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Calcineurin inhibitors (CNIs), which are potent immunosuppressants (ISs), increase the risk for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LTx). Epithelial-mesenchymal transition (EMT) is a key process in which epithelial cancer cells lose their polarity, resulting in cancer progression and metastasis. The aim of this study was to evaluate the effect of sirolimus (SRL) individually and in combination with other ISs to reduce EMT.HCC SK-Hep1 cells were used and various ISs (SRL, tacrolimus, cyclosporine A, or mycophenolate mofetil) were administered at 2 dosages and in combination therapies. Mice were transplanted with SK-Hep1 cells (in the liver) and were monitored after 2 weeks.The in vitro treatment with SRL showed a dose-dependent attenuation of cell proliferation and migration in case of the individual and IS combination treatments; further, decreased levels of pro-EMT proteins, namely, N-cadherin, transforming growth factor-β, ZEB1, Slug, and Snail were observed. In contrast, E-cadherin expression was upregulated after both the individual and IS combination treatments. These results were also observed in the samples from mice transplanted with the SK-Hep1 cells.The present study demonstrated that SRL reduced HCC metastasis by inhibiting EMT. Thus, our findings provide a rationale for the use of SRL in combination with ISs in HCC LTx patients.

BACKGROUND Living liver donation is generally considered safe, but donors may experience short or long-term complications. The purpose of this study was to assess healthcare resource utilization after liver donation in living liver donors in comparison to the general population. METHODS Outpatient or emergency department visits and hospital admissions were compared between living liver donors who underwent hepatic resection for living liver donation between 2004 and 2018 and the matched general population. Healthcare resource utilization data for 5 years after liver donation were collected from the National Health Insurance Service (NHIS) database. For every living liver donor, 4 individually matched nondonors were selected from the NHIS database using age, sex, preexisting comorbidities, and previous healthcare utilization history. RESULTS A total of 1886 living liver donors and 7309 nondonors were included. In the first year after donation, living liver donors required more outpatient department visits (7 [4-13] vs. 3 [1-7], P < 0.001) and more emergency department visits (13.33% vs. 0.15%, P < 0.001) compared to matched nondonors. A similar trend persisted for 5 years after donation. The number of hospital admissions of living liver donors was higher for up to 2 years after donation with longer hospital length of stay (13.0 [10.5-16.0] vs. 5.0 [3.0-9.0] days, P < 0.0001). CONCLUSIONS Healthcare resource utilization in living liver donors for 5 years after donation were higher compared to matched nondonors. The higher healthcare resource demand may be related to postoperative complications or lowered threshold for healthcare resource utilization after donation.Supplemental Visual Abstract; http://links.lww.com/TP/C291.

Minimally invasive surgery has been introduced for liver transplantations. Although laparoscopic or robot-assisted living donor hepatectomy is being used, minimally invasive surgery is rarely performed in recipients during liver transplantation. A 63-year-old patient (body mass index: 21.9 kg/m

Pure laparoscopic donor right hepatectomy is a complex procedure, and the safety and feasibility of this operation remain unclear. This study aimed to evaluate the clinical outcomes and learning curve of this operation performed by a single surgeon.We retrospectively reviewed the initial 100 donors who underwent pure laparoscopic donor right hepatectomy or open donor right hepatectomy by a single surgeon from December 2012 to May 2019. Endpoints analyzed included intraoperative results, postoperative complications, and learning curve, which was evaluated using the cumulative sum method based on the operation time. We divided the pure laparoscopic donor right hepatectomy group into initial and recent groups based on the time point of overcoming the learning curve.The operative time was significantly shorter in the recent pure laparoscopic donor right hepatectomy group (n = 57; 181.0 ± 35.7 min) than in the open donor right hepatectomy (n = 50; 203.0 ± 37.3 min) and initial pure laparoscopic donor right hepatectomy (n = 43; 282.2 ± 59.2 min) groups (P.001). Moreover, the length of hospital stay in the recent pure laparoscopic donor right hepatectomy group was significantly reduced compared to that in the open donor right hepatectomy group (7.7 ± 1.2 vs 5.8 ± 1.4; P.001). The complication rate was reduced from 10% in the open donor right hepatectomy group and 8% in the initial pure laparoscopic donor right hepatectomy group to 2% in the recent pure laparoscopic donor right hepatectomy group.As technology advances, the surgical outcomes of pure laparoscopic donor right hepatectomy are comparable and the operation time of pure laparoscopic donor right hepatectomy is superior to those of open donor hepatectomy.

Donor-type ABO blood group antigens (dABOAgs) have been detected in ABO-incompatible adult living donor liver transplantation (ABOi ALDLT) grafts, but their fate and role in ABOi ALDLT rejection remain uncertain.The 0-day,1-month, and 1-year serial liver graft biopsies from thirty ABOi ALDLT recipients were retrospectively evaluated. ABO antigen expression was quantitatively and serially measured by the mean number of positively-stained vascular structures (endothelium of the capillaries, arteries, hepatic veins, and portal veins) within the portal tracts (sS).The dABOAg sS counts of 0-day,1-month, and 1-year liver graft biopsies (32.3, 20.8, and 20.6, respectively) decreased significantly (p 0.001). Early rejection in the1-month biopsy was observed in 8/30 (26.7%) recipients, four (13.3%) of whom showed antibody-mediated rejection. The sS counts tended to rebound in grafts showing early rejection, with minimal changes from the 0-day to1-month period, but increased to pre-transplantation levels after 1 year, compared to that in grafts without early rejection (36.0, 20.4, 19.6 vs. 23.7, 21.9, 23.0, respectively; p = 0.040).While dABOAg expression decreased after ABOi ALDLT, recipients showing early rejection showed sustained graft dABOAg expression. Therefore, dABOAg expression may be involved in the mechanism of accommodation in ABOi transplantation.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare delayed-type hypersensitivity reaction that causes skin abnormalities and mucosal involvement of the entire body. This is a case report of DRESS occurring in a liver transplantation recipient after taking drugs. A 57-year-old female patient with hepatocellular carcinoma underwent living donor liver transplantation in April 2019. She had no previous medical histories relevant to allergic diseases. There were no adverse events during hospitalization. She was admitted to evaluate and treat a headache occurring at one month after transplantation. However, she suffered from adverse drug reactions after taking anticonvulsants, showing skin rash, itching sense, and fever with eosinophilia. Piperacillin/Tazoperan was administered for ten days as an empirical antibiotic. Skin biopsy was performed on postoperative day 106 for erythematous maculopapular rash in the arms, legs, and torso. Her symptoms improved after discontinuation of the suspected medication with conservative skin treatment and high-dose steroid treatment. This case suggests that suspicion of drug history is essential for early diagnosis and management of DRESS.

Factors of early and late recurrence after curative resection of hepatocellular carcinoma (HCC) may be different. The aim of this study was to identify clinical factors, including liver stiffness measurement (LSM), which are associated with HCC recurrence after curative resection. Patients who underwent preoperative LSM and primary curative resection for HCC between October 2015 and May 2018 were retrospectively reviewed, with 1 year as the cut-off between early and late recurrence. Recurrence was observed in 42/149 (28.2%) patients over a median follow-up of 38.3 months (early recurrence: 10 [6.7%] patients; late recurrence: 32 [21.5%] patients). Multivariate analysis identified LSM (P = 0.026) and tumor size (P = 0.010) as the only factors that were significantly associated with recurrence-free survival. Compared with patients without recurrence, those with early recurrence had larger tumor size (P = 0.035) and those with late recurrence had higher LSM (P = 0.024). Receiver-operating characteristic analysis indicated that the optimal LSM cut-off value for predicting HCC recurrence was 7.4 kPa. Tumor size was associated with early HCC recurrence after curative resection and LSM was associated with late recurrence. LSM cut-off of 7.4 kPa is recommended in predicting recurrence.

BACKGROUND Accurate volumetric evaluation of donors' livers before surgery is crucial for successful living-donor liver transplantation. However, there are few studies on the volumetric evaluation in the recently popularized pure laparoscopic donor hepatectomy method, in contrast to the number of studies for conventional donor hepatectomy. We aimed to analyze the difference between estimated graft weight and actual graft weight in pure laparoscopic donor right hepatectomy (PLDRH) and conventional donor right hepatectomy (CDRH) procedures. MATERIAL AND METHODS The medical records of 612 donors who underwent right hepatectomy in living-donor liver transplantation between January 2014 and December 2020 were retrospectively reviewed. The CDRH group targeted patients from January 2014 to October 2015, and the PLDRH group targeted patients from March 2016 to December 2020. RESULTS There were 119 and 376 donors who underwent CDRH and PLDRH, respectively. Although there was no significant difference in the estimated graft weights (P=0.994) and actual graft weights (P=0.489) between the groups, the estimated graft weights were significantly higher than the actual graft weights in both groups. However, the estimated graft weight and actual graft weight showed linear correlations in both the CDRH (r=0.81, P0.001) and PLDRH (r=0.76, P0.001) groups, with the CDRH group having greater linearity. CONCLUSIONS The estimates of graft weight were similar between the 2 groups. However, since the actual graft weight tended to be smaller in the PLDRH group, this should be considered before surgery.

Pediatric acute liver failure (PALF) is a common cause of liver transplantation (LT) but showed poor post-LT outcomes. We reviewed 36 PALF patients and 120 BA patients who underwent LT in our institution. The cause of PALF was unknown in 66.7%. PALF patients were older (6.2 vs. 2.9 years) with higher PELD scores (31.5 vs. 24.4) and shorter waitlist time (15.7 vs. 256.1 days) (p < 0.01). PALF patients showed higher rates of post-transplant renal replacement therapy (RRT) (13.9% vs. 4.2%) and hepatic artery complications (13.9% vs. 0.8%), while portal vein complications rates were lower (0% vs. 10.8%), (p < 0.05). Although PALF patients showed lower 5-year survival rates (77.8% vs. 95.0 %, p < 0.01), the 5-year survival rates of patients who lived beyond the first year were comparable (96.6% vs. 98.3%, p = 0.516). The most common cause of deaths within one year was graft failure (75.0%) in PALF patients, but infection (67.7%) in BA patients. In multivariate analysis, lower body weight, hepatic artery complications and post-transplant RRT were associated with worse survival outcomes (p < 0.05). In conclusion, physicians should be alert to monitor the immediate postoperative graft dysfunction and hepatic artery complications and patients on post-transplant RRT in order to improve survival outcomes in PALF patients.

The impact of renal replacement therapy (RRT) on the long-term survival outcomes of pediatric liver recipients remains controversial.A total of 224 patients aged18 years, who underwent liver transplantation (LT), were divided into two groups: patients who underwent renal replacement therapy (RRT) (group R, n = 25, 11.2%) and those who did not (group N, n = 199, 88.8%). The posttransplant patient survival outcomes according to RRT use constituted the primary end-point. RRT was initiated preoperatively in 12 patients (48.0%) and postoperatively in 13 [early:6 months after LT (n = 5, 20.0%) and late: ≥6 months after LT (n = 8, 32.0%)]. The indications for RRT included liver disease involving the kidney (44.0%) and hepatorenal syndrome (56.0%).The age at the time of LT (71.6 vs. 19.1 months) was higher, the pediatric end-stage liver disease score was lower (9.9 vs. 21.2), and the duration of hospitalization posttransplantation (41.0 vs. 27.0 days) was longer, while the rates of hepatic artery thrombosis (8.0% vs. 3.5%) were higher in group R (p .05). The number of patients (60.0% vs. 93.0%; p .001) and graft survival rates (68.0% vs. 93.0%; p .001) were significantly lower in group R. Multivariate analysis revealed that posttransplant RRT and hepatic artery complications were risk factors for patient survival outcomes. Renal function was recovered in 7 patients (28.0%) in group R, and 9 (36.0%) eventually underwent kidney transplantation.The survival outcomes of children requiring posttransplant RRT were significantly worse than those of children, who did not undergo RRT. Physicians should pay meticulous attention to patients requiring post-LT RRT.

Few data are available on discharge criteria after living liver donation(LLD).To identify the features for fit for discharge checklist after LLD to prevent unnecessary re-hospitalizations and to provide international expert recommendations.Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central.Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. The critical outcomes included were complications rates and liver function (defined by elevated bilirubin and INR) (CRD42021260725).57/1710 studies were included in qualitative analysis and 28/57 on the final analysis. No randomized controlled trials were identified. The complicatios rate was reported in 20/28 studies and ranged from 7,8% to 71,2%. Post hepatectomy liver function was reported in 13 studies. The Quality of Evidence(QoE) was Low and Very-Low for complications rate and liver function test, respectively.Monitoring and prevention of donor complications should be crucial in decision making of discharge. Pain and diet control, removal of all drains and catheters, deep venous thrombosis prophylaxis and use routine imaging (CT scan or liver ultrasound) before discharge should be included as fit for discharge checklist(QoE; Low | GRADE of recommendation; Strong). Transient Impaired liver function (defined by elevated bilirubin and INR), a prognostic marker of outcome after liver resection, usually occurs after donor right hepatectomy and should be monitored. Improving trends for bilirubin and INR value should be observed by day 5 post hepatectomy and be included in the fit for discharge checklist. (QoE; Very-Low | GRADE; Strong). This article is protected by copyright. All rights reserved.

Indocyanine green (ICG) near-infrared fluoroscopy has been recently implemented in pure laparoscopic donor hepatectomy (PLDH). This study aims to quantitatively evaluate the effectiveness of ICG fluoroscopy during liver midplane dissection in PLDH and to demonstrate that a single injection of ICG is adequate for both midplane dissection and bile duct division. Retrospective analysis was done with images acquired from recordings of PLDH performed without ICG (pre-ICG group) from November 2015 to May 2016 and with ICG (post-ICG group) from June 2016 to May 2017. 30 donors from the pre-ICG group were compared with 46 donors from the post-ICG group. The operation time was shorter (P = 0.002) and postoperative peak aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were lower (P = 0.031 and P = 0.019, respectively) in the post-ICG group than the pre-ICG group. Within the post-ICG group, the color intensity differences between the clamped versus nonclamped regions in the natural, black-and-white, and fluorescent modes were 39.7 ± 36.2, 89.6 ± 46.9, and 19.1 ± 36.8 (mean ± SD, P < 0.001), respectively. The luminosity differences were 37.2 ± 34.5, 93.8 ± 32.1, and 26.7 ± 25.7 (P < 0.001), respectively. Meanwhile, the time from when ICG was injected to when the near-infrared camera was turned on for bile duct visualization was 85.6 ± 25.8 minutes. All grafts received from the 46 donors were successfully transplanted. In conclusion, ICG fluoroscopy helps to reduce operation time and lower postoperative AST/ALT levels. ICG injection visualized with black-and-white imaging is most effective for demarcating the liver midplane during PLDH. A single intravenous injection of ICG is sufficient for midplane dissection as well as bile duct division.

This study aimed to classify the anatomical types of biliary strictures, including intrahepatic biliary stricture (IHBS), after living donor liver transplantations (LDLTs) using right liver grafts and evaluate their prognosis. Among 692 adult patients who underwent right liver LDLT, 198 recipients with biliary strictures (28.6%) were retrospectively reviewed. Based on data obtained during the first cholangiography, the patients' biliary strictures were classified into the following three types according to the levels and number of branches involved: Types 1 (anastomosis), 2 (second-order branch [a, one; b, two or more; c, extended to the third-order branch]), and 3 (whole graft [a, multifocal strictures; b, diffuse necrosis]). IHBS was defined as a nonanastomotic stricture. Among the 198 recipients with biliary strictures, the IHBS incidence rates were 38.4% (n = 76). The most common type of IHBS was 2c (n = 43, 56.6%), whereas Type 3 (n = 10, 13.2%) was uncommon. The intervention frequency per year significantly differed among the types (Type 1, 2.3; Type 2a, 2.3; Type 2b, 2.8; Type 2c, 4.3; and Type 3, 7.2; p 0.001). The intervention-free period for more than 1 year, which was as follows, also differed among the types: Type 1, 84.4%; Type 2a, 87.5%; Type 2b, 86.7%; Type 2c, 72.1%; and Type 3, 50.0% (p = 0.048). The graft survival rates of Type 3 (80.0%) were significantly lower than those of the other types (p = 0.001). IHBSs are relatively common in right liver LDLTs. Although Type 3 IHBSs are rare, they require more intensive care and are associated with poorer graft survival rates than anastomosis strictures and Type 2 IHBS.

Since minimally invasive surgery has been incorporated in overall surgery, pure laparoscopic technology is involved in most hepatectomies, including right hepatectomy, in patients with hepatocellular carcinoma (HCC). However, its feasibility and safety in right hepatectomy are still controversial owing to the limited literature. This study aimed to compare the short- and long-term outcomes of pure laparoscopic right hepatectomy (PLRH) with those of open right hepatectomy (ORH) in patients with HCC.The prospectively collected medical records of 327 patients with HCC who underwent right hepatectomy between January 2010 and April 2020 at Seoul National University Hospital were retrospectively reviewed. We performed 1:1 propensity score matching between the PLRH and ORH groups. The primary end point was short-term outcomes, including hospital stay, blood loss, and morbidity; the secondary end point was long-term outcomes, including overall and recurrence-free survival.Forty-nine patients were included in each group. Patients who underwent PLRH had a shorter postoperative hospital stay than those who underwent ORH (12.2 vs 8.9 days; P .001). The requirement for blood transfusion was significantly lower in the PLRH group than in the ORH group (10.2% vs 2.0%; P = .010). The operative time (P = .479) and proportion of major complications (P = .487) were comparable between the groups. There were no significant differences in overall survival (P = .524) and the recurrence-free survival rate (P = .576) between the groups.Postoperative outcomes, including oncological outcomes, were comparable between PLRH and ORH, showing that PLRH can be a safe and feasible option to replace ORH in patients with HCC.

In recent years, laparoscopic techniques for liver resection or living donor hepatectomy have become common surgical methods. However, reports on laparoscopic surgeries for recipients are lacking. Our center has launched the minimally invasive living donor liver transplantation (LDLT) program in March 2020, which is led by two surgeons who are experienced in laparoscopic surgeries. Recently, we reported our first successful pure laparoscopic recipient explant hepatectomy and the first laparoscopic explant hepatectomy and robotic-assisted graft implantation. In this article, we introduce a series of minimally invasive surgical cases that were conducted by a single experienced surgeon to share our early experiences leading to our recent successes. We included 10 cases performed from June 2020 to May 2021 in our initial attempt at laparoscopic explant hepatectomy, graft implantation using midline incision, and robotic-assisted graft implantation surgery. The first four cases required open conversion during the liver mobilization process because of bleeding. The next two cases required open conversion to facilitate portal vein and hepatic artery division. We successfully performed pure laparoscopic explant hepatectomy in the last four cases. For the last case, we attempted to perform graft implantation using a robotic system, but bleeding required open conversion. All patients recovered without any significant acute postoperative problems and were discharged within 2 weeks. All 10 patients were followed up at outpatient clinics, and only one of the 10 patients had a late complication of LDLT. This study has shown that the minimally invasive approach in LDLT may be conducted safely without significant complications if it is performed by highly experienced surgeons working in high-volume centers.

Liver cancer is a leading cause of death worldwide where somatic mutation plays a key role in tumorigenesis. As such, many recent researches have been conducted using DNA sequencing methods to study somatic mutations in liver cancer, such as whole-exome sequencing (WES), panel sequencing, and whole-genome sequencing (WGS). However, our understanding of genomic landscape of liver tumorigenesis has been limited by a low number of quality samples from diverse clinical contexts. Here, we explore comprehensive genomic landscape of liver cancer throughout its tumorigenesis using large-scale whole-genome sequencing of hepatocellular carcinoma (HCC) in various cancer stages and liver conditions. Total 500 patients of HCCs were enrolled in this study and whole-genome sequenced. 462 samples that passed quality control were included for final analysis. Most of the samples (427; 92%) were obtained from surgical resection and the rest (35; 8%) from liver transplantation. We used a standard WGS analysis pipeline from read mapping to variant calling of single-base substitution (SBS), indel, structural variation (SV), and copy number variation (CNV). Downstream data analyses were performed using in-house scripts with a particular focus on mutational signatures. To study how genome changes as HCC progresses, we classified samples into three groups by T stage: T1, T2, and T3/4. The number of samples for each group was 205 (44%), 222 (48%), and 35 (8%), respectively. There was no significant difference in the number of SBSs and indels, but the number of SVs was significantly higher in T3/4 (the mean of T1/2 vs. T3/4 = 51 vs. 93; p=0.001). Major mutational signatures were SBS5, 40 (both clock-like), 12 (unknown), and 22 (aristolochic acid) for SBSs and ID1, 2, 5 (all clock-like), and 3 (tobacco smoking) for indels. The proportion of ID2, characterized by 1bp deletion at homopolymer site, was increased in the samples of higher T stage (the mean proportion of T1/2 vs. T3/4=11% vs. 16%; p=0.01). The higher-stage samples also harbored more frequent whole-genome duplication (WGD) and loss of heterozygosity (LOH) (the frequency of WGD in T1/2 vs. T3/4=42% vs. 68%, p Citation Format: Seongyeol Park, Suk Kyun Hong, Joonoh Lim, YoungRok Choi, Boram Yi, Jaemo Koo, June-Young Koh, Ryul Kim, Nam-Joon Yi, Jeong Seok Lee, Kyung-Suk Suh, Kwang-Woong Lee, Young Seok Ju. Large-scale whole genome sequencing of hepatocellular carcinoma reveals stepwise cancer evolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2056.

In living donor liver transplantation (LDLT) of the right lobe, polytetrafluoroethylene (PTFE) grafts may be used for anterior drainage. This study aimed to determine the risk factors of PTFE graft-associated complications. Data from patients who underwent LDLT of the right lobe with middle hepatic vein reconstruction using PTFE grafts between January 2005 and December 2012 were retrospectively reviewed. Among 360 patients, PTFE graft-associated complications occurred in 17 patients (group B) (4.7%); recipients without these complications comprised group A (95.3%). The 1-, 6- and 12-month patency rates were significantly lower in group B (P < 0.001, P = 0.002 and P = 0.007). In group B, eight patients (47.1%) required surgical intervention, three patients (17.6%) suffered from infectious complications, and 14 patients (82.4%) experienced PTFE graft migration into the adjacent organs, namely the common bile duct (n = 3, 17.6%), stomach (n = 1, 5.9%), duodenum (n = 5, 29.4%) and jejunum (n = 5, 29.4%). The proportion of recipients who underwent hepaticojejunostomy, had abdominal adhesions and received interventions in/around the liver after LDLT was higher in group B (P < 0.001). Although the incidence of PTFE graft-associated complication is low, close long-term follow-up is needed, especially in patients with risk factors.

Objective The Expert Consensus Guidelines initiative on MIDH for LDLT was organized with the goal of safe implementation and development of these complex techniques with donor safety as the main priority. Background Following the development of minimally invasive liver surgery, techniques of MIDH were developed with the aim of reducing the short- and long-term consequences of the procedure on liver donors. These techniques, although increasingly performed, lack clinical guidelines. Methods A group of 12 international MIDH experts, 1 research coordinator, and 8 junior faculty was assembled. Comprehensive literature search was made and studies classified using the SIGN method. Based on literature review and experts opinions, tentative recommendations were made by experts subgroups and submitted to the whole experts group using on-line Delphi Rounds with the goal of obtaining >90% Consensus. Pre-conference meeting formulated final recommendations that were presented during the plenary conference held in Seoul on September 7, 2019 in front of a Validation Committee composed of LDLT experts not practicing MIDH and an international audience. Results Eighteen Clinical Questions were addressed resulting in 44 recommendations. All recommendations reached at least a 90% consensus among experts and were afterward endorsed by the validation committee. Conclusions The Expert Consensus on MIDH has produced a set of clinical guidelines based on available evidence and clinical expertise. These guidelines are presented for a safe implementation and development of MIDH in LDLT Centers with the goal of optimizing donor safety, donor care, and recipient outcomes.

There is much controversy regarding enhanced recovery for recipients of liver transplants from deceased and living donors. The objectives of this Review were to summarise current knowledge on individual enhanced recovery elements on short-term outcomes, identify key components for comprehensive pathways, and create internationally accepted guidelines on enhanced recovery for liver-transplant recipients. The ERAS4OLT.org collaborative partnered by the International Liver Transplantation Society performed systematic literature reviews on the effect of 32 relevant enhanced perioperative recovery elements on short-term outcomes, and global specialists prepared expert statements on deceased and living donor liver transplantation. The Grading Recommendations, Assessment, Development and Evaluations approach was used for rating of quality of evidence and grading of recommendations. A virtual international consensus conference was held in January, 2022, in which results were presented, voted on by the audience, and discussed by an independent international jury of eight members, applying the Danish model of consensus. 273 liver transplantation specialists from 30 countries prepared expert statements on elements of enhanced recovery for liver transplantation based on the systematic literature reviews. The consensus conference yielded 80 final recommendations, covering aspects of enhanced recovery for preoperative assessment and optimisation, intraoperative surgical and anaesthetic conduct, and postoperative management for the recipients of liver transplants from both deceased and living donors, and for the living donor. The recommendations represent a comprehensive overview of the relevant elements and areas of enhanced recovery for liver transplantation. These internationally established guidelines could direct the development of enhanced recovery programmes worldwide, allowing adjustments according to local resources and practices.

BACKGROUND The number of pediatric patients awaiting liver transplantation has decreased. Due to its increased use in Korea, split liver transplantation (SLT) may be a substitute for living donor liver transplantation (LDLT); however, the outcomes of pediatric SLT and LDLT in Korea remain unreported. MATERIAL AND METHODS We reviewed data of Korean patients aged18 years who received SLT from 2005 to 2014, based on the Korea national database and compared to recipients who underwent LDLTs at Seoul National University Hospital during the same period. RESULTS A total of 63 and 56 patients were included in SLT and LDLT, respectively. The most common indication for LT was biliary atresia (60.3% in SLT vs 67.9% in LDLT). The Pediatric End-Stage Liver Disease score did not differ between the groups (P0.05). The 1-, 3-, and 5-year overall survival rates were 92.1%, 90.2%, and 86.6% in the SLT and 96.4%, 94.6%, and 94.6% in the LDLT groups, respectively (P=0.21); the corresponding graft survival rates were 88.9%, 87.1%, and 83.6% in the SLT and 92.9%, 91.0%, and 91.0% in the LDLT groups, respectively (P=0.31). Fulminant hepatic failure was a risk factor for graft failure [OR, 8.77 (1.08-70.92); P=0.042], but not overall survival [OR, 11.78 (0.56-247.29); P=0.11]. CONCLUSIONS The graft and overall survival rates of SLT and LDLT were not different in pediatric patients in Korea, and fulminant hepatic failure was the only risk factor affecting graft survival outcomes.

Background: The effects of multidrug resistance-1 (MDR1), ABCC2, and P450 oxidoreductase (POR)*28 gene polymorphisms on tacrolimus metabolism following a switch to once-daily dosing have not been elucidated. We investigated the effects of recipient and donor CYP3A5, MDR1, ABCC2, and POR*28 polymorphisms on tacrolimus pharmacokinetics following a switch to once-daily tacrolimus dosing.Methods: Eighty-seven liver transplant recipients who were switched from twice- to once-daily tacrolimus dosing following living-donor liver transplantation and 81 matched donors were genotyped for CYP3A5, MDR1 (1236C>T, 2677G>T/A, and 3435C>T), ABCC2 (-24C>T, 1249G>A, and 3972C>T), and POR*28. Tacrolimus dose-adjusted trough levels (C0/dose) before and after the switch were determined and calculated based on past medical records. Recipients were divided into two groups, one group constituted of 38 patients with a C0/dose decrease of less than 30% following conversion (group 1) and the other constituted of 49 patients with a C0/dose decrease of ≥30% (group 2).Results: CYP3A5 *1/*3 and *3/*3 were more frequent in recipients in group 1 (60.5% vs. 36.8%), while CYP3A5 *1/*1 was more frequent in group 2 (59.2% vs. 32.7%) (p = 0.016). The proportions of donor ABCC2 1249G>A genotypes AA and AG were higher in group 2 than in group 1 (20.4% vs. 5.3%; p = 0.042). Conclusion: Recipient CYP3A5 polymorphism and donor ABCC2 1249G>A polymorphism affected tacrolimus pharmacokinetics following the switch to once-daily dosing. Dose adjustment to maintain therapeutic tacrolimus levels following the switch to once-daily dosing should be considered based on polymorphisms in both the recipient and donor.