Impact of intra-operative cholangiography and parenchymal resection to donor liver function in living donor liver transplantation

Feng Gao, Xiao Xu, Yang-Bo Zhu, Qiang Wei, Bin Zhou, Xiao-Yong Shen, Qi Ling, Hai-Yang Xie, Jian Wu, Wei-Lin Wang and Shu-Sen Zheng

Hangzhou, China

Impact of intra-operative cholangiography and parenchymal resection to donor liver function in living donor liver transplantation

Feng Gao, Xiao Xu, Yang-Bo Zhu, Qiang Wei, Bin Zhou, Xiao-Yong Shen, Qi Ling, Hai-Yang Xie, Jian Wu, Wei-Lin Wang and Shu-Sen Zheng

Hangzhou, China

BACKGROUND:Living donor liver transplantation (LDLT) has been widely accepted over the past decade, and hepatic dysfunction often occurs in the donor in the early stage after liver donation. The present study aimed to evaluate the effect of intraoperative cholangiography (IOC) and parenchymal resection on liver function of donors in LDLT, and to assess the role of IOC in influencing the biliary complications and improving the overall outcome.

METHODS:Data from 40 patients who had donated their right lobes for LDLT were analyzed. Total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (GGT) at different time points were compared, and the follow-up data and the biliary complications were also analyzed.

RESULTS:The ALT and AST values were significantly increased after IOC (P＜0.001) and parenchymal resection (P＜0.001). However, the median values of TB, ALP and GGT were not significantly influenced by IOC (P＞0.05) or parenchymal resection (P＞0.05). The biochemical changes caused by IOC or parenchymal resection were not correlated with the degree of post-operative liver injury or the recovery of liver function. The liver functions of the donors after operation were stable, and none of the donors suffered from biliary stenosis or leakage during the follow-up.

CONCLUSIONS:IOC and parenchymal resection may induce a transient increase in liver enzymes of donors in LDLT, but do not affect the recovery of liver function after operation. Moreover, the routine IOC is helpful to clarify the division line of the hepatic duct, thus reducing the biliary complication rate.

(Hepatobiliary Pancreat Dis Int 2014;13:259-263)

living donor liver transplantation;intra-operative;

liver imaging;

liver function;

hepatectomy

Introduction

Living donor liver transplantation (LDLT) has been widely accepted over the past decade.[1-3]The safety of the living liver donor, during and after the surgical procedure, is of paramount importance because the procedure is performed on a healthy individual. In spite of careful quality selection of liver donor, hepatic dysfunction in the donor after donating a big portion of his/her liver often occurs.[4-7]Thus several methods have been introduced for the safety of liver donor. The use of ultrasonography and intra-operative cholangiography (IOC) to identify hepatic veins, portal structures and biliary anatomy enables surgeons to define the plane of dissection. Various modifications of electrocautery (unipolar or bipolar) and ultrasonic harmonic scalpels have been made to reduce blood loss and operative time. However, heat and mechanic injury during hepatectomy and the loss of liver volume may be worrisome for the donor safety in LDLT.[6-8]In this study, we aimed to 1) determine the dynamic changes of liver function caused by IOC and parenchymal resection; 2) assess its influence on the recovery of liver function after operation; and 3) evaluate the effect of IOC onthe reduction of the biliary complication rate and the improvement of the overall results.

Methods

In this retrospective study, 40 donors (36 men and 4 women) aged from 27 to 65 years (mean 44.6) who had donated their right lobes (not including the middle hepatic vein) for LDLT between January and October 2009 in our hospital were enrolled. Donor hepatectomy was performed by the same surgical team. There were three rounds of IOC during the donor operation through a tube inserted into the cystic duct after cholecystectomy 15 mL meglumine diatrizoate (2:1 diluted with normal saline) each round. The first IOC was performed to examine the variance of the biliary tract. Hepatic resections were performed with a Cavitronic Ultrasound Surgical Aspirator (CUSA) (Valleylab Inc., Boulder, CO, USA), unipolar electrocautery, Ligaclips, prolene sutures, and ties but without the use of the Pringle maneuver. The division line was determined by the transient obliteration of inflow from the right-sided hepatic arterial and right-sided portal venous flow. The second IOC was performed immediately after the parenchymal division to determine the proper cut line of the right hepatic duct. The liver lobe was separated after the right hepatic vein, right hepatic artery, and right portal vein were dissected. The third IOC was performed before the abdominal closure to examine whether there was the biliary stenosis or leakage.

All donors were examined for total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (GGT) pre-operation, pre-IOC, post-IOC (30 min) (30 min after the first IOC), pre-hepatectomy, post-parenchymal resection and post-operation. In order to determine the biochemical changes of intra-operation, delta-IOC and delta-hepatectomy values were recorded to reveal the difference between post-IOC (30 min) to pre-IOC in the first round and post-parenchymal resection to pre-hepatectomy, respectively. Meanwhile, the difference from 7-day to 1-day post-operation was taken as a delta-operative value for the recovery of postoperative liver function. All the donors for LDLT were routinely followed up at the outpatient clinic, and the follow-up time was defined as the length of time from surgery to the last follow-up (November, 2013) or death.

Informed consent was obtained from all the donors. Each organ donation was approved by the Institutional Review Board, First Affiliated Hospital, Zhejiang University School of Medicine and in accordance with the guidelines of the Ethics Committee of the hospital, the regulations of the Chinese Government, and theDeclaration of Helsinki.

Statistical analysis

SPSS software (SPSS Inc., version 11.0, Chicago, IL, USA) was used for all statistical analyses. All quantitative results were presented as mean ±standard deviation and compared by the Student'sttest or Mann-WhitneyUtest. Correlations were calculated with Pearson's productmoment correlation coefficient analysis. APvalue of less than 0.05 was considered statistically significant.

Results

General status of donors during operation

All the donors experienced a smooth operative procedure. Their liver lobes were separated after the right hepatic vein, right hepatic artery, and right portal vein were identified and dissected. Blood samples were taken at each period of operation. The estimated average blood loss was ＜300 mL, and none of the donors required a blood transfusion or suffered complication related surgery.

Biochemical changes during operation

Biochemical changes of the donors in each period of operation are shown in Fig. 1 and Table. The ALT and AST values were significantly increased after the first IOC, with the serum level ranging from 21.08±10.96 U/L to 33.32±15.24 U/L, 23.19±13.06 U/L to 37.38±17.28 U/L, respectively (P＜0.001). The serum ALT and AST values were further increased significantly after parenchymal resection from 40.92±16.50 U/L to 51.62±20.51 U/ L, 47.74±19.09 U/L to 60.08±25.88 U/L, respectively (P＜0.001). TB, ALP and GGT values were not affected significantly by IOC or parenchymal resection (allP＞0.05).

Fig. 1.Serum biochemical changes in each period of operation.

Table.Serum biochemical changes in each period of operation

Fig. 2.The liver enzyme changes caused by IOC (delta-IOC values) are not correlated with the degree of post-operative liver injury or the recovery of liver function (delta-operative values) (P＞0.05).

Fig. 3.The liver enzyme changes during parenchymal resection (delta-hepatectomy values) are not correlated with the degree of postoperative liver injury or the recovery of liver function (delta-operative values) (P＞0.05).

Biochemical changes after operation

The serum biochemical values in all donors decreased gradually after operation, and there were no complications of the biliary tract. The biochemical changes caused by IOC (delta-IOC values) or parenchymal resection (deltahepatectomy values) were not correlated with the degree of post-operative liver injury or the recovery of liver function (delta-operative values) (P＞0.05) (Figs. 2 and 3). Follow-up revealed that the liver function of the donors was stable, and none of them suffered from biliary stenosis or leakage.

Discussion

With the advances of surgical techniques, LDLT has become a generally accepted option to treat patients with end-stage liver disease and increase the availability of grafts for transplantation.[9]LDLT is characterized by an augmented transplant organ pool and the ability to perform an elective operation with a graft in optimal conditions. The outcomes of LDLT and deceased donor liver transplantation (DDLT) were comparable.[9,10]And an accurate pre-surgical assessment of anatomic variations in biliary, vascular and hepatic morphologies is helpful to reduce the complication risks.[11,12]However, pre-operative endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) is too invasive for healthy donors to perform and may cause complications, while magnetic resonance cholangiopancreatography (MRCP) is not accurate enough to estimate the small bile duct.[13,14]IOC, currently as the best method to estimate the variance of biliary tract in donor hepatectomy, has been accepted in LDLT by more and more centers.[6,15]

Our center took the lead in IOC application in 2001, and now IOC is performed routinely in each donor to examine the variance of the biliary tract, and determine the proper division line for the hepatic duct, while the third routine IOC is performed to confirm whether there was a biliary stenosis or leakage after parenchymal resection. The routine use of IOC has improved the success rate of operation and reduced the incidence of biliary complications despite of the transient hepatic dysfunction in our study. It is well known that the increase of ALT and AST values represent the acute injury of hepatic cells. IOC-induced liver injury might result from the toxicity of contrast medium; while the milder fluctuation of TB indicated that the liver function was well compensated.[6-8]The remnant liver volume was sufficient to help the liver to regain its function in early stage after operation.

Shindoh et al[16]reported that gentlein situmanipulation with the destruction of Kupffer cells produced a significant effect on hepatic injury in a rat model. During parenchymal handling and separation, cell membrane damage released liver enzymes into the circulation.[17]The techniques for hepatectomy have been dramatically improved in the past decade. At present, CUSA and electric coagulation, as the most common methods, have been adopted in more and more centers. These techniques quicken the procedure of hepatectomy and attenuate liver injury.[18-22]However, they may also lead to electrical and heat injuries.[19,20,23]Our patients had a transient increase of liver enzymes after parenchymal resection; however, the liver function was well compensated and the damaged liver was recovered in the early stage after operation. We therefore consider CUSA and electric coagulation efficient in hepatectomy for LDLT.

In this study, the AST and ALT levels continued to increase after the parenchymal resection, which might result from the compound effects of IOC, parenchymal resection or any other intraoperative factors. However, the elevated liver enzymes caused by IOC (delta-IOC values) or parenchymal resection (delta-hepatectomy values) were decreased in a short period after operation, and were not correlated with the degree of postoperative liver injury or the recovery of liver function (delta-operative values). The liver injury caused by IOC or parenchymal resection during the operation was mild and the damaged hepatic cells restored their function within a short period.

Biliary complications such as biliary stenosis and leakage are the main complications of biliary reconstruction that constitutes one of the most troublesome aspects of right lobe LDLT. Biliary complications account for 9% to 67% of LDLT cases.[6,24-26]Our routine IOC application in donor operation allowed us to obtain clear images of the biliary duct and thus to separate the bile duct more accurately and to prevent biliary complications. Indeed, there was no biliary complication in our 40 donors. Our study demonstrated that IOC application significantly improved the overall outcome of LDLT.

In conclusion, IOC and parenchymal resection caused a transient increase of liver enzymes, but did not affect the recovery of liver function after operation. IOC techniques allowed us to obtain clear images of the biliary duct, to separate the bile duct more accurately and therefore, to prevent biliary complication and finally, to foster the recovery of the donors after LDLT.

Contributors:GF and XX contributed equally to this work. GF and XX proposed the study. GF, ZYB and WQ performed research and wrote the first draft. ZYB, WQ, ZB, SXY, LQ and XHY collected and analyzed the data. XX, WJ, WWL and ZSS reviewed the manuscript.All authors contributed to the design and interpretation of the study and to further drafts. ZSS is the guarantor.

Funding:This study was supported by grants from the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81121002), Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents (2012-236), Zhejiang Provincial Education Department Project (Y201018972), and Zhejiang Provincial Natural Science Foundation of China (LQ12H03002).

Ethical approval:Informed consent was obtained from all donors. Each organ donation was approved by the Institutional Review Board, First Affiliated Hospital, Zhejiang University School of Medicine, and was strictly in accordance with the guidelines of the Ethics Committee of the hospital, the current regulation of the Chinese Government, and theDeclaration of Helsinki.

Competing interest:No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

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Received December 5, 2013

Accepted after revision March 10, 2014

Author Affiliations: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery (Gao F, Xu X, Zhu YB, Wei Q, Ling Q, Wu J, Wang WL and Zheng SS), Department of Radiology (Shen XY), Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Gao F, Xu X, Ling Q, Xie HY, Wu J, Wang WL and Zheng SS), Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health (Xie HY and Zheng SS), First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; and Department of General Surgery, The Second Hospital of Ningbo City, Ningbo 315502, China (Zhou B)

Shu-Sen Zheng, MD, PhD, FACS, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou 310003, China (Tel/Fax: 86-571-87236567; Email: zyzss@zju.edu.cn)

? 2014, Hepatobiliary Pancreat Dis Int. All rights reserved.

10.1016/S1499-3872(14)60252-6