Hypothermic oxygenated machine perfusion (HOPE) was introduced in liver transplantation (LT) to mitigate ischemia-reperfusion injury. Available clinical data mainly concern LT with donors after circulatory-determined death, whereas data on brain-dead donors (DBD) are scarce. To assess the impact of end-ischemic HOPE in DBD LT, data on primary adult LTs performed between March 2016 and June 2018 were analyzed. HOPE was used in selected cases of donor age >80 years, apparent severe graft steatosis, or ischemia time ≥10 hours. Outcomes of HOPE-treated cases were compared with those after static cold storage. Propensity score matching (1:2) and Bayesian model averaging were used to overcome selection bias. During the study period, 25 (8.5%) out of 294 grafts were treated with HOPE. After matching, HOPE was associated with a lower severe post-reperfusion syndrome (PRS) rate (4% versus 20%, p = 0.13) and stage 2–3 acute kidney injury (AKI) (16% versus 42%, p = 0.046). Furthermore, Bayesian model averaging showed lower transaminases peak and a lower early allograft dysfunction (EAD) rate after HOPE. A steeper decline in arterial graft resistance throughout perfusion was associated with lower EAD rate. HOPE determines a significant reduction of ischemia reperfusion injury in DBD LT.
HLSC-EV treatment, even in a short-duration model, was feasible and effectively reduced liver injury during hypoxic NMP.
Prompted by the utilization of extended criteria donors, dual hypothermic oxygenated machine perfusion (D‐HOPE) was introduced in liver transplantation to improve preservation. When donors after neurological determination of death (DBD) are used, D‐HOPE effect on graft outcomes is unclear. To assess D‐HOPE value in this setting and to identify ideal scenarios for its use, data on primary adult liver transplant recipients from January 2014 to April 2021 were analyzed using inverse probability of treatment weighting, comparing outcomes of D‐HOPE‐treated grafts (n = 121) with those preserved by static cold storage (n = 723). End‐ischemic D‐HOPE was systematically applied since November 2017 based on donor and recipient characteristics and transplant logistics. D‐HOPE use was associated with a significant reduction of early allograft failure (OR: 0.24; 0.83; p = .024), grade ≥3 complications (OR: 0.57; p = .046), comprehensive complication index (−7.20 points; p = .003), and improved patient and graft survival. These results were confirmed in the subset of elderly donors (>75‐year‐old). Although D‐HOPE did not reduce the incidence of biliary complications, its use was associated with a reduced severity of ischemic cholangiopathy. In conclusion, D‐HOPE improves postoperative outcomes and reduces early allograft loss in extended criteria DBD grafts.
Background. Liver graft viability assessment has long been considered a limit of hypothermic oxygenated machine perfusion (HOPE). Aim of this study was assessing correlations of easily available perfusate parameters (PP) (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, glucose, lactate, and pH) with graft features and outcome. Methods. In the period October 2018–February 2020, perfusate samples were obtained every 30 minutes during 50 dual-HOPE (D-HOPE) procedures. Correlations of PP with graft factors, 90-day graft loss, early allograft dysfunction (EAD), L-GrAFT score, acute kidney injury, and comprehensive complication index were analyzed using Pearson coefficient, receiver-operating characteristics analysis and by univariable and multivariable regression. Results. Median D-HOPE time was 122 minutes. All parameters were normalized to liver weight. Only macrovesicular steatosis (MaS) significantly impacted PP levels and slope. Grafts with ≥30% MaS exhibited significantly different PP values and slope. Graft loss and EAD rate were 2% (n = 1) and 26% (n = 13). All PP except lactate correlated with EAD, 90-minute alanine aminotransferase showing the highest area under the receiver-operating characteristics curve (0.84). However, at multivariable analysis, the only factor independently associated with EAD was MaS (odds ratio, 5.44; confidence interval, 1.05-28.21; P = 0.04). Ninety minutes lactate dehydrogenase had the strongest correlation with L-GrAFT (R = 0.70; P < 0.001). PP correlated poorly with comprehensive complication index and grades 2–3 acute kidney injury rate. Conclusions. PP were predictive of graft function after transplant, but their association with graft survival and clinical outcomes requires further evaluation. MaS influenced levels of PP and was the only independent predictor of EAD.
Background & Aims Several studies have shown that new direct‐acting antivirals maintain their efficacy in liver transplant (LT) recipients with severe hepatitis C virus (HCV) recurrence. We determined the clinical impact of sofosbuvir/ribavirin in LT through the changes in liver function and fibrosis state at 24 and 48 weeks after treatment. Methods Between June 2014 and July 2015, 126 patients (30 F3, 96 F4 Metavir stage) were enrolled to receive sofosbuvir + ribavirin (24 weeks, 118 patients) or sofosbuvir + simeprevir + ribavirin (12 weeks, 8 patients); treatment was initiated at a median time of 4.3 years from LT. Median follow‐up after therapy completion was 461 days. Results All 30 F3 patients achieved a sustained virological response at week 24 after treatment (SVR24) and showed a distinct amelioration of the AST‐to‐platelet ratio index (APRI), FIB‐4 and liver stiffness at elastography by week 24 post‐therapy, which were maintained at week 48. Of the 96 F4 cirrhotic patients, 72 (75%) achieved SVR24 accompanied by significant improvement of liver function, which was maintained at week 48 (Child B‐C 22% baseline, 11% week 24, 7% week 48); APRI, FIB‐4 and liver stiffness further improved significantly between weeks 24 and 48 of follow‐up. Among the 77 responders (27 F3, 50 F4) who underwent elastography at baseline and at the end of follow‐up, 39 (50.6%; 18 F3, 21 F4) exhibited a regression in fibrosis stage. Conclusion At about 1 year from the completion of successful sofosbuvir‐based therapy, patients with post‐LT HCV and severe fibrosis experienced a long‐term liver function improvement accompanied by a regression of fibrosis stage in half of them.
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