The impact of time to death in donors after circulatory death on recipient outcome in simultaneous pancreas-kidney transplantation.

The time to arrest donors after circulatory death is unpredictable and can vary. This leads to variable periods of warm ischemic damage prior to pancreas transplantation. There is little evidence supporting procurement team stand-down times based on donor time to death (TTD). We examined what impact TTD had on pancreas graft outcomes following donors after circulatory death (DCD) simultaneous pancreas-kidney transplantation. Data were extracted from the UK transplant registry from 2014 to 2022. Predictors of graft loss were evaluated using a Cox proportional hazards model. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. Three-hundred-and-seventy-five DCD simultaneous kidney-pancreas transplant recipients were included. Increasing TTD was not associated with graft survival (adjusted hazard ratio HR 0.98, 95% confidence interval 0.68-1.41, P = .901). Increasing asystolic time worsened graft survival (adjusted hazard ratio 2.51, 95% confidence interval 1.16-5.43, P = .020). Restricted cubic spline modeling revealed a nonlinear relationship between asystolic time and graft survival and no relationship between TTD and graft survival. We found no evidence that TTD impacts pancreas graft survival after DCD simultaneous pancreas-kidney transplantation; however, increasing asystolic time was a significant predictor of graft loss. Procurement teams should attempt to minimize asystolic time to optimize pancreas graft survival rather than focus on the duration of TTD.

Normothermic machine perfusion versus static cold storage in donation after circulatory death kidney transplantation: a randomized controlled trial.

Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation after circulatory death (DCD) donors have been used to increase transplant rates, but these organs are susceptible to cold ischemic injury in the storage period before transplantation, the clinical consequence of which is high rates of delayed graft function (DGF). Normothermic machine perfusion (NMP) is an emerging technique that circulates a warmed, oxygenated red-cell-based perfusate through the kidney to maintain near-physiological conditions. We conducted a randomized controlled trial to compare the outcome of DCD kidney transplants after conventional static cold storage (SCS) alone or SCS plus 1-h NMP. A total of 338 kidneys were randomly allocated to SCS (n = 168) or NMP (n = 170), and 277 kidneys were included in the final intention-to-treat analysis. The primary endpoint was DGF, defined as the requirement for dialysis in the first 7 d after transplant. The rate of DGF was 82 of 135 (60.7%) in NMP kidneys versus 83 of 142 (58.5%) in SCS kidneys (adjusted odds ratio (95% confidence interval) 1.13 (0.69-1.84); P = 0.624). NMP was not associated with any increase in transplant thrombosis, infectious complications or any other adverse events. A 1-h period of NMP at the end of SCS did not reduce the rate of DGF in DCD kidneys. NMP was demonstrated to be feasible, safe and suitable for clinical application. Trial registration number: ISRCTN15821205 .

Donor Liver Blood Tests and Liver Transplant Outcomes: UK Registry Cohort Study.

BACKGROUND: Safely increasing organ utilization is a global priority. Donor serum transaminase levels are often used to decline livers, despite minimal evidence to support such decisions. This study aimed to investigate the impact of donor "liver blood tests" on transplant outcomes. METHODS: This retrospective cohort study used the National Health Service registry on adult liver transplantation (2016-2019); adjusted regressions models were used to assess the effect of donor "liver blood tests" on outcomes. RESULTS: A total of 3299 adult liver transplant recipients were included (2530 following brain stem death, 769 following circulatory death). Peak alanine transaminase (ALT) ranged from 6 to 5927 U/L (median = 45). Donor cause of death significantly predicted donor ALT; 4.2-fold increase in peak ALT with hypoxic brain injury versus intracranial hemorrhage (adjusted P < 0.001). On multivariable analysis, adjusting for a wide range of factors, transaminase level (ALT or aspartate aminotransferase) failed to predict graft survival, primary nonfunction, 90-d graft loss, or mortality. This held true in all examined subgroups, that is, steatotic grafts, donation following circulatory death, hypoxic brain injury donors, and donors, in which ALT was still rising at the time of retrieval. Even grafts from donors with extremely deranged ALT (>1000 U/L) displayed excellent posttransplant outcomes. In contrast, donor peak alkaline phosphatase was a significant predictor of graft loss (adjusted hazard ratio = 1.808; 1.016-3.216; P = 0.044). CONCLUSIONS: Donor transaminases do not predict posttransplant outcomes. When other factors are favorable, livers from donors with raised transaminases can be accepted and transplanted with confidence. Such knowledge should improve organ utilization decision-making and prevent future unnecessary organ discard. This provides a safe, simple, and immediate option to expand the donor pool.

Multi-Centre UK Analysis of Simultaneous Pancreas and Kidney (SPK) Transplant in Recipients With Type 2 Diabetes Mellitus.

90% of the UK diabetic population are classified as T2DM. This study aims to compare outcomes after SPK transplant between recipients with T1DM or T2DM. Data on all UK SPK transplants from 2003-2019 were obtained from the NHSBT Registry (n = 2,236). Current SPK transplant selection criteria for T2DM requires insulin treatment and recipient BMI < 30 kg/m2. After exclusions (re-transplants/ambiguous type of diabetes) we had a cohort of n = 2,154. Graft (GS) and patient (PS) survival analyses were conducted using Kaplan-Meier plots and Cox-regression models. Complications were compared using chi-squared analyses. 95.6% of SPK transplants were performed in recipients with T1DM (n = 2,060). Univariate analysis showed comparable outcomes for pancreas GS at 1 year (p = 0.120), 3 years (p = 0.237), and 10 years (p = 0.196) and kidney GS at 1 year (p = 0.438), 3 years (p = 0.548), and 10 years (p = 0.947). PS was comparable at 1 year (p = 0.886) and 3 years (p = 0.237) and at 10 years (p = 0.161). Multi-variate analysis showed comparable outcomes in pancreas GS (p = 0.564, HR 1.221, 95% CI 0.619, 2.406) and PS(p = 0.556, HR 1.280, 95% CI 0.563, 2.911). Comparable rates of common complications were demonstrated. This is the largest series outside of the US evaluating outcomes after SPK transplants and shows similar outcomes between T1DM and T2DM recipients. It is hoped dissemination of this data will lead to increased referral rates and assessment of T2DM patients who could benefit from SPK transplantation.

MicroRNA antagonist therapy during normothermic machine perfusion of donor kidneys.

Normothermic machine perfusion (NMP) is a novel clinical approach to overcome the limitations of traditional hypothermic organ preservation. NMP can be used to assess and recondition organs prior to transplant and is the subject of clinical trials in solid organ transplantation. In addition, NMP provides an opportunity to deliver therapeutic agents directly to the organ, thus avoiding many limitations associated with systemic treatment of the recipient. We report the delivery of oligonucleotide-based therapy to human kidneys during NMP, in this case to target microRNA function (antagomir). An antagomir targeting mir-24-3p localized to the endothelium and proximal tubular epithelium. Endosomal uptake during NMP conditions facilitated antagomir co-localization with proteins involved in the RNA-induced silencing complex (RISC) and demonstrated engagement of the miRNA target. This pattern of uptake was not seen during cold perfusion. Targeting mir-24-3p action increased expression of genes controlled by this microRNA, including heme oxygenase-1 and sphingosine-1-phosphate receptor 1. The expression of genes not under the control of mir-24-3p was unchanged, indicating specificity of the antagomir effect. In summary, this is the first report of ex vivo gymnotic delivery of oligonucleotide to the human kidney and demonstrates that NMP provides the platform to bind and block detrimental microRNAs in donor kidneys prior to transplantation.

Comparing outcomes in right versus left kidney transplantation: A systematic review and meta-analysis.

INTRODUCTION: Transplantation of right kidneys can pose technical challenges due to the short right renal vein. Whether this results in inferior outcomes remains controversial. METHOD: Healthcare Database Advanced Search (HDAS) was used to identify relevant studies. Two authors independently reviewed each study. Statistical analyses were performed using random effects models and results expressed as HR or relative risk (RR) with 95% confidence intervals. Subgroup analyses were performed in kidneys from deceased donors (DD) and living donors (LD). RESULTS: A total of 35 studies (257,429 participants) were identified. Both deceased and living donor right kidneys were at increased risk of delayed graft function (DGF; RR = 1.12[1.06-1.18] and RR = 1.33[1.21-1.46] respectively; both p < .0001). In absolute terms, for each 100 kidney pairs of DD kidneys transplanted there are 2.72 (1.67-3.78, p < .00001) excess episodes of DGF in right kidneys. Graft thromboses and graft loss due to technical failure was also significantly more likely in right kidneys, in both DD and LD settings. There was no evidence that laterality alters long term graft survival in LD or DD. CONCLUSION: Right kidneys have inferior early outcomes, with higher rates of DGF, technical failure and graft thrombosis. However, these differences are small in absolute terms, and long-term graft survival is equivalent.

Neutrophils induce paracrine telomere dysfunction and senescence in ROS-dependent manner.

Cellular senescence is characterized by an irreversible cell cycle arrest as well as a pro-inflammatory phenotype, thought to contribute to aging and age-related diseases. Neutrophils have essential roles in inflammatory responses; however, in certain contexts their abundance is associated with a number of age-related diseases, including liver disease. The relationship between neutrophils and cellular senescence is not well understood. Here, we show that telomeres in non-immune cells are highly susceptible to oxidative damage caused by neighboring neutrophils. Neutrophils cause telomere dysfunction both in vitro and ex vivo in a ROS-dependent manner. In a mouse model of acute liver injury, depletion of neutrophils reduces telomere dysfunction and senescence. Finally, we show that senescent cells mediate the recruitment of neutrophils to the aged liver and propose that this may be a mechanism by which senescence spreads to surrounding cells. Our results suggest that interventions that counteract neutrophil-induced senescence may be beneficial during aging and age-related disease.

Too Fat for Transplant? The Impact of Recipient BMI on Pancreas Transplant Outcomes.

BACKGROUND: In many transplant centers, a recipient body mass index (BMI) >30 kg/m2 would be considered a contraindication for pancreas transplantation. This study aims to investigate the impact of recipient BMI on graft outcomes after pancreas transplantation. METHODS: Retrospective data on all UK solid organ pancreas transplants from 1994 to 2016 were obtained from the National Health Service Blood and Transplant UK Transplant Registry, n = 2618. Cases missing BMI data were excluded, resulting in a final cohort of n = 1452. Graft and patient survival analysis were conducted using Kaplan-Meier plots and Cox regression models. RESULTS: The mean recipient BMI was 24.8 kg/m2 (±2.4). There were 507 overweight (BMI 25-29.9) and 146 obese (>30) recipients receiving pancreas transplants. Univariate analysis showed no statistically significant difference between overweight BMI categories compared with normal BMI (18.5-24.9 kg/m2). Multivariate analysis revealed increasing recipient BMI had a significant impact on graft survival (P = 0.03, hazard ratio 1.04, 95% confidence interval, 1.00-1.08). Receiver operating characteristic curve analyses revealed no value of BMI that provided both specific and sensitive discrimination between death and survival of both grafts or patients. Recipients on dialysis with a BMI >30 kg/m2 had a statistically significant decrease in both graft (P = 0.002) and patient survival (P = 0.015). CONCLUSIONS: Analysis of available UK Pancreas data has shown recipient BMI is an independent risk factor for patient survival after transplantation. However, we have been unable to define a specific cutoff value above which patients have poorer outcomes. Obese patients on hemodialysis had the poorest graft survival, and preemptive transplantation may be beneficial in this cohort.

Interventions for preventing thrombosis in solid organ transplant recipients.

BACKGROUND: Graft thrombosis is a well-recognised complication of solid organ transplantation and is one of the leading causes of graft failure. Currently there are no standardised protocols for thromboprophylaxis. Many transplant units use unfractionated heparin (UFH) and fractionated heparins (low molecular weight heparin; LMWH) as prophylaxis for thrombosis. Antiplatelet agents such as aspirin are routinely used as prophylaxis of other thrombotic conditions and may have a role in preventing graft thrombosis. However, any pharmacological thromboprophylaxis comes with the theoretical risk of increasing the risk of major blood loss following transplant. This review looks at benefits and harms of thromboprophylaxis in patients undergoing solid organ transplantation. OBJECTIVES: To assess the benefits and harms of instituting thromboprophylaxis to patients undergoing solid organ transplantation. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 10 November 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs designed to examine interventions to prevent thrombosis in solid organ transplant recipients. All donor types were included (donor after circulatory (DCD) and brainstem death (DBD) and live transplantation). There was no upper age limit for recipients in our search. DATA COLLECTION AND ANALYSIS: The results of the literature search were screened and data collected by two independent authors. Dichotomous outcome results were expressed as risk ratio (RR) with 95% confidence intervals (CI). Random effects models were used for data analysis. Risk of bias was independently assessed by two authors using the risk of bias assessment tool. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We identified nine studies (712 participants). Seven studies (544 participants) included kidney transplant recipients, and studies included liver transplant recipients. We did not identify any study enrolling heart, lung, pancreas, bowel, or any other solid organ transplant recipient. Selection bias was high or unclear in eight of the nine studies; five studies were at high risk of bias for performance and/or detection bias; while attrition and reporting biases were in general low or unclear. Three studies (180 participants) primarily investigated heparinisation in kidney transplantation. Only two studies reported on graft vessel thrombosis in kidney transplantation (144 participants). These small studies were at high risk of bias in several domains and reported only two graft thromboses between them; it therefore remains unclear whether heparin decreases the risk of early graft thrombosis or non-graft thrombosis (very low certainty). UFH may make little or no difference versus placebo to the rate of major bleeding events in kidney transplantation (3 studies, 155 participants: RR 2.92, 95% CI 0.89 to 9.56; I² = 0%; low certainty evidence). Sensitivity analysis using a fixed-effect model suggested that UFH may increase the risk of haemorrhagic events compared to placebo (RR 3.33, 95% CI 1.04 to 10.67, P = 0.04). Compared to control, any heparin (including LMWH) may make little or no difference to the number of major bleeding events (3 studies, 180 participants: RR 2.70, 95% CI 0.89 to 8.19; I² = 0%; low certainty evidence) and had an unclear effect on risk of readmission to intensive care (3 studies, 180 participants: RR 0.68, 95% CI 0.12 to 3.90, I² = 45%; very low certainty evidence). The effect of heparin on our other outcomes (including death, patient and graft survival, transfusion requirements) remains unclear (very low certainty evidence). Three studies (144 participants) investigated antiplatelet interventions in kidney transplantation: aspirin versus dipyridamole (1), and Lipo-PGE1 plus low-dose heparin to "control" in patients who had a diagnosis of acute rejection (2). None of these reported on early graft thromboses. The effect of aspirin, dipyridamole and Lipo PGE1 plus low-dose heparin on any outcomes is unclear (very low certainty evidence). Two studies (168 participants) assessed interventions in liver transplants. One compared warfarin versus aspirin in patients with pre-existing portal vein thrombosis and the other investigated plasmapheresis plus anticoagulation. Both studies were abstract-only publications, had high risk of bias in several domains, and no outcomes could be meta-analysed. Overall, the effect of any of these interventions on any of our outcomes remains unclear with no evidence to guide anti-thrombotic therapy in standard liver transplant recipients (very low certainty evidence). AUTHORS' CONCLUSIONS: Overall, there is a paucity of research in the field of graft thrombosis prevention. Due to a lack of high quality evidence, it remains unclear whether any therapy is able to reduce the rate of early graft thrombosis in any type of solid organ transplant. UFH may increase the risk of major bleeding in kidney transplant recipients, however this is based on low certainty evidence. There is no evidence from RCTs to guide anti-thrombotic strategies in liver, heart, lung, or other solid organ transplants. Further studies are required in comparing anticoagulants, antiplatelets to placebo in solid organ transplantation. These should focus on outcomes such as early graft thrombosis, major haemorrhagic complications, return to theatre, and patient/graft survival.

Novel delivery of cellular therapy to reduce ischemia reperfusion injury in kidney transplantation.

Ex vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimize organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC® ) possess potent immunomodulatory properties that could minimize ischemia reperfusion injury. We investigated the potential capability of MAPC cells in kidney NMP. Pairs (5) of human kidneys, from the same donor, were simultaneously perfused for 7 hours. Kidneys were randomly allocated to receive MAPC treatment or control. Serial samples of perfusate, urine, and tissue biopsies were taken for comparison. MAPC-treated kidneys demonstrated improved urine output (P = .009), decreased expression of injury biomarker NGAL (P = .012), improved microvascular perfusion on contrast-enhanced ultrasound (cortex P = .019, medulla P = .001), downregulation of interleukin (IL)-1ß (P = .050), and upregulation of IL-10 (P < .047) and Indolamine-2, 3-dioxygenase (P = .050). A chemotaxis model demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (P < .001). Immunofluorescence revealed prelabeled MAPC cells in the perivascular space of kidneys during NMP. We report the first successful delivery of cellular therapy to a human kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to transplantation.

Cell therapy during machine perfusion.

There has been increasing use of organs from extended criteria or donation after circulatory death donors to meet the demands of the transplant waiting list. Over the past decade, there has been considerable progress in technologies to preserve organs prior to transplantation to improve the function of these marginal organs. This has led to the development of normothermic machine perfusion, whereby an organ is perfused with warmed, oxygenated blood and nutrients to resume normal physiological function in an isolated ex-vivo platform. With this advance in preservation comes significant opportunities to recondition, repair and regenerate organs prior to transplantation using cellular therapies. This review aims to discuss the possibilities of machine perfusion technology; highlighting the potential for organ-directed reconditioning and the future avenues for investigation in this field.

Early protocol computer tomography and endovascular interventions in pancreas transplantation.

BACKGROUND: Early vascular complications following pancreatic transplantation are not uncommon (3%-8%). Typically, cross-sectional imaging is requested in response to clinical change. We instituted a change in protocol to request imaging pre-emptively to identify patients with thrombotic complications. METHODS: In 2013, protocol computer tomography angiography (CTA) at days 3-5 and day 10 following pancreas transplantation was introduced. A retrospective analysis of all pancreas transplants performed at our institution from January 2001 to May 2019 was undertaken. RESULTS: A total of 115 patients received pancreas transplants during this time period. A total of 78 received pancreas transplant without routine CTA and 37 patients with the new protocol. Following the change in protocol, we detected a high number of subclinical thromboses (41.7%). There was a significant decrease in invasive intervention for thrombosis (78.6% before vs 30.8% after, p = .02), and graft survival was significantly higher (61.5% before vs 86.1% after, p = .04). There was also a significant reduction in the number of graft failures (all-cause) where thrombosis was present (23.4% before vs 5.6% after, p = .02). Patient survival was unaffected (p = .48). CONCLUSIONS: Implementation of early protocol CTA identifies a large number of patients with subclinical graft thromboses that are more amenable to conservative management and significantly reduces the requirement for invasive intervention.

Prehabilitation prior to surgery for pancreatic cancer: A systematic review.

INTRODUCTION: Prehabilitation aims to improve fitness and outcomes of patients undergoing major surgery. This systematic review aimed to appraise current available evidence regarding the role of prehabilitation in patients undergoing oncological pancreatic resection. METHODS: A systematic literature search of PUBMED, MEDLINE, EMBASE databases identified articles describing prehabilitation programmes before pancreatic resection for malignancy. Data collected included timing of prehabilitation, programme type, duration, adherence and post-operative outcome reporting. RESULTS: Six studies, including 193 patients were included in the final analysis. Three studies included patients undergoing neoadjuvant therapy followed by resection and 3 studies included patients undergoing upfront resection. Time from diagnosis to surgery ranged between 2 and 22 weeks across all studies. Two studies reported a professionally supervised exercise programme, and four described unsupervised programmes. Exercise programmes varied from 5 days to 6 months in duration. Adherence to exercise programmes was better with supervised programmes (99% reaching weekly activity goal vs 85%) and patients not undergoing neoadjuvant therapy (90% reaching weekly activity goal vs 82%). All studies reported improvement in muscle mass or markers of muscle function following prehabilitation. Two studies reported the impact of Prehabilitation on postoperative outcomes and Prehabilitation was associated with lower delayed gastric emptying and a shorter hospital stay with no impact on other postoperative outcomes. CONCLUSION: Early evidence demonstrates that Prehabilitation programmes may improve postoperative outcomes following pancreatic surgery. However current Prehabilitaton programmes for patients undergoing pancreatic resection report diverse exercise regimens with no consensus regarding timing or length of Prehabilitation, warranting a need for standardisation of Prehabilitation programmes in pancreatic surgery.

Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis.

BACKGROUND: Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review seeks to compare sites and patterns of recurrence after resection between patients undergoing upfront surgery (US) or after NAT. METHODS: The EMBASE, SCOPUS, PubMed, and Cochrane library databases were systematically searched to identify eligible studies that compare recurrence patterns between patients who had NAT (followed by resection) with those that had US. The primary outcome included site-specific recurrence. RESULTS: 26 articles were identified including 4986 patients who underwent resection. Borderline resectable pancreatic cancer (BRPC, 47% 1074/2264) was the most common, followed by resectable pancreatic cancer (RPC 42%, 949/2264). The weighted overall recurrence rates were lower among the NAT group, 63.4% vs. 74% (US) (OR 0.67 (CI 0.52-0.87), p = 0.006). The overall weighted locoregional recurrence rate was lower amongst patients who received NAT when compared to US (12% vs 27% OR 0.39 (CI 0.22-0.70), p = 0.004). In BRPC, locoregional recurrence rates improved with NAT (NAT 25.8% US 37.7% OR 0.62 (CI 0.44-0.87), p = 0.007). NAT was associated with a lower weighted liver recurrence rate (NAT 19.4% US 30.1% OR 0.55 (CI 0.34-0.89), p = 0.023). Lung and peritoneal recurrence rates did not differ between NAT and US cohorts (p = 0.705 and p = 0.549 respectively). NAT was associated with a significantly longer weighted mean time to first recurrence 18.8 months compared to US (15.7 months) (OR 0.18 (CI 0.05-0.32), p = 0.015). CONCLUSION: NAT was associated with lower overall recurrence rate and improved locoregional disease control particularly for those with BRPC. Although the burden of liver metastases was less, there was no overall effect upon distant metastatic disease.

Haemostatic Efficacy of Topical Agents During Liver Resection: A Network Meta-Analysis of Randomised Trials.

BACKGROUND: Hepatic resection carries a high risk of parenchymal bleeding both intra- and post-operatively. Topical haemostatic agents are frequently used to control bleeding during hepatectomy, with multiple products currently available. However, it remains unknown which of these is most effective for achieving haemostasis and improving peri-operative outcomes. METHODS: A systematic review and random-effects Bayesian network meta-analysis of randomised trials investigating topical haemostatic agents in hepatic resection was performed. Interventions were analysed by grouping into similar products; fibrin patch, fibrin glue, collagen products, and control. Primary outcomes were the rate of haemostasis at 4 and 10 min. RESULTS: Twenty randomized controlled trials were included in the network meta-analysis, including a total of 3267 patients and 7 different interventions. Fibrin glue and fibrin patch were the most effective interventions for achieving haemostasis at both 4 and 10 min. There were no significant differences between haemostatic agents with respect to blood loss, transfusion requirements, bile leak, post-operative complications, reoperation, or mortality. CONCLUSIONS: Amongst the haemostatic agents currently available, fibrin patch and fibrin glue are the most effective methods for reducing time to haemostasis during liver resection, but have no effect on other peri-operative outcomes. Topical haemostatic agents should not be used routinely, but may be a useful adjunct to achieve haemostasis when needed.