Mr John Fallon, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This large open labelled multi-centre randomised control trial is an exciting development in the field of liver HMP. The key strength of this work is that 43% (n=27) of the HMP-O2 livers had continuous perfusion, having been placed on device at the donor. This is the first trial in liver HMP to do this and is an important development. Made possible by Organ Recovery Systems portable Lifeport Liver device, especially considering 81% travelled by air, a current limitation of the portable NMP devices. They demonstrated a nonsignificant reduction in EAD with 11% in HMP-O2 and 16% in SCS, while the finding is not significant it is in keeping with the 5 other published RCTs on HMP liver. The lack of significance may derive from the fact that within the intervention group only 24% were ECDs (including 5 DCD), upon sub-group analysis of these ECDs they find the reduction of EAD to be significant (20% in HMP-O2 and 33.3% in SCS p=0.004). This is in keeping with previous large RCTs that the beneficial effects of HMP-O2 are amplified in the ECD cohort, especially in DCDs seen in Rijn et al’s 2021 trial published in the New England Journal who perfused only DCD livers. None of their secondary outcomes reach significance, but with PNF only occurring in the SCS group with 3 patients and a further 2 (n=5 6.8%) went on to require re-transplant also due to ischaemic cholangiopathy. In HMP-O2 only 1 required retransplant, this was due to HAT. Biliary complications were nearly double in the SCS group (26.4% vs 12.7%) which is impressive, but again this failed to reach significance. The trends are encouraging, but the lack of significance is disappointing, the trial having not been powered for overall EAD rates. An increase cohort size and a focus on EADs could have led to more dramatic results with potentially significance in many of the outcomes. An interesting note is the preservation fluid used in HMP-O2 was Vasosol, a UW-like solution with the addition of nitric oxide donors and vasodilators, this is the first HMP RCT across all organs to utilise this solution and could, in part be responsible for some of the beneficial trends. Unfortunately, the study was not sufficiently powered to compare continuous HMP-O2 with end-ischaemic HMP-O2 and SCS, the overall storage duration being comparable, but the percentage of that time being perfusion obviously being highest in the continuous group. They demonstrate safety and non-inferior efficacy of a novel portable device, which as it becomes more popular and people become more familiar with placing livers on device at retrieval more data should emerge on continuous HMP-O2, this trial was an important step.
Aims:
To assess if HMP-O2 improves liver transplant outcomes compare to cold storage.
Interventions:
Livers were randomised to intervention, which was HMP-O2 on the Lifeport Liver Transporter device, perfused with Vasosol, or control, which was static cold storage.
Participants:
179 adult whole liver transplant recipients.
Outcomes:
The primary outcome was early allograft dysfunction (EAD) as defined by the Olthoff criteria. Secondary outcome measures were PNF, AKI, graft survival, biliary complications. Vascular complications and death. Additional exploratory outcomes were hospital LOS, ICU LOS, lactate clearance, bleeding, incisional hernia and SAEs.
Follow Up:
12 months
BACKGROUND AND AIMS:
In liver transplantation, cold preservation induces ischemia, resulting in significant reperfusion injury. Hypothermic oxygenated machine perfusion (HMP-O 2 ) has shown benefits compared to static cold storage (SCS) by limiting ischemia-reperfusion injury. This study reports outcomes using a novel portable HMP-O 2 device in the first US randomized control trial.
APPROACH AND RESULTS:
The PILOT trial (NCT03484455) was a multicenter, randomized, open-label, noninferiority trial, with participants randomized to HMP-O 2 or SCS. HMP-O 2 livers were preserved using the Lifeport Liver Transporter and Vasosol perfusion solution. The primary outcome was early allograft dysfunction. Noninferiority margin was 7.5%. From April 3, 2019, to July 12, 2022, 179 patients were randomized to HMP-O 2 (n=90) or SCS (n=89). The per-protocol cohort included 63 HMP-O 2 and 73 SCS. Early allograft dysfunction occurred in 11.1% HMP-O 2 (N=7) and 16.4% SCS (N=12). The risk difference between HMP-O 2 and SCS was -5.33% (one-sided 95% upper confidence limit of 5.81%), establishing noninferiority. The risk of graft failure as predicted by Liver Graft Assessment Following Transplant score at seven days (L-GrAFT 7 ) was lower with HMP-O 2 [median (IQR) 3.4% (2.4-6.5) vs. 4.5% (2.9-9.4), p =0.024]. Primary nonfunction occurred in 2.2% of all SCS (n=3, p =0.10). Biliary strictures occurred in 16.4% SCS (n=12) and 6.3% (n=4) HMP-O 2 ( p =0.18). Nonanastomotic biliary strictures occurred only in SCS (n=4).
CONCLUSIONS:
HMP-O 2 demonstrates safety and noninferior efficacy for liver graft preservation in comparison to SCS. Early allograft failure by L-GrAFT 7 was lower in HMP-O 2 , suggesting improved early clinical function. Recipients of HMP-O 2 livers also demonstrated a lower incidence of primary nonfunction and biliary strictures, although this difference did not reach significance.
Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
CMV infection which is refractory to standard treatment is a challenging clinical problem, resulting in patient morbidity and increased healthcare costs, mainly due to prolonged and repeat admissions. In the SOLSTICE trail, Maribavir was shown to be more effective than standard treatment protocols for refractory CMV infection in post-transplant patients. This post-hoc analysis of the SOLISTICE trial used trial data to calculate the reduction in healthcare costs that could be achieved by using Maribavir in this patient population. The analysis demonstrated a third to two thirds reduction in costs over an 8-week period when using Maribavir. Healthcare cost analyses are complex and subject to many assumptions, which the authors acknowledge introduces significant bias. However, the most striking omission from the analysis is the cost of the Maribavir treatment itself, which is significantly higher than standard therapy. With the additional limitation of a short duration of study, the reliability and applicability of the reported cost savings cannot be readily determined.
Aims:
The aim of this study was to use the data from the randomised controlled trial, SOLSTICE, to estimate the cytomegalovirus (CMV) related health care resource utilization (HCRU) costs of maribavir (MBV) versus investigator-assigned therapy (IAT), among hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients.
Interventions:
Participants in the SOLSTICE trial were randomised to either receive IAT or MBV therapy.
Participants:
352 patients that had either HSCT (40%) or SOT (60%).
Outcomes:
The key outcomes were the cost of hospitalisation with IAT versus MBV therapy, and cost difference (i.e. cost savings) with MBV.
Follow Up:
N/A
BACKGROUND:
Cytomegalovirus (CMV) infections among hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients impose a significant health care resource utilization (HCRU)-related economic burden. Maribavir (MBV), a novel anti-viral therapy (AVT), approved by the United States Food and Drug Administration for post-transplant CMV infections refractory (with/without resistance) to conventional AVTs has demonstrated lower hospital length of stay (LOS) versus investigator-assigned therapy (IAT; valgancilovir, ganciclovir, foscarnet, or cidofovir) in a phase 3 trial (SOLSTICE). This study estimated the HCRU costs of MBV versus IAT.
METHODS:
An economic model was developed to estimate HCRU costs for patients treated with MBV or IAT. Mean per-patient-per-year (PPPY) HCRU costs were calculated using (i) annualized mean hospital LOS in SOLSTICE, and (ii) CMV-related direct costs from published literature. Probabilistic sensitivity analysis with Monte-Carlo simulations assessed model robustness.
RESULTS:
Of 352 randomized patients receiving MBV (n = 235) or IAT (n = 117) for 8 weeks in SOLSTICE, 40% had HSCT and 60% had SOT. Mean overall PPPY HCRU costs of overall hospital-LOS were $67,205 (95% confidence interval [CI]: $33,767, $231,275) versus $145,501 (95% CI: $62,064, $589,505) for MBV and IAT groups, respectively. Mean PPPY ICU and non-ICU stay costs were: $32,231 (95% CI: $5,248, $184,524) versus $45,307 (95% CI: $3,957, $481,740) for MBV and IAT groups, and $82,237 (95% CI: $40,397, $156,945) MBV versus $228,329 (95% CI: $94,442, $517,476) for MBV and IAT groups, respectively. MBV demonstrated cost savings in over 99.99% of simulations.
CONCLUSIONS:
This analysis suggests that Mean PPPY HCRU costs were 29%-64% lower with MBV versus other-AVTs.
Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
Hepatorenal syndrome (HRS) resulting in renal dysfunction results in poorer outcomes following liver transplantation (LT). The efficacy of Terlipressin in reducing HRS in liver failure patients was investigated in the CONFIRM trial, which showed significantly improved rates of HRS, but no difference in mortality at 90 days. This post-hoc analysis of the CONFIRM trial aimed to determine the difference in renal outcomes (pre and post LT) and 1-year survival in patients who had Terlipressin versus those who did not. The analysis found significant improvements in renal outcomes and 1-year survival in the Terlipression group. However, sub-group analysis showed that patients with more severe liver and renal disease showed poorer outcomes with terlipressin use, indicating a need for careful patient selection. Further trials will be required to better define the patient sub-group that will derive the most benefit from Terlipressin therapy.
Aims:
This post hoc analysis of the CONFIRM trial aimed to examine whether terlipressin was effective in reducing the need for renal replacement therapy (RRT) and improving posttransplant outcomes in liver transplant recipients.
Interventions:
Particpants in the CONFIRM trial were randomised to receive either terlipressin plus albumin or placebo.
Participants:
300 liver transplant recipients from the CONFIRM trial.
Outcomes:
The main outcomes of interest were the incidence of hepatorenal syndrome-type 1 (HRS-1) reversal, need for RRT (pretransplant and posttransplant), and overall survival.
Follow Up:
12 months
Hepatorenal syndrome-acute kidney injury (HRS-AKI), a serious complication of decompensated cirrhosis, has limited therapeutic options and significant morbidity and mortality. Terlipressin improves renal function in some patients with HRS-1, while liver transplantation (LT) is a curative treatment for advanced chronic liver disease. Renal failure post-LT requiring renal replacement therapy (RRT) is a major risk factor for graft and patient survival. A post hoc analysis with a 12-month follow-up of LT recipients from a placebo-controlled trial of terlipressin (CONFIRM; NCT02770716) was conducted to evaluate the need for RRT and overall survival. Patients with HRS-1 were treated with terlipressin plus albumin or placebo plus albumin for up to 14 days. RRT was defined as any type of procedure that replaced kidney function. Outcomes compared between groups included the incidence of HRS-1 reversal, the need for RRT (pretransplant and posttransplant), and overall survival. Of the 300 patients in CONFIRM (terlipressin n = 199; placebo, n = 101), 70 (23%) underwent LT alone (terlipressin, n = 43; placebo, n = 27) and 5 had simultaneous liver-kidney transplant (terlipressin, n = 3, placebo, n = 2). The rate of HRS reversal was significantly higher in the terlipressin group compared with the placebo group (37%, n = 16 vs. 15%, n = 4; p = 0.033). The pretransplant need for RRT was significantly lower among those who received terlipressin ( p = 0.007). The posttransplant need for RRT, at 12 months, was significantly lower among those patients who received terlipressin and were alive at Day 365, compared to placebo ( p = 0.009). Pretransplant treatment with terlipressin plus albumin in patients with HRS-1 decreased the need for RRT pretransplant and posttransplant.
Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
There is considerable variation in the use of intraoperative vasoactive drugs in liver transplantation. This network meta-analysis attempted to synthesise the available data comparing outcomes - primarily rate of acute kidney injury (AKI) - between different vasoactive drug protocols utilised in liver transplantation. 25 trials were included in the analysis, and the effect of vasoconstrictor-, somatostatin infusion- and vasodilator - based strategies were compared. The quality of evidence of the included trials was generally low, and differences in outcome definition and inconsistent reporting of confounding factors made data synthesis which reached meaningful conclusions difficult. Unsurprisingly, no significant differences in effect on the primary outcome between the varies vasoactive drugs were found in this systematic review. Terlipressin was highlighted as its benefit in reducing AKI in liver failure patients with hepatorenal syndrome and in patients with septic shock is well established. The authors argued that this implies that terlipressin could confer a similar benefit in liver transplantation and warrants further study. However, the difficulties encountered in this review highlights that the confounding effects of donor and patient factors would require any such trial to have a large sample size to be sufficiently powered to detect a significant effect.
Aims:
This study aimed to assess the role of vasoactive agents versus any other drug, placebo, or standard of care on acute kidney injury (AKI) or other perioperative outcomes among adult liver transplant recipients.
Interventions:
Electronic databases including MEDLINE (Ovid), CINAHL (EBSCOhost), EBM Reviews (Ovid), EMBASE (Ovid), PubMed, and Google Scholar were searched. Three reviewers performed study screening and selection, and two reviewers independently extracted data. The Cochrane risk of bias (RoB) assessment tool version 2.0 was used to assess the risk of bias.
Participants:
25 studies were included in the review.
Outcomes:
The main outcomes of interest included acute kidney injury (AKI), intraoperative blood loss, graft complications, cardiovascular complications, pulmonary complications, infectious complications other than pneumonia, neurological complications, duration of mechanical ventilation, intensive care unit and hospital length of stay, and hospital mortality.
Follow Up:
N/A
We conducted a systematic review and network meta-analyses evaluating the effects of different intraoperative vasoactive drugs on acute kidney injury (AKI) and other perioperative outcomes in adult liver transplant recipients. We searched multiple electronic databases using words from the "liver transplantation" and "vasoactive drug" domains. We included all randomized controlled trials conducted in adult liver transplant recipients comparing 2 different intravenous vasoactive drugs or 1 against a standard of care that reported AKI, intraoperative blood loss, or any other postoperative outcome. We conducted 4 frequentist network meta-analyses using random effect models, based on the interventions' mechanism of action, and evaluated the quality of evidence (QoE) using Grading of Recommendations, Assessment, Development, and Evaluations recommendations. We included 9 randomized controlled trials comparing different vasopressor drugs (vasoconstrictor or inotrope), 3 comparing a somatostatin infusion (or its analogues) to a standard of care, 11 comparing different vasodilator infusions together or against a standard of care, and 2 comparing vasoconstrictor boluses at graft reperfusion. Intravenous clonidine was associated with shorter duration of mechanical ventilation, intensive care unit, and hospital length of stay (very low QoE), and some vasodilators were associated with lower creatinine level 24 h after surgery (low to very low QoE). Phenylephrine and terlipressin were associated with less intraoperative blood loss when compared with norepinephrine (low and moderate QoE). None of the vasoactive drugs improve any other postoperative outcomes, including AKI. There is still important equipoise regarding the best vasoactive drug to use in liver transplantation for most outcomes. Further studies are required to better inform clinical practice.
Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This multicentre trial enrolled kidney and liver transplant recipients receiving organs from CMV-positive donors, and randomised them to either fixed-duration prophylaxis, or guided by immune monitoring. In the study group, CMV ELISpot was used to monitor, and prophylaxis stopped if positive (indicating immune reactivity). The study failed to confirm non-inferiority of the immune monitoring strategy, although the overall rates of CMV infection were similar, with earlier CMV infection seen in the study group. However, duration of prophylaxis was shorter in the study arm. The failure to demonstrate non-inferiority is due to a lack of statistical power – in reality, the infection rates were very similar between groups. The study also fails to stratify randomisation by recipient serostatus, leading to an imbalance between the two arms of the study. This is important, as the risk of CMV infection is likely different between the two subgroups. Despite these limitations, it does appear that immune monitoring-guided prophylaxis is a reasonable strategy, resulting in a shorter duration of prophylaxis and a relatively low risk of clinically relevant CMV disease.
Aims:
The aim of this study was to compare the effect of an immune monitoring–guided approach versus the current standard for tailoring the duration of antiviral prophylaxis to measure cytomegalovirus (CMV)-specific immunity in solid-organ transplant recipients.
Interventions:
Participants were randomised to receive a duration of antiviral prophylaxis according to immune–guided monitoring or a fixed duration (control).
Participants:
193 kidney and liver transplant recipients CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins.
Outcomes:
The two primary endpoints were proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. The secondary endpoints were the incidence of all CMV events including untreated CMV replication, high-level CMV-DNAemia, patient survival, graft survival and incidence of acute rejection.
Follow Up:
1 year
BACKGROUND:
The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation.
METHODS:
In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus.
RESULTS:
Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001).
CONCLUSIONS:
Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection.
Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This manuscript reports long-term (48 month) outcomes from the HOPE-ECD-DBD trial, which compared end-ischaemic HOPE with static cold storage in extended criteria DBD livers. The authors report a reduction in late onset complications in the HOPE group with superior graft survival mainly due to a reduction in deaths with a functioning graft. Whilst numbers in the original study were small (23 in each arm) follow-up was complete for all participants still alive. Whilst the overall complication rate was higher in the SCS arm, it is not entirely clear what the main cause of complications was – no individual complication had significantly higher rates, and notably there was no difference in the rate of biliary complications. Ultimately the small sample size and secondary nature of the analysis mean that conclusions are limited due to lack of power, but the paper certainly shows the importance of long-term follow-up when assessing preservation strategies.
Aims:
This study aimed to report the long-term outcomes of the HOPE-ECD-DBD randomised controlled trial, which investigated the effect of hypothermic oxygenated machine perfusion (HOPE) versus static cold storage (SCS) in patients who underwent liver transplantation using extended criteria donor-donation after brain death (ECD-DBD) allografts.
Interventions:
Participants in the original trial were randomised to either the HOPE group or the SCS group.
Participants:
46 liver transplant recipients that received extended criteria donor donation after brain death allografts.
Outcomes:
The main outcomes of interest were incidence of late-onset morbidity, readmissions, long-term graft survival, and patient survival.
Follow Up:
48 months (median)
BACKGROUND:
While 4 randomized controlled clinical trials confirmed the early benefits of hypothermic oxygenated machine perfusion (HOPE), high-level evidence regarding long-term clinical outcomes is lacking. The aim of this follow-up study from the HOPE-ECD-DBD trial was to compare long-term outcomes in patients who underwent liver transplantation using extended criteria donor allografts from donation after brain death (ECD-DBD), randomized to either HOPE or static cold storage (SCS).
METHODS:
Between September 2017 and September 2020, recipients of liver transplantation from 4 European centers receiving extended criteria donor-donation after brain death allografts were randomly assigned to HOPE or SCS (1:1). Follow-up data were available for all patients. Analyzed endpoints included the incidence of late-onset complications (occurring later than 6 months and graded according to the Clavien-Dindo Classification and the Comprehensive Complication Index) and long-term graft survival and patient survival.
RESULTS:
A total of 46 patients were randomized, 23 in both arms. The median follow-up was 48 months (95% CI: 41-55). After excluding early perioperative morbidity, a significant reduction in late-onset morbidity was observed in the HOPE group (median reduction of 23 Comprehensive Complication Index-points [p=0.003] and lower incidence of major complications [Clavien-Dindo ≥3, 43% vs. 85%, p=0.009]). Primary graft loss occurred in 13 patients (HOPE n=3 vs. SCS n=10), resulting in a significantly lower overall graft survival (p=0.029) and adverse 1-, 3-, and 5-year survival probabilities in the SCS group, which did not reach the level of significance (HOPE 0.913, 0.869, 0.869 vs. SCS 0.783, 0.606, 0.519, respectively).
CONCLUSIONS:
Our exploratory findings indicate that HOPE reduces late-onset morbidity and improves long-term graft survival providing clinical evidence to further support the broad implementation of HOPE in human liver transplantation.
Mr John Fallon, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This small, open-registry randomised trial was unfortunately severely limited by sample size, and to some extent follow-up and design. Having recruited and randomised 80 patients, the majority were either lost to follow-up (n=32), discontinued the intervention (n=17) or hospitalised and excluded from analysis (n=2), therefore only 29 patients were included in the analysis. However, despite the smaller sample size some differences were seen. The prehabilitation group experience an improvement in LFI (4.18+/-0.92 at baseline, down to 3.72+/-0.76 at 30 days, p=0.05), a frailty index derived from performance-based tests on grip, standing and balance, while the standard of care cohort had no improvement. There were no other significant differences in outcome measures within the groups during the 30-day period. There was one difference between the groups after 30 days found, CPS was significantly better in the prehabilitation group (6.70+/-1.83 vs 8.44+/-1.83, p=0.02), though the starting CPS was numerically lower in the prehabilitation group. Conceptually the trial makes good sense, and there is good evidence across many surgical fields that improved physical fitness prior to surgery improves outcomes, and that supervised activity with a trainer or physiotherapist is an effective way of delivering this. However, due to low numbers, poor compliance, and inadequate follow-up the present study has not added good quality evidence to the field. They found some potential positive tendencies in the form of improved frailty and lowering of CPS, but these patients were only assessed over 30 days, and none received a liver transplant and as a result no conclusions can be drawn from its potential benefit to its intended surgical intervention of liver transplantation.
Aims:
To assess effects of prehabilitation in a cohort of patients with liver cirrhosis awaiting liver transplantation.
Interventions:
Patients received active prehabilitation or standard care. The standard care was oral and written instruction on nutrition and physical exercise which contained a list of safe activity and a recommendation of at least 20minutes of activity 3 times per week. The active prehabilitation group had the standard of care, plus supervised physical exercise with a physiotherapist for a minimum of 20 minutes 3 times per week.
Participants:
80 cirrhotic patients awaiting liver transplant.
Outcomes:
The chosen outcome measure were changes in patients: MELD score (model for end-stage liver disease), Child-Pugh score (CPS), liver frailty index (LFI) and quality of life measure by the EQ-5D questionnaire.
Follow Up:
30-days
BACKGROUND:
The high prevalence of liver cirrhosis in Slovakia leads to a great need for transplant treatment. The outcome of liver transplantation is influenced by several factors.
AIM:
The main objective of this study is to test the effectiveness of prehabilitation compared to standard of care.
Patient in F. D. Roosevelt Teaching Hospital, Slovakia, Banská Bystrica.
POPULATION:
The participants consisted of patients with liver cirrhosis (55 men, 25 women).
METHODS:
The patients were randomized to the active prehabilitation group (N.=39) or the standard of care group (SOC) (N.=41). SOC represents the standard of care for patients prior to liver transplantation, consisting of a formal oral interview lasting 30 minutes. In addition to SOC, each patient with decompensated liver cirrhosis also underwent a prehabilitation intervention that included rehabilitation and nutrition support. Patients completed the exercises under the supervision of a physician during hospitalisation.
RESULTS:
After one month, the liver frailty index improved in the prehabilitation group (P=0.05). No improvement in MELD (Model of End Stage Liver Disease) was found in the group that underwent the prehabilitation program (P=0.28), and no improvement was found in the Child-Pugh score after one month (P=0.13). In the prehabilitation groups compared with the SOC group, differences were not found in the MELD score (P=0.11). Better clinical outcomes according to the Child-Pugh score was found for the prehabilitation group compared with the SOC group (P=0.02). According to LFI, there was no difference between the groups (P=0.26). Very low adherence was found after three months. Only three patients in the SOC group and six patients in the prehabilitation group came to the check-up. Due to low adherence after 3 months in patients with liver cirrhosis, it is not possible to make an adequate comparison between groups after three months.
CONCLUSIONS:
Despite the great effort to maintain adherence, it was not possible to draw a conclusion about the effectiveness of prehabilitation in patients before liver transplantation compared to standard of care because the main problem in Slovak patients with liver cirrhosis is low adherence. More studies are needed to identify the barriers that lead to low adherence in patients with liver cirrhosis.
CLINICAL REHABILITATION IMPACT:
A promising result was found due to improvement of the Liver Frailty Index and the Child-Pugh Score after one month in the prehabilitation group.
Mr John Fallon, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This prospective randomised study assesses a large number of transplant liver biopsies on paediatric patients. The design and outcomes were simple, and the authors aim to add to existing literature that demonstrates using a larger 16G needle is not associated with increased bleeding risk but does potentially offer a higher quality biopsy. They found that there was no difference in bleeding complications between 16G and 18G needles (11 vs 10 p=0.82) with no difference in volume of hemoperitoneum measure on protocol US done 24hours following biopsy (31ml vs 35ml. p=0.70). Using both gauges of needles provides adequate specimens for diagnostic purposes with two inadequate biopsies using 16G and three using 18G (p=1). There was a higher median of complete portal tracts (CPTs) in the 16G compared with the 18G (20 vs 18, p0.029). When assessing the severity of certain types of liver disease having a greater number of CPTs reduces the risk of underestimating the severity. However, given there was no difference in specimen adequacy, it did not prove relevant in the present study. In this cohort they demonstrate both a low and equivalent risk in terms of bleeding complications and it would appear reasonable to use either gauge of needle.
Aims:
To assess the impact of needle gauge on specimen quality and haemorrhagic complications in a paediatric population undergoing liver biopsy.
Interventions:
16G or 18G Bard biopsy needle used for US-guided liver biopsy.
Participants:
282 Paediatric patients undergoing liver biopsy.
Outcomes:
The outcome measures were haemorrhagic complications and specimen adequacy along with number of complete portal tracts within the specimen.
Follow Up:
24-hours post-procedure
PURPOSE:
The objective of this study was to analyzed the impact of needle gauge (G) on the adequacy of specimens and hemorrhagic complications in pediatric patients undergoing ultrasound (US)-guided transplanted liver biopsies.
METHODS:
The study included 300 consecutive biopsies performed in 282 pediatric patients (mean age 6.75 ± 3.82 years, range 0.84-17.90) between December 2020 and April 2022. All pediatric patients that referred to our institution for US-guided core-needle liver biopsy (CNLB) were randomized to undergo 16-G or 18-G CNLB. Hemorrhagic complications were qualitatively evaluated. The number of complete portal tracts (CPTs) per specimen was counted and specimen adequacy was assessed based on the American Association for the Study of Liver Diseases guidelines.
RESULTS:
The incidence of bleeding was 7.00% (n = 21) and adequate specimens for accurate pathological diagnosis were obtained from 98.33% (n = 295) of patients. There was no significant difference in the incidence or amount of bleeding between the 16-G and 18-G groups (11 vs 10, p = 0.821; 35.0 mL vs 31.3 mL, p = 0.705). Although biopsies obtained using a 16-G needle contained more complete portal tracts than those obtained using an 18-G needle (20.0 vs 18.0, p = 0.029), there was no significant difference in specimen inadequacy according to needle gauge (2 vs 3, p = 1.000).
CONCLUSIONS:
Biopsy with a 16-G needle was associated with a greater number of CPTs but did not increase the adequate specimen rate. There was no significant difference in the complication rate between 16-G biopsy and 18-G biopsy.
Mr John Fallon, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This large multi-centre double-blinded randomised trial demonstrated a higher vaccine response using MF59-adjuvanated and high-dose influenza vaccines compared with standard vaccine, but this did not lead to improved clinical outcomes, with no difference in the incidence of influenza. Overall, the trial is robustly designed with clear outcome measures, though choosing the main clinically relevant outcome, clinical efficacy, as a secondary measure due the samples size this would require. The vaccine response in standard vaccine was 42%, 60% in MF-59-adjuvanted and 66% in the high dose group, while these differences are significant, if it does not translate to clinical outcome it is more difficult to make a case for their use given the increased cost and potential side effect burden. Adverse events occurred in 84% and 86% in the MF59-adjuvanted and high dose cohorts and only 59% for the standard vaccine, but all were mild side effects, such as: pain, redness, swelling, arthralgia, fatigue, and headache. De novo anti-HLA antibodies and biopsy-proven acute rejection was rare across all groups. Despite the vaccine response rate differences, when scrutinising seroprotection by strains within the trivalent vaccine (H1N1, H3N2 & B), one can see the potential cause for the lack of clinical efficacy. Across all three groups baseline protection is around 60% for H1N1 and around 30% for the other strains, likely due to the large number of participants (83%) who have previously received an influenza vaccine, and given the majority of participants are primary recipients, they are likely to have been immunocompetent at the time of the previous vaccine. They have demonstrated MF59-adjuvanted and high-dose vaccines to be safe in the solid organ transplant population, and given pervious evidence of clinical benefit in high risk populations such as the elderly, these vaccine could provide clinical benefit in transplant populations, but definitive evidence to alter practice is not provided here.
Aims:
They aimed to evaluate whether MF59-adjuvanated or high-dose influenza vaccines elicited better immunogenicity, were safe had better clinical efficacy compared to standard vaccine.
Interventions:
Intervention vaccines were MF59-adjuvanated and high-dose influenza vaccine versus control, standard influenze vaccine.
Participants:
598 adults who received a solid organ transplant >3 months prior to enrolment.
Outcomes:
The primary outcome was antibody response rate at day 2 post-vaccine. The secondary clinical outcomes were influenza confirmed on PCR and vaccine reactogenicity. The secondary immunogenicity outcomes were: geometric mean titres of haemagglutination inhibition, seroproctection rates, seroconversion rates, seroconversion factors for each strain.
Follow Up:
180 days
BACKGROUND:
The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population.
METHODS:
Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction-confirmed influenza and vaccine reactogenicity.
RESULTS:
A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12-1); P < .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16-1]; P < .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08-1]; P < .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild.
CONCLUSIONS:
In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate.
Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
Temporary portocaval shunt (TPCS) formation is a frequently utilised in liver transplantation to reduce portal hypertension and blood loss during the hepatectomy phase. The benefit of this technique has been proven in acute liver failure, where physiological portosystemic shunts are not well developed, but the benefit in cases of chronic liver disease with cirrhosis is less clear. This unblinded randomised trial investigated the efficacy of TPCS in chronic liver patients undergoing live donor liver transplant. Intra-operative parameters including inotrope requirement, blood loss and renal function were significantly improved in the TPCS group. However, these superior haemodynamic parameters did not result in meaningful post-operative benefit, with no significant differences in key clinical parameters including morbidity, mortality and length of stay between the two groups. The technique should thus continue to be utilised on a case by case basis.
Aims:
This study aimed to investigate the role of temporary portocaval shunt (TPCS) during recipient hepatectomy in live donor liver transplant recipients.
Interventions:
Participants were randomised to TPCS versus no TPCS.
Participants:
60 live donor liver transplantation (LDLT) recipients.
Outcomes:
The primary outcomes are intraoperative haemodynamic parameters (systolic blood pressure, diastolic blood pressure, mean arterial pressure), blood loss, transfusion requirement, renal function, and duration of surgery. The secondary outcomes include early graft dysfunction, morbidity, mortality, total ICU and hospital stay.
Follow Up:
90 days
OBJECTIVE:
The primary objectives were to compare intra operative hemodynamic parameters, blood loss, renal function, and duration of surgery with and without TPCS in live donor liver transplantation (LDLT) recipients. Secondary objectives were post-operative early graft dysfunction (EGD), morbidity, mortality, total ICU and hospital stay.
BACKGROUND:
Blood loss during recipient hepatectomy for liver transplantation (LT) remains a major concern. Routine use of temporary portocaval shunt (TPCS) during LT is not yet elucidated.
METHODS:
A single centre, open label, randomized control trial. The sample size was calculated based on intraoperative blood loss. After exclusion, a total of 60 patients, 30 in each arm (TPCS versus no TPCS) were recruited in the trial.
RESULTS:
The baseline recipient and donor characteristics were comparable between the groups. The median intra-operative blood loss (P = 0.004) and blood product transfusions (P<0.05) were significantly less in TPCS group. TPCS group had significantly improved intraoperative hemodynamics in anhepatic phase as compared to no-TPCS group (P<0.0001), requiring significantly less vasopressor support. This led to significantly better renal function as evidenced by higher intraoperative urine output in TPCS group (P=0.002). Because of technical simplicity, TPCS group had significantly fewer IVC injuries (3.3 vs. 26.7%, P=0.026) and substantially shorter hepatectomy time and total duration of surgery (529.4 ± 35.54 vs. 606.83 ± 48.13 mins, P<0.0001). ). Time taken for normalisation of lactate in the immediate post-operative period was significantly shorter in TPCS group (median, 6 h vs. 13 h; P=0.04). Although post-operative endotoxemia, major morbidity, 90day mortality, total ICU and hospital stay were comparable between both the groups, tolerance to enteral feed was earlier in the TPCS group.
CONCLUSION:
In LDLT, TPCS is a simple and effective technique that provides superior intraoperative hemodynamics and reduces blood loss and duration of surgery.
CET Conclusion