Managements of bile leakage after liver transplantation: Commentary on recent findings

Abstract

Bile leakage remains a formidable challenge in post-liver transplantation management, posing significant risks to patient outcomes and graft survival. This editorial provides a critical appraisal of the recent clinical study by Gu et al, which compared the efficacy of stent placement vs endoscopic nasobiliary drainage (ENBD) for treating post-transplant bile leaks. By retrospectively analyzing data from their institutional cohort of liver transplant recipients with bile leaks, the authors evaluated the therapeutic success rates and clinical outcomes between the stent and ENBD groups, with a focused discussion on the relative advantages of each approach. Gu et al demonstrated that both stent placement and ENBD were effective in managing post-transplant bile leaks, with comparable therapeutic outcomes. However, the study also recognized its limitations, such as the lack of an assessment of the impact of bile leak severity on outcome and the absence of long-term follow-up data. The editorial further highlights the pressing need for advancing research on long-term complications post-liver transplantation and underscores the pivotal role of clinical stratification and physician expertise in guiding therapeutic decisions. In summary, Gu et al’s study enhances our understanding of mitigating post-transplant complications like bile leaks and offers evidence-based insights to refine clinical protocols. This commentary aims to contextualize current research trends and future directions in the field, advocating for sustained innovation and evidence-driven practice.

Key Words: Liver transplantation; Postoperative complication; Bile leakage; Stent placement; Endoscopic nasobiliary drainage

Core Tip: Both stent placement and endoscopic nasobiliary drainage are effective in controlling bile leakage after liver transplantation and both have high success rates. They are both minimally invasive procedures that can be tailored to patient-specific factors such as biliary stricture or risk of infection. Recent advances in endoscopic techniques and stent design continue to improve their efficacy and safety, making them the preferred first-line treatment for managing bile leaks after liver transplantation.

TO THE EDITOR

Over the past 50 years, liver transplantation has evolved into a routinely performed procedure in many countries, with the annual global volume now exceeding 40000 cases[1]. Consequently, the management of post-transplant complications has gained increasing clinical significance. Bile leakage is a common complication following liver transplantation, occurring in 2% to 25% of recipients, particularly in living-donor transplants[2]. It usually presents with symptoms of abdominal pain, fever, and jaundice, and can result from a variety of causes, including surgical instrument injuries and biliary ischemia from vascular complications. Over the last decade, therapeutic approaches for bile leaks have advanced significantly, with endoscopic interventions such as stent placement and endoscopic nasobiliary drainage (ENBD) emerging as first-line treatments[3]. These techniques have ushered in a minimally invasive era for managing post-transplant biliary complications. The study by Gu et al[4] further validates the efficacy of stent placement and ENBD in addressing post-liver transplantation bile leaks while providing a comparative analysis of these two modalities.

MANAGEMENTS OF BILE LEAKAGE AFTER LIVER TRANSPLANTATION

Traditional surgical approaches for post-liver transplantation bile leaks primarily include biliary reconstruction procedures (such as biliary anastomosis and choledochojejunostomy), T-tube placement, surgical repair and reconstruction (including anastomotic repair and biliary-enteric reconstruction), and percutaneous transhepatic biliary drainage[5]. With the growing acceptance of minimally invasive techniques and enhanced recovery after surgery concepts, stent placement and ENBD have gained significant attention in contemporary clinical practice. Currently, there is a relative paucity of clinical studies comparing stent placement and ENBD for managing post-liver transplantation bile leaks. The choice of surgical approach primarily depends on the specialist’s evaluation and the patient’s clinical condition. With rapid advancements in minimally invasive techniques, a considerable number of patients have now undergone stent placement or ENBD for post-transplant bile leak management.

Gu et al[4] demonstrated that stent placement has similar efficacy and prognosis compared to ENBD for bile leakage after liver transplantation, and both approaches are recommended based on similar success rates and postoperative complications. However, current studies of ENBD with stent placement are currently focused on clinical applications such as bile leakage after non-liver transplantation[6-8], and fewer studies have been conducted for the post-liver transplantation period; therefore, this clinical study has important implications for optimizing management strategies in the perioperative period of liver transplantation. In addition, Gu et al[4] showed that stent placement is more suitable than ENBD for patients at high risk of bile duct stenosis, and this difference is due to the fact that stents provide internal biliary support and help prevent bile duct stenosis compared to ENBD. In contrast, ENBD is more suitable for bile duct infections because it can drain bile directly from the outside, which not only helps to control bile leakage, but also effectively monitors the amount and nature of bile, thus providing an important basis for diagnosis and treatment. In addition, ENBD, as a temporary measure, is usually implemented quickly when a patient develops symptoms of biliary tract infection, which can quickly relieve the patient’s discomfort and minimize further damage to liver function caused by the infection. However, ENBD has its limitations, such as the fact that the drainage tube passes through the nasal cavity, which may cause some discomfort to the patient, and the need for both the patient and the healthcare provider to maintain the external drainage system to ensure its proper functioning and prevent infection. In addition, ENBD may not be suitable for all patients, especially those with abnormal nasal anatomy or those who cannot tolerate nasal cannulae. When choosing ENBD, physicians need to consider the specific condition of the patient, the severity of the infection, and the patient’s tolerance to ensure the safety and effectiveness of the treatment[9]. There are obvious shortcomings in the management of biliary strictures with ENBD. Because it cannot provide long-term internal support for the bile duct, it may not be effective in preventing bile duct stenosis in patients who have severe bile duct injury or are at risk for bile duct stenosis. In addition, the drainage tubes of ENBDs may become clogged due to solid components in the bile, requiring frequent replacement or flushing, which increases the pain and difficulty of patient care[10]. The study by Gu et al[4] did not describe in detail the specific specifications or technical parameters of the stents and nasobiliary tubes used, which have a potential impact on treatment outcomes, and it is hoped that future studies will add descriptions of technical parameters, such as the diameters of the stents and nasobiliary tubes, based on the perspective of technical considerations in the treatment process. Based on these findings, we have briefly summarized the advantages and disadvantages of stent placement and ENBD for the treatment of bile leakage after liver transplantation in Table 1. In the face of these challenges, it is necessary to further optimize the treatment strategy, combining stent placement and ENBD with the individual patient’s condition, in order to achieve the best therapeutic effect. A study by Gu et al[4] showed no significant difference between the two approaches in terms of short-term prognosis and postoperative biliary stenosis, despite higher leukocyte counts, total bilirubin and direct bilirubin levels in the stenting group, suggesting that the patients in this group had more severe hepatic impairment. However, the above assertions are based on short-term follow-up conclusions, for long-term prognosis, we expect a longer follow-up in the future to draw more convincing conclusions. In addition, for the difficulty of determining whether a patient has a biliary tract infection after liver transplantation, blood culture and drainage fluid bile culture have limited clinical value, and Grobe et al’s study[11] found that next-generation sequencing performed better than culture-based methods in detecting bacterial spp. in bile after liver transplantation, which undoubtedly provides us with a new way of thinking. The assessment of the severity of bile leakage is the key to optimize the treatment strategy, and the study by Gu et al[4] did not assess the severity of bile leakage, which undoubtedly reduced the general applicability of the article’s conclusions. In recent years, the assessment of the severity of bile leakage has been very well established, and the imaging techniques, such as computed tomography cholangiography and magnetic resonance cholangiopancreatography, are able to clearly show the location, extent and relationship with surrounding tissues, providing an important basis for assessment[12]. In addition, endoscopic retrograde cholangiopancreatography (ERCP) combined with biliary pressure measurement techniques can dynamically assess the functional status of the biliary system and further quantify the severity of bile leakage[13]. Laboratory tests, bile composition analysis and changes in the levels of inflammatory markers also provide an aid in assessing the severity of bile leakage. The absence of long - term outcomes is a significant limitation of this study. Long - term prognosis post - bile leakage treatment is crucial for evaluating the durability and safety of treatment methods. For instance, biliary stent placement might lead to long - term biliary stricture or stent migration. Although ENBD demonstrates remarkable short - term effects, its impact on patients’ long - term quality of life remains unclear. The lack of long - term follow - up data prevents a comprehensive assessment of the two treatment methods in preventing biliary stricture, reducing infection recurrence, and improving long - term survival rates. Additionally, it restricts a thorough evaluation of postoperative quality of life, such as nutrition absorption, pain management, and psychological well - being. Future studies should focus on long - term follow - up to better compare the advantages and disadvantages of these two treatments. This would not only help enhance clinical treatment strategies but also offer more precise prognostic information for patients, thereby better guiding clinical decision - making.

Table 1 Comparison of stent placement with endoscopic nasobiliary drainage in the management of bile leakage after liver transplantation.

Characteristics	Stent placement	Endoscopic nasobiliary drainage
Advantages	The procedure offers higher patient comfort, is repeatable, and provides long-term biliary support	The procedure is relatively simple and allows for direct monitoring of bile
Disadvantages	The procedure is relatively complex, with a higher risk of surgical complications such as stent displacement and blockage. It does not allow for direct monitoring of bile and requires long-term placement	It is temporary in nature, and there is a need to be vigilant about complications associated with the nasobiliary tube
Efficacy and outcomes	More suitable for patients at high risk of biliary stricture, with a high treatment success rate, low incidence of biliary stricture, and minimal impact on liver function	More suitable for biliary tract infections, with a high treatment success rate, low incidence of bile duct strictures, and minimal impact on liver function

The management of bile leakage after liver transplantation has been optimized by precision medicine, materials engineering, and interdisciplinary collaboration. Future research should focus on the construction of precise stratification and prediction models, innovative applications of smart intervention technologies, and patient-centered multidisciplinary collaboration models. The development of a dynamic stratification system integrating multi-omics features (e.g., inflammatory factors in serum/bile, bile microbiome, and imaging parameters) combined with machine learning algorithms to realize intelligent risk classification is of great significance for the management of bile leakage after liver transplantation[14]. Recent studies have shown that the combination of bile metabolomics and computed tomography image texture analysis can predict moderate-to-severe bile leakage in advance[15,16]. In terms of intelligent interventions, advancing the integration of robot-assisted ERCP with flexible cholangioscopy platforms to improve the success rate of complex biliary interventions also holds great promise. This article critically evaluates the clinical study by Gu et al[4], which examined the efficacy and prognosis of stent placement and ENBD for the treatment of patients with bile leakage after liver transplantation. The analysis paid particular attention to the potential of stent placement and ENBD, while the associated influencing factors were analyzed in detail. These findings provide evidence-based medical evidence.

CONCLUSION

The treatment of bile leaks post-liver transplantation stands at a transformative juncture. ERCP with stent placement or ENBD has become a key minimally invasive approach, reducing patient burden and decreasing surgical intervention needs. While rapid advancements in endoscopic techniques have made these methods comparable to surgery, challenges persist in managing complex cases like large anastomotic leaks or altered surgical anatomy. The field requires robust multicenter trials, technological innovation, and precision medicine frameworks to overcome these challenges. Further research is urgently needed to focus on specific determinants of postoperative complications after liver transplantation, with an emphasis on comprehensive management of both long-term and near-term complications to enhance patients’ quality of life. Given the limitations of clinical retrospective studies, future research should strictly define inclusion and exclusion criteria, prioritize prospective cohort studies, and conduct multicenter, large-sample studies. These studies should focus on optimizing stent design, improving diagnostic accuracy, and developing standardized regimens based on severity stratification to enhance therapeutic effects and improve the survival rate and quality of life for postoperative liver transplantation patients.