EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Key words : Donor complication, Left hepatectomy, Living donor liver transplantation

In Japan, although deceased donor liver transplant rates have been increasing since the reform of the organ transplant law in 2010, living donor liver transplant (LDLT) accounts for 95% of all liver transplants according to the latest survey.¹ In countries with limited availability of deceased donor organs, such as Japan, LDLT is commonly used.

One of the biggest disadvantages of LDLT is the risk of postoperative complications to the donor. Previous studies have reported that the most frequent postoperative complication for the donor is bile leakage, which occurs more frequently in cases of right hepatectomy (RH) than in cases of left hepatectomy (LH).^2-6 However, several recent studies have reported a similar incidence of bile leakage for RH and LH.^7-11

Most cases of postoperative bile leakage respond well to conservative therapy, such as antibiotics. However, in our experience, we have encountered some severe cases of bile leakage requiring inter-vention, such as percutaneous drainage, endoscopic retrograde biliary drainage (ERBD), or reoperation. In this study, we aimed to evaluate the risk factors for postoperative severe bile leakage requiring intervention in addition to conservative therapy and to report the characteristics of LDLT donors.

Materials and Methods

Patients
Between August 2000 and March 2017, 466 living donors underwent donor hepatectomy at Kumamoto University Hospital. Nine patients who underwent posterior sectionectomy and 4 patients aged <20 years who underwent donor surgery were excluded. The same surgical team treated and managed all reported cases.

We conducted this study in accordance with the 2013 Declaration of Helsinki and the 2018 Declaration of Istanbul. Ethical approval was obtained from the Institutional Review Board of Kumamoto University (approval No. 1826). Written informed consent was obtained from all donors.

Donor and graft selection
At our institution, donors for LDLT were selected from spouses or relatives up to the third degree of kinship (eg, parents, offspring, siblings, grand-parents, uncles, aunts). The age of the LDLT donors was limited to <70 years. If the right liver graft (RLG) was procured, the donor age was limited to ≤65 years. Routine preoperative work-up and imaging studies were performed, including dynamic com-puted tomography (drip infusion cholecysto-cholangiography). The preoperative estimated ratio of the liver remnant needed to be ≥30%, and the estimated graft-to-recipient weight ratio (GRWR) needed to be ≥0.7, as measured by a 3-dimensional image analysis system (SYNAPSE VINCENT; Fujifilm Corp). The first choice of graft was the left liver graft (LLG) when the estimated GRWR was ≥0.7; RLG was used when the preoperative estimated GRWR in the LLG was ≤0.7 and the estimated GRWR of the RLG ≥0.7 and the estimated ratio of the liver remnant after the RLG procurement was ≥30%. Some cases were exempted from this general rule, for example, if there were multiple vascular orifices that were too difficult to reconstruct in the recipient. However, anatomical variations, including the bile duct branching pattern, were not considered contraindications for graft selection unless graft procurement would adversely affect the donor’s residual liver.

Bile duct branching pattern
Branching patterns of the biliary tree of the right lobe were classified as follows: type I, typical anatomy (ie, the common hepatic duct was formed by fusion of the right and left hepatic ducts); type II, triple confluence of the right anterior segmental duct, right posterior segmental duct, and left hepatic duct into the common hepatic duct; type III, drainage of the right posterior segmental duct into the left hepatic duct; and type IV, drainage of the right posterior segmental duct into the common hepatic duct (Figure 1).

Surgical procedure
Briefly, after isolation of the hepatic pedicle, the demarcation line was confirmed by temporarily clamping the vessels on the graft side. The hepatic parenchyma was transected using an ultrasonic dissector or surgical aspirator and electrocautery, without inflow occlusion of the blood supply. Before 2005, parenchymal bleeding was controlled with bipolar forceps as a coagulation device. After 2006, the VIO Soft-Coagulation System with monopolar electrode (Erbe, Elektromedizin GmbH) was introduced. The bile duct was divided based on intraoperative cholangiography images using C-arms. In the case of LH procedures, the Spiegel lobe is generally not removed as part of the graft. After systemic administration of heparin, the hepatic artery, portal vein, and hepatic vein were divided, and the graft liver was excised. The remnant biliary stump was closed by using continuous 6-0 absorbable monofilament sutures. Cholangiography was perfor-med to ensure the absence of bile leakage and stricture. For procedures performed before 2005, a biliary drainage tube via the remnant cystic duct (C-tube) and a peritoneal drainage tube were placed. After 2005, both were determined as not useful for the prevention of bile leakage. If the drain was placed, it was removed within 1 week unless bile leakage was detected at that time. After 2006, the peritoneal drain was not routinely placed.

Statistical analyses
We expressed quantitative data as median (minimum to maximum range) and qualitative data as frequency (percentage). We analyzed categorical variables by using the X² test and analyzed continuous variables by using the Mann-Whitney U test. We used binomial logistic regression analysis to assess the associations of predictive risk factors with severe bile leakage. We considered P < .05 as statistically significant. We used IBM SPSS software version 25.0 (IBM Corp) for all statistical analyses.

Variables
The preoperative variables were age, sex, and body mass index (BMI). The operative and postoperative variables were type of hepatectomy, coagulation device, operative time, blood loss, and length of postoperative hospital stay. Bile leakage was defined as the presence of bile-stained fluid in the abdominal drain or in the intra-abdominal fluid collection. The severity of bile leakage was categorized in accor-dance with the Clavien-Dindo classification.12 Clavien-Dindo grade IIIa bile leakage required percutaneous drainage or ERBD. Clavien-Dindo grade IIIb bile leakage required repeat laparotomy. Bile leakage worse than Clavien-Dindo grade IIIa was recognized as a severe complication. Extremely severe bile leakage was defined by cases that required ERBD or reoperation.

Donor characteristics associated with severe bile leakage
Of the 453 donors, 21 (4.6%) developed severe postoperative bile leakage. The perioperative risk factors among those with severe bile leakage and those without bile leakage are shown in Table 1. The severe bile leakage group had a significantly larger proportion of male patients (P = .045) and longer postoperative hospitalization (P < .001) than the group without bile leakage. Multivariate analysis showed that male sex was significantly associated with severe bile leakage (odds ratio of 2.873; 95% CI, 1.045-7.898; P = .04) (Table 2). No significant dif-ferences in age, BMI, type of hepatectomy, coagulation device, operative time, or blood loss were found between the bile leakage group and the group without bile leakage.

Clinical features and treatment of donors with severe bile leakage
The clinical features and treatment of patients with severe bile leakage are summarized in Table 3. The median interval from donor hepatectomy to the occurrence of bile leakage was 13.0 days (range, 1-31 d). The most frequent bile leakage site was the transection surface of the hepatic parenchyma (n = 13). Although 15 cases, including the above 13 cases, improved by only percutaneous drainage (including postponement of intraoperative drain removal), 6 cases required an additional procedure, such as ERBD or reoperation. Interestingly, all 6 of these cases that required an additional procedure had undergone LH. In recipients, bile leakage requiring percutaneous drainage was observed in only 1 case. Clinical course of patients with extremely severe bile leakage Among patients with extremely severe bile leakage, ERBD was performed in 4 patients who failed to demonstrate an improvement in bile leakage with percutaneous drainage only, which was performed to decrease the pressure of the bile duct and consequent leakage. Case 7 and case 20 did not achieve effective biliary drainage and decreased percutaneous drainage fluid; therefore, they were discharged with a percutaneous drain and long-term percutaneous drainage was required for about 3 months. In case 10 and case 13, decreased percu-taneous drainage fluid was achieved inversely with sufficient biliary drainage with use of an endoscopic nasobiliary drainage (ENBD) tube. Thereafter, the ENBD tube could be removed followed by removal of the percutaneous drain within 1 month.

Reoperation was performed in 2 cases. Case 17 underwent emergency surgery with closure of the right anterior segmental duct leakage site with interrupted 6-0 absorbable monofilament sutures because of acute severe abdominal pain due to bile peritonitis. Case 19 underwent Roux-en-Y choledoc-hojejunostomy because of refractory intractable bile leakage from the complete transected right posterior superior segmental duct, which was impossible to treat by ERBD. Case 19 had a type III branching pattern (Figure 2A), and the right posterior superior segmental duct may have been injured during transection of the hepatic parenchyma near the hilar plate. Postoperative computed tomography revealed fluid collection on the hepatic transection surface (Figure 2B), and percutaneous transhepatic drainage was initiated. The right posterior superior segmental duct was not detected on endoscopic retrograde cholangiopancreatography, and a complete transec-ted type was suspected (Figure 2C). Although a few attempts at ERBD were performed, placement of the stent into the complete transected right posterior superior segmental duct was too difficult, and thus Roux-en-Y choledochojejunostomy was performed at 6 months postoperatively. The postoperative course was uneventful.

Although the type of hepatectomy was not signifi-cantly associated with severe bile leakage, extremely severe bile leakage requiring ERBD or reoperation was only observed in our patients who underwent LH. To date, no studies have reported that LH is a potential risk factor for severe bile leakage.

Many cases of bile leakage following donor hepatectomy were derived from the transection surface of the hepatic parenchyma, which could be treated by conservative management. We thought that extremely severe bile leakage was caused by injury to the major bile duct during transection of the hepatic parenchyma near the hilar plate. We hypothesize a few reasons why LH may cause intractable bile leakage. During donor surgery, the parenchymal transection lines used for RH and LH are basically the same. However, near the hilar plate, it is necessary to change direction to the left Glissonean sheath in the case of LH. At that time, the transection line could be in close proximity to the posterior segmental duct, which flows into the left hepatic duct. In addition, the psychology of wanting to avoid a small-sized graft may be affected, resulting in a far-right transection line. In our experience, the posterior segmental duct with the type III branching pattern is particularly prone to remnant bile duct injury and intractable leakage. We thought that preoperative anatomical evaluation of the branching pattern and running course of the biliary tree of the right lobe and careful transection of the hepatic parenchyma near the hilar plate would be important. However, over our study period, regardless of the type of hepatectomy, no cases of biliary stricture were observed. This may be because safety of the donor was given the highest priority when setting the dissection line in the hilar plate.

Previous studies have reported the risk factors for biliary complications, including donor age, length of donor operation, number of biliary orifices of the graft, and the techniques used to confirm the biliary anatomy before bile duct division.¹⁰ Our data suggested that male sex was significantly associated with severe bile leakage. All patients with severe bile leakage in the LH group were male. Although the exact reason is unknown, a deep and insufficient operative field due to a narrow costal arch and strong build might influence the incidence of injury to the major bile duct. For reference, after stratifying by BMI, male sex was found to be a significant risk factor for severe bile leakage in patients with BMI above 22 but not in those with BMI below 22 (data not shown).

Although previous reports have indicated no correlation between hepatic parenchymal dissection using the VIO System and postoperative bile leakage,^13-15 1 study found that the VIO System was an independent predictor of late-onset bile leakage, with the late-onset group having significantly more severe cases than the early-onset group that required invasive treatment such as abdominal paracentesis and ERBD.¹⁶ In this study, the type of coagulation device, such as the VIO System or bipolar forceps, was not significantly associated with the incidence of postoperative severe bile leakage. However, the VIO System was used for hemostasis in all cases of extremely severe bile leakage. In any case, rough hemostasis near the hilar plate should be particularly avoided.

Previous studies have reported that endoscopic management, such as ENBD and endoscopic biliary stenting, is effective for donor bile leakage.^6,17,18 However, the optimal strategy for treating patients with severe bile leakage has not yet been established. Our strategy for treating severe bile leakage is as follows. First, percutaneous drainage is indicated for patients who demonstrate little improvement in symptoms despite conservative treatment. Second, endoscopic treatment is indicated for patients in whom the amount of percutaneous drainage fluid does not decrease on the assumption of injury to the major bile duct rather than injury to the transection surface of the hepatic parenchyma. The bile leakage site can be identified by endoscopic retrograde cholangiography and can be treated by ENBD. If long-term ERBD is required, endoscopic biliary stenting can be performed. Third, surgical treatment is chosen for patients who are not able to undergo endoscopic treatment or for patients with acute or severe peritonitis due to bile.

Our study had several limitations. This was a retrospective study conducted at a single center. Moreover, the number of patients who underwent ERBD because of bile leakage was small. Therefore, accumulation of further experience and continuous improvement are necessary.

This is the first study to show that LH is a potential risk factor for injury to the major bile duct, especially the remnant biliary tree of the right lobe, followed by extremely severe bile leakage. Preoperative anato-mical evaluation of the running course of the biliary tree of the right lobe and careful transection of the hepatic parenchyma near the hilar plate are impor-tant to avoid severe bile leakage.

Volume: 23 Issue: 6 June 2025

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