Liver Graft Regeneration in Right Lobe Adult Living Donor Liver Transplantation

Optimal portal flow is one of the essentials in adequate liver function, graft regeneration and outcome of the graft after right lobe adult living donor liver transplantation (ALDLT). The relations among factors that cause sufficient liver graft regeneration are still unclear. The aim of this study is to evaluate the potential predisposing factors that encourage liver graft regeneration after ALDLT. The study population consisted of right lobe ALDLT recipients from Chang Gung Memorial Hospital-Kaohsiung Medical Center, Taiwan. The records, preoperative images, postoperative Doppler ultrasound evaluation and computed tomography studies performed 6 months after transplant were reviewed. The volume of the graft 6 months after transplant divided by the standard liver volume was calculated as the regeneration ratio. The predisposing risk factors were compiled from statistical analyses and included age, recipient body weight, native liver disease, spleen size before transplant, patency of the hepatic venous graft, graft weight-to-recipient weight ratio (GRWR), posttransplant portal flow, vascular and biliary complications and rejection. One hundred forty-five recipients were enrolled in this study. The liver graft regeneration ratio was 91.2 ± 12.6% (range, 58–151). The size of the spleen (p = 0.00015), total portal flow and GRWR (p = 0.005) were linearly correlated with the regeneration rate. Patency of the hepatic venous tributary reconstructed was positively correlated to graft regeneration and was statistically significant (p = 0.017). Splenic artery ligation was advantageous to promote liver regeneration in specific cases but splenectomy did not show any positive advantage. Spleen size is a major factor contributing to portal flow and may directly trigger regeneration after transplant. Control of sufficient portal flow and adequate hepatic outflow are important factors in graft regeneration.     

Results of Using the Cystic Duct for Reconstruction of One of the Multiple Bile Ducts in Right Lobe Living Donor Liver Transplantation

BackgroundIn right-lobe liver grafts, variations in the biliary tree anatomy can result in multiple bile duct orifices. We present our experience of 10 patients in which biliary reconstruction was performed with the cystic duct for 1 of the anastomoses with 2 separated ducts. Also, we investigated whether the bile duct anastomosis technique, number of bile duct anastomoses, and use of biliary stents affect the rate of biliary complications.MethodsWe evaluated patients who underwent right-lobe living donor liver transplantation (LDLT) at İstinye University Hospital and İstanbul Aydın University Hospital between December 2017 and June 2020. The patients were divided into 4 groups: duct-to-duct (D-D), duct-to-sheath, double duct-to-duct, and duct-to-duct plus cystic duct-to-duct. Biliary complication rates were compared among these 4 groups, between single- and double-duct groups, and between stent (+) and stent (−) groups.ResultsNinety-three patients who underwent right-lobe LDLT (60 men, 33 women) with a mean age of 51 ± 13 years were included. Mean follow-up time was 18.5 ± 8.3 months. The overall biliary complication rate was 17.2% for all patients, 12.1% for the D-D (single-duct) group (33 patients), 16.1% for the duct-to-sheath group (31 patients), 26.3% for the double duct-to-duct group (19 patients), 20% for the duct-to-duct plus cystic duct-to-duct group (10 patients), 20% for the double-duct group (60 patients), 14.5% for the stent (+) group (69 patients), and 25% for the stent (−) group (24 patients). There were no significant differences among these groups in terms of biliary complication rates. Bile stricture occurred in only 1 cystic duct anastomosis (10%), and no bile leakage was observed.ConclusionsMultiple D-D biliary reconstruction using the cystic duct with external drainage tubes is feasible and safe for LDLT.     

Outcomes of Donor Evaluations for Adult-to-Adult Right Hepatic Lobe Living Donor Liver Transplantation

The purpose of this study is to determine the role of liver biopsy and outcome of patients undergoing donor evaluation for adult-to-adult right hepatic lobe living donor liver transplantation (LDLT). Records of patients presenting for a comprehensive donor evaluation between 1997 and February 2005 were reviewed. Liver biopsy was performed only in patients with risk factors for abnormal histology. Two hundred and sixty patients underwent a comprehensive donor evaluation and 116 of 260 (45%) were suitable for donation, 14 of 260 (5.4%) did not complete evaluation and 130 of 260 (50%) were rejected. Four patients underwent unsuccessful hepatectomy surgery due to discovery of intraoperative abnormalities. Between 1997 and 2001, the acceptance rate of donor candidates (63%) was higher than 2002-2005 (36%), p < 0.0001. Sixty-six of the 150 eligible patients (44%) fulfilled criteria for liver biopsy and 28 of 66 (42%) had an abnormal finding. Less than half of the patients undergoing donor evaluation were suitable donors and the donor acceptance rate has declined over time. A large proportion of the patients undergoing liver biopsy have abnormal findings. Our evaluation process failed to identify 4 of 103 who had aborted donor surgeries.     

活体右半肝供肝切取的经验

目的对活体右半肝供肝切取手术经验进行总结。方法回顾性分析我中心单一外科小组2007年8月至2008年12月期间连续实施右半肝切取的76例供者资料。术前综合考虑移植物大小、残肝比例、有无脂肪肝、肝中静脉类型及受体术前门静脉高压情况,以确定是否带肝中静脉。术中以缺血线确定肝切平面,以术中B超了解肝中静脉的走向及分支,肝切线在肝中静脉左或右侧紧贴肝中静脉。行术中胆道造影,了解胆道结构及变异。记录手术时间,术中失血量,术后住院时间,术后住院期间总胆红素、国际标准化比值(INR)和ALT水平变化情况以及术后各种并发症发生情况。结果 76例供体均顺利完成手术,手术时间(8.3±1.3)h,术中失血量(325±127)ml,术中均未输血。总胆红素、INR和ALT水平于术后第12天恢复正常。本组供体术后住院期间最常见并发症是伤口感染(共5例),胆汁郁积4例,断面漏胆4例;11例患者于术后4～7d出现不同程度的胃排空障碍;均经相应处理后好转。术后住院9～21d,中位时间14d。结论充分的术前评估以及精准的术中操作能够保证供肝的顺利切取并有利于供体的术后恢复。     

Selective Use of Older Adults in Right Lobe Living Donor Liver Transplantation

Many centers are reluctant to use older donors (>44 years) for adult right-lobe living donor liver transplantation (RLDLT) due to concerns about possible increased morbidity in donors and poorer outcomes in recipients. Since 2000, 130 adult RLDLTs have been performed at our institution. Recipients were divided into those who received a right lobe graft from a donor ≤age 44 (n = 89, 68%; median age 30) and those who received a liver graft from a donor age >44 (n = 41, 32%; mean age 52). The two donor and recipient populations had similar demographic and operative profiles. With a median follow-up of 29 months, the severity and number of complications in older donors were similar to those in younger donors. No living donor died. Older donor allografts had initial allograft dysfunction compared to younger donors. Complication rates were similar among recipients in both groups but there was a higher bile duct stricture rate with older donor grafts (27% vs. 12%; p = 0.04). One-year recipient graft survival was 86% for older donors and 85% for younger donors (p = 0.95). Early experience with the use of selected older adults (>44 years) for RLDLT is encouraging, but may be associated with a higher rate of biliary complications in the recipient.     

Living Donor Liver Transplantation with Left Liver Graft

Small-for-size syndrome in LDLT is associated with graft exposure to excessive portal perfusion. Prevention of graft overperfusion in LDLT can be achieved through intraoperative modulation of portal graft inflow. We report a successful LDLT utilising the left lobe with a GV/SLV of only 20%. A 43 year-old patient underwent to LDLT at our institution. During the anhepatic phase a porto-systemic shunt utilizing an interposition vein graft anastomosed between the right portal branch and the right hepatic vein was performed. After graft reperfusion splenectomy was also performed. Portal vein pressure, portal vein flow and hepatic artery flow were recorded. A decrease of portal vein pressure and flow was achieved, and the shunt was left in place. The recipient post-operative course was characterized by good graft function. Small-for-size syndrome by graft overperfusion can be successfully prevented by utilizing inflow modulation of the transplanted graft. This strategy can permit the use of left lobe in adult-to-adult living donor liver transplantation.     

The Right Small-for-Size Graft Results in Better Outcomes than the Left Small-for-Size Graft in Adult-to-Adult Living Donor Liver Transplantation

BACKGROUND: The recent outcome of adult-to-adult living donor liver transplantation (ALDLT) using small-for-size grafts (SFSGs; GRWR <0.8%) has been excellent after right grafts were exclusively used in large-volume ALDLT centers. METHODS: We compared the outcome of ALDLTs using 11 right SFSGs (group R) with that using 18 left SFSGs (group L) of our center. The dysfunction of graft was defined dysfunction as hyperbilirubinemia (>5 mg/dl), prolonged prothrombin time (>2 INR), or uncontrolled ascites (>1,000 ml/day) on 3 consecutive days in posttransplant 7 days, and the dysfunction score (DS; the sum of points given per each sign) of the graft was used to describe the SFSG dysfunction severity. RESULTS: The pretransplant recipient status was similar between the groups, but the 1-year mortality rate was 0% in group R and 33.3% (n = 6) in group L (p = 0.038). The ICU stay was longer in group L (20 days) than in group R (11 days; p = 0.004). Hyperbilirubinemia in group R vs. L was noted in 54.5% vs. 50%, prolonged prothrombin time in 18.2% vs. 50%, and uncontrolled ascites in 54.5% vs. 100%. The DS was lower in group R than in group L (1.3 vs. 2; p = 0.007). The DS was zero in four right liver recipients. On multivariate analysis, the only factor affecting DS was the graft side. CONCLUSION: The clinical signs of SFSG dysfunction were less arduous and there was no 1-year mortality in cases in group R. Therefore, the right SFSG may be used for ALDLT in the future base on the transplant center's experience.     

Left Lobe Living Donor Liver Transplantation in Adults

Adult left lobe (LL) living donor liver transplantation (LDLT) has not generally been recognized as a feasible procedure because of the problem of graft size. The objectives of this study were to assess the feasibility and short‐ and long‐term results of adult LL LDLT in comparison with right lobe (RL) LDLT. Data on 200 consecutive LL LDLTs, including five retransplants, were retrospectively compared with those of 112 RL LDLTs, in terms of survival, complications and donor morbidity. The mean graft weight to standard volume ratio of LL grafts was 38.7% whereas that of RL grafts was 47.6% (p < 0.0001). The 1‐, 5‐ and 10‐year patient survival rates of LL LDLT were 85.6%, 77.9% and 69.5%, respectively, which were comparable to those of RL LDLT (89.8%, 71.3% and 70.7%, respectively). The incidence of small‐for‐size syndrome was higher in LL LDLT (19.5%) than in RL LDLT (7.1%) (p < 0.01). The overall donor morbidity rates were comparable between LL (36.0%) and RL (34.8%), whereas postoperative liver function tests and hospital stay were significantly better (p < 0.0001) in LL donors. In conclusion, adult LL LDLT has comparable outcomes to that of RL LDLT. LL LDLT is viable and is the first choice in adult LDLT.     

Simplified Unification Patch Venoplasty for Anomalous Portal Vein Branching in Living Donor Liver Transplantation With Right Lobe Graft

Double portal vein (PV) branches during living donor liver transplantation (LDLT) with right lobe grafts have been considered challenging both in terms of donor safety and the complexity of vascular reconstruction in the recipient. Herein, we describe our experience with 24 adult LDLT recipients during which we employed unification patch venoplasty to reconstruct right lobe grafts with double PV orifices. We retrospectively reviewed the outcomes of 195 adult LDLT recipients receiving right lobe grafts, including 24 cases of adult LDLT recipients in which unification patch venoplasty was used to treat double PVs from January 2010 to June 2015. The anomalous portal vein branches of the donors were of type II in 7 cases (29.2%), type III in 15 cases (62.5%), and type IV in 2 cases (8.3%). We used propensity score matching analysis to compare the clinical outcomes of these recipients with those of 59 recipients who underwent adult LDLT using right lobe grafts with normal PVs in the same period. Intraoperative PV stenting was necessary in 2 (8.3%) of the 24 recipients undergoing unification patch venoplasty. During the follow-up period, all PVs remained patent until death or censoring. No significant difference in terms of postoperative vascular complications was evident between the 2 groups. Moreover, no major complications requiring reoperation or endoscopic and/or radiologic intervention developed in any of the 24 living donors with double PVs. In conclusion, our simplified unification patch venoplasty could be safe and feasible when used to reconstruct double PV orifices in right lobe LDLT from donors with complex PV anomalies.     

Selection of Safe Donors for Living Donor Liver Transplant Using Extended Right Lobe Graft

Extended right lobectomy (ERL) for living donor liver transplant (LDLT) is selectively performed in many transplant centers and has shown excellent recipient outcomes as reported in previous studies. Yet, there is no universally accepted indication for ERL in respect to donor safety. Current study was designed to stratify risk factors of adverse donor outcome after ERL. A total of 79 living donors who underwent ERL for LDLT were included in analysis. Donors were classified as safety and hazard donor groups according to postoperative findings relevant to posthepatectomy liver failure classification by the International Study Group for Liver Surgery. On multivariable analysis, left lateral section volume <20% of total liver volume and nonpreservation of segment 4a venous drainage were the independent risk factors impairing postoperative outcomes. Despite the short-term impairment of liver function in hazard donor groups, all donors recovered and showed satisfactory remnant liver regeneration. However, these findings have implications in establishing selection criteria of donors eligible for ERL donation. In conclusion, LDLT using ERL graft can be safely performed provided so that left lateral section volume/total donor liver is ≥20% besides conventional donor selection criteria. Also, efforts to preserve segment 4a vein must be made in performing ERL graft procurement in LDLT donors.     

Initial Clinical Effect of Intraportal Insulin Administration on Liver Graft Regeneration in Adult Patients Underwent Living Donor Right Lobe Liver Transplantation

ObjectiveInsulin is one factor responsible for hepatotrophic regeneration in animal models. This study assessed the clinical effects of intraportal administration of insulin on liver graft regeneration in adult patients undergoing right lobe living donor liver transplantation (LDLT).MethodsBetween July 2005 and September 2007, 19 right lobe LDLT adult recipients voluntarily received posttransplant intraportal insulin administration. The present study describes 15 patients without postoperative vascular and bile duct complications, with more than 1 month survival and with complete clinical data who were enrolled to receive intraportal insulin therapy (group I; n = 15). Another consecutive 15 right lobe LDLT adult recipients without any stimulation regeneration who met the same criteria were enrolled in as noninsulin therapy control group (group NI; n = 15). Group I recipients were treated postoperatively with intraportal insulin infusion, as follows. An 18-gauge catheter was inserted into right gastro-omental vein during surgery, to administer regular insulin just after the operation at the rate of 2 U/h for 1 week. Graft volume (GV) was measured by computed tomography on postoperative days (POD) 7 and 30. Liver functions and serum insulin levels were also measured at POD 7 and POD 30. The liver graft regeneration rate was defined as ratio of posttransplant GV/harvested GV and posttransplant graft-to-recipient weight ratio (GRWR)/operative GRWR.ResultsThe rate defined as ratio of POD 7 GV/harvested GV among group I was significantly greater than that of group NI (186.07 ± 35.40% vs 160.61 ± 22.11%; P < .05). The rate defined as ratio of POD 7 GRWR/operation GRWR was also significantly higher in group I than group NI (178.95 ± 35.84% vs 156.56 ± 18.53%; P < .05), whereas there was no significant difference in terms of regeneration rates at 1 month post-LDLT. Intraportal insulin administration may significantly downregulate POD 7 total bilirubin, aspartate aminotransferase, and alanine aminotransferase levels (P < .05). These results suggested that intraportal insulin administration augmented liver regeneration during the first postoperative week by improving hepatic function in LDLT recipients.     

活体右半供肝血管和胆管变异及重建处理

成人到成人的活体右半肝移植在东、西方国家已成为一种可以接受的治疗终末期肝病的有效措施。由于尸体供器官的缺乏以及肝移植适应证的扩大，供需矛盾愈来愈突出，在东方国家脑死亡供器官不被接受，这种矛盾更加明显，很多终末期肝病患者在等待肝源过程中死亡。成人间活体右半肝移植缩短了受体等待移植的时间，一定程度上缓解了器官短缺，尤其适用于急性肝功能衰竭患者，在一些国家甚至成为主要的供器官来源，例如在日本。1994年日本Yamaoka等成功开展了世界首例活体右半肝移植，但并非在成人间。1997年香港首先开展成人间活体右半肝移植，即活体扩大右半肝移植。自此，成人间活体右半肝移植在世界范围的各大移植中心广泛开展，但在手术技术上存在一些争论。现就成人间活体右半肝移植供肝血管及胆管解剖变异和在受体重建时的相应处理复习文献，并总结如下。     

Early Graft Function After Living Donor Kidney Transplantation Predicts Rejection But Not Outcomes

Poor early graft function (EGF) after deceased donor kidney transplantation (DDKT) has been intensely studied. Much less is known about poor EGF after living donor kidney transplantation (LDKT). Data were collected on 469 LDKTs performed between 1/1/97 and 12/31/01 to determine risk factors for and outcomes associated with poor EGF, defined as either delayed or slow graft function (DGF or SGF). The incidence of DGF and SGF were 4.7% and 10.7%, respectively. Diabetic etiology (OR 2.22; p = 0.021) and warm ischemia time (WIT) (OR 1.05 per min increment; p = 0.0025) emerged as independently associated with poor EGF. Neither functional graft survival nor 1-year graft function differed among the EGF groups. However, DGF and SGF strongly predisposed to acute rejection (AR), which compromised functional graft survival (p = 0.0007) and 1-year graft function. Therefore, we conclude that diabetic etiology of renal disease and WIT are the dominant risk factors for poor EGF after LDKT. Poor EGF did not directly compromise functional graft survival but strongly predisposed to AR. We suggest that immunosuppression should be intensified in the poor EGF setting to maximize LDKT longevity, as AR does impair functional graft survival.     

Graft Regeneration in Pediatric Living Donor Liver Transplantation

Objective

Due to the shortage of cadaver liver grafts in Asia, more than 90% of biliary atresia (BA) patients require living donor liver transplantation (LDLT), but the factors that influence liver graft regeneration in pediatric patients are still unclear. The aim of this study was to evaluate the potential predisposing factors that encourage liver graft regeneration in pediatric liver transplantation (LT).

Methods

Case notes and Doppler ultrasound and computed tomography studies performed before and 6 months after transplantation of 103 BA patients who underwent LDLT were reviewed. The predisposing factors that triggered liver regeneration were compiled from statistical analyses and included the following: age, gender, body weight and height, spleen size, graft weight–to–recipient weight ratio (GRWR), post-transplantation total portal flow, and vascular complications.

Results

Seventy-two pediatric recipients were enrolled in this study. The liver graft regeneration rate was 29.633 ± 36.61% (range, −29.53–126.27%). The size of the spleen (P = .001), post-transplantation portal flow (P = .004), and age (P = .04) were correlated lineally with the regeneration rate. The GRWR was negatively correlated with the regeneration rate (P = .001) and was the only independent factor that affected the regeneration rate. When the GRWR was >3.4, patients tended to have poor and negative graft regeneration (P = .01).

Conclusion

Large-for-size grafts have negative effect on regeneration rates because liver grafts that are too large can compromise total portal flow and increase vascular complications, especially when the GRWR is >3.4. Thus, optimal graft size is more essential than other factors in a pediatric LDLT patient.     

Laparoscopic Hepatectomy for a Modified Right Graft in Adult-to-Adult Living Donor Liver Transplantation

Background

We performed a modified right hepatectomy completely by laparoscopic techniques preserving the middle hepatic vein (MHV) branches in adult-to-adult living donor liver transplantation (LDLT).

Patients and Methods

Two young women (24 and 25 years old) volunteered to be live donors for their parents who had hepatocellular carcinomas. As the donors expressed concerns about scarring, we performed a laparoscopic procedure using a hand port device. Mobilization of the right liver and the hepatic parenchymal transection were performed under pneumoperitoneum. Parenchymal transection was performed using a laparoscopic ultrasonic aspirator without the Pringle maneuver. During parenchymal transection, major MHV branches >5 mm were preserved using Hem-o-lock clips. The graft was extracted through the hand port site. On the back table, the 3 MHV branches were reconstructed using an artificial vascular graft. The livers were transplanted without complications.

Results

The operative times for the donors were 765 and 898 minutes. The donors did not require transfusions or reoperation; they were discharged on postoperative days 10 and 14 with normal liver functions.

Conclusion

A hepatectomy performed completely by laparoscopic techniques for a right graft with preservation of the MHV branches was technically feasible.     

Retrograde Arterial Flush of the Liver Graft in Living Donor Liver Transplantation

ABSTRACT?

Formal hepatic arterial flush to preserve the liver graft in living donor liver transplantation (LDLT) is not recommended by most transplant centers because direct cannulation may injure the intima of the hepatic artery. The authors describe a method of retrograde arterial flush of the liver graft without arterial cannulation by hepatic venous outflow occlusion (HVOO) in LDLT. First, we proved no backflow of the hepatic artery without HVOO by portal flush to pig livers. Then we used HVOO on 15 LDLT cases (Group HVOO). The results were compared with those of 24 counterpart LDLT cases (Group non-HVOO) without hepatic artery flush. The two-week posttransplantational liver functions were not different between two groups except that the day-three and day-seven serum bilirubin levels were lower in Group HVOO (day-three total bilirubin: 4.99 ± 4.04 mg/dl versus 7.65 ± 4.33 mg/dl, p =.016; day-seven total bilirubin: 5.06 ± 5.02 mg/dl versus 9.57 ± 6.09, p =.005). The rates of vascular complications, six-month graft survival, and biliary anastomotic stricture in Group HVOO were 0, 93.3, and 13.3% respectively, which were not different from those of Group non-HVOO. In summary, to avoid intima injury, the retrograde arterial flush of liver graft by HVOO is safe in LDLT. The short-term results showed the effect of decreasing early functional cholestasis but the long-term benefits need further evaluation, especially with regards to biliary anastomotic complications.     

Strategy for Selective Middle Hepatic Vein Reconstruction in Living Donor Liver Transplantation Using Right Lobe Graft: A Retrospective Observational Study

BackgroundThe aim of this study was to verify the safety and feasibility of our selection criteria for middle hepatic vein (MHV) reconstruction in living donor liver transplantation (LDLT) using right lobe grafts.MethodsA total of 153 LDLTs were performed using right lobe grafts in a tertiary hospital from 2006 to 2016. Among them, 52 cases without MHV reconstruction were compared with 101 recipients who underwent LDLT using right lobe graft with MHV reconstruction. Both groups were compared regarding indications for reconstruction, short-term and long-term complications, operative details, and outcomes.ResultsThe two groups differed only in cold ischemic time (108.19 ± 49.81 minutes vs 146.37 ± 58.74 minutes) preoperatively. Short-term posttransplant outcomes, long-term overall survival, and long-term disease-free survival showed no significant differences between the 2 groups. After propensity score matching for both groups with and without MHV reconstruction to eliminate selection bias, the 2 groups were comparable.ConclusionsWe found that our selection criteria for performing MHV reconstruction in LDLT using right lobe graft were feasible and safe. A routine MHV reconstruction is not necessary if the right lobe graft graft-to-recipient weight ratio is ≥1.0, right hepatic vein draining territory volume is ≥0.8, and recipient Model for End-Stage Liver Disease score is <20.