Stent placement can achieve same prognosis as endoscopic nasobiliary drainage in treatment of bile leakage after liver transplantation

doi:10.21203/rs.3.rs-5012818/v1

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Stent placement can achieve same prognosis as endoscopic nasobiliary drainage in treatment of bile leakage after liver transplantation

https://doi.org/10.21203/rs.3.rs-5012818/v1

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Background

Both stent placement and endoscopic nasobiliary drainage are commonly employed for treating bile leakage following liver transplantation. However, little research compared the advantages of both.

Methods

Data of patients with bile leakage after liver transplantation were retrospectively collected in our center. The efficiency and prognosis were compared between two groups.

Results

We retrospectively collected data from total 50 patients diagnosed with bile leakage within one month after liver transplantation. Among them, 40 patients underwent endoscopic nasobiliary drainage (ENBD) and 9 patients received stent placement. Baseline patient characteristics, except white blood cell count (WBC), total bilirubin (TB), and direct bilirubin (DB) levels, were comparable between the two groups. Additionally, there was no significant difference in the rates of reconveyance or post-operative biliary stricture.

Conclusion

Both stent placement and endoscopic nasobiliary drainage are recommended for treating bile leakage after liver transplantation, as they exhibit similar efficacy and prognosis.

bile leakage

liver transplantation

Stent placement

endoscopic nasobiliary drainage

Biliary complications including biliary anastomotic stricture and bile leakage, were major source of morbidity after liver transplantation, with an incidence of 5%-32%¹. According to the UK’s National Health Service, bile duct complications after liver transplantation include bile leakage, bile duct strictures, bile duct stones, and sphincter of Oddi dysfunction. Among these, bile leakage is one of the most common complications, with an incidence rate ranging from 2–25%, which is more common in living donor liver transplantation than in deceased donor².

Bile leakage is the second most common biliary complication of liver transplantation, which could be classified in two categories: early (within 4 weeks of the transplant) and late (beyond 4 weeks of the transplant)³. Early bile leakage is considered as a result of technical problems rather than related to the type of biliary reconstruction(Fig. 1)³. However, it’s associated with either planned or inadvertent T-tube removal¹. Thus, early bile leakage usually occurs at the anastomotic site or T-tube insertion site. It is often accompanied by infection, pain, and delayed graft function, posing a threat to patient survival and quality of life.

Endoscopy plays a pivotal role in the diagnosis and treatment of biliary diseases. Notably, endoscopic sphincterotomy, stenting, and drainage have been recommended for managing biliary leakage^4–6. According to a systematic review, the success rate of endoscopic therapy for bile leak ranges from 68–98.3%⁷.

In patients who have undergone liver transplantation, endoscopic nasobiliary catheter or plastic stent placement emerges as a safe and effective treatment for bile duct strictures following bile leak resolution⁸. Favorable outcomes are more likely when the duct injury measures less than 5 mm or occurs extrahepatically, and when there is no associated abscess or biloma⁹. However, the comparative efficiency and long-term prognosis of endoscopic nasobiliary catheter versus plastic stent placement have received limited attention in previous studies. Therefore, this comprehensive investigation aimed to analyze patient-related factors and compare the advantages and disadvantages of these two methods.

We retrospectively analyzed adult patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for bile leakage after liver transplantation at our center between June 2016 and January 2023. For this study, we included only those patients who underwent ERCP within 30 days after surgery. All patients had received either piggyback liver transplantation or right lobe liver transplantation. Routine deployment of double abdominal drains around the first hepatic porta and posterior of the liver occurred, and T-tubes or internal stents were used according to the bile duct diameter. Standard perioperative management protocols were followed for both donor and recipient operations. Graft preservation involved the use of either Histidine–Tryptophan–Ketoglutarate or University of Wisconsin solution. Postoperatively, all patients were closely monitored, and ERCP was performed upon diagnosis of bile leakage.

Continuous and categorical variables were compared using Student’s t-test and the chi-square test, The results were given as means ± standard deviation unless otherwise indicated. An alpha level of 0.05 indicated statistical significance. Listwise deletion was used to handle missing data in each variable. All statistical analyses were performed using SPSS 20.0 (Armonk, NY: IBM Corp).

Total 50 patients after cadaveric liver transplantation were included in this retrospective research. Among them, one patient was failed due to difficult gastroscope access. 40 patients underwent ENBD and 9 patients received stent placement. We analyzed various factors including demographic data, causes for liver transplantation, T-tube placement, prognosis, incidence of fever, and laboratory values. Demographics and characteristics of these patients were showed in Table 1.

Table 1

Demographics and characteristics
	ENBD(N = 40)	STENT(N = 9)	p
Age (years)	49.83 ± 10.253	51.56 ± 7.299	0.000
Male	35(87.5%)	7(77.8%)
Cause for LT
Hepatocellular carcinoma	18(45.0%)	5(55.6%)
Decompensated cirrhosis	12(30.0%)	2(22.2%)
acute-on-chronic liver failure	4(10%)	1(11.1%)
Acute liver failure	1(2.5%)	1(11.1%)
others	5(12.5%)	0
T-tube placement	4(10%)	2(22.2%)
Fever	14(35%)	3(33.3%)
WBC	7.5769 ± 4.10888	9.1778 ± 7.23356	0.030
CRP	37.3282 ± 39.18221	31.3000 ± 34.81982	0.931
PCT	2.3752 ± 5.25436	1.2014 ± 1.51013	0.263
Ab	36.8513 ± 3.60671	38.6444 ± 4.52469	0.357
AST	134.8205 ± 346.00600	54.2222 ± 29.24371	0.198
ALT	177.8974 ± 236.18133	130.7778 ± 152.20034	0.460
GGT	162.0769 ± 145.96816	119.2222 ± 59.37335	0.089
ALP	134.9487 ± 86.02324	136.1111 ± 66.69978	0.230
TB	57.7692 ± 49.96286	102.2222 ± 98.45148	0.000
DB	44.5128 ± 42.60768	78.3333 ± 81.31421	0.001
ENBD, endoscopic nasobiliary drainage; LT, liver transplantation; WBC, white blood cell; CRP, C-reactive protein; PCT, procalcitonin; Ab, albumin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transpeptidase; ALP, alkaline phosphatase; TB, total bilirubin; DB, direct bilirubin.

Table 2. Prognosis and stricture
	ENBD(N = 40)	STENT(N = 9)	p	Binary logistic regression
Recovery	28(70%)	8(88.9%)	0.412	0.292
Biliary stricture	9(28)	2(7)	0.635	0.890
ENBD, endoscopic nasobiliary drainage

The ENBD group had an average age of 49.83 ± 10.253 years old, significantly younger than the stent group, which had an average age of 51.56 ± 7.299 years (p = 0.000). In terms of gender distribution, the ENBD group comprised 87.5% males, while the stent group had 77.8% male patients.

Hepatocellular carcinoma was the cause in 45.0% of the ENBD group and 55.6% of the stent group. Decompensated cirrhosis was observed in 30.0% of the ENBD group compared to 22.2% in the stent group. Acute-on-chronic liver failure accounted for 10% in the ENBD group and 11.1% in the stent group. Acute liver failure was less common in the ENBD group (2.5%) compared to the stent group (11.1%). Other causes were noted in 12.5% of the ENBD group, with no cases in the stent group.

Incidence of fever was almost similar in both groups, with 35% in the ENBD group and 33.3% in the stent group. Laboratory values showed a higher WBC count in the stent group (9.1778 ± 7.23356) compared to the ENBD group (7.5769 ± 4.10888), p = 0.030. TB and DB levels were significantly higher in the stent group (p = 0.000 for TB and p = 0.001 for DB), suggesting more severe liver function impairment in this group. No significant differences were noted in C-reactive protein (CRP), procalcitonin (PCT), albumin (Ab), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP) levels between the two groups. About 26 patients of ENBD group underwent secondary operation within 1 month for stent placement. And leakage recurred in 3 of them. Dualistic Logistic Regression Model was further used to confirm the significance of types of operation in patients’ prognosis and post-operation biliary stricture, which also came out negative (p = 0.392 and 0.890).

T-tube placement is a risk factor of bile leakage. 10% of the patients in ENBD group and 22.2% in the stent group were underwent T-tube placement. Fisher's exact test was taken as only one of the stent group was failed to reconvey from leakage, and the p = 0.412 was more then 0.05, showing no significant difference between two groups.

Patients died or underwent biliary surgery in 6 months after transplantation was not involved in the analysis of biliary stricture. 3 patients took biliary surgery due to failure of treatment, 11 patients died due to infection and graft failure. Finally, 9 patients in ERCP group and 2 patients in stent group result biliary stricture, 17 patients in ERCP group and 7 patients in stent group were not. Fisher's exact test was taken, resulting no significant difference in biliary stricture between two groups (p = 1.0). Further, binary logistic regression was also taken, showing no significant difference between two groups, p = 0.292 for recovery and p = 0.890 for biliary stricture. These results were showed in table 2.

In conclusion, though our study highlights significant differences in age, WBC, TB, and DB levels between the ENBD and stent groups, there was no significant difference in prognosis and post-operation biliary stricture.

The bile leakage can be a postoperative complication such as gallbladder removal or liver transplantation, or damage to the bile ducts and biliary system¹⁰. Around 2.7% of the deceased donor liver transplantation was suffered bile leakage after surgery, which rises over 10% of patients undergoing liver transplantation^10,11. The rate of bile leakage can be much higher in patients with cholangiojejunostomy then the conventional. Endoscopic techniques are recommended as first line treatment of biliary complications after liver transplantation with a success rate of 70–100%¹². However, ERCP was limited in patients after cholangiojejunostomy, especially with Rouxen-Y gastric bypass¹³. Endoscopic ultrasound (EUS) or endoscopic ultrasound-directed transgastric ERCP (EDGE) can help overcome the challenge of cholangiojejunostomy, However, it is a double-step technique, only 40% patients completed conventional ERCP during the index procedure. And it’s also combined with 17% metal stent dislodged. Bile leakage in patients after LT is always followed by infection, immune dysfunction and delayed wound healing. It’s difficult to build a reliable and long-term trace to ensure the success rate at the first attempt. And failed invasion operation would significantly increase the risk of gastrointestinal perforation.

There much research has confirmed the important role of Endoscopic treatment in bile leakage after LT, but little compared the difference of stent and ENBD. Stents provide a long-term solution and are less invasive compared to surgical options. They are often left in place for several weeks to months to ensure healing. Compared to ENBD, stents can provide internal biliary support, which help prevent bile duct stenosis. Covered retrievable metal stent and plastic ones are alternative according to site, size of fistula, infection status and economical support. Covered retrievable metal stent are self-expanding, which can expand to a larger diameter and provide better drainage. It’s more durable and are less likely to become occluded over time compared to plastic stents. However, stents are typically placed in the common bile ducts, which may be ineffective for bile leakage at the liver section in LDLT, unless across the leak site¹¹, when plastic ones can be placed in the hepatic ducts. Due to the smaller diameter, multiple plastic stents are recommended to prevent stenosis of bile ducts in long terms¹⁴. Though there was single-center experience reported that endoscopic retrograde biliary drainage by plastic stents contains same outcomes and post-surgery infection compared to ENBD¹⁵, stents seem to suffer higher rate and longer duration of fever. Stents placement procedure bring damage to the epithelium that allow a conduit for bacteria to enter. And stents could also be obstructed and blocked by bacterial biofilm and biliary sludge, leading to delayed infection and re-operation^16,17.

ENBD allows for the direct external drainage of bile, which can be beneficial in managing the leak and in monitoring the volume and nature of the bile for diagnostic and therapeutic purposes. However, ENBD is temporary and can be uncomfortable for the patient due to the tube's passage through the nose. It also requires careful maintenance of the external drainage system and keeping water electrolyte balance. Though ENBD alone can rapidly cure postoperative bile leakage after hepatectomy without bilioenteric anastomosis¹⁸, for patients after liver transplantation, it’s used to followed by stent placement to avoid delayed bile duct stenosis in our center.

Thus, ENBD was much recommended for patients with biliary infections while stents placement was supported in patients with risk of bile duct stenosis. Unfortunately, it's difficult to figure out whether the patients after LT suffered cholangitis. Bacteriological sampling through blood cultures and drainage fluid with bile cultures can help determine the pathogenic bacterium of most cholangitis, which mainly are Escherichia coli and Klebsiella spp.¹⁹ However, the biliary colonizing bacteria would mix it²⁰. Risk factors of post-operative biliary stricture including biliary or vascular anatomical variants, local inflammation, and poor surgical expertise²¹.

There were several limitations in this research. First, we hadn’t assessed the severity degree of bile leakage of patients. And ENBD progress contains less damage, faster and can cooperated with external negative pressure device, thus serious patients tend to receive ENBD rather than stent. Secondly, it’s a retrospective study, due to the data deficiency of recovery days after operation, it’s difficult to compare the recovery period of two groups. Further, the sample size is small, more date would be required to verify the results.

In conclusion, this study showed that both stent placement and ENBD are recommended for treating bile leakage after liver transplantation, as they exhibit similar efficacy and prognosis.

ENBD Endoscopic nasobiliary drainage

WBC White blood cell count

TB Total bilirubin

DB Direct bilirubin

ERCP Endoscopic retrograde cholangiopancreatography

CRP C-reactive protein

PCT Procalcitonin

Ab Albumin

AST Aspartate aminotransferase

ALT Alanine aminotransferase

GGT Gamma-glutamyl transpeptidase

ALP Alkaline phosphatase

EUS Endoscopic ultrasound

EDGE Endoscopic ultrasound-directed transgastric ERCP

Acknowledgements

Not applicable.

Disclosure

The authors declared no confict of interest

Authors’ contribution

GYJ collected the data, performed statistical analysis, drafted the manuscript. CZT participated in the data collection. LQY contributed to study concept and design, checked the data and revised the manuscript. All authors have read and approved the final manuscript.

Funding

None.

Data Availability

The datasets generated and/or analysed during the current study are not publicly available due to protect the privacy of the patient but are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

This research was approved by the “Clinical Trial Ethics Review Committee of Shulan (Hangzhou) Hospital” (No. KY2023063) and all methods were performed in accordance with the relevant guidelines and regulations. Consent to participate was waived due to retrospective design of this study by the “Clinical Trial Ethics Review Committee of Shulan (Hangzhou) Hospital”.

Consent for publication

Not applicable.

Competing interests

No potential conflict of interest relevant to this article was reported.

Kochhar G, Parungao JM, Hanouneh IA, Parsi MA. Biliary complications following liver transplantation. World J Gastroenterol 2013;19:2841-2846.
Jung DH, Ikegami T, Balci D, Bhangui P. Biliary reconstruction and complications in living donor liver transplantation. Int J Surg 2020;82s:138-144.
Thuluvath PJ, Pfau PR, Kimmey MB, Ginsberg GG. Biliary complications after liver transplantation: the role of endoscopy. Endoscopy 2005;37:857-863.
Londoño MC, Balderramo D, Cárdenas A. Management of biliary complications after orthotopic liver transplantation: the role of endoscopy. World J Gastroenterol 2008;14:493-497.
Lisotti A, Fusaroli P, Caletti G. Role of endoscopy in the conservative management of biliary complications after deceased donor liver transplantation. World J Hepatol 2015;7:2927-2932.
Larghi A, Tringali A, Rimbaş M, et al. Endoscopic Management of Benign Biliary Strictures After Liver Transplantation. Liver Transpl 2019;25:323-335.
Chon HK, Shin EJ, Kim SH. The Need for a Better-Designed Study of the Outcomes of Endoscopic Management of Bile Leak. Clin Endosc 2020;53:633-635.
Liao JZ, Zhao Q, Qin H, et al. Endoscopic diagnosis and treatment of biliary leak in patients following liver transplantation: a prospective clinical study. Hepatobiliary Pancreat Dis Int 2007;6:29-33.
de'Angelis N, Catena F, Memeo R, et al. 2020 WSES guidelines for the detection and management of bile duct injury during cholecystectomy. World J Emerg Surg 2021;16:30.
Fang C, Yan S, Zheng S. Bile Leakage after Liver Transplantation. Open Med (Wars) 2017;12:424-429.
Morelli J, Mulcahy HE, Willner IR, et al. Endoscopic treatment of post-liver transplantation biliary leaks with stent placement across the leak site. Gastrointest Endosc 2001;54:471-475.
Magro B, Tacelli M, Mazzola A, Conti F, Celsa C. Biliary complications after liver transplantation: current perspectives and future strategies. Hepatobiliary Surg Nutr 2021;10:76-92.
Tyberg A, Nieto J, Salgado S, et al. Endoscopic Ultrasound (EUS)-Directed Transgastric Endoscopic Retrograde Cholangiopancreatography or EUS: Mid-Term Analysis of an Emerging Procedure. Clin Endosc 2017;50:185-190.
Tabibian JH, Asham EH, Goldstein L, et al. Endoscopic treatment with multiple stents for post-liver-transplantation nonanastomotic biliary strictures. Gastrointest Endosc 2009;69:1236-1243.
Park SY, Park CH, Cho SB, et al. The safety and effectiveness of endoscopic biliary decompression by plastic stent placement in acute suppurative cholangitis compared with nasobiliary drainage. Gastrointest Endosc 2008;68:1076-1080.
Johnson KD, Perisetti A, Tharian B, et al. Endoscopic Retrograde Cholangiopancreatography-Related Complications and Their Management Strategies: A "Scoping" Literature Review. Dig Dis Sci 2020;65:361-375.
Chandrasekhara V, Khashab MA, Muthusamy VR, et al. Adverse events associated with ERCP. Gastrointest Endosc 2017;85:32-47.
Ishii H, Ochiai T, Murayama Y, et al. Risk factors and management of postoperative bile leakage after hepatectomy without bilioenteric anastomosis. Dig Surg 2011;28:198-204.
Sokal A, Sauvanet A, Fantin B, de Lastours V. Acute cholangitis: Diagnosis and management. J Visc Surg 2019;156:515-525.
Tajeddin E, Sherafat SJ, Majidi MR, Alebouyeh M, Alizadeh AH, Zali MR. Association of diverse bacterial communities in human bile samples with biliary tract disorders: a survey using culture and polymerase chain reaction-denaturing gradient gel electrophoresis methods. Eur J Clin Microbiol Infect Dis 2016;35:1331-1339.
Cantù P, Mauro A, Cassinotti E, Boni L, Vecchi M, Penagini R. Post-operative biliary strictures. Dig Liver Dis 2020;52:1421-1427.

No competing interests reported.

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Stent placement can achieve same prognosis as endoscopic nasobiliary drainage in treatment of bile leakage after liver transplantation

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Abstract

Background

Methods

Results

Conclusion

Figures

Introduction

Materials and methods

Results

Discussion

Conclusion

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References

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