Efficacy of Percutaneous Transhepatic One-Stage Biliary Fistulization for Biliary Stricture with Hepatolithiasis after Liver Transplantation

Summary

This retrospective single‑center study evaluated percutaneous transhepatic one-stage biliary fistulization (PTOBF) in 25 post‑liver transplant patients with biliary stricture and stones. In this small cohort, PTOBF was associated with favorable stricture resolution and stone clearance rates, suggesting significant clinical potential. Prospective studies are needed to confirm efficacy and safety.

Abstract

With the increasing maturity of percutaneous transhepatic cholangioscopy and biliary drainage techniques, PTOBF has gradually emerged as a novel minimally invasive treatment for biliary strictures and hepatolithiasis. This retrospective single‑center study included 25 post‑liver transplant patients diagnosed with biliary strictures and stones between January 2022 and December 2025, aiming to further evaluate the clinical efficacy and safety of PTOBF. The degree of stricture, distribution of stones, total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fibrinogen (FIB), γ-glutamyl transpeptidase (r-GGT), prothrombin time (PT), C-reactive protein(CRP), postoperative complication rate, stricture resolution rate, and stone clearance rate, etc., were analyzed. A total of 73 PTOBF procedures were performed on the 25 patients to manage strictures. The mean bile duct diameter after dilatation was 5.472 ± 0.667 mm. The stricture resolution rate was 92.0% (23/25). During a mean follow-up period of 19.1 ± 8.2 months, the final stone clearance rate was 88.0% (22/25). Compared with preoperative levels, postoperative levels of DBIL, ALT, AST, and FIB were significantly reduced. In this small retrospective cohort, PTOBF was associated with favorable stricture resolution and stone clearance rates, suggesting significant clinical potential. Prospective studies are needed to confirm efficacy and safety.

Introduction

In 1963, the world's first liver transplantation was performed by Professor Starzl, known as the "Father of Liver Transplantation"¹. With rapid technological advancements, liver transplantation has become a common treatment modality for various end-stage liver diseases^2,3. However, a frequent complication following liver transplantation is biliary stricture, with an incidence rate of approximately 15–30%⁴, of which over 80% occur at anatomical locations such as the biliary anastomosis⁵. Biliary strictures can secondarily lead to a series of adverse symptoms, including cholangitis, hepatolithiasis, and decreased liver function, and may even cause serious consequences such as allograft rejection and graft failure⁶. Clinically, endoscopic retrograde cholangiopancreatography (ERCP) has been preliminarily applied in the interventional treatment of post-transplant biliary strictures. However, ERCP techniques often require incision of the duodenal papillary sphincter, a drawback that has sparked considerable debate⁷.

Currently, the treatment of biliary strictures after liver transplantation remains a medical challenge, often necessitating multiple courses of sequential surgical interventions, including dilatation of the strictured bile duct, stent placement, and stone clearance^8,9. Percutaneous transhepatic one-stage biliary fistulization (PTOBF) involves successful percutaneous transhepatic bile duct puncture under ultrasound guidance, followed by direct dilation of the tract to 16F, insertion of a protective sheath, and subsequent use of a rigid choledochoscope for stone removal and management of biliary strictures. This procedure has been preliminarily applied in the clinical intervention of biliary tract disease^10,11,12. However, the application of PTOBF specifically for post‑liver transplant biliary strictures with stones has not been systematically evaluated. Therefore, this retrospective study aims to precisely evaluate the clinical outcomes of PTOBF in post‑liver transplant patients with biliary strictures and concomitant hepatolithiasis. The predefined outcomes include stricture resolution rate, stone clearance rate, procedure‑related complications, and changes in liver function biomarkers (DBIL, ALT, AST, FIB, TBIL, γ‑GGT, PT) and inflammatory marker (CRP).

This study provides novel clinical evidence regarding the efficacy and safety of PTOBF in post-liver transplantation biliary strictures with concomitant hepatolithiasis. The findings may support the broader clinical application of PTOBF as a minimally invasive one-stage intervention strategy.

Protocol

This study was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (No.YKLS201709). The ethics committee approved a waiver of informed consent for this retrospective analysis of medical records. Written informed consent was obtained from all patients for the PTOBF procedure. The images presented in the article were obtained with the patients' full informed consent.

A retrospective analysis was conducted of the clinical data of 25 patients with biliary strictures who underwent liver transplantation and were treated with PTOBF at the First Affiliated Hospital of Guangzhou Medical University from January 2022 to December 2025. All consecutive patients who met the inclusion criteria were included. If a patient underwent multiple PTOBF procedures and had multiple postoperative test results, the analysis results from all procedures were collected. The cohort included 24 male patients and 1 female patient. Inclusion criteria: diagnosed as post-liver transplantation status by preoperative imaging or medical history inquiry, concurrently complicated with biliary stricture; underwent percutaneous transhepatic one-stage biliary fistulization choledochoscopy surgery; preoperative liver function Child-Pugh grade A or B; underwent preoperative contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) examinations. Exclusion criteria: concurrent liver cancer or cholangiocarcinoma; severe coagulation disorders; allergy to the contrast agent iopromide.

PTOBF procedure
The main processes of PTOBF are shown in Figure 1. The materials involved in this process can be found in the "Table of Materials" file. Based on preoperative magnetic resonance cholangiopancreatography (MRCP), ultrasound, and other imaging examinations, the location of hepatolithiasis and the degree of biliary stricture were assessed (Figure 1A). The choice of puncture approach was determined by the target bile duct: for left intrahepatic bile ducts, an anterolateral approach was used to puncture segment 2 or segment 3; for right intrahepatic bile ducts, an intercostal approach was used to puncture segment 5 or segment 8 (Figure 1B–C). After the puncture needle accurately entered the target bile duct and smooth bile drainage was observed, a guidewire was immediately inserted. Using a one‑step method, an 8F dilator was introduced percutaneously along the guidewire into the liver, and successively larger dilators were exchanged to gradually dilate the tract to 16F. Subsequently, a 16F protective sheath was advanced together with the dilator into the bile duct; the dilator was withdrawn, leaving the distal end of the sheath within the hepatobiliary duct, thereby establishing an artificial passage connecting the hepatobiliary duct to the external environment (Figure 1D). After choledochostomy was completed, a choledochoscope was inserted and advanced along the biliary tree to select the target bile duct for further stone extraction and stricture dilation. Every effort was made to achieve complete stone clearance and to correct the stricture. Membranous strictures were dilated directly using a rigid choledochoscope and sheath: based on the degree of luminal narrowing, the diameter of the rigid choledochoscope tip was used as a reference, and blunt dilation was performed by placing a guidewire and a drainage tube. For tubular strictures, electrocautery incisions were made at the 3, 6, 9, and 12 o’clock positions (with the routine placement of a dispersive electrode plate; cutting power set at 15 W and coagulation power at 20 W), or combined with balloon dilation (balloon size selected according to the anastomotic diameter, typically 6–8 mm; after passing through the stricture, contrast medium was injected to inflate the balloon under pressure, gradually reaching 1.01 × 10⁶ Pa and maintained for 3–5 min) (Figure 1E). Under C‑arm X‑ray guidance, an 18F support drainage tube was placed beyond the distal end of the stricture. A drainage tube was left in the tract postoperatively, cholangiography was performed to assess biliary patency, and postoperative CT cholangiography was repeated to evaluate the outcome of the PTOBF procedure.

Follow-up
All 25 patients were successfully followed up via telephone and outpatient visits, with a mean follow-up period of (19.1 ± 8.2) months. The follow-up deadline was December 31, 2025.

Outcome measures
The main blood parameters observed were total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fibrinogen (FIB), gamma‑glutamyl transferase (γ-GGT), prothrombin time (PT), and C‑reactive protein (CRP) before and after the procedure. In addition, operative time, number of procedures, postoperative complication rate, stricture resolution rate, and stone clearance rate were analyzed. Biliary strictures were classified as severe or mild‑to‑moderate: Severe stricture was defined as a diameter ratio of the proximal bile duct at the stricture to the dilated distal bile duct < 1/2 on imaging, or the presence of a tubular or “door‑gap‑like” stricture under choledochoscopy. Mild‑to‑moderate stricture was defined as a diameter ratio ≥ 1/2 on imaging, or a membranous stricture under choledochoscopy. Resolution of the hepatic duct stricture and stone clearance were determined by intraoperative and postoperative cholangioscopy and imaging analyses. The stone clearance rate was defined as the proportion of patients with no residual stones after the final procedure and no detection of hepatolithiasis during follow‑up. The stricture resolution rate was defined as the proportion of patients with no evidence of biliary stricture during follow‑up after the final procedure. Stone recurrence was defined as the proportion of patients in whom intrahepatic bile duct stones were diagnosed by imaging more than six months after the final treatment during the follow‑up period.

Safety assessment
Among the 25 patients, one experienced intraoperative bleeding. Under choledochoscopy, the bleeding bile duct mucosa was locally irrigated with normal saline containing norepinephrine, which induced local vasospasm and reduced bleeding. Within 24 h after the procedure, the drainage fluid from the biliary drainage tube was light yellow, with no bloody fluid observed. Within one month postoperatively, a total of three complications occurred among the 25 patients, including two cases of septic shock and one case of chronic liver failure. After treatment, including anti-infection therapy, fluid resuscitation, enzyme inhibition, acid suppression, and fasting, all patients showed symptom improvement. During the follow‑up period, only one of the 25 patients developed liver failure three months after the procedure. All patients who experienced complications related to PTOBF in this study were on daily immunosuppressive therapy. The occurrence of complications may be associated with their own immunosuppressive status or may be the result of a combination of the PTOBF procedure and the patients’ underlying condition. Clinical, symptomatic, and supportive treatment was administered. This study retrospectively collected patient data.

Statistical analysis
Statistical analysis was performed using SPSS 25.0 software and SPSSAU. Normally distributed continuous data were reported as mean ± standard deviation (x̄ ± s), and comparisons between groups were conducted using the paired or independent-samples t-test. Categorical data were described as frequencies and percentages, and comparisons between groups were conducted using the χ² test. A p-value < 0.05 was considered statistically significant.

Results

Baseline patient characteristics
A total of 25 patients with biliary strictures after liver transplantation were enrolled in this study. The mean age was (51.760 ± 15.954) years. Among them, 22 patients had anastomotic strictures of the bile duct after liver transplantation. Biliary strictures occurred more than 10 years after liver transplantation in 9 patients and within 5 years after liver transplantation in 11 patients. There were 18 patients with severe strictures and 7 with moderate strictures. All 25 patients had concurrent hepatolithiasis; the stones were distributed at the biliary/ choledochojejunostomy anastomosis in 22 patients, in the common bile duct at the hepatic hilum in 8 patients, in the right hepatic lobe in 6 patients, and in the left hepatic lobe in 7 patients. Child-Pugh scores were all B. Hepatitis B was present in 9 patients (Table 1).

PTOBF surgical situations
The 25 patients underwent a total of 73 PTOBF procedures. Of these, 5 patients underwent 5 or more procedures, 7 patients underwent 1 procedure, and 13 patients underwent 2 to 4 procedures. The mean number of procedures per patient was (2.920 ± 1.956). Based on PTOBF, 2 patients underwent stricture incision using electrosurgical instruments to relieve obstruction, and 1 patient underwent balloon dilation for obstruction relief. The mean operative time was (52.082 ± 18.077) min, and the mean intraoperative blood loss was (4.027 ± 3.738) mL. Only 1 of the 25 patients experienced an intraoperative complication, which was bleeding (Table 2).

Postoperative outcomes and follow-up results
The mean bile duct diameter after surgical dilation was (5.472 ± 0.667) mm, and the stricture resolution rate was 92.0% (23/25) (Table 2). Postoperative short-term complications occurred in 3 patients, including 2 with septic shock and 1 with chronic liver failure; symptoms improved significantly after 2–3 days of anti-infection, fluid resuscitation, enzyme inhibition, acid suppression, and fasting treatment. The mean postoperative hospital stay was (12.315 ± 5.595) days. Compared to preoperative levels, DBIL, ALT, AST, and FIB decreased significantly after treatment (Table 3). The final stone clearance rate was 88.0% (22/25), the recurrence rate was 20.0% (5/25), and the rate of repeat stone removal surgery was 16.0% (4/25). The long-term postoperative complication rate was 4.0% (1/25), which was liver failure.

In summary, in this retrospective, uncontrolled cohort, PTOBF was associated with favorable clinical outcomes in patients with biliary strictures after liver transplantation. Among those with concurrent hepatolithiasis, several procedural advantages were observed, including a clear visual field, multiple puncture routes available, preservation of the sphincter of Oddi, a high stone clearance rate, and limited procedural trauma. These findings suggest that PTOBF may represent a feasible and well-tolerated treatment option for post‑transplant biliary strictures, although further prospective, controlled studies are needed to confirm its safety and efficacy.

DATA AVAILABILITY:
The datasets supporting the findings of this study are available in Zenodo at https://zenodo.org/records/20199354. All data generated or analyzed during this study are included in this published article.

Figure 1: PTOBF procedure. (A) Preoperative MRCP image analysis of biliary stricture and hepatolithiasis. (B) Intraoperative ultrasound localization of the puncture site, puncture route, and target hepatic bile duct. (C) Ultrasound analysis of the target hepatic bile duct for puncture. (D) Intraoperative puncture and stage I fistulization (percutaneous biliary drainage) procedure. (E) Postoperative choledochoscopic management of hepatic bile duct stricture. Abbreviations; MRCP = magnetic resonance cholangiopancreatography. Please click here to view a larger version of this figure.

Characteristic	Category	N	Value
Mean age (years)	-	25	51.760 ± 15.954
Bile duct anastomotic stricture after LT	-	22	88.00%
Time to stricture onset	≤5 years	11	44.00%
	5–10 years	5	20.00%
	>10 years	9	36.00%
Stricture severity	Severe	18	72.00%
	Moderate	7	28.00%
Stone distribution	Bile duct/ Choledochojejunostomy anastomosis	22	88.00%
	Common bile duct at hepatic hilum	8	32.00%
	Right hepatic lobe	6	24.00%
	Left hepatic lobe	7	28.00%
Immunosuppressants	Taking immunosuppressants	24	96.00%%
Child-Pugh		B	100.00%
Concurrent Hepatitis B	Yes	9	36.00%

Table 1: Baseline clinical characteristics of patients (n = 25). All the basic information, clinical diagnosis, and treatment data of the patients involved in this study. Abbreviations; LT = liver transplantation; N = number of people.

Characteristic	Category	n	Value
Number of PTOBF procedures (n = 25)	1	7	2.920 ± 1.956
	2~4	13
	≥5	5
Mean operative time (min) (n = 73)	-	-	52.082 ± 18.077
Intraoperative blood loss (mL) (n = 73)	-	-	4.027 ± 3.738
Bile duct diameter after dilation (mm) (n = 25)	-	-	5.472 ± 0.667
Hospital stay (days) (n = 73)	-	-	12.315 ± 5.595

Table 2: Surgical details. The main surgical records and hospitalization information of all the patients involved in this study.

Indicator	Preoperative	Postoperative	t	p
TBIL (µmol/L)	47.54 ± 69.88	31.97 ± 25.37	1.066	0.296
DBIL (µmol/L)	38.11 ± 33.02	22.26 ± 27.73	2.282	0.025*
ALT (U/L)	79.30 ± 61.14	42.86 ± 35.79	2.76	0.010**
AST (U/L)	68.27 ± 47.61	41.65 ± 24.03	2.572	0.016*
CRP (mg/L)	16.91 ± 19.51	4.26 ± 2.04	1.706	0.114
FIB (g/L)	4.93 ± 1.50	4.04 ± 1.63	2.011	0.049*
r-GGT (U/L)	297.13 ± 235.03	248.72 ± 203.13	0.949	0.345
PT (s)	13.90 ± 1.54	13.18 ± 3.29	1.032	0.305

Table 3: Levels of liver function and inflammatory markers before and after surgery. Comparative analysis of preoperative and postoperative blood indicators of liver function and inflammatory response in patients. Abbreviations; TBIL = total bilirubin (TBIL); DBIL = direct bilirubin; ALT = alanine aminotransferase; AST = aspartate aminotransferase; FIB = fibrinogen; r-GGT = γ-glutamyl transpeptidase; PT = prothrombin time; CRP = C-reactive protein.

Discussion

Patients with biliary strictures and concomitant stones after liver transplantation often present with poor physical condition and complex biliary anatomy, typically requiring multiple surgical procedures and resulting in high rates of residual stones. Consequently, minimally invasive approaches for relieving biliary strictures and clearing stones have emerged as a new generation of treatment modalities¹³. With technological advancements, following open biliary reconstruction, ERCP has become the primary method for treating biliary strictures after liver transplantation. In a study involving endoscopic treatment of 165 patients with post-liver transplantation biliary strictures, researchers achieved initial technical success in 89.1% of patients using ERCP endoscopic intervention. However, for patients with non-anastomotic strictures, the treatment efficacy rate decreased to 29.1%; furthermore, for patients with concomitant hepatolithiasis, ERCP endoscopic treatment showed poor efficacy, leading to prolonged operative time and increased risks¹⁴. In the present study, all patients with non-anastomotic intrahepatic biliary strictures and multiple strictures achieved favorable treatment outcomes, with no significant intraoperative complications observed, and no obvious stricture recurrence after treatment.

In this retrospective, single‑center, uncontrolled cohort of 25 patients with post‑liver transplantation biliary strictures complicated by hepatolithiasis who underwent PTOBF, the procedure required multiple sessions but was associated with relatively complete stricture resolution. The mean number of procedures per patient was 2.920 ± 1.956, the mean single operative time was 52.082 ± 18.077 min, and the mean intraoperative blood loss was 4.027 ± 3.738 mL. Only 1 of the 25 patients experienced an intraoperative complication (bleeding). When contextualized against previously reported outcomes of ERCP and other methods from the literature, the observations in this cohort—including operative time, blood loss, number of procedures, complication rates, stone clearance rates, and stricture resolution rates—appear promising. However, because of the absence of a direct comparator group and the retrospective, uncontrolled design, no direct comparative claims can be made. Notably, in this study, the majority of post‑liver transplantation biliary strictures were successfully treated through conventional PTOBF techniques, including electrosurgical stricture incision, balloon dilation, and combined placement of internal stents or gradual dilation with drainage tubes. However, some challenging biliary strictures remain, including tertiary biliary strictures and complete bile duct occlusion after liver transplantation; anatomical abnormalities may also increase the difficulty of ultrasound-guided percutaneous transhepatic catheter placement.

The results from PTOBF in this cohort also included evaluation of liver function biochemical markers. Postoperative levels of DBIL, ALT, AST, and FIB were significantly reduced compared with preoperative values, suggesting an association between PTOBF and improved biochemical parameters in this patient group. Although TBIL, C-reactive protein (CRP), and r-GGT and PT levels showed decreasing trends postoperatively, the differences were not statistically significant. These findings suggest the complexity and diversity of the internal environment in liver transplant patients, where liver function and inflammatory responses are regulated by multiple molecular pathways in vivo^15,16. Given the study design, causality cannot be established, and the observed improvements should be interpreted as associations rather than definitive evidence of efficacy.

PTOBF combined with choledochoscopy and endoscopic instruments was associated with favorable stricture resolution and stone clearance rates in this cohort, with good patient acceptance, comfort, and low surgical risk. However, the procedure requires a thorough preoperative understanding of the patient's biliary anatomy and places greater demands on the operator's expertise^17,18. During the 73 surgical procedures in this study, to prevent stricture recurrence due to scar hyperplasia after surgery, the same patient often needed to return to the hospital every 3 months for further dilation of the strictured bile duct, which also requires high patient treatment compliance. Additionally, this study is a single‑center study with a relatively limited sample size and lacks a control group; therefore, future multicenter studies with larger sample sizes, more detailed classifications of patient populations, biliary obstruction locations, and stone types in prospective, systematic research are necessary to confirm the safety and effectiveness of PTOBF.

Currently, therapeutic percutaneous transhepatic cholangioscopy has become a first-line treatment option for common bile duct stones alongside traditional surgery. Furthermore, the Rendezvous technique combines endoscopy and PTC, reaching the same stricture site through two different approaches to achieve convergence¹⁹, representing a new direction for individualized treatment of patients with post-liver transplantation strictures in the future²⁰. Percutaneous transhepatic cholangioscopy allows detailed observation of intrahepatic bile duct anatomy through the camera and can be equipped with various specialized accessories for corresponding diagnostic and therapeutic procedures, such as guidewires, electrocautery hooks, balloon dilators, and biliary stents. It has become an important tool for diagnosing unexplained biliary strictures and treating refractory choledocholithiasis, and its application in patients with biliary diseases does not increase surgery-related adverse events or risks, with definitive therapeutic effects^21,22. The future direction focuses on PTOBF verification, standardized reports, peroral or percutaneous digital cholangioscopy utilizing the SpyGlass system, comparative studies, and multi-center prospective evaluations, which are of great significance²³.

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Abdominal probe	Hitachi Aloka	5–1 MHz C25P	Used in anaylsis
Biliary balloon dilation catheter	Changmei Medical Equipment Co., Ltd.	6 mm × 6 cm	Used in surgical procedure
Center-slotted puncture guide / Center-slotted needle guide	Hitachi Aloka	0°-15°-30°	Used in anaylsis
Color Doppler ultrasound diagnostic system	Hitachi Aloka	S-70	Used in anaylsis
Electrosurgical system	HuTong	GD350-B	Used in surgical procedure
Fascial dilator	HuaMei	8 ~ 16 F	Used in surgical procedure
Hydrophilic guidewire	COOK	0.035 inch × 150 cm	Used in surgical procedure
Intracavitary irrigation pump	Jielun	NA	Used in surgical procedure
Normal saline	Sihao Pharmaceutical Co., Ltd.	100 mL	Used in surgical procedure
Pneumatic intracorporeal lithotripter	APL	APL-2	Used in surgical procedure
PTC needle (Percutaneous Transhepatic Cholangiography needle)	COOK	18 G	Used in surgical procedure
Rigid choledochoscope	Richard Wolf GmbH	12 F × 33 cm	Used in surgical procedure
Stone grasping forceps	KangJi	5 F	Used in surgical procedure
Stone retrieval basket	PuRuiXiSi	2.2Fr	Used in surgical procedure