Duct-to-duct biliary reconstruction in patients with primary sclerosing cholangitis undergoing liver transplantation

Abstract

Background

Reconstruction of biliary drainage after liver transplantation (LTx) in patients with primary sclerosing cholangitis (PSC) has been a matter of controversy. Over recent years, the traditional method of Roux-en-Y hepaticojejunostomy (RY) has been challenged by duct-to-duct (DD) biliary reconstruction.

Methods

This study represents a retrospective review of biliary complications, patient and graft survival after LTx in PSC patients based on type of biliary reconstruction. Outcomes of DD reconstruction in this group of patients and non-PSC patients are compared.

Results

A total of 53 primary LTx procedures were performed for PSC between August 2005 and July 2010. Seven patients were excluded because unexpected cholangiocarcinoma was found in the explants (n = 3) or because they received partial livers (n = 4). Biliary reconstruction was performed as DD in 18 patients and RY in 28 patients. There were no bile leaks. Anastomotic stricture occurred in two (11%) patients in the DD group and one (4%) in the RY group. Two (7%) patients in the RY group developed non-PSC intrahepatic strictures and one had recurrence of PSC. Rates of 1- and 3-year patient and graft survival in the RY and DD groups were 96.7% and 96.7%, and 100% and 94.5%, respectively. In a group of 34 randomly selected patients transplanted for a non-PSC diagnosis with DD reconstruction during the same period, the anastomotic stricture rate was 9% and 1- and 3-year patient and graft survival rates were 97.0% and 88.5%; differences were not significant.

Conclusions

Duct-to-duct biliary reconstruction at the time of LTx in selected PSC patients is both effective and safe, and shows outcomes comparable with those of RY reconstruction in these patients and those of DD reconstruction in non-PSC patients.

Introduction

Primary sclerosing cholangitis (PSC) is a chronic and progressive cholestatic liver disease of unknown aetiology, which is characterized by diffuse obliterative inflammation and fibrosis of the intra- and extrahepatic bile ducts leading to recurrent episodes of cholangitis, biliary cirrhosis, increased risk of cholangiocarcinoma (CCA), and, ultimately, death from liver failure or cancer in a high percentage of patients.^1,2 Therapeutic options, including medical therapy,³ endoscopic intervention^4–6 and surgical excision,⁷ have shown limited results. Liver transplantation (LTx) is the only definitive treatment to offer longterm survival in PSC patients with cirrhosis and liver failure.^8,9

The preferred method of biliary reconstruction in conventional LTx for most indications is duct-to-duct choledocho–choledochostomy (DD). Roux-en-Y choledochojejunostomy (RY) has been the procedure of choice when DD is not possible for a variety of reasons in LTx. In many transplant programmes, RY is the established procedure of biliary reconstruction in patients with PSC. This is mostly because of concern that undetected residual PSC disease may remain in the extrahepatic bile duct, that the disease may recur and that strictures may form or CCA develop in the remnant recipient distal bile duct. In recent years, the traditional method of RY after LTx in PSC patients has been challenged by some transplant centres and reports of safe DD biliary reconstruction with outcomes similar to those of RY in selected groups of patients with PSC have been published.^10–12

The purpose of this study was to evaluate our experiences of DD and RY biliary reconstruction after LTx in PSC patients. A single-centre, retrospective analysis was performed to evaluate patient and graft survival and the incidence of biliary complications in these two groups of patients. Outcomes of DD biliary reconstruction in PSC patients were compared with outcomes of DD in a cohort of patients transplanted for other indications during the same period.

Materials and methods

From August 2005 to July 2010, 693 LTx procedures were performed. A retrospective review of outcomes of 53 primary LTx procedures for PSC with respect to the type of biliary reconstruction was conducted with the approval of our institutional review board. Seven patients were excluded because unexpected CCA was found in the explant (n = 3) or because they received partial livers only (n = 4). Biliary reconstruction was undertaken as DD in 18 and RY in 28 of the remaining 46 patients. The median follow-up period was 36 months. In addition to the biochemical tests, postoperative complication rates and rates of 1- and 3-year patient and graft survival were compared between the two groups. The outcomes of 34 patients who underwent DD reconstruction after LTx for non-PSC indications were also compared with those of our cohort of 18 patients who underwent DD reconstruction after LTx for PSC.

The decision to utilize DD biliary reconstruction was based on the presence of: (i) normal pre-transplant cholangiographic features of the extrahepatic bile ducts; (ii) normal findings in brushing or cytology; (iii) intraoperative evaluation of the common bile duct by the operating surgeon; (iv) absence of periductal oedema, inflammation and wall thickening; (v) normal-looking mucosa; (vi) easy passage of biliary probes through the bile duct and into the duodenum, and (vii) a distal bile duct diameter of ≥5 mm.

The diagnosis of biliary strictures was suggested by elevations in liver biochemistry, in particular, in total bilirubin and/or alkaline phosphatase (ALP) levels. This was confirmed by subsequent imaging with magnetic resonance cholangiopancreatography, retrograde endoscopic cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography.

Results

There were no significant differences between the two groups in serum levels of bilirubin or ALP at 1 and 3 months after LTX (Table 1). No anastomotic bile leaks developed in the post-LTx period in either the DD or RY patient groups. Anastomotic strictures occurred in two patients in the DD group and one patient in the RY group (Table 2). Strictures in the DD group were treated successfully utilizing ERCP and dilatation with stenting. The only anastomotic stricture in the RY group was treated by a percutaneous approach. None of these patients required operative reconstruction of the strictures. Two patients in the RY group developed localized intrahepatic biliary strictures and one patient was diagnosed with recurrent PSC 4 years after LTx. One patient in the DD group died of unknown reasons 2 years after LTx and one patient in the RY group died shortly after LTx secondary to sepsis and complications of enterocutaneous fistula, not related to the RY. Rates of 1- and 3-year patient and graft survival did not differ significantly between the two groups (Table 2). No cancer developed in the bile duct remnant in any patient.

Table 1.

Bilirubin and alkaline phosphatase (ALP) levels at 1 and 3 months postoperatively

	Bilirubin at 1 month, mg/dl	Bilirubin at 3 months, mg/dl	ALP at 1 month, IU/l	ALP at 3 months, IU/l
PSC with DD reconstruction	1.34 ± 0.86	0.72 ± 0.51	231.76 ± 185.56	164.25 ± 143.80
PSC with RY reconstruction	1.22 ± 1.45	0.53 ± 0.21	167.15 ± 99.90	178.00 ± 137.64

Values are mean ± standard deviation.

All P-values were >0.05, indicating statistical insignificance.

PSC, primary sclerosing cholangitis; DD, duct-to-duct; RY, Roux-en-Y.

Table 2.

Comparison of the outcomes of duct-to-duct (DD) and Roux-en-Y (RY) biliary reconstruction

	DD reconstruction	RY reconstruction	P = value
Patients, n	18	28
Anastomotic stricture, n (%)	2 (11%)	1 (4%)	0.312
1-year patient and graft survival	100%	96.7%	0.412
3-year patient and graft survival	94.5%	96.7%	0.742

The comparison of outcomes in 34 randomly selected patients who underwent LTx with DD biliary reconstruction for non-PSC indications with outcomes in the 18 PSC patients who underwent DD reconstruction showed similar results in the two groups with respect to the rate of post-LTx anastomotic strictures, as well as patient and graft survival (Table 3).

Table 3.

Comparison of the outcomes of duct-to-duct (DD) reconstruction in patients with and without primary sclerosing cholangitis (PSC)

	PSC patients with DD reconstruction	Non-PSC patients with DD reconstruction	P-value
Number of patients, n	18	34
Anastomotic stricture, n (%)	2 (11%)	3 (9%)	0.788
1-year patient and graft survival	100%	97.0%	0.466
3-year patient and graft survival	94.5%	88.5%	0.472

Discussion

Biliary complications after LTx, especially at the anastomosis, are relatively common and can be categorized as resulting from technical, vascular, graft-related or immunological factors.^13–16 These complications are thought to be more prevalent and disease recurrence is considered to be a cause of graft loss after LTx in patients transplanted for PSC.^16–18

Traditionally, RY hepaticojejunostomy has been the method of choice for reconstruction of the biliary tree after LTx in PSC patients. This preference has mainly represented a response to the assumption that the distal bile duct remnant may potentially be involved with the active disease process and that stricture formation may result from disease progression or recurrence, or that the bile duct remnant may represent a site at increased risk for development of CCA.

In the light of better understanding of the pathology of biliary involvement in PSC, and evidence that the extrahepatic biliary system is not always affected by the disease process, some authors have questioned whether RY should be so strictly regarded as the only choice for biliary reconstruction. Recently, several reports from different transplant centres have presented data supporting the feasibility of conventional DD biliary reconstruction in selected groups of patients transplanted for PSC and have demonstrated excellent outcomes comparable with those of traditional RY biliary reconstruction.^10–12 Therefore, we examined whether the type of biliary reconstruction has any impact on incidences of complications and outcomes at our centre.

In our patient population, the incidence of biliary anastomotic stricture in the DD group was 11%, which was not significantly higher than the 4% incidence in the RY group. By contrast, intrahepatic biliary stricture occurred in 7% of the RY group, but none was detected in the DD group. There were no bile leaks in either group. In a study by Vito et al., biliary anastomotic stricture occurred in 19% of DD and 10% of RY patients transplanted for PSC, and biliary leak occurred in 6% of DD and 20% of RY patients.¹¹ These authors also compared outcomes in their PSC-DD patients with those in a group of patients undergoing LTx with DD biliary construction for primary biliary cirrhosis (PBC). Anastomotic stricture occurred in 10% of the PBC-DD patients and 19% of the PSC-DD group, but this difference was not statistically significant.¹¹ In the present study, outcomes in 18 DD patients were compared with those in a group of 34 patients who received LTX for a non-PSC diagnosis and biliary stricture rates were identified as 11% and 10%, respectively. In another study by Heffron and colleagues, outcomes in 38 patients who underwent RY were compared with those in 22 patients who underwent DD biliary reconstruction after LTX for PSC.¹⁰ The authors found no significant difference in rates of anastomotic stricture formation, bile leak, need for revision or recurrence of PSC between the two groups of patients.¹⁰

Welsch and Wigmore reviewed outcomes of 362 PSC patients reported in the UK Liver Transplant Registry, of whom 264 underwent RY and 98 underwent DD biliary reconstruction.¹² They found no significant difference between the two groups in rates of bile leak. However, biliary strictures were seen more frequently in the DD group (8% vs. 2%; P = 0.05).¹² A similar pattern was observed in our patient population, but the lower number of cases in each of our study arms make the study insufficiently powered to show equivalence. Welsch and Wigmore also noted a significantly higher rate of loss of patients with functioning grafts in the DD group, but did not disclose the causes of patient loss in this population.¹² They also did not clarify whether patients who received DD biliary reconstruction did so because their intraoperative general condition indicated it was appropriate, or whether the decision to perform DD reconstruction was based on a specific protocol pertaining to the condition of the recipient's bile duct, which was followed at all the reporting centres.¹²

Biliary reconstruction with RY has been suggested to represent a risk factor for the development of non-anastomotic biliary stricture (NAS) after LTx.^19,20 In the present study, we observed two patients with NAS in the RY group and none in the DD group. Hoekstra et al. reviewed a series of 486 consecutive adult PSC LTx patients, in whom biliary reconstruction was performed as either DD or RY depending on the condition of the extrahepatic bile duct.²¹ These authors observed a 17% incidence of NAS in their patients. By univariate analysis, PSC as the indication for LTx, type of biliary reconstruction (RY vs. DD), and postoperative cytomegalovirus infection were found to be significantly associated with NAS. By multivariate logistic regression analysis, only PSC as the indication for LTx and cytomegalovirus infection remained as independent risk factors for NAS. Roux-en-Y reconstruction was not found to be an independent risk factor for NAS.²¹

Cholangiocarcinoma develops in 8–18% of patients with longstanding PSC.^22,23 This is based on development of bile duct epithelial dysplasia, which is reported to precede the development of CCA.^24,25 Whether this reflects the result of immunological factors directed towards the biliary epithelium, alterations in the composition of bile in patients with PSC, or a continuous inflammatory response by cytokines produced in these patients is not clear.^26–28 One of the arguments against DD biliary reconstruction in patients transplanted for PSC is the risk for development of CCA in the bile duct remnant. It has been suggested that as much remnant recipient bile duct as possible should be excised in PSC patients with extrahepatic disease or in the presence of epithelial dysplasia at the time of LTx.⁹ However, in patients with a healthy extrahepatic biliary system, there is no clear evidence to prohibit the use of the remnant bile duct for DD reconstruction. There are no reports in the literature of the appearance of CCA in the remnant bile duct after RY reconstruction or when the remnant bile duct is used in DD reconstruction in PSC patients.

In recent years, there have been reports of the use of choledochoduodenostomy for biliary reconstruction after LTx in PSC patients without significant differences in patient and graft survival. However, higher rates of complications such as anastomotic stricture and leak, or cholangitis, have been reported after this procedure.^29,30

We appreciate that this study is not powered to show the equivalence of the two procedures; however, we believe that DD biliary reconstruction after LTx for PSC is a viable alternative to the traditional RY reconstruction in a selected group of patients. It is an especially useful alternative in the presence of normal-looking bile duct when the condition of the small intestine is less favourable for a RY procedure. It appears to be safe and is technically less demanding, and results in comparable longterm complications and patient and graft survival rates.

Conflicts of interest

None declared.