Overall Bottom Line

Improvements in organ selection, procurement and preservation have dramatically reduced the incidence of biliary complications after LT.
Despite standardization of surgical methods in biliary reconstruction, immunosuppression, and post-operative management, biliary complications continue to be a major cause of morbidity and mortality after LT.
Early and aggressive evaluation of transplant recipients with a suspicion of biliary complication is paramount due to the potential for graft and patient injury.
Biliary complications include biliary strictures, bile leaks, biliary stones/debris, sphincter of Oddi dysfunction, mucoceles and hemobilia.
The combination of endoscopic and percutaneous therapy has minimized the need for post-transplant biliary surgery to address complications.

Section 1: Background

Definition of disease

Two types of biliary reconstruction can typically be performed during a LT: choledocho-choledochostomy (duct-to-duct anastomosis) or choledochojejunostomy (duct-to-bowel anastomosis).
Instances in which there is pre-existing biliary disease (i.e. PSC), prior biliary surgery, or donor-recipient duct size mismatch, a duct-to-bowel anastomosis is favored.
Both types of biliary reconstruction can be complicated by strictures, bile leak, obstruction from biliary stones and debris.
Less common biliary complications include sphincter of Oddi dysfunction, mucoceles and hemobilia.

Disease classification

Biliary complications can be classified by a post-transplant timeline.
Early complications consist of those occurring less than 30 days post-transplant and often reflect problems of handling and harvesting the graft, preservation injuries and any unappreciated underlying graft disease.
The most common early biliary complication is a bile leak which is usually attributed to technical failure or vascular insufficiency.
Late complications consist of those occurring more than 90 days post-transplant.
Of these complications, biliary strictures are the most prevalent and tend to occur 5–8 months post-transplant.
The investigation of a patient with suspected biliary complications in the late period requires imaging of the hepatic arterial system and may require a liver biopsy to exclude any rejection or recurrence of disease.

Incidence/prevalence

Biliary complications after LT are a major source of morbidity with an overall incidence of 5–32%.
Biliary strictures comprise almost 40% of all biliary complications after LT with an incidence of 5–15% after deceased donor LT but as high as 28–32% after living donor LT.
Bile leaks are the second most common biliary complication after transplant with an incident of 2–25%.
Filling defects in the form of biliary stones, debris, and casts comprise 3–12% of biliary complications post-transplant.
Sphincter of Oddi dysfunction comprises 2–3% of all biliary complications.

Economic impact

Exact figures are not available but biliary complications have a major impact on the quality of life for a LT recipient – requiring frequent hospital readmissions, repeated imaging and invasive procedures.
Repeat admissions and imaging, along with occasional re-operation, add to the significant monetary cost of LT and to the emotional toll these patients suffer.

Etiology

Non-anastomotic stricture:
- Macroangiopathic – hepatic artery stenosis.
- Microangiopathic – prolonged cold and warm ischemia times, donation after cardiac death, prolonged use of vasopressors in the donor.
- Immunogenic (usually presenting later than 1 year post-transplant) – chronic rejection, ABO incompatibility, PSC, AIH.
- Infection – opportunistic, recurrent hepatitis B or C.
Anastomotic stricture:
- Scar formation (fibrosis).
- Local ischemia.
- Technical issues.
- Small caliber of the bile ducts.
- Mismatch in duct size between donor and recipient.
- Bile leak in the post-operative period.
Bile leaks:
- T-tube biliary reconstruction.
- Roux-en-Y anastomosis.
- Reperfusion injury.
- Hepatic artery thrombosis.
- Cytomegalovirus infection.
- Inappropriate suture material.
- Tension at the anastomosis.
- Excessive use of electrocauterization for control of bleeding.
Biliary stones/casts:
- Sloughed biliary epithelium (due to prolonged cold storage time).
- Chronic rejection.
- Infection.
- Bile stasis.
Sphincter of Oddi dysfunction:
- Stenosis – scarring and inflammation, i.e. passage of gallstone through papilla, intraoperative manipulation of the common bile duct.
- Dyskinesia – secondary to functional disturbance of the sphincter leading to intermittent biliary blockage.
Use of donation after cardiac death organs, split livers and living donor LTs are efforts to increase the donor pool. However, transplants using these organs are associated with a significant risk of biliary complications due to smaller duct sizes, more complex peripheral anastomosis, and ischemic injury that occurs prior to organ retrieval.

Section 2: Prevention

In addition to careful donor selection, preservation and retrieval, careful dissection of the hilar area is paramount to guarantee adequate blood supply to the donor duct.
Likewise, in living donor LTs, preservation of an adequately vascularized right duct is vital.
As more centers are standardizing biliary reconstruction during LTs, surgeons are favoring duct-to-duct anastomosis when possible.
A choledocho-choledochostomy allows preservation of the sphincter of Oddi, decreased operative time, less frequent bacterial colonization of the biliary tract and endoscopic access to the biliary tree.
These factors will lower the frequency of bile leaks and hence biliary strictures.

Screening

A high index of suspicion should always be maintained for biliary complications in the post-LT patient as the life of the graft and patient are at stake.
Because of immunosuppression and hepatic denervation, the clinical picture can vary widely.
The time frame for concern is also broad as bile leaks can occur in the immediate post-operative period and biliary strictures can occur weeks to years after transplant.

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