Venous Outflow Reconstruction Using an Expanded Polytetrafluoroethylene Vascular Graft in Living-Donor Liver Transplant: A Single-Center Experience

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1 ARTICLe Venous Outflow Reconstruction Using an Expanded Polytetrafluoroethylene Vascular Graft in Living-Donor Liver Transplant: A Single-Center Experience Chia-Yu Lai, 1 Shao-Min Han, 2 Yi-Ju Chen, 1 Shou-Sen Huang, 1 Cheng-Chung Wu, 1 Shao-Bin Cheng 1,3 Abstract Objectives: Limited studies have focused on the feasibility and technical requirements of using expanded polytetrafluoroethylene vessel grafts for venous outflow reconstruction in a living-donor liver transplant using right liver grafts without the middle hepatic vein. Materials and Methods: Between August 2007 and December 2012, thirty-two patients who had received an expanded polytetrafluoroethylene vascular graft for outflow reconstruction during a living-donor liver transplant using a right liver graft without the middle hepatic vein were retrospectively reviewed. Preoperative and operative data, complications, and mortality were compared among patients who received the expanded polytetrafluoroethylene grafts with individual anastomoses (n = 18) or confluent anastomoses (n =14). Results: For patients who had received an individual and a confluent anastomosis, graft reconstruction time was 25.8 and 14.9 minutes (P =.000). No cases of graft occlusion occurred during first 72 hours after surgery. Although 5 patients (15.6%) died within 90 days, none of the deaths were associated with the vascular grafts. Operative mortality was not statistically different between patients who had From the 1 Division of General Surgery and Liver Transplantation, Department of Surgery, Taichung Veterans General Hospital; the 2 Division of Hematology/ Medical Oncology, Department of Medicine, Taichung Veterans General Hospital; and the 3 Faculty of Medicine, Chung-Shan Medical University, Taichung, Taiwan Acknowledgements: Chia-Yu Lai and Shao-Min Han equally contributed to this manuscript. The authors have no conflicts of interest to disclose, and there was no funding for this study. Special thanks to Chieh-Lin Jerry Teng for advice on composition. Corresponding author: Shao-Bin Cheng, MD, Division of General Surgery, Department of Surgery, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, Taiwan Phone: ext Fax: sbc@vghtc.gov.tw Experimental and Clinical Transplantation (2014) 3: received an individual anastomosis (3/18, 16.7%) and those who had received a confluent anastomosis (2/14, 14.3%) (P = 1.000). Conclusions: Individual and confluent anastomoses using an expanded polytetrafluoroethylene vascular graft is a feasible approach to venous outflow reconstruction in a living-donor liver transplant using right liver grafts without the middle hepatic vein. Key words: Liver transplant, Expanded polytetrafluoroethylene, Occlusion, Anastomosis Introduction A liver transplant may be the only curative therapy for various end-stage hepatic diseases including viral or autoimmune hepatitis, hepatic malignancies, cholestatic liver diseases, alcoholic liver cirrhosis, metabolic liver diseases, fulminant hepatic failure, and Budd-Chiari syndrome. 1 With more patients awaiting a liver transplant, the shortage of deceased-donor grafts has become a worldwide issue. 2 Living-donor grafts were introduced as an alternative graft source in the 1990s to overcome this shortage 3 and it is now in widespread use. The balance between an adequate liver graft size and donor safety is one of the most critical issues in a living-donor liver transplant. A study conducted by Fan and associates 4 showed that recipients implanted with an extended right lobe liver graft had better postoperative hepatic and renal function and reduced hospital mortality than did those patients who had received a right lobe liver graft without the middle hepatic vein (MHV). However, the risk of transient postoperative liver dysfunction is increased in donors who undergo an extended right lobectomy. Therefore, to protect the safety of living donors, right liver grafts Copyright Başkent University 2014 Printed in Turkey. All Rights Reserved. DOI: /ect

2 242 Chia-Yu Lai et al /Experimental and Clinical Transplantation (2014) 3: Exp Clin Transplant without the MHV are used more commonly. 5 The absence of the MHV may result in right anterior sector congestion and thereby, has a dismal outcome. To minimize this complication in recipients who receive right liver grafts without the MHV, numerous approaches have been proposed to reconstruct the outflow. One of these approaches is to establish the drainage conduit with a cryopreserved cadaveric allograft, but the unreliable sources of cryopreserved cadaveric venous grafts are problematic. 6 The recovery of autologous grafts from recanalized native portal veins, hepatic veins, inferior mesentery veins, and umbilical veins is another option, 7 but the unpredictable quality of these autologous vessels and the additional procedures for graft recovery are major concerns. Another option is to use an artificial material, instead of cryopreserved cadaveric and recovered autologous venous grafts. Regarding possible artificial materials for reconstructing venous drainage in a living-donor liver transplant, Yi and associates 8 report using an expanded polytetrafluoroethylene (eptfe) vessel grafts in 26 recipients who received a right liver graft without the MHV. This previous study not only demonstrates the importance of venous outflow reconstruction in a living-donor liver transplant, but also reveals the feasibility of eptfe vascular graft. However, few studies have examined the use of eptfe graft in this type of procedure. Therefore, we conducted a retrospective study to investigate the technical aspects of using eptfe grafts for venous outflow reconstruction in living-donor liver transplants using a right liver graft without the MHV. We used 2 types of anastomoses (individual and confluent) for bridging the hepatic veins of the grafted liver to the recipient s inferior vena cava. criteria and were enrolled in this study. This study was approved by the institutional review board of Taichung Veterans General Hospital, Taiwan. All protocols conformed with the ethical guidelines of the 1975 Helsinki Declaration. venous outflow reconstruction procedure and patency evaluation The venous outflow was reconstructed using an eptfe vascular graft with either individual or confluent anastomosis. The details of each type of anastomosis are shown in Figure 1A and 1B. During the operation, an ultrasonography was routinely performed to identify the patency of the intraparenchymal hepatic veins. A parenchymal transection was performed with a Cavitron Ultrasonic Surgical Aspirator (Cooper Medical Corp; Santa Clara, CA, USA). All MHV branches larger than 5 mm in diameter for segments 5 and 8 (V5 and V8), and the IRHV were preserved and clipped with a plastic clip (Weck Hem-o-Lok Polymer Locking Ligation System; Teleflex Medical, Research Triangle Park, NC, USA) on the graft side. The clipped V5, V8, or IRHV was anastomosed to the eptfe graft (GORE-TEX Stretch Vascular Graft, 4 mm 7 mm; GORE-TEX, W. L. Gore & Associates, Inc., Newark, DE, USA) with a continuous 7-0 Prolene suture (Ethicon PROLENE 7-0; Amtec Medical, Antrim, UK) in an end-to-end fashion for individual anastomosis or an end-to-side fashion for confluent anastomosis after the donor hepatectomy was completed. When the grafted liver was re-perfused, the eptfe vascular graft was anastomosed to the recipient s common trunk of the middle and left hepatic vein or to the inferior vena cava with a continuous 7-0 Prolene suture. Figure 1A. Individual Anastomosis Materials and Methods Patients From August 2007 to December 2012, patients who received a living-donor liver transplant using a right liver graft without the MHV for various end-stage liver diseases were retrospectively reviewed. All patients whose anterior sector outflow branch (V5 and V8) in the MHV territory or inferior right hepatic vein (IRHV) was larger than 5 mm in diameter for reconstructing the venous outflow were given a synthetic eptfe graft. Finally, 32 patients met the Branches of the middle hepatic vein from segment 5 (V5) and the inferior right hepatic vein (IRHV) were preserved and reconstructed with an expanded polytetrafluoroethylene (eptfe) vascular graft to the inferior vena cava (IVC) in an end-to-end pattern.

3 Chia-Yu Lai et al /Experimental and Clinical Transplantation (2014) 3: Figure 1B. Confluent Anastomosis Both V5 and V8 were reconstructed with the eptfe vascular graft in an end-to-end pattern. This vascular graft was then anastomosed to another eptfe vascular graft in an end-to-side pattern, draining to the IVC. Abbreviations: eptfe, expanded polytetrafluoroethylene; IVC, inferior vena cava; RHV, right hepatic vein To evaluate the patency of the grafted vessels, Doppler ultrasound was performed within 6 hours after the operation and was repeated every 24 hours for 72 hours. Neither antiplatelet agents nor anticoagulants were prescribed after liver transplant. Statistical analyses The statistical analyses was performed with the chi-square and the Mann-Whitney U tests, using SPSS software (SPSS: An IBM Company, version 20, IBM Corporation, Armonk, NY, USA). Statistical significance was set at P <.05. Results The patients clinical characteristics are shown in Table 1. The mean age (standard deviation) of the patients was 48.0 ± 12.2 years. Further, 75% were men (24/32) and 25% were women (8/32). Viral hepatitisrelated cirrhosis was the leading underlying disease, accounting for 87.5% (28/32) of the study cohort. Ten of these 28 patients (35.7%) had concurrent hepatocellular carcinoma. The mean body mass index and model for end-stage liver disease scores were 25.3 ± 4.8 and 23.2 ± During the study, 18 and 14 eptfe vascular grafts for venous outflow were reconstructed with an individual anastomosis or a confluent anastomosis. The age, sex, and body mass indexes were not significantly different between patients who received an individual and those who received a confluent anastomosis for venous outflow reconstruction (Table 1). Hepatitis B-associated liver cirrhosis (n=22, 68.8%) and hepatitis C-associated liver cirrhosis (n=5, 15.6%) were the most common indications for a living-donor liver transplant. Moreover, 65.6% of the patients (21/32) had Child- Pugh C cirrhosis. However, the severity of the underlying diseases was not significantly different between patients who received an individual anastomosis and those who received a confluent anastomosis. Table 1. Patients Clinical Characteristics Compared By Type of Anastomosis Used For Venous Reconstruction All Patients Individual Confluent P Value (n=32) (n=18) (n=14) Sex (n, %).053 Male 24 (75) 11 (61.1) 13 (92.9) Female 8 (25) 7 (38.9) 1 (7.1) Age (y, mean ± SD) 48.0 ± ± ± Body mass index (kg/m 2, mean ± SD) 25.3 ± ± ± MELD score (mean ± SD) 23.2 ± ± ± Child-Pugh Classification (n, %).679 A 3 (9.4) 1 (5.6) 2 (14.3) B 8 (25.0) 5 (27.8) 3 (21.4) C 21 (65.6) 12 (66.7) 9 (64.3) Underlying diseases.253 HBV-related cirrhosis HCV-related cirrhosis HBV + HCV-related cirrhosis Fulminant hepatic failure Biliary atresia Primary biliary cirrhosis Concurrent HCC (n, %) 10 (31.3) 4 (22.2) 6 (42.9).267 Abbreviations: HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; MELD, model for end-stage liver disease Comparison of operation parameters between the study groups The average graft weight was grams among all recipients (Table 2), and was and grams for patients who received an individual anastomosis and a confluent anastomosis (P =.955; Table 2). The mean graft/recipient weight ratio (GRWR) in all recipients was 1.03%. Moreover, the GRWR was Table 2. Operative Data Compared By Types of Anastomosis All Patients Individual Confluent P Value (n=32) (n=18) (n=14) Graft weight (g) ± ± ± GRWR (%) 1.03 ± ± ± Operation time (min) ± ± ± Anhepatic time (min) 51.8 ± ± ± Bench table time (min) 24.8 ± ± ± Cold ischemic time (min) 73.1 ± ± ± eptfe reconstruction time (min) 21.0 ± ± ± 0.6 <.001 Abbreviations: eptfe, expanded polytetrafluoroethylene; GRWR, graft/recipient s body weight ratio Data are presented as means ± SD and were compared among patients receiving individual or confluent anastomosis.

4 244 Chia-Yu Lai et al /Experimental and Clinical Transplantation (2014) 3: Exp Clin Transplant 1.03% and 1.02% in patients who received an individual anastomosis or a confluent anastomosis (P =.896). The overall operative time (P =.107), the time for the anhepatic phase (P =.722), and the time for cold ischemia (P =.135) were not significantly different between the groups. The bench table time was 25.2 and 24.2 minutes for patients who received an individual anastomosis and a confluent anastomosis (P =.896). However, the eptfe reconstruction time was significantly lower in patients who received a confluent anastomosis compared with those who received an individual anastomosis (25.8 vs 14.9 min; P =.000). Patency of the venous conduit and patient survival No eptfe vascular graft occlusions were observed in any recipients during the first 72 hours after the operation. Regarding patient mortality, 5 patients (15.6%) died within 90 days after the living donor liver transplant (Table 3). None of the deaths were associated with the eptfe vascular grafts. The operative mortality rate was not statistically different between patients who received an individual anastomosis (3/18, 16.67%) and those patients who received a confluent anastomosis (2/14, 14.29%) (P = 1.000). One hundred eighty days after the liver transplant, 26 patients (81.3%) were alive. Of these 26 patients, none of them had serum alanine aminotransferase more than twice the upper limit. Table 3. Clinical Characteristics of Patients With Operation-Associated Mortality No. Diagnosis MELD GRWR Anastomosis Cause of Death Score Type 1 HBV Confluent Liver failure 2 HCV/HCC Individual AMI 3 HBV Individual Fungemia 4 HBV Individual ARDS 5 HBV Confluent CMV infection Abbreviations: AMI, acute myocardial infarction; ARDS, acute respiratory distress syndrome; CMV, cytomegalovirus; GRWR, graft/recipient weight ratio; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; MELD, model for end-stage liver disease Discussion The increasing use of living grafts has been alleviating the global shortage of organ sources for liver transplant since the 1990s. Lo and associates 9 proposed that using extended right liver grafts with the MHV was superior when performing a livingdonor liver transplant. However, donors must be free of steatosis, and the residual liver volume must be greater than 30%. 10 However, the incidence of transient postoperative liver dysfunction and prolonged hospital stay is significantly increased. 11 Because of these clinical limitations, a right liver graft without the MHV is adopted with greater frequency. Outflow reconstructions have become a key issue for postoperative grafted liver function and avoiding catastrophic complications in patients who undergo this intervention. 12,13 We confirmed the feasibility of using an eptfe as a vascular graft for venous outflow reconstruction in a living-donor liver transplant using a right liver graft without the MHV. In our study, no eptfe vascular graft occlusions were observed during the first 72 hours after a liver transplant. This result is comparable to the study of Pomposselli and associates, 14 which compared the early patency rates between autologous, cryopreserved cadaveric, and eptfe grafts for venous drainage reconstruction in a liver transplant. This study showed that the early patency rates among these 3 types of graft were not significantly different, suggesting the eptfe graft can be an acceptable alternative. In our study cohort, however, comparisons of graft patency between autologous, cryopreserved cadaveric, and eptfe grafts were not analyzed because autologous and cryopreserved vascular grafts are not routinely used in our clinical practice. In Taiwan, cryopreserved vessel grafts are limited because available donors are hard to find. Additionally, the quality of autologous vascular grafts from patients who require a liver transplant usually are not satisfied. Extending on the studies of Pomposselli and associates and Yi and associates, 8,14 we further developed the individual anastomosis and the confluent anastomosis with eptfe for venous outflow reconstruction in a living-donor liver transplant (Figure 1). The option of using either an individual anastomosis or a confluent anastomosis was based on the size of the anterior sector outflow branch and the clinical requirements of our study cohort. Because infection and graft disruption are major causes of graft failure in liver transplants, we analyzed the incidence of these 2 complications in the 2 groups. Neither infection nor graft disruption episodes were observed in patients receiving either type of anastomosis, suggesting that individual and confluent anastomoses with the eptfe graft were equally effective and safe. Notably, neither

5 Chia-Yu Lai et al /Experimental and Clinical Transplantation (2014) 3: antiplatelet drugs nor anticoagulants were routinely used in our patients because most recipients had a bleeding tendency because of liver cirrhosis. Although none of the patients experienced eptfe graft occlusion during the first 72 hours after surgery, occlusion still could have occurred subsequently. However, our data show that all 26 patients who were alive 180 days after the transplant had serum alanine aminotransferase concentrations less than twice the upper limit, which indirectly suggests that liver congestion did not occur regardless of conduit patency eventually. Delayed eptfe graft obstruction might not have a notable clinical significance in a living-donor liver transplant because intraparenchymal collateral drainage might compensate for it. If so, this compensation might have contributed to the relatively high patient survival. Our study showed the operation-associated mortality rates were 16.7% and 14.3% (P = 1.000) in patients who received an individual anastomosis and those patients who received a confluent anastomosis, suggesting the 2 types of anastomoses are equally feasible in living-donor liver transplant. Furthermore, all the mortalities resulted from the patients underlying diseases and were not associated with the eptfe vascular graft itself. In terms of the technique requirements for vascular outflow reconstruction by eptfe, our study showed the eptfe reconstruction time was significantly shorter in patients who received a confluent anastomosis than it was in those who received an individual anastomosis (14.9 vs 25.8 min, P <.001). The fewer operations needed for the confluent anastomosis might be one reason for this difference. The total operative time, anhepatic time, cold ischemic time, and bench table time were not significantly different between the patients who received an individual anastomosis and those who received a confluent anastomosis. These results suggest that individual and confluent anastomoses are technically achievable. The patients clinical requirements remained the only consideration for choosing the appropriate anastomosis for venous outflow reconstruction by eptfe in living-donor liver transplant using a right liver graft without the MHV. In summary, our study shows that the eptfe vascular graft can be a reliable and safe conduit for venous outflow reconstruction in living-donor liver transplant using a right liver graft without the MHV. Both individual and confluent anastomoses were equally effective. The major limitations of this study were its retrospective nature and the small number of patients. Another limitation was the lack of image study for graft patency in the long-term. Studies with a randomized-control design with a larger cohort are warranted to identify whether eptfe vascular graft can eventually replace both allogeneic and autologous grafts for venous outflow reconstruction in living-donor liver transplant. References 1. Starzl TE, Marchioro TL, Vonkaulla KN, Hermann G, Brittain RS, Waddell WR. Homotransplantation of the liver in humans. Surg Gynecol Obstet. 1963;117: de Villa VH, Lo CM, Chen CL. Ethics and rationale of living-donor liver transplantation in Asia. Transplantation. 2003;75(suppl 3):S2-S5. 3. Fan ST. Live donor liver transplantation in adults. Transplantation. 2006;82(6): Fan ST, Lo CM, Liu CL, Wang WX, Wong J. Safety and necessity of including the middle hepatic vein in the right lobe graft in adult-toadult live donor liver transplantation. Ann Surg. 2003;238(1): Liu CL, Fan ST. Adult-to-adult live-donor liver transplantation: the current status. J Hepatobiliary Pancreat Surg. 2006;13(2): Shi XM, Tao YF, Fu ZR, Ding GS, Wang ZX, Xiao L. Reconstruction of the middle hepatic vein tributary in adult right lobe living donor liver transplantation. Hepatobiliary Pancreat Dis Int. 2011;10(6): Lee SG. Techniques of reconstruction of hepatic veins in living-donor liver transplantation, especially for right hepatic vein and major short hepatic veins of right-lobe graft. J Hepatobiliary Pancreat Surg. 2006;13(2): Yi NJ, Suh KS, Lee HW, et al. An artificial vascular graft is a useful interpositional material for drainage of the right anterior section in living donor liver transplantation. Liver Transpl. 2007;13(8): Lo CM, Fan ST. Surgical techniques in right lobe liver transplantation. Transplant Proc. 2000;32(7): Fan ST, Lo CM, Liu CL, Yong BH, Chan JK, Ng IO. Safety of donors in live donor liver transplantation using right lobe grafts. Arch Surg. 2000;135(3): Lo CM, Fan ST, Liu CL, Yong BH, Chan JK, Wong J. Increased risk for living liver donors after extended right lobectomy. Transplant Proc. 1999;31(1-2): Kubota T, Togo S, Sekido H, et al. Indications for hepatic vein reconstruction in living donor liver transplantation of right liver grafts. Transplant Proc. 2004;36(8): Sano K, Makuuchi M, Miki K, et al. Evaluation of hepatic venous congestion: proposed indication criteria for hepatic vein reconstruction. Ann Surg. 2002;236(2): Pomposelli JJ, Akoad M, Khwaja K, et al. Evolution of anterior segment reconstruction after live donor adult liver transplantation: a single-center experience. Clin Transplant. 2012;26(3):