INTRODUCTION
Liver transplantation represents the definitive therapy for a range of end-stage liver diseases[1]. While advances in surgical techniques and postoperative care have significantly improved patient survival, biliary complications remain a significant obstacle to long-term success. The incidence of biliary complications after liver transplantation varies widely, largely depending on factors such as surgical technique, type of graft, and institutional experience[2]. Biliary leakage alone occurs in approximately 5%-7% of cases, making it one of the most frequently reported postoperative complications[3]. Its etiology is multifactorial and includes both patient- and procedure-related factors. Given its serious implications, biliary leakage demands timely recognition, accurate diagnosis, and a tiered therapeutic strategy that incorporates minimally invasive and surgical options[4].
RISK FACTORS
Intraoperative factors such as technical difficulties during biliary anastomosis, excessive tension on the bile duct, or poor duct-to-duct alignment are major contributors[5]. The use of living donor liver grafts increases the risk due to smaller duct caliber and anatomical variability[6]. Biliary leakage is particularly concerning due to its potential to cause sepsis, prolonged hospitalization, and graft loss[7]. The condition reflects the vulnerability of the biliary system, which depends entirely on hepatic arterial perfusion and is exposed to technical stresses during transplantation. Ischemia-related injury is another key risk factor[8]. The biliary epithelium is particularly susceptible to ischemic insult because of its dependence on the hepatic artery for blood supply. Hepatic artery thrombosis or prolonged cold and warm ischemia times increase the likelihood of leakage by compromising epithelial integrity. Additionally, pre-existing diseases such as primary sclerosing cholangitis or biliary atresia may predispose patients to postoperative complications due to underlying inflammation and fibrosis[9]. Acute cellular rejection and its management may significantly impact the risk of biliary complications, including leakage. This relationship is multifactorial, involving both the direct effects of immune injury on the biliary epithelium and the side effects of immunosuppressive regimens. A multidisciplinary approach, involving hepatologists, transplant surgeons, and infectious disease specialists, is essential to optimize immunotherapy while minimizing the risk of biliary leakage and infections.
DIAGNOSIS OF BILIARY LEAKAGE
Timely and accurate diagnosis is central to the effective management of biliary leakage. Clinically, patients may present with nonspecific symptoms including abdominal pain, fever, jaundice, or bilious output from surgical drains. Laboratory tests may reveal elevated bilirubin, alkaline phosphatase, and white blood cell count. However, definitive diagnosis relies on imaging and interventional studies. Initial assessment often begins with ultrasonography, which can detect perihepatic fluid collections, although its sensitivity for identifying the precise site of leakage is limited. Computed tomography angiography may help rule out vascular complications such as hepatic artery thrombosis. Magnetic resonance cholangiopancreatography is another highly valuable modality, providing detailed visualization of the biliary anatomy and identifying both leaks and associated strictures in a non-invasive manner[10]. Despite advances in imaging, endoscopic retrograde cholangiopancreatography (ERCP) remains the gold standard for both diagnosis and therapy. It allows direct visualization of the biliary tree, localization of the leak, and immediate therapeutic intervention. This dual capability makes ERCP the preferred modality in most transplant centers when biliary leakage is suspected[11]. Imaging modalities such as magnetic resonance cholangiopancreatography and contrast-enhanced computed tomography represent significant costs, especially in healthcare systems with limited resources. An economic analysis of the diagnostic pathway for biliary leakage is both relevant and necessary to optimize resource allocation without compromising diagnostic accuracy.
THERAPEUTIC STRATEGIES
ERCP is widely considered the first-line treatment for biliary leakage following liver transplantation. The endoscopic approach typically involves biliary sphincterotomy to lower intraductal pressure, combined with the placement of a plastic stent or nasobiliary drain to divert bile flow away from the site of leakage. This facilitates healing by promoting low-pressure drainage and reducing bile extravasation. In cases where leakage coexists with strictures, balloon dilation of the stricture followed by stent placement can achieve favorable outcomes. The technical success rate of ERCP in managing post-transplant bile leaks is approximately 76.2%, with clinical resolution achieved in 64.3% of patients[11]. These outcomes underscore the utility of ERCP as a safe and effective minimally invasive option[12].
For patients with surgically altered anatomy, such as those with a Roux-en-Y hepaticojejunostomy, ERCP may not be technically feasible. In these cases, percutaneous transhepatic cholangiography (PTCD) offers a valuable alternative[13]. Under imaging guidance, percutaneous access to the biliary tree allows for external bile drainage and, when necessary, balloon dilation or stent placement. PTCD is particularly useful in critically ill patients who cannot tolerate general anesthesia. Kulkarni et al[14] reported technical success in 70.6% of cases and clinical improvement in 76.5%, supporting the use of PTCD as an effective second-line strategy.
Although most biliary leaks can be managed with endoscopic or percutaneous interventions, surgical revision remains necessary in selected cases. The choice between conservative therapy and early surgical intervention is often influenced by both the patient’s general condition and the institution’s clinical philosophy. While conservative therapy remains first-line in most cases, an individualized and timely switch to surgical repair, especially when failure of minimally invasive strategies is evident. Indications include complete anastomotic dehiscence, failure of minimally invasive approaches, or concurrent biliary and vascular injuries. The most commonly performed surgical procedure is Roux-en-Y hepaticojejunostomy, which diverts bile away from the native ductal system and provides long-term drainage[15]. However, this approach is associated with increased perioperative risk, particularly in patients with sepsis or poor general condition. As such, surgery should be considered a last resort after other methods have failed[16]. Delayed surgical intervention in cases of biliary leakage can lead to rapid clinical deterioration, particularly through the development of biliary peritonitis and sepsis. These complications are not only life-threatening but also contribute to graft dysfunction, multiorgan failure, and increased healthcare burden.
Preventing biliary leakage is a key objective in liver transplantation[17]. One of the most promising strategies involves improving graft quality through machine perfusion techniques. Both hypothermic and normothermic machine perfusion have been shown to enhance bile duct epithelial preservation by reducing ischemia-reperfusion injury, especially in marginal or extended criteria donors. While conventional open liver transplantation remains the gold standard, the application of robotic-assisted surgery is an emerging field, particularly in living donor liver transplantation and select phases of recipient surgery. Robotic surgery offers several technical advantages that could potentially reduce biliary complications, including enhanced precision and dexterity, reduced tissue trauma, and minimally invasive access. These technologies may help reduce the incidence of ischemic cholangiopathy and biliary leakage by maintaining microvascular circulation and bile duct viability during preservation.
CONCLUSION
Biliary leakage following liver transplantation remains a significant source of morbidity and can compromise graft survival if not effectively managed. A multidisciplinary approach that prioritizes early diagnosis and minimally invasive intervention is essential. ERCP serves as the cornerstone of treatment, with PTCD offering a reliable alternative in complex anatomical scenarios. While both ERCP and PTCD are cornerstone minimally invasive therapies, their selection is influenced by multiple factors, including institutional experience, anatomical considerations, and the patient’s clinical condition. Developing a multidisciplinary protocol for biliary complications that integrates input from transplant surgery, endoscopy, and interventional radiology can optimize outcomes and streamline decision-making across institutions. Surgical revision, while effective in selected cases, should be reserved for refractory situations due to its higher risk profile. Preventive strategies, including the use of machine perfusion and meticulous surgical techniques, hold great promise in reducing the incidence of this complication. Ongoing research and technological advancements are expected to refine these strategies further and improve long-term transplant outcomes.
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: China
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P-Reviewer: Matsusaki T S-Editor: Wu S L-Editor: A P-Editor: Xu ZH
