Post-transplant Biliary Strictures Research Articles

Role of Endotherapy in Outcome of Liver Transplant Recipients Complicated by Post-Transplant Biliary Strictures

Role of Endotherapy in Outcome of Liver Transplant Recipients Complicated by Post-Transplant Biliary Strictures

Prolonged warm ischemia time in the recipient is associated with post-transplant biliary stricture following living-donor liver transplantation.

Post-transplant biliary stricture (PBS) is a common and important complication following orthotopic liver transplantation (LT). This study clarified the incidence of PBS and identified its risk factors. We retrospectively reviewed the medical records of 67 patients who underwent living-donor LT (LDLT) at our institute between June 2010 and July 2022 and analyzed their clinical characteristics, prognosis, and risk factors for PBS. Of the 67 patients, 26 (38.8%) developed PBS during the observation period. Multivariate analyses revealed the following independent risk factors for PBS formation: increased red cell transfusion volume per body weight (> 0.2 U/kg; hazard ratio [HR], 3.8; P = 0.002), increased portal vein pressure (PVP) at the end of LT (> 16 mmHg; HR, 2.88; P = 0.032), postoperative biliary leakage (HR, 4.58; P = 0.014), and prolonged warm ischemia time (WIT) (> 48 min; HR, 4.53; P = 0.008). In patients with PBS, the cumulative incidence of becoming stent free was significantly higher in patients with a WIT ≤ 48 min than in those with a WIT > 48 min (P = 0.038). Prolonged WIT is associated with intractable PBS following LDLT.

Biliary stenosis after liver transplant is not associated with cytomegalovirus infection.

Liver transplantation (LT) is the best treatment for end-stage liver disease; however, biliary complications (BCs) still pose a significant challenge. Among the post-transplant BC, strictures and biliary fistulas are the most common. Biliary strictures are classified as anastomotic and non-anastomotic. Some previous studies suggest an association between post-transplant biliary strictures and cytomegalovirus (CMV) infection. In this study, we aimed to identify whether there is an association between CMV infection and biliary strictures in patients undergoing LT. A retrospective study of 175 patients aged ≥18 years undergoing LT at Felicio Rocho Hospital between 2011 and 2017 was conducted. All included patients received grafts perfused with Institut Georges Lopez-1 (IGL-1) solution from brain-dead donors, survived post-transplantation for more than 120 days, and had a minimum follow-up of 12 months after LT. The diagnosis of CMV was made by antigenemia and biliary strictures by magnetic resonance cholangiopancreatography (MRCP). The average age of the recipients was 54 years. Postoperative BCs occurred in 12% of transplants. The most common BC was stricture (9.1%), with a predominance of anastomotic strictures (AS) over non-AS (NAS) (87.5% vs. 12.5%, respectively). CMV infection was confirmed in 22.9% of patients. In the univariate analysis, post-transplant CMV infection correlated with the development of BCs (P=0.01), as well as biliary strictures (P=0.008). In the multivariate analysis, however, only model for end-stage liver disease (MELD) >21 was a risk factor for the development of BCs in general (P=0.02) and biliary strictures (P=0.01). CMV infection was not an independent risk factor for the development of non-anastomotic post-transplant biliary strictures in this study.

Magnetic compression method in the treatment of post-transplant biliary stricture: A case report

Cerrahi tekniklerdeki gelişmelere rağmen biliyer komplikasyonlar hala yaygındır ve karaciğer nakli sonrasında hasta sağkalımını etkilemektedir. Biliyer darlıklar, genellikle endoskopik retrograd kolanjiyopankreatografi ve perkütan transhepatik kolanjiyografi ile tedavi edilmektedir. Bununla birlikte, biliyer anastomozun tam darlığı durumlarında, cerrahi yeniden anastomoz bir tedavi seçeneğidir. Ancak yeniden anastomoz için cerrahi prosedürler invazivdir ve postoperatif adezyon ve hastaların genel durumu nedeniyle uygulanması zordur. Manyetik kompresyon yöntemi, endoskopik retrograd kolanjiyopankreatografi ve perkütan transhepatik kolanjiyografi ile tedavi edilemeyen olgularda, cerrahi gerektirmeyen güvenli bir anastomoz yöntemidir. Burada, canlı donör karaciğer transplantasyonundan sonra manyetik kompresyon yöntemi ile başarılı şekilde tedavi edilen bir olguyu sunuyoruz.

Histological Assessment of the Bile Duct before Liver Transplantation: Does the Bile Duct Injury Score Predict Biliary Strictures?

Histological injury to the biliary tree during organ preservation leads to biliary strictures after liver transplantation. The Bile Duct Injury (BDI) score was developed to assess histological injury and identify the grafts most likely to develop biliary strictures. The BDI score evaluates the bile duct mural stroma, peribiliary vascular plexus (PVP) and deep peribiliary glands (DPGs), which were correlated with post-transplant biliary strictures. However, the BDI score has not been externally validated. The aim of this study was to verify whether the BDI score could predict biliary strictures at our transplant centre. Brain-dead donor liver grafts transplanted at a single institution from March 2015 to June 2016 were included in this analysis. Bile duct biopsies were collected immediately before transplantation and assessed for bile duct injury by two blinded pathologists. The primary outcome was the development of clinically significant biliary strictures within 24 months post-transplant. Fifty-seven grafts were included in the study which included 16 biliary strictures (28%). Using the BDI score, mural stromal, PVP and DPG injury did not correlate with biliary strictures including Non-Anastomotic Strictures. Severe inflammation (>50 leucocytes per HPF) was the only histological feature inversely correlated with the primary outcome (absent in the biliary stricture group vs. 41% in the no-stricture group, p = 0.001). The current study highlights limitations of the histological assessment of bile duct injury. Although all grafts had bile duct injury, only inflammation was associated with biliary strictures. The BDI score was unable to predict post-transplant biliary strictures in our patient population.

S53 Impact of Surgical Anastomotic Techniques on the Development of Post-Transplant Biliary Strictures in the Elderly

S53 Impact of Surgical Anastomotic Techniques on the Development of Post-Transplant Biliary Strictures in the Elderly

Post-Transplant Biliary Strictures: An Updated Review.

Liver transplantation (LT) is the only curative therapy in patients with end-stage liver disease with excellent long-term survival; however, LT recipients are at risk of significant complications. Among these complications are biliary complications with an incidence ranging from 5 to 32% and associated with significant post-LT morbidity and mortality. Prompt recognition and management are critical as these complications have been associated with mortality rates up to 19% and retransplantation rates up to 13%. An important limitation of published studies is that a large proportion does not discriminate between anastomotic strictures and nonanastomotic strictures. This review aims to summarize our current understanding of risk factors and natural history, diagnostic testing, and treatment options for post-LT biliary strictures.

Hepatolithiasis After Living Donor Liver Transplantation in Pediatric Patients: Mechanism, Diagnosis, Treatment, and Prognosis.

There is little information about the outcomes of pediatric patients with hepatolithiasis after living donor liver transplantation (LDLT). We retrospectively reviewed hepatolithiasis after pediatric LDLT. Between May 2001 and December 2020, 310 pediatric patients underwent LDLT with hepaticojejunostomy. Treatment for 57 patients (18%) with post-transplant biliary strictures included interventions through double-balloon enteroscopy (DBE) in 100 times, percutaneous transhepatic biliary drainage (PTBD) in 43, surgical re-anastomosis in 4, and repeat liver transplantation in 3. The median age and interval at treatment were 12.3 years old and 2.4 years after LDLT, respectively. At the time of treatments, 23 patients (7%) had developed hepatolithiasis of whom 12 (52%) were diagnosed by computed tomography before treatment. Treatment for hepatolithiasis included intervention through DBE performed 34 times and PTBD 6, including lithotripsy by catheter 23 times, removal of plastic stent in 8, natural exclusion after balloon dilatation in 7, and impossibility of removal in 2. The incidence of recurrent hepatolithiasis was 30%. The 15-years graft survival rates in patients with and without hepatolithiasis were 91% and 89%, respectively (p = 0.860). Although hepatolithiasis after pediatric LDLT can be treated using interventions through DBE or PTBD and its long-term prognosis is good, the recurrence rate is somewhat high.

Magnetic compression anastomosis for treatment of post-transplant biliary stricture: A case report with dual-graft living donor liver transplantation

Magnetic compression anastomosis for treatment of post-transplant biliary stricture: A case report with dual-graft living donor liver transplantation

Risk Factors for Development of Biliary Stricture After Liver Transplant in Adult Patients: A Single-Center Retrospective Study

Identification of risk factors for biliary stricture after liver transplant and its potential prevention is crucial to improve the outcomes and reduce the complications. We retrospectively analyzed donor and recipient characteristics with intraoperative and postoperative parameters to identify the risk factors for development of post-transplant anastomotic and nonanastomotic biliary strictures with additional analysis of the time onset of those strictures. A total of 412 patients were included in this study. Mean (SD) follow-up time was 79 (35) months (range, 1-152 months). Biliary stricture was diagnosed in 84 patients (20.4%). Multivariate analysis indicated that postoperative biliary leakage (odd ratio [OR], 3.94; P=.001), acute cellular rejection (OR, 3.05; P < .001), donor age older than 47.5 years (OR, 2.05; P=.032), preoperative recipient platelet value < 77.5×103/mL (OR, 1.91; P=.023), University of Wisconsin solution (OR, 1.73; P=.041)), recipient male sex (OR, 1.78; P=.072), portal/arterial flow ratio > 4 (OR, 1.76; P=.083), and intraoperative bleeding > 2850 mL (OR, 1.70; P=.053) were independent risk factors for biliary stricture regardless of the time of their appearance. Multiple risk factors for biliary stricture were determined in this study. Some of these risk factors are preventable, and implementation of strategies to eliminate some of those factors should reduce the development of post-transplant biliary stricture.

Necrotizing pancreatic pseudocyst induced by percutaneous transhepatic cholangiography & endoscopic retrograde cholangiography for biliary strictures after liver transplantation: Case report

Biliary strictures that developed after LT are managed with endoscopic retrograde cholangiography (ERC), percutaneous transhepatic cholangiography (PTC), or surgical revision. In cases where conventional endoscopic access is failed, alternative treatments should be achieved by means of the rendezvous technique, which is a hybrid technique combining PTC and ERC. We describe a rare case of necrotic pseudocyst occurring after the Rendezvous technique for treatment of post-transplant biliary strictures. A case review has been done. A 65-year-old man who presented with hepatocellular carcinoma complicating chronic hepatitis B liver cirrhosis underwent live donor liver transplantation (LDLT) from his son. One year after, he presented mild pruritus. The serum liver enzymes and bilirubin level raised but, liver biopsy was not diagnostic of rejection. ERCP showed stricture of the biliary anastomosis and tried to PTC and ERC, but failed three times. Cannulation of a biliary stricture can be achieved by the Rendezvous technique with progressive balloon dilation and the placement of two plastic stents. The patient was readmitted 2 weeks later with pain and vomiting with fever. CT showed 17 cm large pancreatic necrotic pseudocyst which was possibly a complication of previous intervention. Percutaneous drainage (PCD) of the collection yielded abscess. Despite of drainage and antibiotics management during 4 weeks, symptoms and pancreatitis were not resolved. After repositioning of PCD and irrigating with saline daily, symptoms including fever have improved. Necrotizing pancreatic pseudocyst has been happened rarely as a complication after post-ERCP in liver transplantation patients. and needed intensive treatments and long-term hospitalization for preventing fatal course.

Patients with post-transplant biliary strictures have significantly higher rates of liver transplant failure and rejection: A nationwide inpatient analysis.

Biliary strictures are a common complication of liver transplantation. We assess the impact of post-transplant biliary strictures and describe the outcomes of endoscopic retrograde cholangiopancreatography (ERCP), interventional radiology (IR), and surgical therapies. Using the Nationwide Readmissions Database (NRD), hospitalized liver transplant recipients were identified using the International Classification of Diseases 10th Revision codes. Patients with post-transplant biliary strictures were identified, and outcomes (inpatient mortality, 30-day readmission, transplant rejection/infection/failure, and disposition) were compared with transplant recipients without strictures. Among transplant patients with biliary strictures who underwent therapeutic intervention, corresponding outcomes were compared between IR, surgical interventions, and ERCP. Of the 8300 liver transplant recipients meeting selection criteria, 554 patients (age 48.9±18.2years, mean±SD; 39.5% women) had biliary strictures. Compared with patients without strictures, the adjusted odds ratio (OR) for various outcomes in patients with biliary strictures were as follows: 1.46 (1.20, 1.77; P<0.001) for 30-day non-elective readmission, 2.71 (2.04, 3.59; P<0.001) allograft rejection, 2.32 (1.61, 3.37; P<0.001) liver transplant failure, 3.05 (1.39, 6.73; P<0.01) infection, and 1.41 (1.08, 1.82; P=0.01) disposition to skilled nursing or intermediate care facility. Therapeutic interventions during index hospitalization were performed in 350 patients: ERCP 46.6% (n=163), surgery 41% (n=144), and IR 12.3% (n=43) patients. Compared with ERCP, the adjusted odds for various outcomes were disposition to skilled nursing or intermediate care facility 2.72 (1.08, 6.87; P=0.03) and 2.09 (1.05, 4.15; P=0.036), prolongation of hospitalization 14.4 (3.7, 25.1; P=0.008) and 15.0 (7.4, 22.7; P<0.001), and failure of liver allograft 8.47 (1.47, 48.6; P=0.017) and 12.23 (2.74, 54.4; P=0.001) for IR and surgical interventions, respectively. Post-liver transplant biliary strictures are associated with increased rates of allograft rejection, allograft failure/infections, and readmissions. Compared with ERCP, management of these patients with IR or surgical interventions is associated with significantly higher rates of allograft failure and hospital stay.

Hepatic phaeohyphomycosis due to a novel dematiaceous fungus, Pleurostoma hongkongense sp. nov., and importance of antifungal susceptibility testing

ABSTRACT Pleurostoma species are wood-inhabiting fungi and emerging opportunistic pathogens causing phaeohyphomycosis. In this study, we isolated a dematiaceous fungus, HKU44T, from the subhepatic abscess pus and drain fluids of a liver transplant recipient with post-transplant biliary and hepatico-jejunostomy bypass strictures. Histology of the abscess wall biopsy showed abundant fungal hyphae. The patient survived after a second liver transplant and antifungal therapy. On SDA, HKU44T grew initially as white powdery colonies which turned beige upon maturation. Hyphae were septate and hyaline. Phialides were monophialidic and laterally located, generally closely associated to a cluster of conidia which were usually reniform. Phylogenetic analyses showed that HKU44T is most closely related to, but distinct from, Pleurostoma ootheca and Pleurostoma repens. These suggested that HKU44T is a novel Pleurostoma species, for which the name Pleurostoma hongkongense sp. nov. is proposed. Antifungal susceptibility testing showed that Pleurostoma species possessed high MICs/MECs for fluconazole, 5-flucytosine and the echinocandins; whereas they exhibited a high strain-to-strain variability to the susceptibilities to the other triazoles. As for amphotericin B, ∼65% of the Pleurostoma strains had low MICs (≤1 µg/mL). DNA sequencing should be performed to accurately identify fungi with Pleurostoma/Phialophora-like morphologies, so is antifungal susceptibility testing for patients with Pleurostoma infections.

Magnetic Compression Anastomosis for the Treatment of Post-Transplant Biliary Stricture.

A number of different conditions can lead to a bile duct stricture. These strictures are particularly common after biliary operations, including living-donor liver transplantation. Endoscopic and percutaneous methods have high success rates in treating benign biliary strictures. However, these conventional methods are difficult to manage when a guidewire cannot be passed through areas of severe stenosis or complete obstruction. Magnetic compression anastomosis has emerged as an alternative nonsurgical treatment method to avoid the mortality and morbidity risks of reoperation. The feasibility and safety of magnetic compression anastomosis have been reported in several experimental and clinical studies in patients with biliobiliary and bilioenteric strictures. Magnetic compression anastomosis is a minimally traumatic and highly effective procedure, and represents a new paradigm for benign biliary strictures that are difficult to treat with conventional methods.

Unilateral Versus Bilateral Biliary Drainage for Post-Transplant Anastomotic Stricture

Living donor liver transplantation is the most common type of liver transplantation in Asia. Post-transplant biliary stricture is frequent in living donor liver transplantation, and endoscopic management is considered to be the treatment of choice. However, endoscopic management is still challenging in patients who undergo right lobe living donor liver transplantation because of the anatomical alteration. In this article, we reviewed the recently updated results for proper endoscopic biliary drainage in post-living donor liver transplantation anatomical biliary stricture and compared unilateral and bilateral drainage.

3:45 PM Abstract No. 104 Percutaneous management of biliary strictures following orthotopic liver transplantation: long-term outcomes analysis

To retrospectively evaluate long-term outcomes following percutaneous biliary drainage (PBD) for treatment of posttransplant biliary stricture. Patients with posttransplant biliary stricture managed with an institutional protocol of PBD placement, serial drain upsize and cholangioplasty were reviewed. Biliary drains were removed if cholangiogram demonstrated unobstructed biliary flow, and liver function tests remained stable after placement of an end-hole 5Fr catheter. Stricture patency rates following drain removal were estimated using the Kaplan-Meier method and compared between groups using the Log-rank test. Cox regression analysis was performed to identify predictors of recurrent biliary stricture. 25 patients (15 males, 10 females) were identified for analysis. Patients with primary sclerosing cholangitis comprised the largest subgroup (n = 13, 52%). 40% (n = 10) had anastomotic strictures, 44% (n = 11) had non-anastomotic strictures, and 16% (n = 4) had multifocal strictures. 68% (n = 17) had a single drain, 28% (n = 7) had two drains, and 4% (n = 1) had three or more drains. 44% (n = 11) underwent failed endoscopic treatment prior to PBD. The median duration of biliary drainage was 302 days. 72% patency rate was observed following drain removal at up to 148 months. 8% of patients (n = 2) failed PBD and underwent surgical revision (n = 1) or re-transplant (n = 1). Following drain removal, 20% (n = 5) developed repeat biliary stricture necessitating re-intervention (repeat PBD, n = 4 and repeat transplant, n = 1). Significantly decreased stricture patency was observed for patients requiring multiple vs. single drain (P = 0.034). In univariate analysis, larger final drain size (HR: 0.21, P = 0.027) was associated with lower hazards of drain failure while increased drain dwell time was associated with a higher hazard of drain failure (HR: 1.09, P = 0.020). Percutaneous management of posttransplant biliary stricture provided long-term stricture patency in 72% of patients. Repeat transplant or surgery was needed in 12%. Larger final drain size and increased drain dwell time are associated with higher and lower patency rates, respectively.

Type of Preservation Solution, UW or HTK, Has an Impact on the Incidence of Biliary Stricture following Liver Transplantation: A Retrospective Study.

Organ preservation plays a crucial role in the outcome following solid organ transplantation. The aim of this study was to perform a retrospective outcome analysis following liver transplantation using histidine tryptophan ketoglutarate (HTK) or the University of Wisconsin (UW) solutions for liver graft preservation. We retrospectively reviewed data on adult patients who were liver-transplanted at Karolinska University Hospital between 2007 and 2015. There was evaluation of donor and recipient characteristics, pre- and post-transplant blood chemistry tests, biliary and vascular complications, graft dysfunction and nonfunction, and patient and graft survivals. A total of 433 patients were included in the analyses, with 230 and 203 patients having received livers preserved with HTK and UW, respectively. Mean follow-up was 45 ± 29 months for the HTK group and 42.4 ± 26 for the UW group. There was no difference between the two groups either in terms of patient and graft survival, or of results of postoperative blood chemistry, or incidence of arterial complications, early allograft dysfunction, or primary graft nonfunction. However, the incidence of biliary stricture was higher in the UW group (22.7%) versus the HTK group (13.5%; p=0.013). Use of UW and HTK preservation solution in liver transplantation has no impact on patient and graft survival. However, use of HTK solution results in a lower incidence of posttransplant biliary stricture.

2196 A Case of Successful Endoscopic Management of Choledocholithiasis Complicated by Post-Transplant Biliary Stricture

INTRODUCTION: Post Liver transplant (LT) biliary stones, sludge and casts are a challenge to both advanced endoscopists and patients in the setting of complex anatomy, variable pathologies and multiple co-morbidities. The incidence rate of biliary stones is widely variable from 3.8%-18% and are associated with biliary strictures in roughly 90% of cases, increasing the complexity of the procedure. Here we are presenting a case of elevated liver enzymes and normal bilirubin in a LT patient with a history of post-LT biliary stricture. CASE DESCRIPTION/METHODS: 70 year old male with past medical history of fulminant hepatic failure status post orthotopic LT complicated by biliary anastomotic stricture, presented for management of new onset elevated liver enzymes ten years post LT. At the time of presentation he denied any complains of abdominal pain, nausea, vomiting, fevers, or chills. He denied any new medications or herbal supplements. Afebrile and hemodynamically stable at presentation. Labs showed WBC- 6.3, AST-202, ALT-133, GGT-1368, ALP-439 Total Bilirubin – 0.8 (Normal), INR-1.06 and Tacrolimus level -2.4. Liver biopsy showed bile ductular reaction and sparse to mild portal inflammation with minor ductulitis and endothelialitis. Abdomen ultrasound showed common bile duct with biliary ductal dilatation which may represent stones or sludge. Patient underwent ERCP revealing a large 3 × 2 cm stone in the common hepatic duct proximal to the anastomotic stenosis with marked upstream biliary dilation. The stone was partially crushed with electrohydraulic lithotripsy (EHL) via Spyglass cholangioscopy. The stone fragments were removed using an extraction balloon. Two 10 Fr x 12 cm long angled plastic stents were placed in the right and left biliary systems. A repeat ERCP was performed 8 weeks later and EHL under spyglass was performed. The ducts were subsequently cleared and stenosis resolved. DISCUSSION: Biliary stones and sludge can occur at any time after LT, with a reported incidence of 5%–10%. Our patient presented 10 years post-LT with transaminitis and normal bilirubin. Yu et al reported biliary strictures and cold ischemia time were significantly associated with bile duct stone formation after liver transplantation in a case-control study. Hence we conclude that in following patients post LT who are on immunosuppressants, the physician needs to be vigilant as patients can have a late presentation which can lead to graft loss and increased morbidity and mortality.

Long-term outcome of percutaneous transhepatic biliary drainage for biliary strictures following pediatric liver transplantation.

We present a retrospective analysis of our experience with pediatric liver transplantation (LT), focusing on the long-term outcome of percutaneous transhepatic biliary drainage (PTBD) for post-transplant biliary strictures. Fifty-three PTBDs were performed for 41 pediatric recipients with biliary strictures. The median ages at LT and PTBD were 1.4 and 4.4years, respectively. The median observation period was 10.6years. Post-transplant biliary strictures comprised anastomotic stricture (AS) in 28 cases, nonanastomotic stricture (NAS) in 12, anastomotic obstruction (AO) in 8, and nonanastomotic obstruction (NAO) in 5. The success rate of PTBD was 90.6%, and the 15-year primary patency rate of PTBD was 52.6%. The recurrence rate of biliary strictures after PTBD was 18.8%(9/48), and among the four NAS cases with recurrence, two underwent re-LT. The biliary obstruction rate was 27.1%(13/48). Among the eight cases with AO, five underwent the rendezvous method and three underwent surgical re-anastomosis. Among the five cases with NAO, one underwent re-LT. The recipient survival rate of PTBD treatment was 100%. The graft prognosis of AS by PTBD treatment is good and AO is curable by the rendezvous method and surgical re-anastomosis. However, the graft prognosis of NAS and NAO is poor.

12. Management of Post-transplant Biliary Strictures

12. Management of Post-transplant Biliary Strictures