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 John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This is a very interesting, novel, RCT in heart transplantation. Heart recipients were randomised to standard care or to receive additional therapy with intra-operative hemoadsorption with the Cytosorb system from CytoSorbents, NJ, USA. The hemoadsorption cartridge was integrated into the cardiopulmonary bypass system and has been shown previously to remove cytokines, chemokines, bilirubin, myoglobin and plasma free haemoglobin. Patients were blinded to the treatment allocation, but clinical professionals were not. No sample size calculation could be done due to a lack of prior data on which to base it. The study found statistically significant differences across a range of outcomes, including the primary outcomes. Patients receiving hemoadsorption had a lower vasoactive-inotropic score, frequency of vasoplegic syndrome, risk of AKI, shorter median mechanical ventilation and median intensive care stay (by 3.5 days). The rates of cardiac allograft rejection, 30-day mortality and 1-year survival were similar between the groups, although it may have been too small to show differences in these outcomes. There were no device related complications.
Aims:
This study aimed to investigate the role of intraoperative haemoadsorption in orthotopic heart transplant patients.
Interventions:
Participants were randomised to receive either intraoperative haemoadsorption or standard care.
The primary endpoint was early post-operative haemodynamic instability. Secondary endpoints were changes in procalcitonin (PCT) and C-reactive protein (CRP) levels post-operation, intraoperative change in mycophenolic acid (MPA) concentration, early allograft rejection, frequency of post-operative organ dysfunction, adverse immunological events, major complications, duration of ICU and in-hospital stay, and 1-year survival.
Follow Up:
1 year
AIMS:
The aim of this trial was to compare the clinical effects of intraoperative haemoadsorption versus standard care in patients undergoing orthotopic heart transplantation (OHT).
METHODS AND RESULTS:
In a randomized, controlled trial, OHT recipients were randomized to receive intraoperative haemoadsorption or standard care. Outcomes were vasoactive-inotropic score (VIS), frequency of vasoplegic syndrome (VS) in the first 24 h; post-operative change in procalcitonin (PCT) and C-reactive protein (CRP) levels; intraoperative change in mycophenolic acid (MPA) concentration; frequency of post-operative organ dysfunction, major complications, adverse immunological events and length of in-hospital stay and 1-year survival. Sixty patients were randomized (haemoadsorption group N = 30, control group N = 25 plus 5 exclusions). Patients in the haemoadsorption group had a lower median VIS and rate of VS (VIS: 27.2 [14.6-47.7] vs. 41.9 [22.4-63.2], P = 0.046, and VS: 20.0% vs. 48.0%, P = 0.028, respectively), a 6.4-fold decrease in the odds of early VS (OR: 0.156, CI: 0.029-0.830, P = 0.029), lower PCT levels, shorter median mechanical ventilation (MV: 25 [19-68.8] hours vs. 65 [23-287] hours, P = 0.025, respectively) and intensive care unit stay (ICU stay: 8.5 [8.0-10.3] days vs. 12 [8.5-18.0] days, P = 0.022, respectively) than patients in the control group. Patients in the haemoadsorption versus control group experienced lower rates of acute kidney injury (AKI: 36.7% vs. 76.0%, P = 0.004, respectively), renal replacement therapy (RRT: 0% vs. 16.0%, P = 0.037, respectively) and lower median per cent change in bilirubin level (PCB: 2.5 [-24.6 to 71.1] % vs. 72.1 [11.2-191.4] %, P = 0.009, respectively) during the post-operative period. MPA concentrations measured at pre-defined time points were comparable in the haemoadsorption compared to control groups (MPA pre-cardiopulmonary bypass: 2.4 [1.15-3.60] μg/mL vs. 1.6 [1.20-3.20] μg/mL, P = 0.780, and MPA 120 min after cardiopulmonary bypass start: 1.1 [0.58-2.32] μg/mL vs. 0.9 [0.45-2.10] μg/mL, P = 0.786). The rates of cardiac allograft rejection, 30-day mortality and 1-year survival were similar between the groups.
CONCLUSIONS:
Intraoperative haemoadsorption was associated with better haemodynamic stability, mitigated PCT response, lower rates of post-operative AKI and RRT, more stable hepatic bilirubin excretion, and shorter durations of MV and ICU stay. Intraoperative haemoadsorption did not show any relevant adsorption effect on MPA. There was no increase in the frequency of early cardiac allograft rejection related to intraoperative haemoadsorption use.
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:
This interesting randomised trial aimed to investigate the effect of internal iliac artery (IIA) versus eternal iliac artery (EIA) anastomosis on sexual function after kidney transplantation. It is thought that IIA anastomoses reduce blood flow to the genital tract, but previous retrospective work comparing these techniques found no significant difference in sexual function. 112 patients were included and completed a standardised erectile function questionnaire before- and one year after kidney transplant. The investigators found similar scores for overall sexual satisfaction but poorer scores for erectile function in the IIA group. Although not formally part of the analysis, the authors reported two cases of ureteric leaks in the IIA group and posited that IIA also confers an increased risk of ureter-vesical anastomosis leak. This further supports the conclusion that EIA should be the technique of choice for kidney transplantation.
Aims:
The aim of this study was to investigate the effect of internal versus external iliac artery anastomosis on sexual function in kidney transplant recipients.
Interventions:
Participants were randomly assigned to either the internal iliac anastomosis group and the external iliac artery anastomosis group.
Participants:
122 sexually active male renal transplant recipients.
Outcomes:
The primary outcome was the assessment of sexual function posttransplantation using the Persian version of the International Index of Erectile Function-15 questionnaire (IIEF-15) questionnaire.
Follow Up:
1 year
PURPOSE:
The choice between using the internal or external iliac arteries to supply a transplanted kidney poses a dilemma during renal transplantation. As the internal iliac artery branches to the genital tract, cutting it could potentially result in sexual dysfunction. The purpose of this study was to compare the effects of these two surgical methods on sexual function.
MATERIALS AND METHODS:
122 sexually active male patients under the age of sixty were randomly divided into two groups: the internal iliac anastomosis group and the external iliac artery anastomosis group. Before surgery and one year after the procedure, patients completed the International Index of Erectile Function-15 questionnaire (IIEF- 15), and the difference in scores of each domain was measured.
RESULTS:
Statistically, kidney transplantation improved all domains of IIEF in both groups, except for erectile function in patients who underwent internal iliac artery anastomosis group. Additionally, there were significant differences between the two groups in the domains of erectile function (p-value=0.04) and overall satisfaction (p-value = 0.002), while other domains such as orgasmic function, sexual desire, and intercourse satisfaction did not show any statistically significant differences.
CONCLUSION:
In conclusion, the choice between using the internal or external iliac artery for arterial anastomosis during kidney transplantation does not significantly impact graft function. However, it may negatively affect erectile function in patients who undergo internal iliac artery anastomosis.
Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
This pilot study recruited lung transplant recipients at 2 sites, and randomised them to standard immunosuppression (Tac, MMF, Pred) or a belatacept-based regimen (Tac, Belatacept and pred). The hypothesis was that belatacept-based immunosuppression might reduce the incidence of donor-specific antibodies (DSA), leading to a reduction in the risk of chronic lung allograft dysfunction (CLAD). The study was stopped after recruitment of 27 patients due to 3 deaths in the belatacept arm. Causes of death varied – 2 patients died from COVID-19 infection, one from CLAD related to infection, one from PTLD, one from pulmonary embolus and one from haemothorax. The authors ascribe 4 of these deaths to viral infections. No differences were seen in incidence of CLAD or development of DSA. It is very difficult to interpret these results given the small numbers, but clearly the authors were correct in stopping the study and switching patients to standard immunosuppression. The relationship of four of the deaths to viral infection would suggest that the immunosuppressive regimen may have contributed, and in the absence of any detectable clinical benefit, the conclusion that this regimen is unsafe in lung transplant recipients seem justified.
Aims:
This study aimed to evaluate the feasibility and inform the design of an RCT investigating the efficacy and safety of belatacept following lung transplantation
Interventions:
Participants were randomly assigned to either continue standard-of-care immunosuppression or switch to belatacept.
Participants:
27 lung transplant recipients.
Outcomes:
The primary outcome was to assess the feasibility of randomising 80% of eligible patients within 4 hours posttransplantation. The primary outcome was later changed to survival following the cessation of treatment with belatacept.
Follow Up:
1 year posttransplantation.
BACKGROUND:
Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD.
METHODS:
We conducted a pilot randomized controlled trial (RCT) at 2 sites to assess the feasibility and inform the design of a large-scale RCT. All participants were treated with rabbit antithymocyte globulin for induction immunosuppression. Participants in the control arm were treated with tacrolimus, mycophenolate mofetil, and prednisone, and participants in the belatacept arm were treated with tacrolimus, belatacept, and prednisone through day 89 after transplant then converted to belatacept, mycophenolate mofetil, and prednisone for the remainder of year 1.
RESULTS:
After randomizing 27 participants, 3 in the belatacept arm died compared with none in the control arm. As a result, we stopped enrollment and treatment with belatacept, and all participants were treated with standard-of-care immunosuppression. Overall, 6 participants in the belatacept arm died compared with none in the control arm (log rank P = 0.008). We did not observe any differences in the incidence of DSA, acute cellular rejection, antibody-mediated rejection, CLAD, or infections between the 2 groups.
CONCLUSIONS:
We conclude that the investigational regimen used in this pilot RCT is associated with increased mortality after lung transplantation.
Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion:
Hepatocyte growth factor has cytoprotective and anti-apoptotic effects in renal epithelial cells and has been shown to reduce renal dysfunction in animal models of renal injury. This phase 3, multicentre, double blind RCT investigated the use of ANG-3777 in deceased donor transplant recipients with delayed graft function. Use of the hepatocyte growth factor mimetic did not result in any differences in clinical outcomes, including dialysis requirement, acute rejection or graft function. The study is well designed with adequate blinding and randomisation. It should be noted that the study population was largely (>80%) DBD donors with a mean age of 44, and included around 35% kidneys undergoing hypothermic machine preservation, which may have impacted baseline DGF rates compared to a population with higher DCD or SCS subgroups and potentially represent less injured kidneys. Whether ANG-3777 has a role to play in more injured (e.g. ECD, DCD) kidneys remains unclear.
Aims:
The aim of this study was to investigate the effect of ANG-3777 in deceased donor renal transplant recipients with delayed graft function (DGF).
Interventions:
Participants were randomised to either the ANG-3777 group or the placebo group.
Participants:
253 deceased kidney transplant recipients.
Outcomes:
The original primary outcome was changed from duration of dialysis through day 30 to estimated glomerular filtration rate (eGFR) at day 360 posttransplant. The main secondary outcome was the severity of DGF.
Follow Up:
360 days posttransplantation
In kidney transplant recipients, delayed graft function increases the risk of graft failure and mortality. In a phase 3, randomized, double-blind, placebo-controlled trial, we investigated the hepatocyte growth factor mimetic, ANG-3777 (once daily for 3 consecutive days, starting ≤30 hours posttransplant), in 248 patients receiving a first kidney transplant from a deceased donor. At day 360, estimated glomerular filtration rate (primary endpoint) was not significantly different between the ANG-3777 and placebo groups. There were no significant between-group differences in the duration of dialysis through day 30 or in the percentage of patients with an estimated glomerular filtration rate of >30 mL/min/1.73 m2 at day 360. The incidence of both delayed graft function and acute rejection was similar between ANG-3777 and placebo groups (68.5% vs 69.4% and 8.1% vs 6.5%, respectively). ANG-3777 was well tolerated, and there was a numerically lower incidence of graft failure versus placebo (3.2% vs 8.1%). Although there is insufficient evidence to support an indication of ANG-3777 for patients at risk of renal dysfunction after deceased-donor kidney transplantation, these findings indicate potential biological activity that may warrant further investigation.
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.
CET Conclusion