Anti-intercellular adhesion molecule 1 monomaintenance therapy induced long-term liver allograft survival without chronic rejection.

Calcineurin inhibitors (CNIs) are essential in liver transplantation (LT); however, their long-term use leads to various adverse effects. The anti-intercellular adhesion molecule (ICAM)-1 monoclonal antibody MD3 is a potential alternative to CNI. Despite its promising results with short-term therapy, overcoming the challenge of chronic rejection remains important. Thus, we aimed to investigate the outcomes of long-term MD3 therapy with monthly MD3 monomaintenance in nonhuman primate LT models. Rhesus macaques underwent major histocompatibility complex-mismatched allogeneic LT. The conventional immunosuppression group (Con-IS, n = 4) received steroid, tacrolimus, and sirolimus by 4 months posttransplantation. The induction MD3 group (IN-MD3, n = 5) received short-term MD3 therapy for 3 months with Con-IS. The maintenance MD3 group (MA-MD3, n = 4) received MD3 for 3 months, monthly doses by 2 years, and then quarterly. The MA-MD3 group exhibited stable liver function without overt infection and had significantly better liver allograft survival than the IN-MD3 group. Development of donor-specific antibody and chronic rejection were suppressed in the MA-MD3 group but not in the IN-MD3 group. Donor-specific T cell responses were attenuated in the MA-MD3 group. In conclusion, MD3 monomaintenance therapy without maintenance CNI provides long-term liver allograft survival by suppressing chronic rejection, offering a potential breakthrough for future human trials.

Insights from Seoul National University Hospital's experience: a systematic review of pure laparoscopic donor hepatectomy progression.

Following its initial execution in November 2015, pure laparoscopic donor hepatectomy (PLDH) has gained acceptance as a conventional practice at Seoul National University Hospital (SNUH). It is noteworthy that a significant proportion of cases entail full right hepatectomies, which are acknowledged to be technically demanding. As expertise and knowledge have been accrued, the pure laparoscopic technique has been extended to encompass liver recipients as a viable option in SNUH. The aim of this review is to present the developmental progression of PLDH, with a focus on pure laparoscopic donor right hepatectomy (PLDRH), at SNUH. This includes the standardization process, which can be achieved by sharing the hospital's accumulated experience and previous reports. Various types of graft, including full right, left, left lateral section, and monosegment, were procured by pure laparoscopic technique. The criteria for selection were expanded to include donors with variations in the anatomy of the portal vein and bile duct. Additionally, the procedure of PLDRH was determined to be safe and viable for donors with high body mass index and larger graft weight. In conclusion, this review demonstrates the alterations implemented throughout our evolution from restricted to inclusive criteria for donor selection, leading to a complete shift from open surgery to pure laparoscopic procedures in donor hepatectomy and eventually pure laparoscopic living donor liver transplantation (LDLT) in recipient.

Donor body mass index over 30 is no barrier for pure laparoscopic donor right hepatectomy.

Backgrounds/Aims: Challenges arise when translating pure laparoscopic donor right hepatectomy (PLDRH) results from Asian to Western donors, due to differences in body mass index (BMI). This study compares the outcomes of PLDRH and conventional open donor right hepatectomy (CDRH) in donors with BMI over 30. Methods: Medical records of live liver donors (BMI > 30) undergoing right hepatectomy (2010-2021) were compared: 25 PLDRH cases vs. 19 CDRH cases. Donor and recipient demographics, operative details, and outcomes were analyzed. Results: PLDRH and CDRH had similar donor and recipient characteristics. PLDRH had longer liver removal and warm ischemic times, but a shorter post-liver removal duration than CDRH. Donor complication rates were comparable, with the highest complication being grade IIIa in PLDRH, necessitating needle aspiration for biloma on postoperative day 11. Fortunately, this donor fully recovered without additional treatment. No complications exceeding Clavien-Dindo grade IIIa occurred in either group. Recipient outcomes between the groups were similar. Conclusions: This study supports PLDRH as a viable option for donors with BMI over 30, challenging the notion that high BMI should deter considering PLDRH. The findings provide valuable insights into the safety and feasibility of PLDRH, encouraging further exploration of this technique in diverse donor populations.

Impact of Preformed Donor-specific Antibodies in Comparison to ABO Incompatibility in Living Donor Liver Transplantation: A Propensity Score-Matched Analysis.

BACKGROUND: Immunological factors play a pivotal role in the outcomes of solid organ transplantation. We aimed to elucidate the effects of donor-specific antibodies (DSAs) and ABO compatibility on living donor liver transplantation (LDLT) outcomes. METHODS: A retrospective analysis was conducted on 584 LDLT recipients from 2015 to 2020. The recipients were stratified into 3 groups: ABO-compatible recipients without DSAs (group 1), ABO-compatible recipients with DSAs (group 2), and ABO-incompatible recipients without DSAs (group 3). Propensity score matching was used for balanced comparisons. RESULTS: In the matched comparisons, group 2 exhibited a higher incidence of T cell-mediated rejection compared with group 1 (22.7% versus 4.5%, P = 0.030). Despite this, the 5-y survival rates were similar between groups 1 and 2 (81.6% versus 95.5%, P = 0.085). Group 3, in comparison with group 1, showed elevated rates of cytomegalovirus infection (23.2% versus 7.3%, P = 0.008), T cell-mediated rejection (28.0% versus 7.3%, P = 0.001), and antibody-mediated rejection (13.4% versus 0%, P = 0.001). However, the survival rates were comparable between group 3 and group 1 (82.0% versus 86.5%, P = 0.220, respectively). Comparisons between group 2 and group 3 did not reveal significant differences in postoperative outcomes or survival rates (P > 0.05). CONCLUSIONS: DSA positivity and ABO incompatibility contribute to distinct posttransplant complications in LDLT. The integrated consideration of both factors in pretransplant assessment may enhance risk stratification and inform tailored interventions. Further research is required to corroborate these findings and provide mechanistic insights.

Criteria for selecting living liver donors to optimize recipient outcomes in pure laparoscopic donor right hepatectomy: a cohort study.

BACKGROUND: Although the adoption of pure laparoscopic donor hepatectomy has expanded driven by considerations of donor cosmesis and function, the criteria for selecting candidates for pure laparoscopic donor right hepatectomy (PLDRH) continue to be debated. This study aimed to delineate the distinctive characteristics of donors and recipients who underwent conventional open-donor right hepatectomy (CDRH) during the era of PLDRH. MATERIALS AND METHODS: We conducted a retrospective review of a prospectively collected single-center database encompassing all right hepatectomies at OOOO from April 2016 to December 2021, a period during which there were no absolute contraindications for PLDRH. RESULTS: During the exclusive PLDRH period, there were still 63 cases of CDRH alongside 362 cases of PLDRH. The CDRH donors were older, had a lower estimated remnant liver volume, and a higher incidence of expected multiple openings in the portal vein and bile duct based on preoperative imaging compared with PLDRH donors. In the subgroup analysis, including only donors meeting two or more criteria (age ≥40 y, estimated remnant liver volume ≥35%, or multiple anticipated vessel openings), recipients in the PLDRH group exhibited significantly more early major complications (P=0.029) compared with those in the CDRH group. CONCLUSION: As PLDRH gains traction in practice, it is essential to acknowledge that specific donor conditions, such as advanced age, limited remnant liver volume, and anticipation of multiple portal or bile duct openings, may merit contemplating CDRH as a means of optimizing recipient outcomes.

Risk factors for incisional hernia after liver transplantation in the era of mammalian target of rapamycin inhibitors use: a retrospective study of living donor liver transplantation dominant center in Korea.

Purpose: Incisional hernia (IH) is a common complication after liver transplantation (LT) with an incidence rate of 5% to 46%. This retrospective study aimed to evaluate the risk factors for IH development after LT in the era of mammalian target of rapamycin (mTOR) inhibitors use. Methods: Data on patients who underwent LT between 2015 and 2021 were retrospectively reviewed. The patients were divided into 2 groups (IH group and non-IH group) according to the postoperative occurrence of IH. Results: We analyzed data from 878 patients during the study period, with 28 patients (3.2%) developing IH. According to multivariate analysis, body mass index exceeding 25 kg/m2 and the use of mTOR inhibitors within the first month after LT were the sole significant factors for both IH occurrence and the subsequent need for repair operations. Notably, a history of wound complications, a Model for End-stage Liver Disease score, and the timing of LT-whether conducted during regular hours or at night-did not emerge as significant risk factors for IH after LT. Conclusion: Our study reveals a higher incidence of IH among obese patients following LT, often requiring surgical repair, particularly in cases involving mTOR inhibitor usage within the initial month after LT. Consequently, it is crucial to exercise increased vigilance, especially in obese patients, and exercise caution when considering early mTOR inhibitor administration after LT.

Comparison of postoperative ascites replacement strategies on time to first flatus after living donor liver transplantation: Albumin vs. lactated Ringer's solution.

INTRODUCTION: There is insufficient evidence regarding the optimal regimen for ascites replacement after living donor liver transplantation (LT) and its effectiveness. The aim of this study is to evaluate the impact of replacing postoperative ascites after LT with albumin on time to first flatus during recovery with early ambulation and incidence of acute kidney injury (AKI). METHODS: Adult patients who underwent elective living donor LT at Seoul National University Hospital from 2019 to 2021 were randomly assigned to either the albumin group or lactated Ringer's group, based on the ascites replacement regimen. Replacement of postoperative ascites was performed for all patients every 4 h after LT until the patient was transferred to the general ward. Seventy percent of ascites drained during the previous 4 h was replaced over the next 4 h with continuous infusion of fluids with a prescribed regimen according to the assigned group. In the albumin group, 30% of a total of 70% of drained ascites was replaced with 5% albumin solution, and remnant 40% was replaced with lactated Ringer's solution. In the lactated Ringer's group, 70% of drained ascites was replaced with only lactated Ringer's solution. The primary outcome was the time to first flatus from the end of the LT and the secondary outcome was the incidence of AKI for up to postoperative day 7. RESULTS: Among the 157 patients who were screened for eligibility, 72 patients were enrolled. The mean age was 63 ± 8.2 years, and 73.0 % (46/63) were male. Time to first flatus was similar between the two groups (66.7 ± 24.1 h vs. 68.5 ± 25.6 h, p = .778). The albumin group showed a higher glomerular filtration rate and lower incidence of AKI until postoperative day 7, compared to the lactated Ringer's group. CONCLUSIONS: Using lactated Ringer's solution alone for replacement of ascites after living donor LT did not reduce the time to first flatus and was associated with an increased risk of AKI. Further research on the optimal ascites replacement regimen and the target serum albumin level which should be corrected after LT is required.

Urinary microbiome-based metagenomic signature for the noninvasive diagnosis of hepatocellular carcinoma.

BACKGROUND: Gut microbial dysbiosis is implicated in chronic liver disease and hepatocellular carcinoma (HCC), but the role of microbiomes from various body sites remains unexplored. We assessed disease-specific alterations in the urinary microbiome in HCC patients, investigating their potential as diagnostic biomarkers. METHODS: We performed cross-sectional analyses of urine samples from 471 HCC patients and 397 healthy controls and validated the results in an independent cohort of 164 HCC patients and 164 healthy controls. Urinary microbiomes were analyzed by 16S rRNA gene sequencing. A microbial marker-based model distinguishing HCC from controls was built based on logistic regression, and its performance was tested. RESULTS: Microbial diversity was significantly reduced in the HCC patients compared with the controls. There were significant differences in the abundances of various bacteria correlated with HCC, thus defining a urinary microbiome-derived signature of HCC. We developed nine HCC-associated genera-based models with robust diagnostic accuracy (area under the curve [AUC], 0.89; balanced accuracy, 81.2%). In the validation, this model detected HCC with an AUC of 0.94 and an accuracy of 88.4%. CONCLUSIONS: The urinary microbiome might be a potential biomarker for the detection of HCC. Further clinical testing and validation of these results are needed in prospective studies.

Combined liver-kidney transplantation in pediatric patients.

Combined liver-kidney transplantation (CLKT) is a surgical procedure that involves transplanting both liver and kidney organs. There are two types of CLKT: simultaneous liver-kidney transplantation (smLKT) and sequential LKT (sqLKT). CLKT accounts for a small percentage of liver transplantations (LTs), particularly in pediatric cases. Nevertheless, the procedure has demonstrated excellent outcomes, with high survival rates and lower rejection rates. The main indications for CLKT in pediatric patients differ somewhat from that in adults, in which end-stage kidney disease after LT is the major indication. In children, congenital diseases are common reason for performing CLKT; the examples of such diseases include autosomal recessive polycystic kidney disease with congenital hepatic fibrosis which equally affects both organs, and primary hyperoxaluria type 1, a primary liver disease leading kidney failure. The decision between smLKT or sqLKT depends on the dominant organ failure, the specific pathophysiology, and available organ sources. However, there remain significant surgical and societal challenges surrounding CLKT. Innovations in pharmacology and genetic engineering have decreased the necessity for CLKT in early-diagnosed cases without portal hypertension or kidney replacement therapy. Nonetheless, these advancements are not universally accessible. Therefore, decision-making algorithms should be crafted, considering region-specific organ allocation systems and prevailing medical environments.

Recurrence-free Survival After Liver Transplantation Versus Surgical Resection for Hepatocellular Carcinoma: Role of High-risk MRI Features.

BACKGROUND: This study aimed to evaluate recurrence-free survival (RFS) and overall survival (OS) after liver transplantation (LT) or liver resection (LR) for hepatocellular carcinoma (HCC) and perform subgroup analysis for HCC with high-risk imaging findings for recurrence on preoperative liver magnetic resonance imaging (MRI; high-risk MRI features). METHODS: We included patients with HCC eligible for both LT and LR and received either of the treatments between June 2008 and February 2021 from 2 tertiary referral medical centers after propensity score-matching. RFS and OS were compared between LT and LR using Kaplan-Meier curves with the log-rank test. RESULTS: Propensity score-matching yielded 79 patients in the LT group and 142 patients in the LR group. High-risk MRI features were noted in 39 patients (49.4%) in the LT group and 98 (69.0%) in the LR group. The Kaplan-Meier curves for RFS and OS were not significantly different between the 2 treatments among the high-risk group (RFS, P = 0.079; OS, P = 0.755). Multivariable analysis showed that treatment type was not a prognostic factor for RFS and OS ( P = 0.074 and 0.937, respectively). CONCLUSIONS: The advantage of LT over LR for RFS may be less evident among patients with high-risk MRI features.

Pure laparoscopic donor hepatectomy: Experience of 556 cases at Seoul National University Hospital.

Pure laparoscopic donor hepatectomy (PLDH) has become a routine procedure at Seoul National University Hospital, and the pure laparoscopic method is now being applied to liver recipients as well. This study aimed to review the procedure and outcomes of PLDH to identify any areas that required improvement. Data from 556 donors who underwent PLDH between November 2015 and December 2021 and their recipients were retrospectively reviewed. Among these, 541 patients underwent pure laparoscopic donor right hepatectomy (PLDRH). The mean hospital stay of the donor was 7.2 days, and the rate of grade I, II, IIIa, and IIIb complications was 2.2%, 2.7%, 1.3%, and 0.9%, respectively, without any irreversible disabilities or mortalities. The most common early and late major complications in the recipient were intraabdominal bleeding (n = 47, 8.5%) and biliary problems (n = 198, 35.6%), respectively. Analysis of the PLDRH procedure showed that operative time, liver removal time, warm ischemic time, Δhemoglobin%, Δtotal bilirubin%, and postoperative hospital stay decreased significantly as the number of cases accumulated. In conclusion, the operative outcomes of PLDRH improved as the number of cases increased. However, continuous caution is needed because major complications still occur in donors and recipients even after hundreds of cases.

Preoperative assessment of microvascular invasion risk using gadoxetate-enhanced MRI for predicting outcomes after liver transplantation for single hepatocellular carcinoma within the Milan criteria.

OBJECTIVE: To compare therapeutic outcomes after liver transplantation (LT) between hepatocellular carcinomas (HCC) with low and high risk for microvascular invasion (MVI) within the Milan criteria evaluated preoperatively. METHODS: Eighty patients with a single HCC who underwent LT as the initial therapy between 2008 and 2017 were included from two tertiary referral medical centers in a HBV-predominant population. A preoperative MVI-risk model was used to identify low- and high-risk patients. Recurrence-free survival (RFS) after LT between the two risk groups was compared using Kaplan-Meier curves with the log-rank test. Prognostic factors for RFS were identified using a multivariable Cox hazard regression analysis. RESULTS: Eighty patients were included (mean age, 51.8 years +/- 7.5 [standard deviation], 65 men). Patients were divided into low-risk (n = 64) and high-risk (n = 16) groups for MVI. The RFS rates after LT were significantly lower in the MVI high-risk group compared to the low-risk group at 1 year (75.0% [95% CI: 56.5-99.5%] vs. 96.9% [92.7-100%], p = 0.048), 3 years (62.5% [42.8-91.4%] vs. 95.3% [90.3-100%], p = 0.008), and 5 years (62.5% [42.8-91.4%] vs. and 95.3% [90.3-100%], p = 0.008). In addition, multivariable analysis showed that MVI high risk was the only significant factor for poor RFS (p = 0.016). CONCLUSION: HCC patients with a high risk of MVI showed significantly lower RFS after LT than those without. This model could aid in selecting optimal candidates in addition to the Milan criteria when considering upfront LT for patients with HCC if alternative treatment options are available. CLINICAL RELEVANCE STATEMENT: High risk for microvascular invasion (MVI) in hepatocellular carcinoma patients lowered recurrence-free survival after liver transplantation, despite meeting the Milan criteria. Identifying MVI risk could aid candidate selection for upfront liver transplantation, particularly if alternative treatments are available. KEY POINTS: • A predictive model-derived microvascular invasion (MVI) high- and low-risk groups had a significant difference in the incidence of MVI on pathology. • Recurrence-free survival after liver transplantation (LT) for single hepatocellular carcinoma (HCC) within the Milan criteria was significantly different between the MVI high- and low-risk groups. • The peak incidence of tumor recurrence was 20 months after liver transplantation, probably indicating that HCC with high risk for MVI had a high risk of early (≤ 2 years) tumor recurrence.

Evaluation of the efficacy and safety of conversion from the tacrolimus capsule to tablet in stable liver transplant recipients with maintenance therapy: a 24-week, open-label, single-center, phase IV exploratory clinical study.

Purpose: The tablet form of tacrolimus is more convenient for drug ingestion than the capsule form. We examined the efficacy and safety of tacrolimus tablets and a satisfaction survey after formula conversion in liver transplant (LT) recipients. Methods: This study was an open-label, prospective clinical trial for tacrolimus formula 1:1 conversion from capsule to tablet in 41 adult LT recipients with tacrolimus maintenance therapy of more than 1 month. The primary endpoint was incidence of biopsy-proven acute rejection (BPAR) within 24 weeks. Surveys 1 week before and 4 weeks after formula conversion were conducted for total daily dose of medication, number, scale of discomfort and satisfaction. Results: The overall incidence of BPAR was 0% and there was no graft loss or patient death. The incidence of adverse effects was 34.1% (n = 14) after formula conversion. The most common severe adverse effect was abnormal liver function test (n = 5): biliary complications (n = 4) and alcoholic recidivism (n = 1). Total daily dose and number of tacrolimus doses were significantly lower after formula conversion (P < 0.05) without changes in trough level. According to survey analysis, there was no significant difference in discomfort and satisfaction scales from capsule to tablet conversion (P < 0.05). Conclusion: The present study suggests that the new tablet formula can be a useful treatment option to maintain a consistent level of tacrolimus with a lower total daily dose and number in adult LT recipients.

Soluble suppression of tumorigenicity 2 is a potential predictor of post-liver transplant renal outcomes.

Acute kidney injury is considered an independent prognostic factor for mortality in patients with liver cirrhosis. Non-treated acute kidney injury can progress to hepatorenal syndrome with a poor prognosis. As suppression of tumorigenicity 2 (ST2) is a member of the interleukin-1 receptor family that aggravates inflammation and fibrotic changes in multiple organs, we measured soluble ST2 (sST2) level in the serum and urine of liver-transplant recipients at the time of transplantation. The serum sST2 level significantly increased in liver-transplant recipients with suppressed kidney function compared with that in recipients with normal function. In recipients with severely decreased liver function (model for end-stage liver disease score ≥ 30), the serum sST2 level was higher than that in recipients with preserved liver function (model for end-stage liver disease score ≤ 20, P = 0.028). The serum sST2 level in recipients with hepatorenal syndrome was higher than that in liver-transplant recipients without hepatorenal syndrome (P = 0.003). The serum sST2 level in patients with hepatorenal syndrome was higher than that in recipients without a history of acute kidney injury (P = 0.004). Recipients with hepatorenal syndrome and recovered kidney function showed higher sST2 levels than those who did not recover (P = 0.034). Collectively, an increase in the serum sST2 level reflects a decrease in both kidney and liver functions. Thus, measuring sST2 level at the time of liver transplantation can help predict renal outcomes.

A circulating cell-free DNA methylation signature for the detection of hepatocellular carcinoma.

To address the shortcomings of current hepatocellular carcinoma (HCC) surveillance tests, we set out to find HCC-specific methylation markers and develop a highly sensitive polymerase chain reaction (PCR)-based method to detect them in circulating cell-free DNA (cfDNA). The analysis of large methylome data revealed that Ring Finger Protein 135 (RNF135) and Lactate Dehydrogenase B (LDHB) are universally applicable HCC methylation markers with no discernible methylation level detected in any other tissue types. These markers were used to develop Methylation Sensitive High-Resolution Analysis (MS-HRM), and their diagnostic accuracy was tested using cfDNA from healthy, at-risk, and HCC patients. The combined MS-HRM RNF135 and LDHB analysis detected 57% of HCC, outperforming the alpha-fetoprotein (AFP) test's sensitivity of 45% at comparable specificity. Furthermore, when used with the AFP test, the methylation assay can detect 70% of HCC. Our findings suggest that the cfDNA methylation assay could be used for HCC liquid biopsy.

Hepatitis B immunoglobulin inhibits the secretion of HBV via antigen-antibody precipitation in the multivesicular body.

BACKGROUND AND AIMS: Although the main action of human hepatitis B immunoglobulin (HBIG) is to neutralize hepatitis B virus surface antigen (HBsAg) in serum, HBIG is known to be localized in the cell. However, the effect of intracellularly located HBIG is poorly understood because of the low purity of conventional plasma-derived HBIG (cHBIG). We attempted to elucidate the mechanism of action of internalized HBIG using recombinant HBIG (lenvervimab). METHODS: We used HBsAg producing cell lines, non-HBsAg cell lines and human HBsAg-producing hepatocytes. The autophagosome lysis pathway-related proteins Rab5, calnexin, giantin, and Rab7 were used to localize HBsAg and anti-HBs-IgG in the cytoplasm using Western blotting and confocal microscopy. RESULTS: Intracellular anti-HBs-IgG (lenvervimab and cHBIG) transported via Fc receptor-mediated endocytosis increased the number of autophagosomes. However, there was no change in autolysis. HBsAg and anti-HBs-IgG co-localized in the multivesicular body and precipitated in the cytoplasm. HBsAg secretion into culture medium decreased after lenvervimab treatment. Simultaneously, the amount of cellular HBsAg increased in the cell lines but decreased in human hepatocytes. Furthermore, intracellular lenvervimab is not easily removed from HBsAg cell lines. CONCLUSIONS: Lenvervimab decreases HBsAg secretion, and HBsAg antibody precipitation in the multivesicular body may play an important role.

Anesthesia and Critical Care for the Prediction and Prevention for Small-for-size Syndrome: Guidelines from the ILTS-iLDLT-LTSI Consensus Conference.

BACKGROUND: During the perioperative period of living donor liver transplantation, anesthesiologists and intensivists may encounter patients in receipt of small grafts that puts them at risk of developing small for size syndrome (SFSS). METHODS: A scientific committee (106 members from 21 countries) performed an extensive literature review on aspects of SFSS with proposed recommendations. Recommendations underwent a blinded review by an independent expert panel and discussion/voting on the recommendations occurred at a consensus conference organized by the International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplantation Society of India. RESULTS: It was determined that centers with experience in living donor liver transplantation should utilize potential small for size grafts. Higher risk recipients with sarcopenia, cardiopulmonary, and renal dysfunction should receive small for size grafts with caution. In the intraoperative phase, a restrictive fluid strategy should be considered along with routine use of cardiac output monitoring, as well as use of pharmacologic portal flow modulation when appropriate. Postoperatively, these patients can be considered for enhanced recovery and should receive proactive monitoring for SFSS, nutrition optimization, infection prevention, and consideration for early renal replacement therapy for avoidance of graft congestion. CONCLUSIONS: Our recommendations provide a framework for the optimal anesthetic and critical care management in the perioperative period for patients with grafts that put them at risk of developing SFSS. There is a significant limitation in the level of evidence for most recommendations. This statement aims to provide guidance for future research in the perioperative management of SFSS.

International Liver Transplantation Society Global Census: First Look at Pediatric Liver Transplantation Activity Around the World.

BACKGROUND: Over 16 000 children under the age of 15 died worldwide in 2017 because of liver disease. Pediatric liver transplantation (PLT) is currently the standard of care for these patients. The aim of this study is to describe global PLT activity and identify variations between regions. METHODS: A survey was conducted from May 2018 to August 2019 to determine the current state of PLT. Transplant centers were categorized into quintile categories according to the year they performed their first PLT. Countries were classified according to gross national income per capita. RESULTS: One hundred eight programs from 38 countries were included (68% response rate). 10 619 PLTs were performed within the last 5 y. High-income countries performed 4992 (46.4%) PLT, followed by upper-middle- (4704 [44·3%]) and lower-middle (993 [9·4%])-income countries. The most frequently used type of grafts worldwide are living donor grafts. A higher proportion of lower-middle-income countries (68·7%) performed ≥25 living donor liver transplants over the last 5 y compared to high-income countries (36%; P = 0.019). A greater proportion of programs from high-income countries have performed ≥25 whole liver transplants (52.4% versus 6.2%; P = 0.001) and ≥25 split/reduced liver transplants (53.2% versus 6.2%; P < 0.001) compared to lower-middle-income countries. CONCLUSIONS: This study represents, to our knowledge, the most geographically comprehensive report on PLT activity and a first step toward global collaboration and data sharing for the greater good of children with liver disease; it is imperative that these centers share the lead in PLT.