Endoscopic retrograde cholangiopancreatography for the management of biliary fistula following liver hydatid cyst related surgery or radiological interventions

Abstract

BACKGROUND

Surgery and percutaneous radiological methods [puncture, aspiration, injection, re-aspiration (PAIR)] are the current invasive treatment strategies for patients with hepatic hydatid cyst (HHC). Biliary leak is a common complication in patients who underwent these treatments of HHC. Bile leak should be treated effectively as uncontrolled biliary fistula may lead to life-treating conditions such as severe cholangitis, intraabdominal abscesses and septicemia. Endoscopic retrograde cholangiopancreatography (ERCP) has become the main treatment of post-interventional biliary fistula.

AIM

To evaluate the efficacy and safety of ERCP in the management of biliary fistula following HHC-related surgery or PAIR.

METHODS

We evaluated data of patients who developed bile leakage following HHC-related interventions from endemic area during the period of March 2017 and February 2025. We included 88 patients (50 female, 57%) with a median age of 33 years (range: 8-83 years) at the time of ERCP. Bile leak occurred following surgery in 72 (82%) patients and after PAIR in 16 (18%) patients. Low-grade leakage (< 400 mL/day) was identified in 46 (52%) patients.

RESULTS

Initial mode of ERCP was endoscopic sphincterotomy (ES) with biliary drainage (plastic stent or nasobiliary drain) in 73 (83%) patients and ES alone in remaining 15 (17%) patients. Six patients who initially treated by ES alone had persistent fistula and underwent repeat ERCP with stent placement. ERCP type (ES + biliary stenting) and fistula flow rate (< 400 mL/day) were significantly associated with 20-days complete closure of the fistula [P = 0.020; odds ratio (OR) = 5.27, 95% confidence interval (95%CI): 1.30-21.37] and (P = 0.008; OR = 3.43, 95%CI: 1.37-8.55), respectively. ERCP-related complications were mild pancreatitis in 5 (5.9%) patients and minor bleeding in 4 (4.7%) patients and mild-moderate cholangitis in 4 (4.7%) patients.

CONCLUSION

This case based-study from endemic area demonstrates that ERCP is highly effective and safe for managing bile leakage following both surgery and PAIR. ES + biliary stenting seems better mode of ERCP procedure.

Key Words: Hydatid cyst; Puncture, aspiration, injection, re-aspiration; cirrhosis; Fibrosis; Endoscopic retrograde cholangiopancreatography; Endoscopy

Core Tip: Liver is the most commonly affected organ of hydatid cyst involvement. Majority of patients with hepatic hydatid cysts (HHCs) are diagnosed incidentally or when HHCs-related complications occur. Rupture into intrahepatic bile ducts is the common and serious complication in individuals with HHCs. Surgery and percutaneous radiological methods [puncture, aspiration, injection, re-aspiration (PAIR)] are the current standard treatment strategies for patients with HHC. Biliary leak is a common complication in patients who underwent surgery or PAIR. We investigated efficacy and safety of ERCP in the management of biliary fistula following HHC-related surgery and PAIR.

INTRODUCTION

Hydatid disease which is caused by the larval form of Echinococcus granulosus, is a significant zoonotic disease that leads to mortality and morbidity in Mediterranean countries, the Middle East, Australia, and South America. The increasing population movements have led to a rise in the incidence of hydatid disease in non-endemic regions, such as the United States and Europe[1].

Liver is the most commonly affected organ in hydatid cyst involvement, accounting for 70% of cases. Most of people living with hepatic hydatid cyst (HHC) are diagnosed incidentally or when complications related to the cyst occur[2,3]. Rupture into intrahepatic bile ducts is a common and serious complication in individuals with HHC[4,5].

Surgery is the current standard treatment strategy for HHC. However, percutaneous radiological methods, such as puncture, aspiration, injection, re-aspiration (PAIR), are also effective treatment options for a select group of patients with HHC[6,7]. Biliary leak is a common complication that is reported in 50%-63% of patients who underwent these treatments of HHC[5]. Bile leak should be treated effectively, as uncontrolled biliary fistula can lead to life-threatening conditions such as severe cholangitis, intraabdominal abscesses, and septicemia[5,7]. Endoscopic retrograde cholangiopancreatography (ERCP) is the standard initial therapeutic option for individuals who developed biliary fistula following HHC-related interventions as surgical management of biliary fistula is associated with mortality and morbidity[5]. In these patients, endoscopic sphincterotomy (ES) alone or ES with biliary drainage (plastic or nasobiliary stent) is the recommended mode of ERCP[5,8,9].

In this two-center cohort study, we evaluated the efficacy and safety of ERCP in HHC patients who developed bile leakage following PAIR or surgery. We also tried to identify factors associated with complete closure time of biliary fistula in these patients.

MATERIALS AND METHODS

Study design

This multicenter retrospective cohort study was conducted at two tertiary referral centers in Türkiye, Harran University Hospital and Gazi University Hospital. The study protocol was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Harran University Faculty of Medicine (HRU/21.08.22).

Patient population

We included consecutive patients who developed bile leakage following surgery or radiological intervention for HHC between March 2017 and February 2025. Bile leakage was defined as the presence of bile in percutaneous drains and/or radiological evidence of biliary extravasation. ERCP was considered for patients with continuous bile discharge (daily output > 100 mL) after 10 days of HHC-related intervention[5].

Data collection and baseline assessment

Data were extracted from electronic health records using a standardized data collection form. Baseline demographic characteristics included age, sex, comorbidities, and previous management history. Laboratory parameters included a complete blood count, liver biochemical tests, renal function tests, a coagulation profile (prothrombin time, partial thromboplastin time, international normalized ratio), and inflammatory markers (C-reactive protein, erythrocyte sedimentation rate). Cyst-specific data included size, location, number, and Gharbi classification[10]. Surgical details documented the type of intervention, timing, and immediate post-operative course.

ERCP procedure and follow up

All patients underwent comprehensive pre-procedural imaging, including abdominal ultrasonography, computed tomography, or magnetic resonance cholangiopancreatography. Prophylactic antibiotics were administered according to institutional protocols. Rectal indomethacin (100 mg) was administered to patients for post-ERCP pancreatitis prophylaxis. Procedures were performed under conscious sedation with propofol and midazolam, with continuous cardiorespiratory monitoring. Experienced endoscopists (> 500 ERCP procedures yearly) utilized a side-viewing duodenoscope. Following selective biliary cannulation, cholangiography was performed to confirm and characterize the bile leak. Therapeutic interventions included ES using a standard sphincterotome and/or biliary stenting. Stent selection (plastic biliary stents or nasobiliary drains) was based on leak characteristics and anatomical considerations. Difficult cannulation (inability to achieve selective biliary cannulation by standard ERCP techniques within 10 minutes or up to 5 cannulation attempts) was defined according to the recommended consensus report[11].

Patients were monitored for immediate post-procedural complications, including bleeding, pancreatitis, and perforation. Adverse events were classified according to the lexicon proposed by Cotton et al[12].

Statistical analysis

Data analysis was conducted using SPSS version 27.0 (IBM Corp., Armonk, NY, United States). The Shapiro-Wilk test was used to assess the normality of the distribution. Continuous variables were presented as mean ± SD or median (interquartile range) as appropriate. Categorical variables were expressed as frequencies and percentages. Univariate and multivariate logistic regression analyses were employed to identify parameters associated with early leakage closure. The odds ratios (OR) were computed along with their respective 95% confidence intervals (95%CI). To ensure that important covariates were not overlooked, parameters with P values below 0.20 in univariate analyses were included in the multivariate analyses. These variables were entered simultaneously into the model to assess the independent association between clinical factors and early leakage closure. A two-sided P value of less than 0.05 was considered statistically significant.

RESULTS

Patient demographics and baseline characteristics

We analyzed data from 88 patients (57% female) who developed bile leak following HHC-related interventions and underwent ERCP. The general characteristics of the study population are presented in Table 1. The median age of the patients was 33 years (range: 8-83 years) at the time of ERCP. The median cyst size was 9.5 cm (range: 3-23 cm). Sixty-five patients had single cysts, while 23 patients had multiple cysts. The most common location of HHC was segment VII of the liver (n = 29). According to the Gharbi classification, the distribution of HHC was stage I in 10 (11%) patients, stage II in 36 (41%), stage III in 31 (35%), and stage IV in 11 (13%) patients. Initially, surgery was the preferred management for HHC in 72 (82%) patients, while PAIR was chosen in 16 (18%) patients. Bile leakage originated from the right intrahepatic bile ducts in 62 (70%) patients and from the left intrahepatic bile ducts in 26 (30%) patients. A total of 42 (48%) patients presented with high-grade leakage.

Table 1 General characteristics and management of the study population.

Total patients	n = 88
Gender (female), n (%)	50 (57)
Median age (range; years)	33 (8-83)
Comorbidities, n (%)
Diabetes mellitus	6 (6.8)
Arterial hypertension	4 (4.5)
Coronary artery disease	1 (1.1)
Celiac disease	1 (1.1)
Thalassemia major	1 (1.1)
Gordon syndrome	1 (1.1)
Polycystic kidney disease	1 (1.1)
Median cyst size (cm)	9.5 (4-23)
Gharbi classification, n (%)
Type 1	10 (11)
Type 2	36 (41)
Type 3	31 (35)
Type 4	11 (13)
Cyst characteristics, n (%)
Single cyst	65 (74)
Right lobe	70 (62)
Intervention type (surgery)	72 (82)
Daily fistula output (> 400 mL)	42 (48)
ERCP time (< 10 days), n (%)	38 (43)
Mode of ERCP, n (%)
ES + biliary stenting	73 (83)
ES alone	15 (17)
Number of ERCP procedures, n (%)
1	66 (75)
2	17(19)
3	4 (5)
4	1 (1)
All complications, n (%)
Pancreatitis (mild)	5 (6)
Bleeding (mild)	4 (5)
Infection/cholangitis (non-severe)	4 (5)
Discharge (days), n (%)
1	56 (64)
2	18 (20)
> 3	14 (16)
Median fistula closure time (range; days)	17 (8-93)

ERCP: Endoscopic retrograde cholangiopancreatography; ES: Endoscopic sphincterotomy.

ERCP procedures and technical aspects

Initial treatment options included ES with biliary drainage (using a plastic stent, n = 70, or a nasobiliary catheter, n = 3) in 73 (83%) patients, and ES alone in 15 (17%) patients. Six patients treated with ES alone had persistent fistula and were managed by repeat ERCP with stent placement. We performed a total of 116 ERCP procedures (excluding stent removals) in this study. Single-session treatment was successful in 66 (75%) patients, while 22 (25%) patients required multiple ERCP procedures. Of these, 17 patients underwent two procedures, four patients had three procedures, and one patient required four ERCP procedures. The common bile duct was successfully cannulated in 87 (98.8%) patients during the first ERCP session. In only one (1.2%) patient, cannulation of the common bile duct was achieved in the second ERCP procedure. The difficult cannulation rate was 17% (n = 15) in the study population. Concurrently, common bile duct stones were detected in three patients, all of whom were successfully removed during the same session using by balloon or basket techniques.

Treatment outcomes

Figure 1 shows the mode of ERCP procedure and clinical outcomes of patients with HHC-related biliary fistula. Complete bile leakage closure was achieved in all patients median 20 days (range: 8-93 days) after the initial ERCP procedure. In the ES + biliary stenting group, bile drainage ceased in all patients median 18 days (range: 8-93 days) after first ERCP procedure. In the ES alone group, bile drainage resolved in nine patients median 17 days (range: 12-19 days) after the ERCP procedure while remaining six patients required repeated ERCP with stenting due to persistent bile leaks (> 20 days) with daily output exceeding 200 mL. These patients achieved bile leak closure median 15.5 days (range: 10-25 days) after repeated ERCP. Figure 2 presents the management of patient with post-interventional HCC-related biliary fistula.

Figure 1  Mode of endoscopic retrograde cholangiopancreatography in the management of biliary fistula following hepatic hydatid cyst-related interventions.

Figure 2 Endoscopic retrograde cholangiopancreatography of 20-year-old female who developed biliary fistula following hepatic hydatid cyst-related intervention. A: Cholangiogram shows contrast extravasation from the right intrahepatic duct in a 20-year-old female patient following hepatic hydatid cyst related intervention; B: Sequential pictures show 7 Fr 12 cm biliary stent placement; C: Follow-up endoscopic retrograde cholangiopancreatography shows clearly visible right bile duct and its branches.

Factors associated with 20 days complete closure of the fistula

Predictors of complete fistula closure within 20 days are presented in Table 2. Multivariate regression analysis revealed that ERCP intervention type (ES + biliary drainage) and fistula flow rate (< 400 mL/day) were significantly associated with 20-day complete closure of the fistula (P = 0.020; OR = 5.27, 95%CI: 1.30-21.37) and (P = 0.008; OR = 3.43, 95%CI: 1.37-8.55), respectively.

Table 2 Univariate and multivariate analysis of variables associated with early leakage closure.

Variable	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
Gender
Male	1
Female	1.23 (0.53-2.87)	0.625
Size (cm)
> 9.4	1
< 9.4	1.19 (0.51-2.75)	0.683
Number of cyst
Single	1
Multiple	1.00 (0.38-2.60)	0.991
Garbi classification
1	1
2	1.40 (0.34-5.70)	0.639
3	0.63 (0.160-2.65)	0.530
4	0.571 (0.100-3.27)	0.530
ERCP intervention type
EST	1		1
EST + BD	4.58 (1.19-17.63)	0.027	5.27 (1.30-21.37)	0.020
Fistula flow rate
High	1		1
Low	3.11 (1.29-7.44)	0.011	3.43 (1.37-8.55)	0.008
ERCP complication
Present	1
Absent	1.108 (0.297-4.125)	0.879
Intervention type
PAIR	1
Surgery	1.11 (0.378-3.30)	0.841
Localization of leakage
Right intrahepatic	1
Left intrahepatic	1.13 (0.443-2.89)	0.794
Postoperative hospital stays (day)
> 5	1
< 5	1.0 (0.433-2.30)	1.000
ERCP time (day)
> 10	1
< 10	1.026 (0.441-2.38)	0.953

OR: Odds ratio; 95%CI: 95% confidence interval; ERCP: Endoscopic retrograde cholangiopancreatography; EST: Endoscopic sphincterotomy; BD: Balloon dilation; PAIR: Puncture, aspiration, injection, re-aspiration.

Post-procedure complications

ERCP-associated complications were observed in 13 (15.3%) patients. Post-ERCP pancreatitis developed in five (5.9%) patients, bleeding occurred in four (4.7%) patients, and four (4.7%) patients were complicated by cholangitis. All these complications were minor and managed with conservative measures. No ERCP-related perforation or procedure-related mortality was observed. Three (3.4%) patients developed liver abscesses, which were successfully managed by placing ultrasound-guided percutaneous drainage catheters.

DISCUSSION

Bile leakage following HHC related interventions is a challenging complication that significantly impacts patient outcomes and healthcare resource utilization. ERCP has emerged as the contemporary standard of care for post-operative bile leakage management, supported by extensive clinical evidence and consensus guidelines[5,13-19]. We presented a large cohort of patients who developed bile leaks following HHC-related surgery or PAIR from HHC endemic area. Our study results confirmed that ERCP is safe and effective in managing patients with bile leaks that developed after HHC-related interventions.

HHC-related fistula with daily output > 100 mL is rarely resolve spontaneously. Previous studies suggested that ES alone or ES with biliary stent placement for management of HHC-related fistula. Biliary stenting offers several mechanical and physiological advantages beyond simple leak occlusion. The placement of a stent reduces common bile duct pressure and upstream pressure gradients[5]. This mechanism facilitates healing of leak site as well preventing secondary biliary stenosis and associated complications. Further, biliary stenting enables endoscopic clearance of residual cyst materials from the biliary system[16,19]. Our results showed that ES with biliary stenting was associated with higher probability of 20-days closure of bile leak. Also, some of patients with persistent bile leak following ES alone were successfully managed by biliary stenting. Two large case-based studies reported that closure time of the HHC-related bile leak was shorter in patients who had ES combined with stenting than those managed by ES alone[19,20]. These results suggest that ES with biliary stenting may be better management strategy for bile leak that develops following HHC-related interventions.

We found that daily output (< 400 mL) was significantly associated with 20-days fistula closure. In one study, daily biliary drainage volume < 102 mL was predictor of spontaneous fistula closure[21]. We performed ERCP in only patients who had continuously (> 10 days after HHC related intervention) higher than 100 mL daily output fistula. Other studies did not find any correlation between daily output and fistula closure duration[17,19,20]. Importantly, we performed more robust statistical analysis and we believe that our findings can help physicians in the management of this group of patients.

A previous study reported that a 10 F diameter plastic stent was more effective in treating post-interventional HHC-related biliary fistula[19]. However, we did not observe correlation between the duration of fistula closure and the number or size of biliary stents. In another study[1], the authors recommended using nasobiliary drains instead of plastic stent for patients with HHC-related biliary fistula. Nasobiliary drainage demonstrated favorable clinical outcomes in our three patients, but all patients reported significant discomfort during follow-up. Therefore, we preferred plastic stent as the primary management strategy for most patients with post-interventional HHC-related biliary fistula. Several other factors such as post-operative timing of ERCP, number of HHC, HHC localization or size were not associated with 20-days bile leakage closure in our study population.

Previous studies reported 81%-100% technical and clinical success rates of ERCP in patients with HHC-related biliary fistula[5]. In our study, clinical and technical success rate was 100%. The difficult cannulation rate was 4.7% (n = 4) in the study population. These results strongly suggest that ERCP is the standard care method for post-interventional HHC-related biliary fistula.

Post-ERCP pancreatitis occurred in 5 (5.9%) and bleeding in 4 (4.7%) patients. All these complications were minor and successfully managed by conservatively. Four (4.7%) patients developed cholangitis. No mortality was observed in our study population. Previous study also reported acceptable adverse outcome rates in patients with HHC-related biliary fistula who underwent ERCP. Three patients developed liver abscess and required percutaneous intervention. This adverse outcome seems to be related to surgery or PAIR rather than ERCP procedure.

The retrospective design is the main limitation of our study. We also could not provide long-term outcome of patients who underwent ERCP for the management of post-interventional HHC-related biliary fistula. Importantly, this specific information is not aim of our study as long-term complications are mainly related to PAIR or surgical intervention. Due to lack of a uniform treatment protocol, our results may also be influenced by patient selection bias for each type of ERCP procedure. To overcome this limitation, we carefully collect data of all included patients and all procedures were performed by experienced two gastroenterologists who work in high volume ERCP centers. Future, prospective studies with long-term follow-up would address these limitations and reveal better therapeutic management strategies for patients with post-interventional HHC-related biliary fistula.

CONCLUSION

Our study results suggest that ERCP is effective and safe for the management of post-surgery or PAIR related biliary fistula in patients with HHC. ERCP type and low-output fistula (< 400 mL/day) were predictor of 20-days fistula closure. Therefore, we recommended that standard care of ERCP should include ES with biliary stenting for patients with post-interventional HHC-biliary fistula.

ACKNOWLEDGEMENTS

We thank to Dilek Yapar for reviewing statistical methods and techniques that used in our study.