Endoscopic management of post-living donor liver transplant anastomotic biliary strictures: A quaternary care transplant center experience

Abstract

BACKGROUND

Biliary complications are the Achilles heel of the living donor liver transplantation (LDLT) and compromise the graft survival and the overall survival. Anastomotic biliary strictures (ABS) are the most common and challenging complication within this category. While endoscopic retrograde cholangiopancreatography (ERCP) serves as the standard first-line treatment modality to navigate the strictures, intraductal cholangioscopy, percutaneous transhepatic cholangiography (PTC), and surgical approaches are reserved for the technically challenging cases where standard ERCP remains unsuccessful.

AIM

To investigate the prevalence of ABS across various biliary reconstructions in LDLT recipients and analyze the outcomes of endoscopic interventions.

METHODS

This retrospective cohort study was conducted between March 2019 and December 2024 at the Pakistan Kidney and Liver Institute & Research Centre. Among 820 LDLT recipients, 176 (21.5%) developed ABS and were included. Treatment outcomes were assessed in 114 patients following completion of therapeutic interventions and availability of follow-up data. Categorical data was compared using the χ² test/Fisher’s exact test. Nominal data were analyzed using the t-test and the ANOVA test. Data was analyzed using IBM SPSS version 27.

RESULTS

Frequency of anastomotic biliary stricture was 16.2% (102 of 631), in single duct-duct anastomosis, 34.8% (56 of 161) in two duct-duct anastomosis, and 64.3% (18 of 28) where 2 ducts were reconstructed on a single patch. The dual duct reconstruction exhibited a higher risk for ABS development vs single duct anastomosis (odds ratio = 3.34, 95%CI: 2.33-4.78). A total of 792 ERCPs were performed in 176 patients. Only 114 (65%) cases completed the therapeutic course and were included in the treatment outcome analysis. Stricture resolution with endotherapy alone was achieved in 90.2%. PTC improved the overall stricture resolution rates to 99.1%. Stricture recurred among 15 (13.3%) patients. Procedure-related complications included cholangitis (2.4%), pancreatitis (2.3%), and bleeding in (1.52%); no perforation or death occurred.

CONCLUSION

In the LDLT setting, dual duct biliary reconstruction is strongly associated with ABS. ERCP is a highly effective, safe, and preferred modality for managing post-LDLT ABS.

Key Words: Anastomotic biliary stricture; Endoscopic retrograde cholangiopancreatography; Living donor liver transplantation; Percutaneous transhepatic cholangography; Intraducal cholangioscopy

Core Tip: Anastomotic biliary strictures (ABS) remain the most common and challenging biliary complication after living donor liver transplantation (LDLT). Dual duct biliary reconstruction in the LDLT setting is associated with a significantly high risk of stricture incidence and recurrence. Endoscopic retrograde cholangiopancreatography complemented with intraductal cholangioscopy (IDC) has emerged as a highly effective and safe treatment modality in managing complex biliary strictures. Knowledge and understanding of biliary reconstruction are critical in defining treatment strategies to achieve optimal outcomes. percutaneous transhepatic cholangiography is the preferred modality when endotherapy remains unsuccessful despite using IDC. Surgery serves as a rescue strategy when percutaneous and endoscopic approaches remain unsuccessful to address the ABS.

INTRODUCTION

Liver transplant is an effective curative approach for selected patients with end-stage liver disease and acute liver failure, and has shown excellent survival rates. Deceased donor liver transplant (DDLT) has been the gold standard and preferred modality for several decades. However, owing to the continued shortage of deceased donor organs and the growing number of patients on the waiting list, living donor liver transplant (LDLT) has become an excellent alternative option with comparable survival rates[1]. Although LDLT is a more complex and technically challenging procedure compared to DDLT, it still provides excellent graft and survival outcomes. A recent meta-analysis revealed better 1-, 3- and 5-year survival outcomes in LDLT as compared to DDLT[2].

Although there have been significant advances in surgical methods, immunosuppressive medications, and post-operative management, which have improved the outcomes of LDLT recipients to a great extent, surgical complications continue to pose a challenge. Literature review shows that LDLT recipients experience higher surgical complications as compared to DDLT, with a higher frequency of biliary complications[3]. A meta-analysis demonstrated that the risk of developing biliary complications is higher for LDLT as compared to DDLT, with an odds ratio of 1.96 (95%CI: 1.56-2.47)[4]. Biliary strictures, bile leaks, biloma, biliary casts, and bile duct stones represent the spectrum of biliary complications. With reported rates generally ranging from 13% to 36%, the overall incidence of biliary strictures is higher after LDLT than DDLT[5].

The majority of anastomotic biliary strictures (ABS) occur within the first year of liver transplant surgery, with a mean time of diagnosis within 5-8 weeks. The ABS occurring within the first 3 months of transplant is due to surgical and technical issues, whereas the late ABS, which occur after 3 months, are due to localized ischemia and fibrotic healing processes[5,6]. Several risk factors are linked to the development of ABS and include advanced donor and recipient age, hepatic artery thrombosis, use of multiple biliary anastomoses, and technical issues such as tension at the anastomosis or excessive electrocautery use for biliary ductal bleeding control. Additional contributing factors are prolonged cold and warm ischemia times, small bile duct caliber of the graft, preceding bile leakage, and suboptimal surgical technique[6,7].

ABS can significantly impact long-term patient outcomes, diminish quality of life & lead to graft loss or even mortality. The spectrum of clinical presentation is diverse and includes cholangitis, fever, jaundice, pruritus, anorexia, stomach discomfort, and a cholestatic pattern of liver enzymes[6]. Historically, surgical repair or re-transplantation were the mainstay of managing these complications, carrying considerable risk of morbidity and mortality. However, with the advancements in endotherapy and interventional radiology, there has been a revolutionary change in the management of post-transplant biliary strictures[8]. Endoscopic retrograde cholangiopancreatography (ERCP) has emerged as the preferred first-line modality for the management of ABS in post-LDLT patients, providing a less invasive and highly effective therapeutic modality[9]. Moreover, the advent of intraductal cholangioscopy (IDC) has significantly enhanced the therapeutic landscape of endoscopic management of ABS by providing direct visualization and therapeutic intervention. It serves as a salvage therapy when the challenges created by severely stenosed strictures cannot be overcome by conventional ERCP. Percutaneous transhepatic cholangiography (PTC) and surgery are generally reserved for difficult strictures when ERCP fails or is not feasible[10-12].

This study seeks to assess the occurrence of ABS among the recipients of LDLT, examine the success of ERCP in resolving these strictures, and highlight the evolving importance of IDC as a vital modality for managing complex strictures. This study strives to disseminate valuable insights derived from a leading liver transplant center in Southeast Asia.

MATERIALS AND METHODS

Study design and setting

This was a retrospective cohort study with prospectively controlled database conducted at Pakistan Kidney and Liver Institute and Research Center, a quaternary care transplant center. Medical records of the enrolled patients were reviewed from March 2019 to December 2024, in accordance with the STROBE recommendations for observational studies.

Study population and eligibility criteria

The inclusion and exclusion criteria were determined a priori.

Inclusion criteria: All patients who developed ABS following LDLT during the study period and completed treatment interventions were enrolled in the study.

Exclusion criteria: (1) Non-ABS; (2) Patients who could not complete the therapeutic course or had ongoing treatment interventions were not included in the outcome analysis; and (3) Patients who died or were lost to follow-up before completing the treatment cascade were excluded from outcome analysis

Sampling method and sample size

The non-probability consecutive sampling method was used, in which all patients who fulfilled the criteria of eligibility were selected throughout the study period. A total of 176 patients were selected based on the completeness and availability of medical records. A total of 114 patients completed the therapeutic course and were included in the outcome analysis.

Data collection procedures

Clinical, laboratory, endoscopy, and radiological data were collected retrospectively from hospital electronic medical records, using a standardized data extraction form.

Demographic variables: (1) Age; (2) Sex; and (3) Comorbidities.

Clinical variables: (1) Indications for liver transplant; (2) Type of graft; (3) Type of biliary anastomosis; (4) Time from liver transplant to first ERCP time; and (5) Time to stricture recurrence after initial resolution.

Intervention-related variables: (1) Type of procedure or treatments provided (ERCP/IDC/PTC/surgical revision); (2) Number of ERCPs; (3) ERCP-related complications; and (4) Prophylactic pancreatic duct stenting.

Outcome variables: (1) ABS incidence across different types of biliary reconstructions; (2) ABS resolution and recurrence rates; and (3) Frequency of ERCP-related complications.

Data extraction was performed by two trained investigators, and a third independent reviewer cross-verified the data to minimize extraction errors.

Variables and operational definitions

All study variables were predefined before data collection.

Primary objective: To determine the safety and efficacy of ERCP in managing ABS after LDLT.

Secondary objective: To compare the ABS rates across various biliary ductal reconstruction techniques performed in the setting of LDLT.

Primary outcomes

Primary outcomes including: (1) The ABS resolution rates after scheduled ERCP-guided treatment sessions for 12 months; (2) The ABS stricture recurrence rates and time to recurrence after initial resolution; and (3) Post-ERCP procedure-related complications.

Secondary outcomes

Secondary outcomes including Incidence of ABS across different types of biliary reconstructions during the follow-up period after LDLT.

Operational definitions were applied consistently. Clinically, ABS was suspected based on the presence of cholestatic liver enzymes, either detected in an asymptomatic LDLT recipient during routine evaluation or often accompanied by symptoms like jaundice, fever, and pruritus. Ultrasound served as the initial imaging modality to diagnose the presence of an ABS, while the definitive confirmation was obtained through cross-sectional imaging such as magnetic resonance cholangiopancreatography or triphasic computed tomography scans. The hallmark radiological feature of ABS included a subtle narrowing or an abrupt cutoff at the site of biliary anastomosis with resultant upstream intrahepatic biliary ductal dilatation.

ERCP was the first-line treatment modality for the management of ABS using an Olympus 190 duodenoscope (Olympus Corporation). A cholangiogram mapped the stricture, which was dilated with biliary dilatation balloons or Soehendra dilators, and then stented (7-12 French plastic biliary stents). Figure 1 shows various dilators utilized to dilate the ABS. All patients received pre & post procedural antibiotics as per institutional guidelines and were subsequently scheduled for stent exchanges every 8-12 weeks. Technical success was defined as successful biliary cannulation and traversal of the ABS by placement of the guidewire across the stricture, followed by dilatation of the ABS and deployment of the biliary stent(s). Clinical success was defined as significant improvement/normalization of cholestatic liver enzymes and resolution of symptoms. ERCP failure was defined as the inability to cannulate the bile duct, traverse the stricture, or deploy the stent across the stricture. Among patients where ERCP remained unsuccessful despite successful biliary cannulation, utilization of IDC for direct visualization and assessment of ABS was the preferred option to facilitate the stricture management during the same session. IDC not only served as an adjunct tool, allowing traversal of complex strictures, permitting access and drainage of sectoral biliary branches, but also remained instrumental in providing direct confirmation of stricture resolution. PTC was reserved for cases with biliary cannulation failure, inability to traverse the stricture, and incomplete sectoral duct drainage despite utilization of IDC. Surgical revision was undertaken as a final step, applied only when both initial endotherapy and PTC were unsuccessful or when strictures remained unresolved following at least 12 months of repeated ERCPs ± PTC as an adjunct when indicated. Figure 2 illustrates the management algorithm of ABS at our center.

Figure 1 Gadgets used during Endoscopic retrograde cholangiopancreatography to dilate the strictures. A: Soehendra dilators of various sizes; B: Biliary dilatation balloons of various sizes.

Figure 2 Management algorithm for anastomotic biliary strictures. ¹Cholangioscopy was utilized to facilitate traversal of acutely angulated strictures, enable drainage of sectoral branches, and confirm stricture resolution. ²Failure of stricture resolution was defined as the persistence of the stricture despite 12 months of endoscopic therapy. ³Percutaneous transhepatic cholangiography was employed in cases where primary endoscopic retrograde cholangiopancreatography or cholangioscopy failed, as well as for sectoral duct strictures that were not amenable to endoscopic management. ABS: Anastomotic biliary strictures; ERCP: Endoscopic retrograde cholangiopancreatography.

Stricture resolution was confirmed by ERCP with an occlusion choalngiogram demonstrating disappearance of the stricture waist, spontaneous drainage of contrast from the proximal biliary tree, and absence of resistance to trawl a balloon catheter of appropriate size. IDC was not routinely performed to document stricture resolution. It was reserved for selected cases only where ERCP findings were equivocal to demonstrate complete stricture resolution, persistent cholestatic pattern of liver enzymes despite apparent resolution of ABS on cholangiogram, suspicion of early stricture recurrence, or among cases with complex biliary anatomy and high risk of recurrence.

Post-ERCP complications assessed included bleeding, cholangitis, perforation, and pancreatitis, as well as procedure-related mortality. These complications were diagnosed according to ESGE 2020 guidelines for post ERCP adverse events[13]. Post-ERCP pancreatitis (PEP) was defined as the development of abdominal pain accompanied by a serum amylase or lipase level exceeding three times the upper limit of normal at 24 hours post ERCP, requiring hospitalization. Significant bleeding was considered present if there was clinical evidence, such as hematemesis or melena, or a hemoglobin drop greater than 2 g/dL within 7-10 days following ERCP. Perforation was diagnosed based on radiological confirmation or direct visualization during the ERCP procedure. Cholangitis was defined as the presence of clinical signs of infection, such as fever > 38 °C for more than 24 hours and cholestasis following ERCP. High-risk patients for PEP were defined as patients in whom the double wire technique was used for biliary cannulation and those with contrast opacification of the pancreatic duct.

Bias and missing data

Selection bias was minimized by including all consecutive eligible patients. Information bias was reduced through standardized data collection procedures. Missing or incomplete data were handled by complete-case analysis, with exclusion of patients who had incomplete follow-up, died before completing therapy, or were still undergoing treatment at the time of analysis. To minimize the observer variability, interventions were performed by the experienced operators.

Statistical analysis

Data was analyzed using IBM SPSS version 27. Descriptive statistics were used to find out various n (%). Quantitative variables were assessed for normality and expressed as mean ± SD, or median [interquartile range (IQR)], depending on distribution. Nominal data were analyzed using the t-test, where 2 groups were involved, and for the comparison of more than 2 groups, the ANOVA test was used. Categorical data was compared using the χ² test or Fisher's exact test. Variables that yielded a P < 0.05 were considered statistically significant.

Ethical considerations

Ethical approval was obtained from the Institutional Review Board of Pakistan Kidney and Liver Institute and Research Center (Approval No. 00672025). Due to the retrospective nature of the research and utilization of anonymized data, the requirement for informed consent was waived.

RESULTS

A total of 820 patients underwent LDLT between March 2019 and December 2024. Single-duct to duct biliary reconstruction was the most frequently performed anastomosis in 631 (77%) cases, including 531 right-lobe and 100 left-lobe grafts. Two separate ducts of the graft were anastomosed with the recipients’ two ducts in 161 (20%) cases, and two ducts were reconstructed on a single patch in 28 (3%) cases. ABS rates varied significantly based on the type of biliary reconstruction anatomy. Frequency of ABS was lowest among single duct-duct biliary anastomosis, with a stricture rate of 16.2% (102 of 631), followed by grafts with two separate duct-duct anastomosis, carrying a stricture rate of 34.8% (56 of 161). Notably, the highest stricture rate of 64.3% (18 of 28) was observed where two ducts were reconstructed on a single biliary patch. Risk of development of ABS with two duct anastomosis was significantly higher when compared to single duct anastomosis with an odds ratio of 3.34 (95%CI: 2.33-4.78). Similarly, when we compared 2 ducts on a single patch with 2 ducts anastomosed separately, the risk of developing ABS was significantly higher for the 2 ducts on a single patch, with an odds ratio of 3.38 (95%CI: 1.46-7.80). The incidence of ABS formation among the left lobe graft recipients was significantly lower (8%) compared to patients receiving right lobe grafts (23%; P value = 0.01). Figure 3 illustrates the frequency of different types of donor-recipient ductal anastomosis performed and the corresponding ABS rates.

Figure 3 Incidence of biliary strictures across different reconstruction techniques.

Out of 820 LDLT recipients, 176 (21.5%) patients developed ABS and were included in the study and subsequently analyzed to extract the relevant data. The mean age was 51.5 ± 11 years (range 14-71 years). The majority (74%, n = 130) were males. Diabetes mellitus (27%) and hypertension (19%) were the most prevalent comorbidities observed in the cohort. The median time to ABS development was 5 months (IQR 2.5-8.3 months). Table 1 summarizes the clinical characteristics of the study cohort.

Table 1 Clinical parameters of recipients developing post-liver transplant anastomotic biliary strictures.

Parameter	n (%)
Demographics
Total	176
Male	130 (74)
Female	46 (26)
Male/female	2.82/1
Age distribution (year)
14-18	2 (1)
18-50	67 (38)
> 50	107 (61)
Co-morbid conditions
Diabetes mellitus	47 (27)
Hypertension	33 (19)
Ischemic heart disease	4 (2)
Chronic obstructive pulmonary disease	4 (2)
Indication for liver transplant
Hepatitis C virus	106 (60.23)
Cryptogenic cirrhosis	21 (11.93)
Hepatitis B virus	17 (9.66)
Metabolic dysfunction associated steatohepatitis	8 (4.55)
Budd-Chiari syndrome	7 (3.98)
Hepatitis B & delta virus coinfection	5 (2.84)
Wilson’s disease	3 (1.7)
Alcoholic liver disease	3 (1.7)
Primary biliary cholangitis	2 (1.1)
Hepatitis B & C virus coinfection	2 (1.1)
Primary hyperoxaluria	2 (1.1)
Hepatocellular carcinoma	37 (38.1)
Type of graft with anastomotic biliary stricture
Right lobe	168 (95.45)
Left lobe	8 (4.55)
Type of biliary reconstructions among 820 recipients
Single duct-duct anastomosis	631 (77)
Right lobe	531 (84)
Left lobe	100 (16)
Two separate duct – duct anastomosis	161 (20)
Two ducts on a single patch	28 (3)

Of the 176 patients included in the study, 15 were lost to follow-up, and 7 died during the course of observation. At the time of data analysis, 40 patients were still undergoing endotherapy sessions. Hence, these 62 patients were excluded from the outcome analysis due to the incomplete therapeutic course. Figure 4 shows the participant flow chart. Among the remaining 114 patients, initial stricture resolution was achieved in 102 (90.2%) cases with endothrapy alone, and the success rate was 99.1% when PTC was utilized to manage ABS among cases of ERCP failure. One patient did not achieve stricture resolution despite maximal endo-therapy sessions and was referred for redo surgery (hepaticojejunostomy).

Figure 4 Participant flow diagram. LDLT: Living donor liver transplantation; ABS: Anastomotic biliary strictures; ERCP: Endoscopic retrograde cholangiopancreatography.

After initial resolution, 15 patients (13.27%) experienced stricture recurrence. Among the recurrent strictures, 8 recipients achieved re-resolution and required 3 ± 0.76 additional ERCP sessions. Overall, 106 (93%) recipients demonstrated sustained resolution at the time of analysis, while 7 remained under treatment after initial resolution. Table 2 shows the ERCP outcomes for ABS stricture management.

Table 2 Post-living donor liver transplant anastomotic biliary stricture management outcomes.

Stricture status	Total, n (%)	No. of ERCP (mean ± SD)	Duration between liver transplant to 1st ERCP (months)	Anastomosis, n (%)
				Single	2 ducts	2 ducts on a single patch
Patients completing the therapeutic course	114	5.18 ± 2.01	5.89 ± 5.58 (95%CI: 4.87-6.91)	67 (58.8)	36 (31.6)	11 (9.6)
Stricture resolution with endo therapy alone	102 (90.2)	5.04 ± 2.04	6 ± 5.77 (95%CI: 4.88-7.12)	58 (86.6)	33 (91.7)	11 (100)
Percutaneous transhepatic cholangioscopy referrals (cannulation failure/inability to traverse the stricture via ERCP)	11 (9.7)	6.27 ± 1.35	5.10 ± 3.65 (95%CI: 2.94-7.26)	8 (13.4)	3 (9.3)	-
Redo surgery	1 (0.9)	7.0	3.27	1 (100)	-	-
Combined percutaneous transhepatic cholangioscopy & endotherapy success rates	113 (99.1)	5.16 ± 2.02	5.92 ± 5.59 (95%CI: 4.89-6.95)	66 (98.5)	36 (100)	11 (100)
Stricture recurrence rates	15 (13.27)	7.5 ± 1.9	5.93 ± 4.57 (95%CI: 3.62-8.24)	6 (9.1)	7 (19.4)	2 (18.2)

ERCP: Endoscopic retrograde cholangiopancreatography.

The median time to the stricture formation after liver transplantation was 5 months (IQR 2-9 months), with the majority occurring within the first year. In contrast, the median time to stricture recurrence after the last ERCP was 8 months (IQR 4-19 months), with a range extending up to 34 months. This indicates that recurrence commonly occurred within the first year, but late recurrences were also observed. Figure 5 illustrates the timelines from liver transplantation to the first ERCP and also the time to stricture recurrence after initial resolution. The mean number of ERCPs (stent exchanges) required for stricture resolution varied notably based on the type of anastomosis (with single duct anastomosis requiring fewer ERCPs on average compared to two duct configuration), demonstrating a statistically significant association (P < 0.001). Figure 6 shows the impact of the type of biliary anastomosis on the number of ERCPs required for stricture resolution.

Figure 5 Timelines between liver transplant to first endoscopic retrograde cholangiopancreatigraphy and post-resolution stricture recurrence. ERCP: Endoscopic retrograde cholangiopancreatography.

Figure 6 Comparison of endoscopic retrograde cholangiopancreatography sessions required to achieve resolution for various types of biliary reconstructions. ERCP: Endoscopic retrograde cholangiopancreatography.

The IDC played a crucial role in the management of ABS. IDC was carried out in 18 patients, accounting for 15.8% of the total cohort of 114 patients who completed the therapeutic course. The main indications included facilitating traversal of acutely angulated/extremely tight strictures in 7 (6%) patients, enabling drainage of sectoral branches in 5 patients (4.4%), and performing ductal assessment to optimize endotherapy in 6 patients (5.3%). Of the 7 cases in which ERCP failed to traverse the stricture, IDC achieved success in 6 cases (86%).

A wide range of procedure-related complications was observed in the study cohort of 176 patients undergoing a total of 792 ERCP procedures. Cholangitis was the most frequent complication and developed in 19 (2.40%) procedures, followed by PEP in 18 (2.27%). ERCP-related bleeding occurred in 12 (1.52%) cases; notably, 6 (50%) of these episodes were self-limiting and required no active intervention. Hemostasis was achieved in 4 cases (33.4%) using electrocautery ± balloon tamponade. The remaining 2 cases (16.6%) required combination therapies, including adrenaline injection with hemo-clip placement and adrenaline injection combined with electrocautery. Importantly, no cases of perforation or procedure-related mortality were observed in our cohort. Prophylactic pancreatic duct stenting was performed in 51 (29%) patients during the first ERCP procedure and successfully prevented PEP in 78% (40 of 51) of high-risk cases for PEP.

DISCUSSION

ABS are still considered one of the most difficult complications encountered after LDLT, with higher incidence rates as compared to DDLT. This high incidence rate is likely due to multifactorial reasons, including the technical difficulty, particularly in cases involving multiple or small-calibre bile ducts. The ABS incidence of 21.5% in our study is in keeping with the literature[5]. The time interval from liver transplantation to the development of ABS is highly variable. In our study, ABS developed from 12 days to as late as 5 years after LDLT, with a median of 5 months (IQR 2.5-8.3 months), which is similar to the 5.9 months described by Shin and Joh[10].

Over the years, there has been a definite shift noticed in the management of biliary complications post-transplant. The use of PTC as the primary therapeutic tool for managing biliary complications has gradually decreased, whereas the use of ERCP as the first line of treatment modality has steadily increased. Surgical revision has been a less common practice, especially reserved for difficult and refractory strictures. The overall success rate for stricture resolution with endotherapy alone in our study was 90.02%, which is in line with the global reports on endoscopic therapy for ABS management[10]. The use of IDC as an adjunct to ERCP played a pivotal role in managing the ABS. In our series, ERCP alone failed to traverse the stricture in 7 patients, whereas IDC successfully traversed it in 6 patients, with a success rate of 86%. Our findings are consistent with those of Cho et al[14], who demonstrated 82.5% clinical success rates using IDC in difficult ABS. Sharma et al[15] have also obtained technical success rates of nearly 96% using IDC, whereas the previous experience using cholangioscope-assisted guidewire placement was only 60%, as shown by Woo et al[16]. The increasing success rates with IDC may be attributable to the learning curve effect, with improvement in technical expertise. The results of our study clearly emphasize the progress and innovation in endotherapy, making ERCP the gold standard for managing ABS in LDLT recipients.

The number of ERCPs needed to treat the stricture depends on the number and nature of the ductal anastomosis performed during the liver transplant. In our cohort, patients with a single-duct anastomosis required fewer ERCP sessions for stricture resolution (mean 4.47) than those with double-duct configurations, whether anastomosed separately (mean 5.24) or on a single patch (mean 5.67), confirming prior observations that multiple anastomoses not only increase the risk but also enhance the technical challenge in the endoscopic management[5,9].

ABS recurrence does occur after initial resolution and varies according to the follow-up period. Shin and Joh[10] reported ABS recurrence rates of 13%-44%. Another study showed that stricture recurrence rates after multiple plastic stent placement via ERCP were 3%-20%[6]. The recurrence rate of ABS after an initial resolution was 13.27% in our study, which is well within the rates reported in the literature. Although the time to recurrence was variable, as shown in Figure 5, most of these recurrences were successfully managed by repeated ERCPs, thus decreasing the need for surgical interventions. In our cohort, only one patient required surgical intervention (hepaticojejunostomy), thus confirming the safety and efficacy of endoscopic management in these patients.

Cholangitis (2.40%) and pancreatitis (2.27%) were the two most common post-ERCP complications noted in our study. The incidence of pancreatitis and cholangitis varies from 2.7% to 5.7% and from 1.02% to 4.5%, respectively[17,18]. There were no cases of perforation or ERCP-related mortality in our study. Prophylactic pancreatic duct stenting in the high-risk group for PEP showed favorable results, with 78% of patients showing no PEP, and 22% showing mild PEP, with no cases of moderate to severe PEP; thus, confirming the selective use of pancreatic duct stenting in patients identified as high risk, as per current clinical practice[19-21]. Although the technical success rate of ERCP was high, a proportion of patients were still referred for PTC because of additional challenges, such as inability to cross the stricture or cannulation of sectoral ducts, apart from failed biliary cannulation. These findings underscore the significance of PTC as a preferred rescue modality in cases where ERCP remains unsuccessful.

The strengths of this study include its relatively large sample size, focus on a well-defined single-center cohort, and utilization of both conventional ERCP and advanced cholangioscopic tools. However, its retrospective nature and relatively short follow-up period are potential limitations. Additionally, 55 patients (15 lost to follow-up, 40 still undergoing therapy) had incomplete follow-up, and 7 died before completion of therapy. Exclusion of these patients from outcome analysis could have potentially impacted the study findings and must be kept in consideration. However, a sensitivity analysis may be considered appropriate to assess the magnitude of any resulting bias.

Our findings support current international trends favoring endoscopic management of post-LDLT ABS, and suggest that graft anatomy and stricture characteristics should guide management strategy. Selective use of IDC in difficult cases may enhance technical and clinical success and the avoidance of undesired PTC and surgical referrals. Prospective, multicenter studies are warranted to further define optimal stenting duration, recurrence predictors, and preventive strategies, including refinements in anastomotic techniques during LDLT. As previously noted, our data demonstrated that on average, 4-5 ERCP sessions are required for stricture resolution, depending on the type of biliary anastomosis.

At our center, we primarily used plastic biliary stents for managing ABS. Nonetheless, fully covered self-expandable metallic stents are gaining traction in numerous transplant facilities because of their proven effectiveness, which includes requiring fewer ERCP sessions and a reduced overall treatment time. Even with these benefits, one major drawback of metallic stents is the potential for migration and technical complexity in double-duct anastomosis[22]. Consequently, upcoming studies need to focus on creating novel strategies guiding decisions about choice and feasibility of metal stents in view of the smaller number of ERCPs required for stricture resolution, along with cost effectiveness and less procedure related adverse events than in the multiple plastic stents strategy.

CONCLUSION

ABS continues to be a frequent challenge after LDLT with associated morbidity and mortality. However, they can be successfully managed through ERCP, known for its excellent technical and clinical outcomes and well-established safety profile. The need for endotherapy and stricture recurrence rates tend to rise in cases of complicated biliary anatomies, especially when multiple duct reconstructions are performed. Adding IDC and selective PTC for challenging cases can greatly improve outcomes in complicated biliary strictures. The evidence reiterates the significance of endoscopic therapy as the mainstay of treatment and the need for standardized approaches to improve long-term success.

ACKNOWLEDGEMENTS

Arsalan Saleem Chughtai performed the data analysis, and Saira Imtiaz reviewed the data analysis.