Graft-to-recipient Body Weight Ratio Research Articles

Simultaneous 3-way Paired Exchange Liver Transplantation Without Nondirected Donation: Novel Strategy to Expand the Donor Pool.

Simultaneous 3-way Paired Exchange Liver Transplantation Without Nondirected Donation: Novel Strategy to Expand the Donor Pool.

GRWR Correlates with the Metabolism of Tacrolimus after Pediatric Living Donor Liver Transplantation According to Donor CYP3A5 Polymorphism

Tacrolimus is characterized by high pharmacokinetic variability in combination with a narrow therapeutic range. However, influence of donor CYP3A5 genotype and graft-to-recipient body weight ratio (GRWR) on tacrolimus' pharmacokinetics after pediatric living donor liver transplantation (LDLT) remains unclear. A total of 174 LDLT recipients (<6 y) were grouped according to donor CYP3A5 genotypes (nonexpressor (NEX) or expressor (EX)) and GRWR (<3.0% (SS, small-size) or ≥3.0% (LS, large-size)): SS/NEX (n = 40), SS/EX (n = 38), LS/NEX (n = 48), and LS/EX (n = 48). Pharmacokinetics of tacrolimus and clinical outcomes were analyzed. The relationships between the concentration-dose ratio and donor CYP3A5 genotypes and graft size were examined 3, 7, 14, and 30 days after the transplantation. Tacrolimus C0 levels varied greatly among groups, although recipients started with the same initial dosage. LS/EX recipients had significantly lower C0 levels in comparison with those of other groups. The use of CYP3A5-EX-grafts and a greater GRWR both resulted in significantly higher TAC dose requirements and lower C/D ratios. However, the significance of GRWR no longer exists 3 months after transplantation. The multivariate generalized linear mixed model analysis showed that donor CYP3A5 genotypes (F = 11.876; P = 0.01) and GRWR (F = 4.631; P = 0.033) were independent impact factors for C/D ratios 3, 7, 14, and 30 days after transplantation. Donor CYP3A5-EX genotype was associated with significantly increasing risks of infectious complications and significantly lower Cylex ATP values. However, no significant difference was observed in acute rejections among 4 groups. Monitoring of C0 levels alone is not reliable to guide tacrolimus administration. Donor CYP3A5 and GRWR both significantly affect tacrolimus pharmacokinetics after pediatric LDLT. The use of Cylex ATP tests would be helpful to avoid overimmunosuppression.

"Graft Recipient Weight Ratio" or "Graft Volume Standard Liver Volume Ratio" in clinical practice in living donor liver transplantation.

We enjoyed the recently published article by Toshima et al,1 demonstrating the importance of recipient BMI for choosing graft in living donor liver transplantation (LDLT) to prevent small-for-size graft syndrome (SFSS). They retrospectively analyzed the incidence of SFSS in 694 recipients who underwent LDLT according to required graft volume based on graft-to-recipient body weight ratio (GRWR) or graft weight to standard liver weight (GW/SLW) in strata of recipient body mass index (BMI). They concluded that GRWR was useful, but GW/SLW was not useful in obese recipients (BMI > 30 kg/m2). Small-for-size graft syndrome has high mortality and morbidity after LDLT because of early graft dysfunction. The importance of accurate estimation for required liver volume in LDLT has been growing with increased number of LDLT worldwide due to the shortage of donor organs. GW/SLW was proposed in 1995 by calculating standard liver volume using the formula, which includes body surface area.2 However, the formula might have less generalizability because they calculated standard liver volume in 96 patients in one prefecture in Japan. In addition, the average of height and body weight were 164.8 cm and 56.5 kg, respectively. Therefore, it may be difficult to estimate standard liver volume and graft weight in obese donors and recipients. In fact, Toshima et al showed GW/SLW was not associated with SFSS in obese patients. GRWR has been another way to estimate required liver volume. Since GRWR could take the body weight of a recipient into account, it may give us a better estimation in obese patients. The estimation of graft weight has been performed using volumetric analysis by three-dimensional computed tomography (CT). However, the discrepancy between estimated graft volume and actual graft weight are often observed, and can potentially cause SFSS. A study showed that estimated liver volume was the largest using the venous phase of enhanced CT, while the smallest using unenhanced CT.3 In addition, estimated liver volume by volumetry is provided as “volume” (i.e. mL), while actual graft size is measured by “weight” (i.e. g). To address this difference, another study suggested using conversion factor (1.20 mL/g) in estimation of graft weight.4 Furthermore, the actual graft weight measured on the back table could decrease from preoperatively estimated liver volume due to several factors including dehydration caused by University of Wisconsin solution, and the difference between the virtual and actual resection line of the liver. The coefficient factor of 0.85 in non-cirrhotic liver for graft weight estimation from preoperative CT volumetry has been proposed to address these factors.5 Although Toshima et al described the utility of GRWR in obese patients, they used actual procured graft weight for the analysis. Since graft weight could not be changed once it has been taken out from the donor, it is important to predict actual graft weight more accurately in the setting of preoperative volumetric analysis. We believe that this article by Toshima et al would provide a compelling rationale for further investigations into comprehensive ways to estimate liver volume more accurately, potentially avoiding SFSS and improving donor shortage. Conflict of Interest: The authors declare no conflicts of interest. Author Contribution: Study concept and design: Koichiro Haruki and Toru Ikegami. Drafting of the manuscript: Koichiro Haruki and Kenei Furukawa. Critical revision of the manuscript for important intellectual content: all authors. Study supervision: Toru Ikegami. Final approval of manuscript: all authors.

Pediatric Thoracoscopic Repair of Diaphragmatic Herniation Following Liver Transplantation

Diaphragmatic Hernia (DH) after Liver Transplantation (LT) is a rare complication with unclear pathophysiology. Among 261 LT, we recognized six DH during the post transplant period (2.30%). All patients with DH had received a left lateral segment (LLS) reduced graft. The mean graft weight was 340g with a mean graft-to-recipient body weight ratio (GBWR) of 4.20%. LLS grafts, a GBWR &gt; 4%, previous abdominal surgery and direct trauma during surgery can be enumerated as potential risk factors for DH post-LT. These children underwent prompt surgical intervention to DH without complications. Three patients were treated via laparotomy and three by thoracoscopy. No clinical recurrences were accounted at a mean follow up of 5 years. Historically, the treatment has always been surgical repair via laparotomy but the use of minimally invasive techniques in pediatric surgery has been increasing, and the thoracoscopic approach for DH can bring advantages. The patients in which the thoracoscopic approach was used had shorter operative times and a faster recovery with better cosmetic results. As previous surgical manipulation had been done to the abdominal cavity, thoracoscopy seems to be a safe approach in DH in pediatric LT recipients.

Which is better to use "body weight" or "standard liver weight", for predicting small-for-size graft syndrome after living donor liver transplantation?

AimLittle evidence about whether to apply graft‐to‐recipient body weight ratio (GRWR) or graft weight to standard liver weight (GW/SLW) for graft selection has been published. The aim of the present study was to clarify the importance of the correct use of GRWR and GW/SLW for selecting graft according to the recipients’ physique in living donor liver transplantation (LDLT).MethodsData were collected for 694 recipients who underwent LDLT between 1997 and 2020.ResultsOne of the marginal grafts meeting GW/SLW ≥ 35% but GRWR < 0.7% has been used in more recipients with men and higher body mass index (BMI), and the other meeting GRWR ≥ 0.7% but GW/SLW < 35% has been used in more recipients with women with lower BMI. In the cohort of BMI > 30 kg/m2, the recipients with GRWR < 0.7% had a significantly higher incidence of small‐for‐size graft syndrome (SFSS) compared to those with GRWR ≥ 0.7% (P = 0.008, 46.2% vs 5.9%), and using the cutoff of GW/SLW < 35% could not differentiate. In contrast, in the cohort of BMI ≤ 30 kg/m2, the recipients with GW/SLW < 35% also had a significantly higher incidence of SFSS (P = 0.013, 16.9% vs 9.4%). Multivariate analysis showed that GRWR < 0.7% [odds ratio (OR) 14.145, P = 0.048] was the independent risk factor for SFSS in obese recipients, and GW/SLW < 35% [OR 2.685, P = 0.002] was the independent risk factor in non‐obese recipients.ConclusionProper use of the formulas for calculating GRWR and GW/SLW in choosing graft according to recipient BMI is important, not only to meet metabolic demand for avoiding SFSS but also to ameliorate donor shortages.

The current status and outcomes of pediatric liver transplantation in western China: A multi-center retrospective study.

This retrospective study was conducted to examine the development and current status of pediatric liver transplantation (LT) in western China. Clinical, demographic, morbidity, and mortality data were collected to analyze. It included 260 consecutive pediatric LTs performed at three centers in western China between January 2000 and May 2019. Kaplan-Meier graft survival rates at 1, 3, 5, and 10years were 82.1%, 77.2%, 76.6%, and 76.6%, respectively; corresponding patient survival rates were 84.7%, 80.7%, 80.0%, and 80.0%, respectively. More patients underwent living donor liver transplantation (LDLT; n=188 (73.4%)) than deceased-donor liver transplantation (DDLT; n=68 (26.6%)). Survival was better after LDLT (91.5%, 86.6%, and 80.6% at 1, 3, and 5years, respectively) than after DDLT (80.9%, 72.4%, and 63.9%, respectively; P<.05). Biliary atresia was the leading LT indication (n=141 (55.1%)), followed by metabolic disease (n=36 (14.1%)), which was associated with the best recipient survival (88.5% at 5years). The transplant era and graft-to-recipient body weight ratio (GRWR) also significantly predicted overall survival. Survival rates at 5years were worst in 2000-2005 (54.5%) and best for GRWRs of 0.8%-4% (80.4%). The development of pediatric LT in western China began slowly, but the quantity and quality of pediatric LT has progressed in recent years. This procedure is now a promising and reliable treatment for children with end-stage liver disease in western China.

Laparoscopic living donor right hepatectomy

Objective: Living donor liver transplantation (LDLT) has evolved as a treatment option for patients with end stage liver disease (ESLD) because of an inadequate number of deceased donor organs available. Initially best described for adult to pediatric LDLT in 1989, laparoscopic living donor hepatectomy provides an option for living donation in adults that may result in decreased morbidity for the donor as compared to an open operation. A minimally invasive approach remains somewhat controversial as patient safety and graft integrity are primary concerns during transplantation, however, laparoscopic donor hepatectomy can achieve adequate graft outcomes as well as result in reduced complications and an improved recovery in the donor as compared to an open hepatectomy. Methods: Here, we present a 33-year-old female living donor who underwent a laparoscopic living donor right hepatectomy. The graft-to-recipient body weight ratio (GRWR) was 0.78 and functional liver remnant (FLR) in the donor was 41%. Results: The operation was completed laparoscopically and graft was successfully removed through pfannenstiel incision. Conclusion: A fully laparoscopic living donor right hepatectomy is a feasible option for adult-to-adult living donor liver transplantation.

Liver Regeneration and Factors Influencing Liver Regeneration in Donors and Recipients of Adult Living Donor Liver Transplantation Using Right Lobe Graft

Background: To balance between the appropriate remnant liver volume in the donors and sufficient graft volume in the recipients is very important in adult living donor liver transplantation (LDLT). The aim of this study is to evaluate the liver regeneration rate and the factors associated with the regenerative process in the donors and recipients. Methods: Between May 1999 and March 2010, 197 donors and 98 recipients out of the 450 patients who underwent adult LDLT were evaluated retrospectively. We reviewed the clinical characteristics of the patients, liver regeneration using computerized tomography (CT)-assisted volumetry technique and the factors associated with liver regeneration in the donors and recipients. Results: Using CT-assisted volumetry, the mean proportion of remnant right liver lobe was 62.4%±4.7%, ranging from 50.1% to 77.4%. The ratio of the graft weight to volume by CT-assisted volumetry was 89.8%±12.9% and we created a formula that graft volume (g)= [CT volume (mL)×0.933]+137.97. The liver regeneration rate in donors during the first postoperative week was higher if the remnant liver volume was below 35% than if the remnant liver volume above 35% (P<0.001). After 6 months, the remnant liver grew up to 81.2% of the original liver volume. Liver regeneration in recipients during the first postoperative week was faster if the graft-to-recipient body weight ratio (GRWR) was below 1% than if the GRWR was above 1% (P<0.001). Also, GRWR (P<0.001), portal vein (PV) velocity (cm/sec) (P=0.007) and PV flow volume per 100 g of graft tissue (mL/min) (P=0.002) were associated with liver regeneration in recipients during the early postoperative period by univariate analysis. Conclusions: The process of liver regeneration was most active during the first postoperative week in both the donors and recipients. The proportion of remnant liver in donors, GRWR and portal blood flow in recipients appeared to be the significant factors associated with liver regeneration.

Preoperative estimation of the liver graft weight in adult right lobe living donor liver transplantation using maximal portal vein diameters

An accurate preoperative estimate of the graft weight is vital to avoid small-for-size syndrome in the recipient and ensure donor safety after adult living donor liver transplantation (LDLT). Here we describe a simple method for estimating the graft volume (GV) that uses the maximal right portal vein diameter (RPVD) and the maximal left portal vein diameter (LPVD). Between June 2004 and December 2009, 175 consecutive donors undergoing right hepatectomy for LDLT were retrospectively reviewed. The GV was determined with 3 estimation methods: (1) the radiological graft volume (RGV) estimated by computed tomography (CT) volumetry; (2) the computed tomography-calculated graft volume (CGV-CT), which was obtained by the multiplication of the standard liver volume (SLV) by the RGV percentage with respect to the total liver volume derived from CT; and (3) the portal vein diameter ratio-calculated graft volume (CGV-PVDR), which was obtained by the multiplication of the SLV by the portal vein diameter ratio [PVDR; ie, PVDR = RPVD(2) /(RPVD(2) + LPVD(2) )]. These values were compared to the actual graft weight (AGW), which was measured intraoperatively. The mean AGW was 633.63 ± 107.51 g, whereas the mean RGV, CGV-CT, and CGV-PVDR values were 747.83 ± 138.59, 698.21 ± 94.81, and 685.20 ± 90.88 cm(3) , respectively. All 3 estimation methods tended to overestimate the AGW (P < 0.001). The actual graft-to-recipient body weight ratio (GRWR) was 1.00% ± 0.19%, and the GRWRs calculated on the basis of the RGV, CGV-CT, and CGV-PVDR values were 1.19% ± 0.25%, 1.11% ± 0.22%, and 1.09% ± 0.21%, respectively. Overall, the CGV-PVDR values better correlated with the AGW and GRWR values according to Lin's concordance correlation coefficient and the Landis and Kock benchmark. In conclusion, the PVDR method is a simple estimation method that accurately predicts GVs and GRWRs in adult LDLT.

Feasibility of Reduced-size Orthotopic Liver Transplantation with Fatty Grafts and its Potential Regeneration in Rats

We undertook this study to determine the minimum necessary volume of various grades of fatty liver grafts in reduced-size orthotopic liver transplantation (ROLT) and to elucidate the property of fatty liver regeneration. By modified two-cuff technique, ROLT of different rats was performed with various grades and volumes of fatty liver grafts. The survival rate, graft-to-recipient body weight ratio (GRWR), standard liver volume (SLV) and liver function were detected to determine appropriate steatotic grafts that could be safely adopted in ROLT. In grade II macrovesicular steatosis (MaS) grafts, the 1-week survival rate of 70% ROLT was significantly worse (25%). In grafts with microvesicular steatosis (MiS) undergoing 70%, 60%, and 50% ROLT, 7-day survival decreased according to the graft volume (75%, 75%, and 33.3%). Proliferating cell nuclear antigen (PCNA) and 5-bromo-2'-deoxyuridine (BrdU) labeling index in normal liver graft reached the highest on postoperative day (POD) 3, whereas in fatty grafts the expression peak was on POD 7. Liver regeneration ratios of normal liver graft were higher than mild MaS graft, but grade II MaS grafts hardly regenerated. When compared with moderate MaS grafts B2 (70% ROLT) and mild MaS grafts A3 (60%) groups, the disparities of alanine aminotransferase and total bilirubin were significant. In successful and long-term survival of rat ROLT, MiS or grade II MaS livers could be safely used as grafts only when their GRWR >2.29+/-0.20 (or 2.28+/-0.12) % and SLV >60%; MaS livers in grade II should not be used as grafts. Hepatic regeneration potential of mild MaS or MiS with any grade graft is not obviously impaired after ROLT, but delayed proliferative peak and prolonged cell proliferative cycle are shown.

Early graft dysfunction following adult-to-adult living-related liver transplantation: Predictive factors and outcomes

To describe a condition that we define as early graft dysfunction (EGD) which can be identified preoperatively. Small-for-size graft dysfunction following living-related liver transplantation (LRLT) is characterized by EGD when the graft-to-recipient body weight ratio (GRBWR) is below 0.8%. However, patients transplanted with GRBWR above 0.8% can develop dysfunction of the graft. In 73 recipients of LRLT (GRBWR > 0.8%), we identified 10 patients who developed EGD. The main measures of outcomes analyzed were overall mortality, number of re-transplants and length of stay in days (LOS). Furthermore we analyzed other clinical pre-transplant variables, intra-operative parameters and post transplant data. A trend in favor of the non-EGD group (3-mo actuarial survival 98% vs 88%, P = 0.09; 3-mo graft mortality 4.7% vs 20%, P = 0.07) was observed as well as shorter LOS (13 d vs 41.5 d; P = 0.001) and smaller requirement of peri-operative Units of Plasma (4 vs 14; P = 0.036). Univariate analysis of pre-transplant variables identified platelet count, serum bilirubin, INR and Meld-Na score as predictors of EGD. In the multivariate analysis transplant Meld-Na score (P = 0.025, OR: 1.175) and pre-transplant platelet count (P = 0.043, OR: 0.956) were independently associated with EGD. EGD can be identified preoperatively and is associated with increased morbidity after LRLT. A prompt recognition of EGD can trigger a timely treatment.

Hepatic venous outflow reconstruction in right lobe graft without middle hepatic vein

We explored the pattern of hepatic venous outflow reconstruction in adult right lobe (segments V5-8) living donor liver transplantation (LDLT) without the middle hepatic vein (MHV). The difficulty and challenge of LDLT without MHV is the outflow reconstruction of hepatic vein. We have modified the surgical procedure and here report the results. Retrospective analysis was made of the clinical data of 50 recipients who underwent LDLT using right lobe without MHV. Forty-five recipients (90.0%, 45/50) are alive at median follow up of 10 months. The graft-to-recipient bodyweight ratio (GRWR) was 1.21% +/- 0.49% (range, 0.72% to 1.98%). The recipients of GRWR <0.8% (extra-small graft), 0.8% < GRWR < 1.2% (small graft) and GRWR > 1.2% (ideal graft) were 14, 27 and 9, respectively. Total ratio venous outflowreconstruction of V5, V8 and inferior right hepatic vein was 66.0% (33/50). The overall incidence of small-for-size syndrome was 10.0% (n = 5), the overall graft survival rate was 92.0% (46/50). Graft function and survival rates are not only influenced by graft size, but also by hepatic venous outflow reconstruction; the 'multiple-opening vertical anastomosis' for reconstruction of hepatic vein outflow was used when the GRWR was smaller than 1.2%. This technique alleviates surgical risk in living donors, ensures excellent venous drainage, and reduces the incidence of small-for-size syndrome.

Graft Selection Algorithm Based on Congestion Volume for Adult Living Donor Liver Transplantation

A major concern in adult-to-adult living donor liver transplantation is the selection of graft type; that is, is it is better to use the right lobe with or without the middle hepatic vein (MHV)? This choice has a considerable impact on donor safety, vascular reconstruction and graft function in the recipient. To facilitate making an appropriate choice, on the basis of a preliminary study (n = 17), we herein propose a graft selection algorithm using three parameters: graft-to-recipient body weight ratio (GRWR), percentage remnant liver volume (%RLV) and estimated congestion ratio (ECR). The algorithm was evaluated with 50 consecutive cases with respect to postoperative liver function of donors and recipients and survival of recipients. Postoperative recovery was comparable between the two groups (p = NS). The overall cumulative 18-month survival rate was 86.7% for the 'with MHV graft group', and 76.1% for the gwithout MHV graft grouph (p = NS). For 41 cases (82%), graft types were chosen according to the algorithm, whereas the remaining 9 cases (18%) needed detailed discussion of donor, recipient and operative factors. In conclusion, we constructed a graft selection algorithm based on congestion volume, which will contribute to objective graft-type selection in adult-to-adult LDLT.

Neurologic complications in adult living donor liver transplant recipients

Neurologic complications (NC) after liver transplantation are not uncommon, with serious complications such as central pontine myelinolysis (CPM), often causing disability. We investigated the incidence and features of NC following liver transplantation in adult recipients. We retrospectively reviewed the medical records of 319 adult patients who underwent liver transplantation between January 2004 and May 2005 at the Asan Medical Center. Neurologic complications developed in 49 of 319 patients (15.4%). Although most of these complications were minor, including tremor and foot drop, three patients developed CPM, and one each developed posterior leukoencephalopathy, cerebral hemorrhage, and cerebral infarction. One-yr survival rates were 95.9% in patients without NC and 83.7% in patients with NC (p = 0.004). Hospital stay was prolonged in patients with NC. Graft-to-recipient body weight ratio (GRWR) did not affect occurrence of NC. Neurologic complications were not uncommon in liver transplant recipients. These complications contributed to prolongation of hospital stay, increased in-hospital mortality, and decreased graft and patient survival. Every effort should be made to prevent NC, as well as to detect and treat them as soon as possible.

Factors affecting graft survival after living donor liver transplantation

Living donor liver transplantation (LDLT) has been considered as an alternative option to resolve the shortage of cadaveric donor organs, despite the ethical aspects of the donor procedure. The objective of this study was to analyze the risk factors affecting graft survival in LDLT. From June 1996 to December 2002, 141 patients who underwent LDLT were retrospectively analyzed. Graft survival rates were 82.5%, 80%, 77.3%, and 77.3% at 6 months, 1 year, 3 years, and 5 years, respectively. The factors influencing graft survival in univariate analysis were graft-to-recipient body weight ratio (GRWR) less than 0.8% ( P = .0009), intraoperative transfusion of more than six packed RBC units in addition to the use of cell saver amounts ( P = .0001), left lobe grafts in adults causing small-for-size situations ( P = .0135), and donor age ( P = .0472). The multivariate analysis demonstrated that GRWR less than 0.8% ( P = .002) and intraoperative transfusion of more than six packed RBC units ( P = .014) were independent factors that decreased graft survival rates. The graft selection of greater than 0.8% of GRWR and reduction of intraoperative RBC transfusion improve graft survival.