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1 Original Article / Transplantation Hepatobiliary & Pancreatic Diseases International Graft-to-recipient weight ratio lower to 0.7% is safe without portal pressure modulation in right-lobe living donor liver transplantation with favorable conditions Seung Duk Lee, Seong Hoon Kim, Young-Kyu Kim, Soon-Ae Lee and Sang-Jae Park Goyang, Republic of Korea BACKGROUND: The low graft-to-recipient weight ratio (GRWR) in adult-to-adult living donor liver transplantation (LDLT) is one of the major risk factors affecting graft survival. The goal of this study was to evaluate whether the lower limit of the GRWR can be safely reduced without portal pressure modulation in right-lobe LDLT. METHODS: From 2005 to 2011, 317 consecutive patients from a single institute underwent LDLT with right-lobe grafts without portal pressure modulation. Of these, 23 had a GRWR of less than 0.7% (group A), 27 had a GRWR of 0.7%, <0.8% (group B), and 267 had a GRWR of more than and equal to 0.8% (group C). Medical records, including recipient, donor, operation factors, laboratory findings and complications were reviewed retrospectively. RESULTS: The baseline demographics showed low model for end-stage liver disease score (mean 16.3±8.9) and high percentage of hepatocellular carcinoma (231 patients, 72.9%). Three groups by GRWR demonstrated similar characteristics except recipient body mass index and donor gender. For smallfor-size syndrome, there were 3 (13.0%) in group A, 1 (3.7%) in group B, and 2 patients (0.7%) in group C (P<0.001). Hepatic artery thrombosis was more frequently observed in group A than in groups B and C (8.7% vs 3.7% vs 1.9%, P=0.047). However, among the three groups, graft survival rates at 1 year (100% vs 96.3% vs 93.6%) and 3 years (91.7% vs 73.2% vs 88.1%) were not different (P=0.539). In laboratory measurements, Author Affiliations: Center for Liver Cancer, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea (Lee SD, Kim SH, Kim YK, Lee SA and Park SJ) Corresponding Author: Seong Hoon Kim, MD, PhD, Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsanro, Ilsandong-gu, Goyang, Gyeonggi-do, , Republic of Korea (Tel: ; kshlj@ncc.re.kr) 2014, Hepatobiliary Pancreat Dis Int. All rights reserved. doi: /S (14) there was no group difference in total bilirubin and albumin. However, prothrombin time was longer in group A within postoperative 1 week and platelet count was lower in groups A and B within postoperative 1 month. CONCLUSION: A GRWR lower to 0.7% is safe and does not need to modulate portal pressure in adult-to-adult LDLT using the right-lobe in favorable conditions including low model for end-stage liver disease score. (Hepatobiliary Pancreat Dis Int 2014;13:18-24) KEY WORDS: graft-to-recipient weight ratio; living donor liver transplantation; small-for-size graft; small-for-size syndrome Introduction Living donor liver transplantation (LDLT) is a matured treatment option for patients with endstage liver disease and hepatocellular carcinoma. [1] Graft size, including graft-to-recipient weight ratio (GRWR), should be considered as an initial important step for selecting donors. When the GRWR is less than 0.8%, this small graft is known to be a major risk factor for early graft dysfunction because of its incapability to meet the metabolic, synthetic, and hemodynamic demands of the recipient. [2] Small-for-size syndrome (SFSS) is associated with patients with encephalopathy, coagulopathy, and cholestasis when the GRWR is less than 0.8%. [3] Traditionally, LDLT studies using the left lobe have reported that the small-for-size graft (SFSG) demonstrated poor graft survival. The GRWR 0.8% (or 1.0%) has been recommended to improve the [2, 4] graft survival and prevent early graft dysfunction. To overcome the portal hyperperfusion with SFSS, 18 Hepatobiliary Pancreat Dis Int,Vol 13,No 1 February 15,2014

2 Lowering GRWR safely to 0.7% in LDLT using right-lobe dual-graft liver transplantation and portal pressure modulation, such as portocaval shunt or splenic artery [5, 6] modulation, have been performed. In contrast, recent studies have shown no significant difference in graft survival or even SFSS with the SFSG (a GRWR of less than 0.8% or a graft volume/standard liver volume ratio of less than 40%). [7-9] The graft survival was related not only to SFSG, but also to various factors, including donor liver function or recipient diseases severity. Thus, the safe lower limit of GRWR in LDLT using the rightlobe without portal pressure modulation remains controversial. The present study aimed to assess the graft survival and outcomes according to GRWR and to evaluate the lower limit of safety. Methods Patients Between January 2005 and November 2011, consecutive patients who had undergone LDLT with the right-lobe grafts at the National Cancer Center, Republic of Korea were reviewed retrospectively. The recipients were evaluated in 3 groups: those with GRWR <0.7%, those with GRWR 0.7%, <0.8%, and those with GRWR 0.8%. These patients were analyzed with graft survivals and reviewed for recipient factors [age, gender, body mass index (BMI), model for end-stage liver disease (MELD) score, Child-Turcotte-Pugh (CTP) score, and diseases for LDLT], donor factors (age, gender, graft weight, GRWR, and fatty change of the liver), and operative factors (cold ischemic time, warm ischemic time, operation time, and estimated blood loss). In addition, postoperative complications were evaluated, including postoperative bleeding, vascular, biliary problems, rejection, and SFSS. Laboratory changes with total bilirubin, prothrombin time (PT), albumin, and platelet were analyzed from preoperative 1 day to postoperative 1 year for all three groups. This study was approved by the Ethics Committee of our institution. Operative strategy and surgical techniques At the beginning, a GRWR of 0.8% was chosen as the minimum cut-off value for the recipients. However, if the recipients had a low MELD score without liver failure, donors were young, no fatty change was observed, and the drainage of the anterior segment was secured, a GRWR of less than 0.8% was carefully selected. With the increase of experiences in using small grafts, we decreased the lower limit of GRWR to less than 0.8%. A detailed technical description of the recipient, donor, and bench operation was described previously. [10] Recently, donor right hepatectomy was performed using hanging maneuver by Glisson's approach under upper midline incision. [11] After the donor operation, the liver grafts were flushed with histidine tryptophan ketoglutarate (HTK) solution at 4. Next, to prevent the congestion of the anterior section, expanded polytetrafluoroethylene (eptfe) grafts were used to drain the middle hepatic vein (MHV) branch of 5 mm in diameter. [12] Recipient operations were performed without veno-venous bypass. After recipient total hepatectomy, graft implantation was started with either the right hepatic vein (RHV) or the common orifice of RHV or MHV, or eptfe graft draining the anterior section formed on the bench work anastomosed endto-side to the inferior vena cava (IVC). Any inferior RHV over 5 mm in diameter, if present, was directly anastomosed to the IVC by the minimal anhepatic technique. [13] Briefly, the recipient liver was attached only to the left portal vein, the left hepatic artery, and the common trunk of the middle and left hepatic veins. The prepared right-lobe liver graft was placed orthotopically after side-clamping of the IVC to maintain blood flow. The RHV was anastomosed to the recipient IVC. The right portal vein of the graft was anastomosed to the right or main portal vein of the recipient, with size discrepancy and redundancy being considered. Before reperfusion of the graft, the left hepatic artery and portal vein of the recipient were ligated and divided, and the common trunk of the middle and left hepatic veins was stapled with a vascular stapler. Although the GRWR was lower than 0.8%, portal pressure modulation, such as portocaval shunt, splenectomy or splenic artery modulation was not performed during operation. After reperfusion, hepatic artery anastomosis was performed using surgical microscopy between the right hepatic artery of the graft and the right or left hepatic artery of the recipient. Using Doppler sonography, a radiologist checked the portal vein velocity, hepatic artery resistive index, and hepatic vein flow. Biliary reconstruction was performed by a duct-to-duct anastomosis. Finally, three close-suction drains were placed in the abdominal cavity before closure. SFSS Small-for-size dysfunction defined by Dahm et al was used in this study. [3] SFSS is defined as a dysfunction of a partial liver graft (GRWR <0.8%) during the first postoperative week after the exclusion of other causes. Dysfunction of a partial liver graft is defined by the presence of 2 of the following parameters on 3 consecutive days: an international normalized ratio (INR) >2, total bilirubin >5.8 mg/dl (100 µmol/ L), Hepatobiliary Pancreat Dis Int,Vol 13,No 1 February 15,

3 Hepatobiliary & Pancreatic Diseases International and encephalopathy grade 3 or 4. Other causes of graft dysfunction were categorized as technical (arterial or portal occlusion, outflow congestion, and bile leaks), immunological (rejection), or infection factors (cholangitis and sepsis). Statistical analysis All analyses were performed using SAS version for Windows (SAS institute, Cary, NC, USA). Clinical and pathological variables were analyzed using the Chisquare test or Fisher's exact test and Student's t test or the Mann-Whitney test, depending on the normality of the distribution. Overall survival curves were plotted using the Kaplan-Meier method and curves were compared using the log-rank test. P values <0.05 were considered statistically significant. Results Recipients and donors Between January 2005 and November 2011, there were 317 LDLT using right-lobe graft performed on adult recipients at our institution. Of these recipients, 231 underwent LDLT for hepatocellular carcinoma (HCC). The mean of MELD score and donor age was 16.3 ±8.9 and 32.7±10.7 years, respectively. Among 317 LDLTs, only 9 (2.8%) patients underwent LDLT using an extended right-lobe, including the donor MHV, and others used the right-lobe graft with the RHV or MHV reconstruction with eptfe. There were 23 (7.3%) patients categorized with GRWR <0.7%, 27 (8.5%) with GRWR 0.7%, <0.8%, and 267 (84.2%) with GRWR 0.8%. Baseline demographics for the 3 groups are shown in Table 1. The BMI score was significantly higher in GRWR <0.8% than in GRWR 0.8% (P<0.001). However, recipient age, gender, MELD score, CTP score, and diseases for LDLT were not different among the groups. For donor factors, female donors were significantly more in GRWR <0.7% than in other groups (P<0.001). The mean GRWR among the 3 groups was 0.62 for GRWR <0.7%, 0.75 for GRWR 0.7%, <0.8%, and 1.17 for GRWR 0.8%. The minimum GRWR was 0.51% and the maximum GRWR was 2.06%. Group microvesicular and macrovesicular fatty changes were not significantly different. Regarding operative factors, there were no significant differences in cold ischemic time, warm ischemic time, operation time, and estimated blood loss. However, the intraoperative portal flow velocity by Doppler sonography was significantly different among the groups (P<0.001). We enrolled only one case of splenectomy because of bleeding in this study. Graft survival and cause of death The overall graft survival rates at 1, 2 and 3 years were 100%, 91.7%, 91.7% vs 93.6%, 88.8%, 88.1% in the GRWR <0.7% and 0.8% groups (P=0.539; Fig. 1). In GRWR <0.7%, there was only 1 graft failure because of tumor recurrence. In GRWR 0.7%, <0.8%, 3 graft failures were due to tumor recurrence and 1 was due to postoperative sepsis. In GRWR 0.8%, 18 graft failures were due to tumor recurrence, 2 biliary complications, 2 postoperative bleeding, 2 cerebral hemorrhage, 2 graft dysfunction, and 5 postoperative sepsis. Postoperative complications and laboratory changes The incidence of postoperative bleeding, biliary Table 1. Clinical characteristics of recipients according to GRWR Characteristics GRWR <0.7% (n=23) GRWR GRWR 0.7%, <0.8% 0.8% (n=27) (n=267) P value Recipient Age (yr) 50.4± ± ± Gender (M/F) 19/4 22/5 207/ BMI 26.8± ± ±2.9 <0.001 MELD score 16.9± ± ± CTP score (A vs B&C) Diagnosis (HCC vs Others) 6/17 11/16 99/ /6 23/4 191/ Donor Age (yr) 31.4± ± ± Gender (M/F) 3/20 11/16 179/88 <0.001 Graft weight (g) 470.9± ± ±133.4 <0.001 GRWR 0.62± ± ±0.25 <0.001 Fatty liver Micro (>20%) 2 (8.7%) 1 (3.7%) 32 (12.0%) * Macro (>20%) 1 (4.3%) 0 (0.0%) 26 (9.7%) * Operation Cold ischemic time (min) Warm ischemic time (min) Operation time (min) EBL (ml) ± Intraoperative portal flow velocity (cm/s) 90.0± ± ± ± ± ± ± ± ± ± ± ± ± ±47.0 <0.001 *: Linear-by-linear association test. BMI: body mass index; MELD: model for end-stage liver disease; CTP: Child-Turcotte-Pugh; HCC: hepatocellular carcinoma; GRWR: graft-to-recipient weight ratio; EBL: estimated blood loss. 20 Hepatobiliary Pancreat Dis Int,Vol 13,No 1 February 15,2014

4 Lowering GRWR safely to 0.7% in LDLT using right-lobe Table 2. Complications of recipients according to GRWR (n, %) Complications GRWR GRWR GRWR <0.7% 0.7%, <0.8% 0.8% (n=23) (n=27) (n=267) P value Fig. 1. Graft survival rate of patients with GRWR <0.7%; 0.7%, <0.8%; and 0.8%. Postoperative bleeding 1 (4.3) 0 (0.0) 23 (8.6) * Biliary leakage or stenosis 5 (21.7) 9 (33.3) 77 (28.8) Vascular complications Hepatic artery thrombosis 2 (8.7) 1 (3.7) 5 (1.9) * Portal vein stenosis 0 (0.0) 1 (3.7) 3 (1.1) * Hepatic vein stenosis 0 (0.0) 0 (0.0) 1 (0.4) * Acute cellular rejection 1 (4.3) 4 (14.8) 19 (7.1) * SFSS 3 (13.0) 1 (3.7) 2 (0.7) <0.001 * *: Linear-by-linear association test. GRWR: graft-to-recipient weight ratio; SFSS: small-for-size syndrome. Fig. 2. Laboratory changes of median values of serum total bilirubin, PT, albumin, and platelet from preoperative 1 day to postoperative 12 months according to GRWR. *: Linear-by-linear association test; PT: prothrombin time; INR: international normalized ratio. complication, and acute cellular rejection was not different among the groups (Table 2). However, for vascular complications, the incidence of hepatic artery thrombosis was more significant in GRWR <0.7% than in other groups (P=0.047). There were no significant differences in portal or hepatic vein thrombosis among the groups. SFSS by definition was developed in 6 patients (GRWR: 0.61%, 0.64%, 0.66%, 0.77%, 0.89%, and 1.28%). The incidence of SFSS was significantly higher in GRWR <0.7% than that in GRWR 0.7% (P<0.001). Furthermore, there was no significant difference in hepatic artery thrombosis and SFSS between GRWR 0.7%, <0.8% and 0.8% (P=0.521 and 0.145, respectively). If hepatic artery thrombosis was suspected with either ultrasound or enhanced computed tomography, conventional Hepatobiliary Pancreat Dis Int,Vol 13,No 1 February 15,

5 Hepatobiliary & Pancreatic Diseases International angiography was used to confirm the diagnosis and, if needed, angioplasty was performed by an interventional radiologist. There was no graft failure due to thrombosis of the hepatic artery. For the management of SFSS, in GRWR <0.7%, the splenic artery embolization was performed on one recipient. The remaining 5 recipients were observed without interventions. Of these recipients, 4 demonstrated normalization of liver function by 1 month, 1 in GRWR 0.8% died of liver failure, but there was no death in SFSS patients with GRWR <0.8%. Laboratory measures, including total bilirubin and albumin tests, were not different among the 3 groups. These measures were normalized in 2 weeks after operation (Fig. 2). The median value of PT for GRWR <0.7% was significantly higher from the operation day to postoperative 1 week than the other groups (PT: 2.29 vs 2.02 vs 2.16 and 1.35 vs 1.22 vs 1.23; P=0.039 and 0.019, respectively). Furthermore, the median value of platelet count in GRWR 0.8% was significantly higher from postoperative 2 weeks to postoperative 1 month (platelet count, 10 9 /L: 92.0 vs 95.5 vs 128.0, vs vs 146.5, vs vs 148.5; P=0.007, 0.023, and 0.024, respectively). After 1 month, PT and platelet count became similar among the groups. Discussion In an era of using a right-lobe graft for adult-to-adult LDLT, the graft size has been yet to catch up with the effort of expanding the limitations of donor selection. For this study, with a relatively large number of SFSGs, we compared the outcomes of recipient graft survival and postoperative complications, including SFSS, vascular problems, and laboratory changes according to GRWR. Although there was no significant difference in graft survival among the 3 groups, recipients with GRWR <0.7% had more SFSS and hepatic artery thrombosis, and also showed longer PT and lower platelet count postoperatively than those with GRWR 0.7%. Compared the three groups, we found that GRWR 0.7%, <0.8% group demonstrated similar outcomes as GRWR 0.8%. Thus, a GRWR 0.7% was suggested as a safe lower limit without portal pressure modulation in this study. It is more important to highlight the graft size and GRWR for donor selection by left donor hepatectomy than right donor hepatectomy. Although the left donor hepatectomy had a potential benefit in the morbidity, mortality, extent of surgery, and subsequent recovery compared to the right donor hepatectomy, a small left lobe graft was often associated with liver failure, including coagulopathy, ascites, prolonged cholestasis, and encephalopathy. [14, 15] This problem was highlighted by Kiuchi et al in terms of poor graft survival at 1 year for transplants with a GRWR <1.0%. [2] In recent years, grafts with GRWR <0.8% have been called SFSGs, [3] and they are known to be at a higher risk for the development of SFSS. Because of the use of the right-lobe graft for LDLT and the elucidation of the pathophysiology of SFSS, the severity and incidence for SFSS has been reduced. However, many transplant surgeons still have much concerns for the LDLT with GRWR <0.8%. There has been a better understanding of the pathophysiology of SFSS over the past few years. In particular, portal hyperperfusion, venous congestion, and arterial hypoperfusion, as well as simple insufficiency of liver mass, have been thought as contributory mechanisms. Several of the LDLTs in GRWR <0.8% have shown significant elevation of portal venous pressure. [15] Also, the portal venous pressure >20 mmhg was significantly correlated with poorer graft survival (38% vs 85%) at six months. [16] In a porcine model, recipients who were transplanted with 19.3%-25.3% standard liver volume showed significant increases in portal venous flow, portal pressure, and vascular resistance, along with reduced arterial flow. Furthermore, markers of endothelial and hepatocyte injury were elevated compared to the whole graft group. [17] These findings were correlated with a study which showed that SFSS had sinusoidal endothelial disruption and focal hemorrhage dissecting into connective tissue, along with hepatic artery spasm. [18] In this study, we had 2 patients with hepatic artery thrombosis (8.7%) in GRWR <0.7%, and the patients with GRWR <0.7% showed higher intraoperative portal flow velocity than other groups. These patients with hepatic artery thrombosis might be caused by secondary portal hyperperfusion. It was previously reported that low hepatic artery flow was related to the diversion of blood through the splenic artery (formerly called "splenic artery steal syndrome") but it is now considered to be due to a normal homeostatic mechanism termed as hepatic arterial buffer response. [19] As the hepatic artery buffer response was mediated by adenosine washout, in a porcine small-for-size model, an infusion of adenosine in 20% standard liver size grafts was able to inhibit the hepatic artery buffer response and significantly reduce graft injury as determined by histology. [20] Recent studies [7, 8, 21] have shown that a small graft size alone is insufficient to account for SFSS. A retrospective study of 427 patients [7] undergoing GRWR <0.8% (n=35) and GRWR 0.8% (n=392) found no significant difference in either the incidence of SFSS or graft survival. In addition, donor >44 years was the only significant 22 Hepatobiliary Pancreat Dis Int,Vol 13,No 1 February 15,2014

6 Lowering GRWR safely to 0.7% in LDLT using right-lobe risk factor for poor graft survival in GRWR <0.8%. In another study on 107 patients, [8] there was no difference in graft survival and SFSS between GRWR <0.8% (n=22) and GRWR 0.8% (n=85). Given these results, can we perform LDLT in GRWR <0.8% without any concerns? The answer is still in dispute. One study has reported that CTP scores B and C patients with GRWR <0.8% had a poor graft survival and the prognosis was affected by preoperative disease severity. [22] This study has suggested that a pre-existing portal hypertension may exacerbate the hyperperfusion seen in SFSS. In the present study, LDLT with GRWR <0.7% showed a similar graft survival. However, these patients showed a high portal flow velocity and the significant risk factor was for SFSS compared to LDLT with GRWR 0.7%. Furthermore, there were no significant differences of CTP scores among the groups. However, in univariate analysis, MELD score over 20 and liver cirrhosis without HCC were the significant risk factors for SFSS, but donor age and fatty change were not statistically significant (data not shown). Put together, SFSS resulted not only from a small graft size but also from a graft condition, pre-existing portal hypertension, and recipient MELD or CTP score. However, it should not be ignored that the small graft was correlated with a small-for-need and SFSS. As portal hyperperfusion is thought to be a pathogenesis of SFSS, the prevention was focused on modulating inflow to the liver through a portal vein. Portal pressure modulation included splenic artery modulation (ligation/embolization), portocaval shunts, and splenectomy. Kaido et al [23] have reported a lower limit of GRWR 0.6% in LDLT in combination with portal pressure control, targeting a final pressure below 15 mmhg. Other studies [24, 25] have reported the usefulness of the hemiportocaval shunt in preventing SFSS and improving outcomes for the SFSG. However, these procedures could result in several complications. A hemiportocaval shunt might cause excessive diversion of the portal flow into the systemic circulation, the so-called "portal steal phenomenon". This could result in clinical encephalopathy and a failure of graft regeneration, disturbing the optimal flow to the graft. In addition, splenic artery modulation, such as embolization or ligation, could lead to a massive colliquation of the spleen, necessitating re-laparotomy or septic shock with consequent graft failure. Therefore, portal pressure modulation has both advantages and disadvantages. A number of experiences and studies might be needed to determine the indication and optimal time. In the present study, we obtained good results for recipients with GRWR 0.7% without portal pressure modulation. However, if the SFSS persists for several weeks and the liver function becomes worse, portal pressure modulation might be considered to reduce the liver damage. We had one case of splenic artery embolization after the development of the SFSS, and the patient recovered after the procedure. The MHV is an important issue for LDLT using the right-lobe. A right hepatectomy without the MHC or reconstruction can induce congestion in the anterior section of the right-lobe, reducing functional capacity of the graft. Some studies [26, 27] have reported that the graft without the MHV exhibited congestion of the right anterior section, leading to ascites and severe liver function derangement. This introduced the concept of the non-congestive GRWR as a better measure of graft function than size ratio alone. In this study, we tried to save the middle hepatic branch of over 5 mm in diameter by using eptfe for all patients except in 9 cases where extended right hepatectomy, including MHV, was performed. In particular, we considered that it is very important for the recipients with SFSG to maintain the drainage of the MHV in the graft postoperatively. There are some limitations in this study. First was its retrospective nature, and we enrolled a large portion of HCC patients with a low MELD score. Second, selection bias might influence the outcome. Third, we did not analyze the risk factors related to SFSS except GRWR <0.7%. Fourth, we did not check the change of portal flow before and after portal perfusion during transplantation. In conclusion, using a small size graft plays an important role in the development of SFSS and in the postoperative graft function, although it is not the only factor for graft survival. The limit level of GRWR can be safely lowered to 0.7% without portal pressure modulation in adult-to-adult LDLT using the right-lobe in favorable conditions such as low MELD score. This study has the potential to expand the donor pool for LDLT using the right-lobe. Contributors: KSH proposed the study and performed the research. LSD wrote the first draft and analyzed the data. KYK, LSA and PSJ contributed to the design and interpretation of the study and to further drafts. KSH is the guarantor. Funding: None. Ethical approval: This study was approved by the Ethics Committee of our institution. 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. References 1 Chen CL, Fan ST, Lee SG, Makuuchi M, Tanaka K. Living- Hepatobiliary Pancreat Dis Int,Vol 13,No 1 February 15,

7 Hepatobiliary & Pancreatic Diseases International donor liver transplantation: 12 years of experience in Asia. Transplantation 2003;75:S Kiuchi T, Kasahara M, Uryuhara K, Inomata Y, Uemoto S, Asonuma K, et al. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors. Transplantation 1999;67: Dahm F, Georgiev P, Clavien PA. Small-for-size syndrome after partial liver transplantation: definition, mechanisms of disease and clinical implications. Am J Transplant 2005;5: Tanaka K, Ogura Y. "Small-for-size graft" and "small-for-size syndrome" in living donor liver transplantation. Yonsei Med J 2004;45: Troisi R, Cammu G, Militerno G, De Baerdemaeker L, Decruyenaere J, Hoste E, et al. Modulation of portal graft inflow: a necessity in adult living-donor liver transplantation? Ann Surg 2003;237: Ikegami T, Imura S, Arakawa Y, Shimada M. Transient portocaval shunt for a small-for-size graft in living donor liver transplantation. Liver Transpl 2008;14: Moon JI, Kwon CH, Joh JW, Jung GO, Choi GS, Park JB, et al. Safety of small-for-size grafts in adult-to-adult living donor liver transplantation using the right lobe. Liver Transpl 2010; 16: Hill MJ, Hughes M, Jie T, Cohen M, Lake J, Payne WD, et al. Graft weight/recipient weight ratio: how well does it predict outcome after partial liver transplants? Liver Transpl 2009;15: Lee SG, Hwang S, Park KM, Kim KH, Ahn CS, Lee YJ, et al. Seventeen adult-to-adult living donor liver transplantations using dual grafts. Transplant Proc 2001;33: Kim SH, Cho SY, Park SJ, Lee KW, Han SS, Lee SA, et al. Learning curve for living-donor liver transplantation in a fledgling cancer center. Transpl Int 2009;22: Kim SH, Kim YK. Living donor right hepatectomy using the hanging maneuver by Glisson's approach under the upper midline incision. World J Surg 2012;36: Yi NJ, Suh KS, Lee HW, Cho EH, Shin WY, Cho JY, 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: Kim SH, Yoo JS, Han SS, Park SJ, Lee SA, Lee WJ, et al. Minimal anhepatic technique for living donor liver transplantation using right liver graft. Liver Transpl 2007;13: Kiuchi T, Tanaka K, Ito T, Oike F, Ogura Y, Fujimoto Y, et al. Small-for-size graft in living donor liver transplantation: how far should we go? Liver Transpl 2003;9:S Yagi S, Iida T, Taniguchi K, Hori T, Hamada T, Fujii K, et al. Impact of portal venous pressure on regeneration and graft damage after living-donor liver transplantation. Liver Transpl 2005;11: Ito T, Kiuchi T, Yamamoto H, Oike F, Ogura Y, Fujimoto Y, et al. Changes in portal venous pressure in the early phase after living donor liver transplantation: pathogenesis and clinical implications. Transplantation 2003;75: Fondevila C, Hessheimer AJ, Taurá P, Sánchez O, Calatayud D, de Riva N, et al. Portal hyperperfusion: mechanism of injury and stimulus for regeneration in porcine small-forsize transplantation. Liver Transpl 2010;16: Demetris AJ, Kelly DM, Eghtesad B, Fontes P, Wallis Marsh J, Tom K, et al. Pathophysiologic observations and histopathologic recognition of the portal hyperperfusion or small-for-size syndrome. Am J Surg Pathol 2006;30: Quintini C, Hirose K, Hashimoto K, Diago T, Aucejo F, Eghtesad B, et al. "Splenic artery steal syndrome" is a misnomer: the cause is portal hyperperfusion, not arterial siphon. Liver Transpl 2008;14: Kelly DM, Zhu X, Shiba H, Irefin S, Trenti L, Cocieru A, et al. Adenosine restores the hepatic artery buffer response and improves survival in a porcine model of small-for-size syndrome. Liver Transpl 2009;15: Ikegami T, Masuda Y, Ohno Y, Mita A, Kobayashi A, Urata K, et al. Prognosis of adult patients transplanted with liver grafts <35% of their standard liver volume. Liver Transpl 2009;15: Lo CM, Liu CL, Fan ST. Portal hyperperfusion injury as the cause of primary nonfunction in a small-for-size liver graft-successful treatment with splenic artery ligation. Liver Transpl 2003;9: Kaido T, Mori A, Ogura Y, Hata K, Yoshizawa A, Iida T, et al. Lower limit of the graft-to-recipient weight ratio can be safely reduced to 0.6% in adult-to-adult living donor liver transplantation in combination with portal pressure control. Transplant Proc 2011;43: Yamada T, Tanaka K, Uryuhara K, Ito K, Takada Y, Uemoto S. Selective hemi-portocaval shunt based on portal vein pressure for small-for-size graft in adult living donor liver transplantation. Am J Transplant 2008;8: Takada Y, Ueda M, Ishikawa Y, Fujimoto Y, Miyauchi H, Ogura Y, et al. End-to-side portocaval shunting for a smallfor-size graft in living donor liver transplantation. Liver Transpl 2004;10: Lee S, Park K, Hwang S, Lee Y, Choi D, Kim K, et al. Congestion of right liver graft in living donor liver transplantation. Transplantation 2001;71: Kamei H, Fujimoto Y, Nagai S, Suda R, Yamamoto H, Kiuchi T. Impact of non-congestive graft size in living donor liver transplantation: new indicator for additional vein reconstruction in right liver graft. Liver Transpl 2007;13: Received April 10, 2013 Accepted after revision July 18, Hepatobiliary Pancreat Dis Int,Vol 13,No 1 February 15,2014

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