Mitigating challenges in endoscopic management of post-liver transplant biliary strictures

Abstract

In this editorial, we comment on the paper from Aujla et al on this issue of World Journal of Gastrointestinal Endoscopy. Post-liver transplant biliary strictures (PTBS) can be anastomotic biliary stricture (ABS) and non-ABS, depending on their location in the biliary tree and ABS being the most encountered type. Endoscopic management of PTBS is the first-line therapeutic treatment, with a higher success rate for ABS. However, there are certain challenges encountered during the endoscopic therapy. Inability to pass the guidewire through dense, fibrotic anastomotic strictures is mitigated with the use of peroral cholangioscopy and aggressive dilation using high-pressure balloon dilation followed by placing multiple plastic stents (MPS). Traditional MPS requires three to five repeat endoscopic retrograde cholangiopancreatography over 12-24 months, which can be mitigated by using fully covered self-expandable metal stents (FCSEMS). The increased rate of migration of FCSEMS can be mitigated by the use of dedicated anti-migration stents with specialized flanges. In the case of Roux-en-Y hepaticojejunostomy, deep enteroscopy or rendezvous technique is used to access the ABS. A multidisciplinary approach with the close collaboration between transplant hepatologists, interventional endoscopists, transplant surgeons, and interventional radiologists is the cornerstone of the successful management of PTBS.

Key Words: Post-liver transplant biliary strictures; Anastomotic biliary strictures; Non-anastomotic biliary strictures; Multiple plastic stents; Fully covered self-expandable metal stent

Core Tip: Post-liver transplant biliary strictures (PTBS) are divided into anastomotic and non-anastomotic biliary strictures. Endoscopic therapy with balloon dilation of stricture followed by the placement of multiple plastic stents or fully covered self-expandable metal stents is currently the first-line therapy for PTBS. In cases of stricture recurrence, repeat endoscopic therapy remains a highly effective option. However, endoscopic treatment encounters challenges in certain conditions, such as tight or tortuous stenosis and altered anatomy, which are mitigated through advanced techniques, specialized stent designs, peroral cholangioscopy, deep enteroscopy and multidisciplinary approaches, thereby achieving long-term stricture resolution and reducing the need for surgery.

This editorial refers to “Endoscopic management of post-living donor liver transplant anastomotic biliary strictures: A quaternary care transplant center experience” by Aujla et al, 2026; https://dx.doi.org/10.4253/wjge.v18.i5.119587.

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INTRODUCTION

In this editorial, we comment on the paper from Aujla et al[1] on this issue of World Journal of Gastrointestinal Endoscopy. Liver transplantation (LT) is the definitive, life-saving therapy for end-stage liver disease, acute liver failure, and certain cases of hepatocellular carcinoma. Living donor LT (LDLT) is an effective alternative to deceased donor LT. Advances in surgical techniques, immunosuppressive management, and post-transplant care have dramatically improved LT outcomes. However, biliary complications after LT remain the major problem post-transplant, affecting 5%-35% of LT recipients[2,3]. Biliary leaks and strictures are the most common biliary complications after LT. Other less frequent biliary complications are sphincter of Oddi dysfunction, hemobilia, cystic duct mucoceles, biliary stones, sludge or casts[4-6]. Knowledge and understanding of biliary anastomosis are important in assessing the biliary complications at the anastomotic site. During LT, biliary reconstruction is strictly performed only after all vascular connections are completed, blood flow is established, and perfect hemostasis is achieved. End-to-end duct-to-duct biliary anastomosis (choledocho-choledochostomy) is the biliary reconstruction of choice in patients with healthy, adequately sized native bile ducts as it preserves the physiologic bilioenteric cycle and provides easier access to the biliary tree via endoscopy, if any postoperative complications like strictures or leaks occur[7]. Roux-en-Y hepaticojejunostomy (RYHJ) with biliary-enteric anastomosis is utilized in pediatric patients with preexisting biliary disease, such as biliary atresia or primary sclerosing cholangitis to reestablish bile flow and prevent liver failure. RYHJ is also a widely utilized biliary-enteric reconstruction when there is a marked discrepancy in size between the donor and recipient bile ducts. By connecting the larger jejunum to the smaller bile duct, a tension-free, wide-diameter anastomosis is achieved which significantly lowers the risk of postoperative stricture formation. RYHJ is the preferred technique for biliary reconstruction during liver re-transplantation or complex repairs because the native biliary system often has an inadequate, scarred, or insufficient length to perform a tension-free duct-to-duct anastomosis with the new liver graft[8,9]. Duct-to-duct biliary anastomosis and Roux-en-Y biliary-enteric anastomosis are shown in Figure 1. Duct-to-duct biliary anastomosis is classified based on the number of bile ducts anastomosed together during biliary reconstruction and is of four types, namely, type 1 when single donor duct is anastomosed to a single recipient duct, type 2 when two donor ducts are connected to a single recipient duct, type 3 when three donor ducts are anastomosed to a single recipient duct and type 4 when two recipient ducts (cystic duct and common hepatic duct or right and left hepatic ducts) are anastomosed with the donor duct[10]. Risk factors for biliary complications after LT is given in Table 1[11-14].

Figure 1  Duct-to-duct biliary anastomosis and Roux-en-Y biliary-enteric anastomosis.

Table 1 Risk factors for biliary complications after liver transplantation.

Donor type: Transplanted liver from a living donor or a donation after cardiac (circulatory) death donor; older age of donor; high donor body mass index; macrovascular graft steatosis > 25%

Duct anatomy: Utilizing multiple donor bile ducts increases the complexity and risk of leaks or strictures compared to a single duct

Type of anastomosis: Duct-to-duct biliary anastomosis or Roux-en-Y hepaticojejunostomy carry specific, differing risks for biliary complications

Surgical or technical factors: Excessive dissection of the periductal tissue during the procurement or mobilization of the native liver; excessive use of electrocautery to control bleeding from the peribiliary tissues; presence of tension between the two ends of the biliary anastomosis that can lead to an incomplete seal and subsequently to leaks and formation of peri-hepatic abscesses; mismatched size between donor and recipient bile ducts; ischemia or reperfusion injury; prolonged cold and or warm ischemia times

Placement of T-tubes

Pre-LT cytomegalovirus infection

Diagnosis of primary sclerosing cholangitis as the primary indication for LT

LT performed between donors and recipients with ABO blood group incompatibility

Intra-abdominal infections in the perioperative period

Post-operative bile leak

LT: Liver transplantation.

BILIARY STRICTURES

Post-liver transplant biliary strictures (PTBS) are divided into anastomotic biliary strictures (ABS) and non-ABS (NABS).

ABS

They are characterized as single, short (usually < 5 mm), and localized narrowings at the surgical connection of the bile ducts with an incidence of 4%-9%[15,16]. They primarily result from local ischemia, surgical technique limitations, bile leak or a fibroproliferative healing response at the anastomosis site. Up to 80% of PTBS occur at anastomotic sites, either at duct-to-duct biliary anastomotic site (choledocho-choledochostomy) or biliary-enteric anastomotic site (choledocho-jejunostomy)[5,17]. The majority of ABS cases develop and present within the first 6 to 12 months post-surgery.

NABS

The prevalence of NABS ranges from 10% to 25% of all PTBS and the overall incidence of NABS is 0.5% to 10% among all LT recipients depending on the donor type and surgical techniques (with higher occurrences in living-donor and donation after cardiac death donor transplants)[5,17-20]. NABS are typically classified using the Buis Classification, which divides the affected regions of the biliary tree into four distinct intrahepatic and extrahepatic anatomical zones: Zone A (hilar bifurcation) involves the main hilar bifurcation and the most proximal extrahepatic biliary structures; zone B (central intrahepatic ducts) covers the major hepatic ducts and the intrahepatic biliary tree between first-order and second-order ductal branches; zone C (peripheral intrahepatic ducts) affects the smaller segmental ducts, specifically between second-order and third-order branches; zone D (terminal/septal ducts) involves the most distal, peripheral biliary branches reaching the liver parenchyma[21]. These strictures are often multiple and diffuse. While strictures can present anywhere across these zones, lesions in zones A and B are the most common. Because NABS are tied to arterial ischemia and poor perfusion, strictures involving the peripheral networks (zones C and D) indicate more extensive ischemic damage and are often associated with a worse clinical prognosis and treatment outcome[21]. Buis classification of NABS with four anatomical zones of biliary tree is depicted in Figure 2[21]. The primary causes and risk factors of NABS are shown in Table 2.

Figure 2 Four anatomical zones of biliary tree of non-anastomotic biliary stricture classified by Buis classification. Zone A: Hilar bifurcation; zone B: Central intrahepatic ducts; zone C: Peripheral intrahepatic ducts; zone D: Terminal/septal ducts.

Table 2 Primary causes and risk factors of non-anastomotic biliary stricture.

Ischemic:

Macroangiopathic:

Hepatic artery thrombosis

Microangiopathic:

Prolonged cold and warm ischemia times

Donation after cardiac death

Prolonged use of vasopressors in the donor

Immunogenic:

Chronic rejection

ABO incompatibility

Primary sclerosing cholangitis

Autoimmune hepatitis

Since NABS often present as multiple, diffuse, and narrowing segments, they are much more difficult to access via standard endoscopic techniques. Biliary stenting in these narrow, branching areas frequently fails or occludes, leaving patients highly susceptible to trapped debris, chronic bile stasis, and recurrent cholangitis requiring repeated hospital admissions. While standard anastomotic strictures can appear much later, NABS usually present earlier, commonly diagnosed within the first 3 to 6 months post-transplant.

ENDOSCOPIC MANAGEMENT OF PTBS

The commonly used endoscopic therapy of PTBS includes endoscopic retrograde cholangiopancreatography (ERCP) with balloon dilation followed by the use of multiple plastic stents (MPS) or fully covered self-expandable metal stents (FCSEMS). The complications of endoscopic therapy such as post-ERCP cholangitis can be mitigated by the use of prophylactic antibiotics and optimization of biliary drainage, especially when dealing with multiple biliary strictures, ischemic cholangiopathy or complex hilar strictures where contrast may stagnate. When ERCP is unsuccessful, combining it with percutaneous transhepatic biliary drainage (PTBD) is a highly effective salvage strategy. This hybrid rendezvous approach is particularly valuable for navigating complex bile duct strictures or complete obstructions, pushing the overall clinical success rate past 90%[22]. Endoscopic ultrasound-guided biliary drainage (EUS-BD) is an effective and safe salvage procedure when ERCP fails. By establishing internal drainage directly into the gastrointestinal tract, EUS-BD eliminates the need for external drainage catheters and lowers the risk of adverse events compared to PTBD. However, the endoscopic therapy encounters challenges in certain conditions, such as tight or tortuous stenosis, recurrent strictures, and altered anatomy, which are mitigated through advanced techniques, specialized stent designs, and multidisciplinary approaches, achieving long-term resolution and reducing the need for surgery.

Endoscopic management of ABS

Endoscopic management is the first-line therapeutic treatment of ABS with a higher success rate. Based on the timing of stricture formation, ABS is divided into early stricture, occurring within two months after LT and late stricture, occurring equal or more that 2 months after LT. Early stricture responds very favorably to a single session of ERCP with initial balloon dilation combined with temporary plastic stent placement; the stricture usually resolves within three months and, the patient typically does not require further surgical or endoscopic interventions. Late stricture is treated with balloon dilation and temporary stenting, either with a FCSEMS or with MPS; stents are typically left in place for 6 months to 12 months to achieve optimal stricture resolution and reduce recurrence. The biliary plastic stents are exchanged every 3-months to mitigate the risk of stent occlusion and bacterial cholangitis. The 3-month window for scheduled plastic stent exchange is important to prevent the ‘forgotten stent syndrome’ as the retained plastic stents for long periods can lead to proximal or distal migration, stent breakage, and giant stentolith (stone) formation. Patients with MPS generally require an average of 3 to 5 ERCP procedures to deploy, up-size, and ultimately remove the stents once the stricture has resolved[23-27]. FCSEMS has a 6-month to 1-year dwell time, which helps remodel the bile duct and significantly reduces the rate of stricture recurrence once the stent is removed[28-31].

The choice between MPS and FCSEMS depends on location and length of post-transplant ABS, stent patency duration, reducing the number of repeated interventions, endoscopist preference, and stent availability. Many current protocols suggest FCSEMS as the preferred initial intervention to minimize the frequency of re-interventions for patients, though MPS remains a vital mode of treatment when metal stents are unavailable or contraindicated. The standard approach for managing distal ABS (i.e., strictures far enough below the bifurcation) is to use a 10 mm FCSEMS, which provides robust radial force to dilate the stricture effectively (Figure 3).

Figure 3 Endoscopic therapy of distal anastomotic biliary stricture with fully covered self-expandable metal stents. ABS: Anastomotic biliary stricture; FCSEMS: Fully covered self-expandable metal stents.

FCSEMS have a higher risk of proximal or distal migrating, which is mitigated by the use of “anti-migration” versions with flared ends or anchoring fins. For proximal ABS (i.e., strictures at or just below the bifurcation), MPS are often used (Figure 4), which slowly dilate the stricture while maintaining patency to both lobes.

Figure 4 Endoscopic therapy of proximal anastomotic biliary stricture with multiple plastic stents. ABS: Anastomotic biliary stricture; MPS: Multiple plastic stents.

When a FCSEMS is placed at the bifurcation, its impermeable membrane can span across and block the orifice of the contralateral duct (right or left); this can lead to un-drained hepatic segments, cholangitis, and liver injury. When plastic stents are used, they can be placed in both the left and right hepatic ducts simultaneously to provide bilateral drainage without blocking either side.

Technique of FCSEMS placement involves the passage of a guidewire across a biliary stricture during ERCP and balloon dilation followed by the deployment of the FCSEMS under continuous fluoroscopic guidance. After 6 months, the initial stent is removed and if the stricture recurs after stent removal, new FCSEMS is deployed. The second FCSEMS is often effective for stricture resolution and is removed after three to six months. If the stricture continues to persist even after multiple FCSEMS trials, the alternating technique, such as placing MPS or transitioning to surgical interventions may be required.

The technique for plastic stent placement involves the passage of a guidewire across the biliary stricture, biliary sphincterotomy and balloon dilation of the stricture (inflated to a diameter of 6 mm to 8 mm) followed by MPS (7 Fr to10 Fr) deployment. After 3 months, ERCP is repeated to remove old potentially clogged plastic stents and if the stricture is not resolved, balloon dilation is done followed by the placement of new MPS across the stricture to keep the channel open. Depending on the severity of the stricture, this “remove-dilate-replace” cycle is usually repeated at 3-month intervals. The entire process of stenting and exchanging typically spans about 12 months. An “aggressive” sequential dilation protocol is utilized where the number or diameter of plastic stents is gradually increased with each subsequent procedure.

There are certain challenges in endoscopic management of ABS. The inability to pass the guidewire through dense, fibrotic anastomotic strictures, particularly in LDLT where ducts are smaller, is mitigated with the use of peroral cholangioscopy, specialized catheters such as swing-tip catheters or metal ball-tip cannulas, and aggressive dilation using high-pressure balloon dilation (4-10 mm) followed by placing MPS or FCSEMS. The increased rate of migration of FCSEMS can be mitigated by the use of dedicated anti-migration stents with specialized flanges to secure them in place or by the placement of coaxial double pig-tail plastic stents to anchor the metal stent. In the case of altered anatomy, such as RYHJ, the access to reach ABS becomes difficult using traditional side-viewing endoscope, which can be mitigated by the use of deep enteroscope or the use of rendezvous technique, where a wire is passed through the liver and caught by the endoscope. When strictures are recurrent or refractory to endoscopic and or percutaneous treatment, surgical revision may often be required as a definitive salvage therapy.

Periodic monitoring of liver biochemistries (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin) every 1 months to 3 months is a standard and crucial protocol for detecting recurrent biliary obstruction or cholangitis after stricture resolution. If a patient exhibits symptoms of biliary obstruction, such as jaundice, dark urine, pale stools, or right upper quadrant pain, more urgent liver biochemistry testing is required. In most cases, enzyme and bilirubin levels will gradually normalize following adequate biliary drainage. However, in some patients, moderate elevations may remain the “new normal” without indicating active disease or failure. Periodic laboratory monitoring often works in tandem with imaging modalities (like an ultrasound or magnetic resonance cholangiopancreatography) to fully assess stricture recurrence or complications. Long term surveillance and clinical follow up of patients with ABS are required because strictures often recur. Delayed presentation with onset 6 months or more after LT and a very tight stricture calibre are both established as negative predictors for treatment responsiveness, leading to a higher rate of recurrence.

Endoscopic management of NABS

Endoscopic management of extrahepatic NABS primarily relies on ERCP combined with stricture dilation using a 6 mm to 8 mm balloon followed by a sphincterotomy and the temporary placement of plastic stents (ranging from 7 Fr to 10 Fr). Patients require intermittent ERCP sessions every 3 months for approximately 6 months to 12 months. At each session, the old stents are removed, and casts and debris are removed; the duct is evaluated, and the stricture may be progressively dilated with balloon dilation to accommodate a larger number or diameter of plastic stents until resolution is achieved[32]. NABS are difficult to manage and highly resistant to standard endoscopic therapies. The inherent challenges of NABS center around anatomy, instrumentation, and clinical complications. NABS often present as multiple, widespread stenoses distributed throughout both extrahepatic and small intrahepatic biliary trees. The intrahepatic ducts become progressively narrower and branch repeatedly. Endoscopic tools and guidewires often cannot traverse or dilate these smaller branches without significant trauma. The stricture leads to the recurrent buildup of biliary sludge and the formation of solid, branching casts that block the ducts and trigger frequent episodes of cholangitis. Reaching peripheral intrahepatic ducts endoscopically requires highly specialized, ultra-thin equipment (e.g., direct visualization via cholangioscopy) and advanced cannulation techniques that are technically demanding. In diffuse NABS, placing MPS is frequently impossible, leading to higher stricture recurrence rates and the need for frequent repeat procedures. When standard endoscopic therapies fail, alternative and salvage approaches need to be applied, which include percutaneous transhepatic cholangiography, rendezvous technique or surgical revision (e.g., conversion of duct-to-duct anastomosis to RYHJ). Because NABS are often multiple, long, and diffuse, endoscopic therapies and alternative salvage approaches often fail. Up to 50% of patients experience progressive disease leading to secondary biliary cirrhosis or patients suffer from repeated bouts of uncontrollable cholangitis that ultimately requires liver re-transplantation or leads to death[32-35].

EMERGING RESCUE THERAPY OF PTBS

Magnetic compression anastomosis

For completely obstructed or refractory strictures, magnetic compression anastomosis (MCA) can create a new communication, serving as a salvage technique[36]. MCA is a minimally invasive, non-surgical alternative to treat severe or completely obstructed bile ducts. It is primarily used when standard procedures (like endoscopy or percutaneous drainage) fail because a guidewire cannot pass through the blocked area. The technique of MCA involves the placement of a magnet on either side of the stricture or blockage; one magnet is typically delivered via the bile duct through ERCP, and the other through a PTBD tract. The magnets pull toward each other and sandwich the strictured tissue. The magnetic force induces controlled ischemic necrosis, gradually melting away the blockage. As the tissue dies, a new, open fistula is naturally created as the magnets unite. Once the channel is formed, the magnets are removed, and a temporary stent (usually a FCSEMS) is placed for a few months to keep the newly created passage open while it heals. The success of MCA is highly dictated by stricture length, magnet strength, and bile duct anatomy[37-40]. Pre-MCA assessments are essential for mapping stricture lengths and configuring magnetic power. These parameters can be obtained through cholangiographic assessments using ERCP or PTBD, which are invasive procedures[40,41].

Thermal stricturoplasty

Novel technique such as electro-thermal balloon therapy is used to treat rigid, persistent stricture[42]. It relies on direct cholangioscopic or enteroscopic visualization and localized thermal energy is applied to make precise radial cuts or incisions directly into the stenotic fibrous tissue.

ETHICAL ISSUE

Endoscopic management of PTBS presents significant ethical challenges centered on balancing the need for recurring, minimally invasive procedures against the risk of futile treatment, high complication rates (5%-25% incidence), and the potential need for re-transplantation. Given that many patients with biliary stricture require multiple endoscopic interventions and may remain incurable, determining when further endoscopic treatment is futile and when to refer for re-transplantation is a critical ethical challenge. The need to balance the potential benefits of repeated intervention against risks such as cholangitis, pancreatitis, and further damage to the bile duct requires clear, informed communication with the patient. Unlike anastomotic strictures, NABS are often diffuse, harder to manage, and carry a worse prognosis, sometimes making aggressive, prolonged endoscopic therapy ethically questionable if it only delays necessary re-transplantation.

CONCLUSION

Maintaining a high index of suspicion is vital for early detection of PTBS, which allows for timely endoscopic interventions to prevent severe complications like cholangitis and liver cirrhosis. A clearer understanding of NABS and ABS highlights the fact that endoscopic therapy of ABS has a higher success rate, whereas NABS is notoriously complex to manage. ERCP with balloon dilation followed by the placement of MPS or FCSEMS is currently the gold standard and first-line therapy for PTBS, though, some patients may experience stricture recurrence. In these cases, repeat endoscopic therapy remains a highly effective option before escalating to more invasive percutaneous or surgical treatments. Advances in endoscopic techniques, such as advanced ERCP accessories, use of MPS, removable FCSEMS, peroral cholangioscopy and deep enteroscopy, have helped in mitigating challenges in endoscopic management of PTBS, thereby achieving higher stricture resolution rates and reducing the number of invasive, repeat procedures. A multidisciplinary approach with a close collaboration between transplant hepatologists, interventional endoscopists, transplant surgeons, and interventional radiologists is the cornerstone of the successful management of PTBS.