A Randomized Controlled Prospective Study to Compare the Incidence of Biliary Complications After Liver Transplantation
Phase: NA
Conditions: Liver Transplant; Complications
Sponsor: Vanderbilt University Medical Center

 
 
1 
 
TITLE 
 
 
A randomized controlled prospective study to compare the incidence of biliary 
complications after liver transplantation 
 
 
 
 
 
 
 
 
 
 
Investigators: 
Lanla Conteh, MD 
Lee Gorden, MD 
Andrew Scanga, MD 
 
 
 
 
 
 
 
 
 
 
Protocol Version: 09/08/2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
2 
 
Aim 
To prospectively compare the incidence of biliary complications after liver 
transplantation in patients who are randomized to undergo biliary reconstruction with and 
without biliary stents.  
 
Secondary Aim 
To retrospectively evaluate the incidence of biliary complications after liver 
transplantation in non-randomized patients who undergo biliary reconstruction with or 
without biliary stents in the same time period. 
 
Background 
Despite tremendous advances in other areas of orthotopic liver transplantation, biliary 
reconstruction remains a major hurdle.  Morbidity related to biliary complications has 
been estimated to be as high as 30%.1   The risk of biliary complications can be related to 
the type of transplant performed and the technique used for reconstruction of the bile 
duct. One of the main techniques of performing biliary reconstruction is a 
choledochocholedochostomy which can be performed over an anastomotic stent.  
Although placement of biliary stents is routine practice in many liver transplant centers 
around the country, there is no evidence to support their use. As of now both the 
placement and non-placement of a stent are essentially “standard of care. What has been 
extensively studied in the literature is the use T-tubes. In the early years of liver 
transplant, T-tubes were touted as a great mechanism to prevent anastomotic biliary 
strictures.2 However, their unanimous use is no longer supported as several retrospective 
and prospective studies have shown that their routine use led to more biliary 
complications including bile leaks, cholangitis, displacement of the tube, and bile duct 
obstruction.3-5 Although, biliary stricture formation may been have prevented, the rate of 
biliary complications did not offset this benefit. This was largely due to the fact that a T-
tube created an additional defect in the bile duct wall. Given these findings, in the 1990s, 
many transplant centers started performing biliary reconstruction without the use of T-
tubes.6 
 
 In our center, many of our transplant surgeons now perform the biliary anastomosis over 
a pediatric feeding tube which is used as a stent. The hope is that use of these internal 
stents will help prevent post-operative biliary strictures without the added risk of biliary 
complications seen with T-tubes. It is expected that the stent will migrate out on its own 
in the early days/weeks after a transplant. However, the practice of using stents in biliary 
anastomosis is not uniform and there are no established guidelines to support their 
indiscriminate application. We have designed a prospective randomized trial to evaluate 
the effect of stent placement on biliary complications and its effect on morbidity.  
 
Study Design 
A randomized prospective study will be conducted of patients at Vanderbilt University 
Medical Center (VUMC) who undergo liver transplantation from March 1st, 2014 until 
approximately 120 patients are randomized. We will simultaneously perform a review of 
patients at VUMC who undergo liver transplantation but cannot be randomized for 
logistical reasons (i.e. hepatic encephalopathy, timing of the transplant procedure, or 

 
 
3 
 
language barriers). Data from the two groups will be evaluated independently and 
comparatively. The inclusion of both groups of data is critical to avoid bias in the 
findings due to inadvertent selection of patients who may not have the same risk for 
biliary complications. All data will be de-identified and stored using a secure database, 
REDCap.  
 
 
Inclusion Criteria 
• 18years and older 
• Have receive a decreased full size liver graft 
• Need for hepaticojejunostomies or reduced size grafts 
 
Recruitment 
Informed consent will be sought from new patients undergoing evaluation from liver 
transplant during their clinic visit with the transplant surgeon. For those patients currently 
on the waitlist for transplant, who have already undergone evaluation, consent will be 
sought during their subsequent upcoming clinic visits before transplant. We will also seek 
out patients who are currently hospitalized and are on the liver transplant waitlist. Lastly, 
for those patients with no clinic visits in the near future but for whom transplant is 
imminent, we will reach out to them at their preferred contact number to discuss the 
proposed project and seek informed consent.  
 
Due to timing of the liver transplant procedure or the ability of the patient to understand 
the informed consent document, some patients may not be able to provide informed 
consent and will not qualify for randomization. Use of a stent in these patients will be 
determined at the discretion of the surgeon. A retrospective review of the data for these 
patients will be conducted.  
 
Randomization  
Patients will be prospectively randomized to 2 groups.  
• Group 1 will undergo biliary reconstruction with stent placement at the 
anastomosis site.  
• Group 2 will undergo biliary reconstruction without stent placement.  
Randomization will be performed with sealed envelopes before liver transplantation. The 
envelope will be opened during the operation and the randomization arm will be revealed 
to the surgeon immediately prior to the start of the biliary anastomoses.  
Surgical Procedure 
The surgical procedures are standardized. The operation will be performed exclusively by 

 
 
4 
 
5 hepatobiliary surgery attendings, each with individual experience of over 100 liver 
transplantations. 
 
Follow-up Procedure 
The patient will be followed up per standard of care for their liver transplant. 
If they were randomized to receive a stent placement, they will undergo an abdominal x-
ray about 3 months after transplant.   This x-ray is to see if the stent has been retained in 
the bile duct or if it needs to be extracted by an endoscopic procedure. This abdominal x-
ray is standard of care.    
Outcome 
Our primary outcome of interest is biliary complications. We will compare the incidence 
of biliary strictures, biliary leaks, cholangitis, and stones between the group that receives 
biliary stents and the group that does not. We will determine the time interval between 
transplantation to the occurrence of a complication. We will collect data on reoperations, 
conversion to hepaticojejunostomies, performance of an endoscopic retrograde 
cholangiopancreatography (ERCP) and additional hospital days incurred as a result of the 
biliary complication.  
 
Statistical Analysis 
The probability of being free of a biliary complication and the probability of liver graft 
survival will be estimated by the Kaplan Meier method. Continuous variables will be 
analyzed using Student’s t test, or Wilcoxon’s rank sum test. Categorical variables will be 
analyzed using Chi-square test or Fisher’s exact test. Multivariable proportional hazards 
regression will be performed to adjust potential confounders. A P value of <0.05 will be 
considered statistically significant.  
 
Limitations 
Potential confounders include the etiology of liver disease, the patient’s age at the time of 
transplant, the donor age, gender, body mass index, MELD score, the total operation 
time, cold ischemia time and warm ischemia time.  
 
 
References: 
1. Weiss S, Schmidt SC, Ulrich F, Pascher A, Schumacher G, Stockmann M, Puhl 
G, Guckelberger O, Neumann UP, Pratschke J, Neuhaus P. Biliary reconstruction 
using a side-to-side choledochocholedochostomy with or without T-tube in 
deceased donor liver transplantation: a prospective randomized trial. Ann Surg. 
2009 Nov; 250(5):766-71.  
2. Shaked A. Use of T-tube in liver transplantation. Liver Transpl Surg 1997; 3 (5 
suppl 1):22–23. 
3.  Stratta RJ, Wood RP, Langnas AN. Diagnosis and treatment of biliary tract 
complications after orthotopic liver transplantation. Surgery 1989; 106: 675–684 

 
 
5 
 
4. Vallera RA, Cotton PB, Clavien PA. Biliary reconstruction for liver 
transplantation and management of biliary complications: overview and survey of 
current practices in the United States. Liver Transpl Surg 1995; 1 (3): 143–152. 
5. Soubrane O, Bernard M, Scatton O et al. Randomized Trial of 
Choledochocholedochostomy With or Without a T Tube in Orthotopic Liver 
Transplantation. Ann Surg. 2001 March; 233(3): 432–437. 
6. Sotiropoulos GC, Sgourakis G, Radtke A, Molmenti EP, Goumas K, Mylona S, 
Fouzas I, Karaliotas C, Lang H. Orthotopic liver transplantation: T-tube or not T-
tube? Systematic review and meta-analysis of results. Transplantation. 2009 Jun 
15;87(11):1672-80.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
6 
 
Appendix 1 
 
Data Sheet 
 
Patient age at time of transplant 
Gender 
BMI 
Etiology of cirrhosis 
Listed MELD score 
Calculated MELD score based on the MELD-Na formula 
Total operation time 
Cold ischemia time  
Warm ischemia time 
Stent placed at time of biliary reconstruction  
Biliary complication 
Type of biliary complication 
Leak 
Stricture 
Cholangitis 
Biliary stones 
Retained stent  
 
Additional procedure for stent extraction 
 
Cost of procedure 
 
Complications from this additional procedure 
Management of biliary complication 
ERCP 
Sphicterotomy 
Time to first biliary complication from time of transplant 
Length of hospital stay for biliary complication  
Readmissions 
Time to first readmission  
Indication for readmission