Randomized Trial of Hepaticojejunostomy Versus Duct-to-duct Anastomosis in Right Lobe Living Donor Liver Transplantation

October 24, 2019 updated by: Dr. Kenneth Siu-Ho Chok, The University of Hong Kong
The scarcity of deceased donor organ supply has driven the practice of living donor liver transplantation (LDLT). Right lobe LDLT (RLDLT) has developed over the last 10 years to extend the benefit of LDLT to adult patients. With technical refinement, the results have significantly improved but bile duct complications remain the Achilles heel that affects the recipient's long-term outcome.Hepaticojejunostomy (HJ) was originally the standard technique for bile duct reconstruction in RLDLT but in recent years, duct-to-duct anastomosis (DDA) has been adopted by most transplant centers. The advantages of duct-to-duct reconstruction include a shorter operation time, less infection complications, more physiologic enteric functions and easier endoscopic access to the biliary tract but bile duct complication, particularly stricture is the major concern. The development of stricture is likely to be related to the blood supply of the anastomosis. We hypothesize that HJ has a better blood supply and is associated with a lower overall bile duct complication rate than duct-to-duct anastomosis. We propose a randomized trial to test this hypothesis and to compare various outcome measures between HJ and duct-to-duct reconstruction. The results of the study will set the standard for the technique of biliary reconstruction in RLDLT and will further advance this procedure.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Liver transplantation is a life-saving procedure for patients with end-stage liver disease. The demand for the operation, however, always exceeds the supply from deceased organ donors and living donor liver transplant (LDLT) has been developed to provide an alternative option. LDLT was initially limited to paediatric recipients because of the restriction imposed by the graft size. In order to extend the benefit of LDLT to adult recipients, we proposed the use of a right lobe liver graft from a living donor and performed the first RLDLT for an adult recipient on May 9, 1996. Following the report of our first series of 8 cases in 1997, RLDLT has developed rapidly and has been adopted by many transplant programs around the world. LDLT has the most significant impact in Asia where the issue of organ shortage is most extreme. The availability of RLDLT for adult recipients provides the driving force for a drastic increase in LDLT in recent years. Our recent survey (unpublished data) indicated that the number of LDLT performed in Asia each year has increased by 9 folds since the introduction of RLDLT 10 years ago and is continuously rising. In the year 2005, LDLT accounts for 90% of the 1497 liver transplants performed in Asia (excluding mainland China). In Hong Kong, over two-thirds of the liver transplants are from living donors and the majority (90%) are RLDLT performed for adult recipients. RLDLT involved one of the most complicated and technically demanding surgical procedure. When our first series was reported in 1997, there was a high morbidity and reoperation rate in the recipients. Since then, various advances in technique and management have been introduced, including a better understanding of the minimum graft size requirement and anatomic variants of the right lobe, improved selection criteria for donors and recipients, as well as technical modifications; particularly in venous outflow and biliary reconstruction. There is a learning curve in RLDLT and through the lessons learnt in our first 100 RLDLT, we have dramatically improved the outcome of both the donors and recipients and an excellent graft survival rate of over 90% could be achieved even in high-risk recipients. The major technical hurdle that remains is biliary complication which affects the long-term outcome and quality of life and is occasionally the cause of graft loss and patient death. Hepaticojejunostomy was the standard technique for biliary reconstruction in RLDLT. The reported incidence of biliary complications in early reported retrospective series was high, ranging from 15 to 64%. Wach et al. first reported the technique of duct-to-duct reconstruction for RLDLT in 1998. Biliary stricture developed four weeks later and the anastomosis was subsequently revised to a Roux-e-Y HJ. Nonetheless, duct-to-duct reconstruction has the potential advantages of a shorter operation time, less septic complications, more physiologic enteric functions and easier endoscopic access to the biliary tract and these seem so obvious that duct-to-duct anastomsis has become the preferred technique in many transplant centers. In a retrospective study of 259 adult LDLTs; including 225 RLDLT from the Asan Medical Center in South Korea, Shin Hwang et al. reported an increasing preference for duct-to-duct anastomosis over HJ, with duct-to-duct anastomosis comprising 29.9% of the procedures in 2000 increasing to 69.3% in 2001 and 83.7% in 2002. The 3-year cumulative biliary complication rate, however, increased progressively form 13.7% in 2000 to 15.8% in 2001 and 25.4% in 2002. This rising incidence of biliary complication contrasted sharply with the improving results in other outcome measures of RLDLT which has been attributed to the learning curve effect. The authors demonstrated that for a right lobe graft with a single biliary reconstruction, a graft duct size less than 4 mm in diameter was a risk factor for biliary stricture in duct-to-duct anastomosis but not for HJ. They suggested that duct-to-duct anastomosis had inherent deficiencies that could not be overcome by current surgical techniques and recommended HJ as the preferred approach under such circumstances.We performed a retrospective study at our centre, in 265 RLDLT recipients, 55 (20.8%) developed postoperative BAS. The BAS rates were 21.4% (43/201) for recipients undergoing duct-to-duct anastomosis during transplantation, 18.9% (10/53) for recipients undergoing HJ, and 18.2% (2/11) for recipients undergoing both procedures. BAS and non-BAS patients had comparable demographics. The number of graft bile duct openings (P = 0.516) and the size of the graft's smallest bile duct (5 versus 5 mm, P = 0.4) were not significantly different between BAS and non-BAS patients. Univariate analysis showed that the factors associated with postoperative BAS were the recipient warm ischemia time (55 versus 51 minutes, P = 0.026), graft cold ischemia time (120 versus 108 minutes, P = 0.046), stent use (21.8% versus 7.1%, P = 0.001), postoperative acute cellular rejection (29.1% versus 11.0%, P = 0.001), and University of Wisconsin solution use (21.8% versus 7.1%, P = 0.001). Multivariate analysis showed that the cold ischemia time (odds ratio = 1.012, 95% confidence interval = 1.002-1.023, P = 0.014) and acute rejection (odds ratio = 3.180, 95% confidence interval = 1.606-6.853, P = 0.002) were significant factors. The graft survival rates of BAS and non-BAS patients were comparable. One patient required retransplantation for secondary biliary cirrhosis. In conclusion, BAS remains common after adult RLDLT regardless of DDA or HJ. The graft cold ischemia time and postoperative acute cellular rejection are significantly associated with postoperative BAS. A randomised controlled trial is definitely needed to see which methoid is superior to another. Since we reported the first series of RLDLT in 1997, we have introduced numerous technical refinements; particularly in venous outflow and biliary reconstruction. HJ was originally the standard technique and technical modifications were directed at preserving the blood supply to the graft right hepatic duct during the donor operation. A retrospective study on the first 74 right lobe transplants showed that the biliary complication rate has decreased significantly from 43% in the first 37 patients to 8% only in the second 37 patients. In particular, there was no biliary leakge in the second group of patients. Since then, however, we have switched from HJ to duct-to-duct anastomosis as the preferred technique for biliary reconstruction because of its apparently obvious advantages. With the new technique, however, three of 41 patients (7%) had biliary leakage and 10 (24%) developed biliary stricture at a median of 5.8 months (range 1.5 to 16.9 months) after transplant. These results were comparable to those of the Kyoto group in which the incidence of bile leakage was 10% and that of stricture 23%. A randomized trial is the only way to objectively determine whether HJ or duct-to-duct anastomosis should be the preferred technique for biliary reconstruction in RLDLT. Since the results of biliary reconstruction is highly dependent on the technique of the surgical team, a multi-center study would introduce a serious surgeons' variable that may compromise the interpretation of the results. Hence a randomized trial in a single high volume center using a standard technique by a single surgical team would be the best approach.

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Kenneth Chok, MBBS
  • Phone Number: 085228592111 22553025
  • Email: chok6275@hku.hk

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Queen Mary Hospital
        • Contact:
          • Kenneth Chok, MBBS
          • Phone Number: 085222553025 085222553025
          • Email: chok6275@hku.hk

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • recipient age older than 18 years
  • primary transplant

Exclusion Criteria:

  • recipient refusal/withdrawal
  • haemodynamic instability at the time of biliary reconstruction
  • biliary reconstruction with duct-to-duct anastomosis is unsafe or technically not feasible
  • unhealthy recipient's bile duct, anatomical variant in donor's right duct
  • biliary reconstruction with hepaticojejunostomy is unsafe or technically not feasible
  • excessively edematous bowel, failure to create Roux-en-Y jejunal loop due to excessive
  • bowel adhesions

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Hepaticojejunostomy
Patients undergo right lobe living donor liver transplantation will receive hepaticojejunostomy
Procedure: Hepaticojejunostomy / Duct-to-duct anastomosis
Active Comparator: Duct-to-duct anastomosis
Patients undergo right lobe living donor liver transplantation will receive duct-to-duct anastomosis
Procedure: Hepaticojejunostomy / Duct-to-duct anastomosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biliary complications
Time Frame: 5 years
Compare all biliary-associated complications after operation including leakage and stricture
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Operative time for liver transplantation
Time Frame: intraoperative
Duration of operative time
intraoperative
Gastrointestinal function after liver transplantation
Time Frame: 5 years
Return of gastrointestinal function
5 years
Hospital stay after liver transplantation
Time Frame: 5 years
Duration of hospital stay
5 years
Chances of re-intervention
Time Frame: 5 years
Re-intervention rate
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2012

Primary Completion (Anticipated)

December 31, 2022

Study Completion (Anticipated)

December 31, 2022

Study Registration Dates

First Submitted

October 9, 2019

First Submitted That Met QC Criteria

October 24, 2019

First Posted (Actual)

October 25, 2019

Study Record Updates

Last Update Posted (Actual)

October 25, 2019

Last Update Submitted That Met QC Criteria

October 24, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UW 12-070

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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