Biliary complications are major sources of morbidity after liver transplant due to vulnerable vascularization of the bile ducts. Biliary complications are the “Achilles’ heel” of liver transplant with their high incidence, need for repeated and prolonged treatment, and potential effects on graft and patient survival. Although standardization of reconstruction techniques and improvements in immunosuppression and organ preservation have reduced the incidence of biliary complications, in early reports the morbidity rates are 50%, with related mortality rate 25% to 30%. Prophylaxis is a major issue. Although many risk factors (old donor age, marginal graft, prolonged ischemia time, living-donor liver transplant, partial liver transplant, donation after cardiac death, hepatic arterial thrombosis, organ preservation, chronic rejection, and other donor and recipient characteristics) do not directly affect biliary complications, accumulation of the factors mentioned above, should be avoided. However, no accepted standard has been established. Treatment strategy is a subject of debate. Recently, non­operative treatment of biliary complications have been preferred for diagnosis and therapy, because percutaneous or endoscopic treatment may prevent the need for surgical intervention. In this study, we reviewed our treatment of early and late biliary complications after liver transplant.

Key words : End-stage liver disease, Liver transplantation, Biliary stricture, Bile leakage

Introduction

Biliary complications are major sources of morbidity after liver transplant due to vulnerable vas­cularization of the bile ducts. Biliary complications are the “Achilles’ heel” of liver transplant with their high incidence, need for repeated and prolonged treatment, and potential effects on graft and patient survival. Although standardization of reconstruction techniques and improvements in immuno­suppression and organ preservation have reduced the incidence of biliary complications, in early reports the morbidity rates are 50% with related mortality rate 25% to 30%.^1,2 Prophylaxis is a major issue. Although many risk factors (old donor age, marginal graft, prolonged ischemia time, living-donor liver transplant [LDLT], partial liver transplant, donation after cardiac death [DCD], hepatic arterial thrombosis, organ preservation, chronic rejection, and other donor and recipient characteristics) do not directly affect biliary complications, accumulation of the factors mentioned above, should be avoided. However, no accepted standard is established. Treatment strategy is a subject of debate. Recently, nonoperative treatment of biliary complications has been preferred for diagnosis and treatment of biliary complications, because percutaneous or endoscopic treatment may prevent the need for surgical intervention.^3,4 In this study, we reviewed our treatment of early and late biliary complications after liver transplant.

Materials and Methods

We performed 377 liver transplants (188 pediatric and 189 adult liver transplants) between September 2001 and February 2014 in our center, including 304 LDLT (80%) and 73 deceased-donor liver transplants (DDLT) (20%). Biliary reconstruction was with hepaticojejunostomy in 65 patients (17%) and duct-to-duct reconstruction in 312 patients (83%). We retrospectively evaluated all 377 liver transplant patients for biliary complications, either early (within 6 months of liver transplant) or late (> 6 months after liver transplant) bile leakage and biliary stricture. We analyzed the treatment of 132 patients (35%) who had biliary complications.

In 125 grafts, biliary reconstruction was a duct-to-duct anastomosis over a T-tube or transhepatic catheter. All biliary anastomoses were performed with loupe magnification (original magnification × 2.5). The biliary anastomosis was performed with 6-0 or 7-0 monofilament suture for the duct-to-duct or bilioenteric anastomosis. Intraoperative hepatic blood flow and graft status were assessed with routine Doppler ultrasonography. Doppler ultra­sonography of hepatic perfusion was performed twice per day during the first postoperative week. At the end of the first week, routine abdominal computed tomography scans were obtained. Liver function tests were measured daily during the first 2 weeks. Tacrolimus-based immunosuppressive therapy was used in all patients. No patient received induction therapy.

Since early symptoms of biliary complications often can be nonspecific or missing, we could diagnose bilious secretions or bile duct pathology early via routine ultrasonography. The diagnosis of a bile leakage was suspected from a perihepatic collection on ultrasonogram or marked bile drainage from a surgical drain. We performed percutaneous drainage of perihepatic bilioma in cases without a T-tube. We injected contrast through the bilioma catheter or T-tube and showed when there was any communication of the bilioma with the biliary system. Anastomotic or nonanastomotic stenoses often were associated with jaundice, increased cholestatic enzyme levels, and fever. We observed recurrent cholangitis. We performed percutaneous or endoscopic retrograde cholangiography (ERC) after noninvasive imaging studies. Endoscopic stenting, percutaneous transhepatic internal-external biliary drainage catheter, or surgical reconstruction were performed for treatment of biliary complications.

Results

In 377 liver transplant patients, 132 patients (35%) had biliary complications (leakage and/or stricture) early or late after surgery. Biliary complications were more frequent with LDLT (LDLT, 37%; DDLT, 28%), pediatric liver transplant (pediatric, 36%; adult, 34%), and duct-to-duct anastomosis (duct-to-duct, 38%; hepaticojejunostomy, 15.9%). Early postoperative complications were observed in 69 patients with bile leakage (18%) and 30 patients with biliary stenosis (8%). Late complications were observed in 3 patients with bile leakage (0.8%) and 38 patients with biliary stenosis (10%).

The treatment of early bile leakage included drainage guided by ERC, transhepatic percutaneous biliary drainage (PBD), or surgical revision. The PBD (internal and/or external catheters) was the first choice of treatment for bile leakage. We performed 52 PBD procedures for early bile leakage. In 4 patients, PBD failed and surgical revision was performed. The ERC was performed in 17 patients for early bile leakage. In 10 patients, ERC failed, and further treatment included percutaneous treatment (8 patients) or surgery (2 patients). In 15 patients who had early bile leakage, surgery was the first choice, and in 2 patients, further percutaneous interventions were performed at follow-up.

The treatment of 30 early biliary strictures was by ERC-guided drainage, PBD, or surgical revision. The PBD (internal and/or external catheters) with balloon dilation was the first choice of treatment for early biliary stricture. We performed 32 PBD procedures for early biliary stricture. In 1 patient, PBD failed, and surgical revision was performed. There were 7 ERC procedures performed for early biliary stricture; all these ERC procedures failed, and the patients were treated with percutaneous treatment (8 patients) or surgery (2 patients).

The treatment of 3 patients who had late bile leakage was by ERC-guided drainage, PBD, or surgical revision. We performed PBD procedures for 1 patient; in follow-up, multiple percutaneous procedures were required, and he had biliary anastomosis revision for biliary stenosis. In addition to this patient, 1 patient had successful surgery and 1 patient had successful ERC for late bile leakage.

The treatment of 38 late biliary strictures was by ERC-guided drainage, PBD, or surgical revision. The PBD (internal and/or external catheters and balloon dilation) was the first choice of treatment for late biliary stricture. We performed 28 PBD procedures for late biliary stricture; this failed in 3 patients, and surgical revision was performed. Six ERC procedures were performed for late biliary stricture; in 5 patients, ERC failed, and treatment was with percutaneous treatment. In 3 patients who had late biliary stricture, surgery was the first choice, and all patients were successfully treated without further interventions.

There were 52 PBD procedures performed for early bile leakage. Late biliary strictures developed in 19 patients who had early bile leakage who were treated with PBD (19 of 38 patients [50%] with early bile leakage treated with PBD). Each of these patients had ≥ 3 PBD procedures during follow-up at 1-month intervals. After this prolonged treatment that included multiple interventions, 4 patients had revision surgery after failed repeated percutaneous treatment. In 21 patients, surgery was the first choice for treatment of biliary complications; 4 patients developed biliary complications at follow-up. We observed 2 patients who had bile leakage, treated successfully with PBD. There were 2 biliary strictures that developed after surgical treatment; 1 patient had surgical revision of hepaticojejunostomy, and the other biliary stricture was treated by PBD.

Discussion

Biliary complications are frequent causes of morbidity after liver transplant. Many factors related to recipient, graft, operative course, and postoperative course are associated with biliary complications (leakage or stricture). These factors include recipients with advanced recipient age and more impaired liver function, LDLT, ischemia-reperfusion injury, prolonged warm or cold ischemia time, arterial complications, type of reconstruction, and type of liver graft.⁵ It is reported in many studies that LDLT is a major risk factor for biliary complications.⁶ Therefore, graft and operative risk factors should be evaluated separately for DDLT and LDLT. Small duct size and the possibility of multiple duct orifices increase the risk of biliary complications.⁷ Devascularization of the bile duct during hilar dissection also contributes to these risk factors.⁸ Although previous studies showed that ischemia-reperfusion injury with prolonged warm or cold ischemia time and preservation methods are risk factors for biliary complications,⁹ in recent reports, ischemia-reperfusion injury seems to be associated more often with ischemic, nonanastomotic complications.¹⁰ In addition, preexisting bile leakage is associated with later biliary stricture.¹¹

Biliary strictures are among the most common complications after liver transplant with high mortality.¹² However, the incidence of stricture has decreased with recent improvements. Biliary stricture can present at any time after transplant, but most present within 1 year after transplant.¹³ In various studies, the incidence of biliary stricture is higher after LDLT than DDLT due to devascularization of the bile duct, technical difficulty of biliary reconstruction (small or multiple ducts), and bile leakage from the cut surface, which causes fibrosis around the anastomosis.¹⁴ In our study, we revealed a significantly higher incidence of biliary stricture after LDLT than DDLT (10%). The treatment of anastomotic stricture has improved during the past 2 decades. In the primary treatment of biliary strictures, mostly endoscopic and percutaneous methods are preferred over surgery. Surgery is reserved for patients who have failed noninvasive treatment.⁴ The success rate of ERC varied from 40% to 92% in various reports.^15,16 Recurrent strictures following ERC can be treated successfully with interventional dilation and/or stenting. However, many institutes prefer surgery or percutaneous treatment.

Bile leakage from an anastomosis or cut surface is the second most common complication after liver transplant. The incidence of bile leakage is 8.2%.17 Most patients are treated with an endoscopic approach or percutaneous radiography-guided drainage to divert bile away from the leakage and maintain bile drainage to the intestines.

The choice of percutaneous interventional radiology or endoscopy as the first treatment option for biliary complications may seem obvious because these methods are less invasive than surgical revision. However, when choosing the treatment modality, we must consider treatment-related morbidity and mortality, recurrence rates, quality of life, and retransplant rates. The main disadvantages of interventional techniques are the frequent use of prolonged drainage with catheters (minimum, 3-6 mo) and the need for repeated treatment sessions under anesthesia. In addition, retransplant rates after PBD or ERC are 0% to 20%, and in surgical series, the incidence of retransplant was 12%.¹⁸ The risk of complications (such as hemobilia, pancreatitis, sepsis, cholangitis, or intestinal bleeding) after percutaneous or endoscopic treatment also is ignored due to the benefit of avoiding surgical interventions. In a previous study, minor and major complication rates of PBD were 11% and 2%.¹⁹ Most complications are minor and amenable to medical treatment. However, they can be life threatening and cause death.

We preferred PBD for treatment of biliary complications as the first treatment option. We performed 52 PBD procedures for early bile leakage. Each of these patients had ≥ 3 PBD procedures during follow-up at 1-month intervals. After all these prolonged and multiple interventions, 4 patients had revision surgery after failed repeated percutaneous modalities. Late biliary strictures developed in 19 patients who had early bile leakage that was treated with PBD (19 of 38 patients [50%] with early bile leakage treated with PBD). In 21 patients, surgery was the first choice for treatment of biliary complications, and 4 of these patients developed biliary complications at follow-up. We observed 2 patients who had bile leakage that was treated successfully with PBD. There were 2 biliary strictures that developed after surgical treatment; 1 patient had a surgical revision of hepaticojejunostomy and the other biliary stricture was treated with PBD.

The treatment strategies differ between different centers. Many reported series showed excellent results with PBD and ERC procedures with low complication rates. When choosing the treatment modality, treatment-related morbidity and mortality, recurrence rates, quality of life and retransplant rates of the procedure should be considered. For early bile leakage, a surgical approach cannot be avoided in most patients, after prolonged treatment with repeated sessions of percutaneous or endoscopic tools.

In conclusion, on the basis of the current literature, no strong recommendation can be provided for the initial treatment of biliary complications. Further investigations with long-term follow-up should be designed to compare treatment strategies.

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