.
In patients with surgically altered anatomy, conventional duodenoscope-based ERCP may be unsuccessful. In Roux-en-Y gastric bypass anatomy, EUS-directed transgastric ERCP (EDGE) creates a temporary gastrogastric fistula to permit access for standard duodenoscope-based intervention23. In patients with hepaticojejunostomy or other altered biliary anatomy, alternative approaches may include device-assisted enteroscopy, EUS-guided biliary drainage, or percutaneous intervention. EUS-guided biliary drainage (EUS-BD) establishes a direct transluminal biliary-enteric fistula for decompression when transpapillary access cannot be achieved and may serve as an alternative to percutaneous transhepatic biliary drainage.
Although these approaches may avoid some morbidity associated with percutaneous intervention, they carry specific risks, including lumen-apposing metal stent migration, fistula-associated leakage, bleeding, and peritoneal infection. Available evidence is largely non-transplant-specific, and prospective transplant-specific cohorts remain limited. Standardized protocols for fistula creation, stent indwelling duration, and fistula closure after treatment have not been established. Accordingly, these techniques currently serve primarily as rescue approaches rather than replacements for conventional first-line ERCP23–25.
- Biliary stenting
Biliary stent placement is a core component of ERCP-based treatment for biliary strictures after liver transplantation. Stents maintain biliary patency, facilitate dilation of narrowed segments, and reduce the risk of recurrent obstruction. Multiple-stent strategies are also used for complex or multifocal strictures to improve biliary drainage and reduce recurrence26.
MPS is commonly used for anastomotic strictures. Published protocols generally involve placement of two to three 10 Fr plastic stents, with subsequent exchange at approximately 3-month intervals and progressive increases in stent size or number when feasible. Treatment is often continued for about 12 months and may be extended in refractory cases. Stent removal is typically considered after clinical improvement, normalization or substantial improvement of liver biochemistry, and endoscopic evidence of adequate biliary drainage. Continued follow-up after stent removal is advisable because recurrence may occur27.
Comparative studies suggest that MPS and FCSEMS achieve broadly similar stricture-resolution rates, approximately 93%–97%, in post-transplant anastomotic biliary strictures, although results vary across studies and treatment protocols13. Reported recurrence rates after complete stent removal range from 21%–33% for both modalities, although observational studies indicate variation according to stent indwelling duration and stricture severity13,15.
Stent migration is an important limitation of FCSEMS. Conventional FCSEMS may have migration rates of up to 9.8%, although this risk may be reduced by over-the-scope clip anchoring or anchor-fluked FCSEMS28,29. In contrast, MPS is more commonly associated with stent occlusion caused by biliary sludge. Both strategies share procedure-related risks, including post-ERCP pancreatitis, biliary infection, and hemorrhage. FCSEMS may additionally be associated with cholecystitis and intrastent hyperplasia, whereas MPS-related complications predominantly include sludge-induced occlusion and recurrent cholangitis13,30,31.
FCSEMS may reduce the number of ERCP procedures required compared with MPS; one comparative study reported a median of two procedures with FCSEMS versus four with MPS13. Treatment duration also differs between the approaches. Standard MPS protocols generally require approximately 12 months of staged exchanges at 3-month intervals, whereas FCSEMS is typically left in place for 6–12 months as a continuous treatment course13,30.
FCSEMS may be considered in patients in whom reducing the number of repeat endoscopic procedures is an important treatment goal, provided that migration risk and other stent-related adverse events are taken into account. MPS remains an established alternative, particularly when metal stents are unsuitable or repeated staged treatment is preferred. Neither approach provides satisfactory curative outcomes for diffuse NAS, in which endoscopic intervention generally provides palliative biliary decompression. Despite growing comparative evidence, no consensus has been established on optimal stent selection, and treatment should be individualized based on stricture anatomy, patient comorbidities, and local endoscopic expertise13.
- Balloon dilation
Balloon dilation mechanically widens biliary strictures to restore bile flow and reduce biliary stasis and infection. Careful control of dilation pressure and duration is important because excessive dilation may result in perforation or pseudoaneurysm formation24. Non-compliant balloons are gradually inflated to the intended diameter, and stent placement may subsequently be performed to maintain patency. Combined balloon dilation and stenting have been associated with better efficacy and lower recurrence than stenting alone.
4. Evaluation of endoscopic therapy and complication management
- Efficacy of endoscopic therapy
A retrospective study reported longer median overall survival among patients who underwent scheduled endoscopic treatment than among untreated patients, 19.7 years versus 7.7 years15. Because this finding is based on observational data, the difference should be interpreted in the context of potential selection- and treatment-related confounding. In a long-term cohort of 165 patients treated endoscopically for biliary strictures after liver transplantation, the initial technical success rate was 83.6%, the treatment failure rate was 24.2%, and the recurrence rate was 21.2%. Median overall survival among patients with anastomotic strictures was 17.6 years. The same cohort reported a 15-year graft survival rate of 70.6%32. These findings support the potential long-term effectiveness of endoscopic treatment, although outcomes may vary according to stricture type, patient characteristics, treatment protocol, and study design.
- Complication management in endoscopic therapy
Endoscopic treatment of post-transplant biliary strictures carries recognized risks, including pancreatitis, biliary infection, hemorrhage, and perforation. Reported rates of post-ERCP pancreatitis range from 3.47%–14.7%, hemorrhage from 0.004%–0.07%, and perforation is reported in approximately 0.05% of procedures8,33.
Prophylactic nonsteroidal anti-inflammatory drugs and pancreatic stent placement may reduce the risk of post-ERCP pancreatitis. Biliary infection is associated with procedural contamination and immunosuppression and requires attention to aseptic technique and appropriate antibiotic use. Management of biliary perforation depends on severity. Minor perforations may be managed conservatively, whereas larger perforations accompanied by peritonitis or hemodynamic instability may require urgent surgical repair34. Rare complications, including gas embolism and nerve injury, further emphasize the importance of careful monitoring and multidisciplinary management35. An overview of the classification, diagnosis, and endoscopic management of biliary strictures after liver transplantation is provided in Figure 1.

Figure 1: Overview of the classification, diagnosis, and endoscopic management of biliary strictures after liver transplantation. The illustration outlines the background and clinical importance of biliary strictures after liver transplantation, distinguishes anastomotic and non-anastomotic strictures, and highlights their differences in timing, pathogenesis, treatment response, recurrence, and prognosis. Please click here to view a larger version of this figure.