Mechanism, potential, and concerns of immunotherapy for hepatocellular carcinoma and liver transplantation

In the last decade, immunotherapy (IT) has revolutionized oncology and found indications in many cancers, including hepatocellular carcinoma (HCC). In HCC, IT has become the leading systemic therapy for advanced diseases. At the same time, it carries the promise of being a valuable therapy in other settings, including intermediate-stage and unresectable disease, as a downstaging or conversion modality. More controversial is the role of IT in relationship to liver transplantation (LT): on one side, it could be a helpful tool to control or downstage HCC before LT or to treat tumor recurrence after LT, while on the other, it carries the risk of graft rejection and graft loss. This review aims to cover these concerns in depth and unravel the current literature

The Enhanced Recovery After Surgery Pathway Is Safe, Feasible and Cost-Effective in Delayed Graft Function After Kidney Transplant

Background/Objectives: Enhanced recovery after surgery (ERAS) pathways are still underutilized in kidney transplantation (KT), and their feasibility after delayed graft function (DGF) is unknown. We aimed to evaluate safety and cost savings after ERAS implementation in KT recipients with DGF. Methods: A retrospective analysis of KT recipients enrolled in the ERAS program with DGF (≥1 dialytic treatment during the first postoperative week or creatinine≥ 2.5 mg/dL on postoperative day 10) between 2010 and 2019 was performed. Recipient, donor, and transplant data, outcomes, and 1-year post-KT costs were collected, comparing recipients within the ERAS target (≤5 days, “early discharge group”) to those discharged later (>5 days, “late discharge group”). Results: Out of 170 KT recipients with DGF, 33 (19.4%) were in the “early discharge group” and 137 (80.5%) in the “late discharge group”. Recipient, donor, and transplant characteristics were similar in the two groups. The length of hospital stay (LOS) of the “early discharge group” was significantly shorter, with fewer in-hospital dialysis sessions (p < 0.001) compared to the “late discharge group”. One year post-KT, no significant differences were observed in postoperative complications, readmissions, or number of outpatient visits. Five-year graft and patient survival along with five-year graft function were similar between the two cohorts. First-year costs were significantly higher in the “late discharge group” (p < 0.001), with a median excess cost (∆) of EUR 4515.76/patient. Factors influencing first-year costs post-KT were LOS for KT, recipient age, and use of expanded-criteria grafts. Conclusions: The ERAS approach is safe in KT recipients with DGF and allows for economic savings, while its implementation does not cause worse clinical outcomes in recipients

Re-Evaluation of the Role of Antifibrinolytic Therapy with Lysine Analogs in Liver Transplantation in The Post-Aprotinin Era

Purpose of review: Hemorrhage, blood and blood product transfusions and the need for surgical re-exploration for bleeding can have a detrimental effect on patient outcome during liver surgery. Following the suspension of aprotinin from the market only the antifibrinolyticstranexamic acid (TA) and epsilon-aminocaproic acid (EACA) are left as pharmacological options to reduce hemostatic activation and associated bleeding complications. Considering the apparent usefulnes of aprotinin in liver surgery and transplantation, its loss has left a void within the armamentarium of drugs available to reduce blood loss. The need for large independent safety studies has become evident. The current review focuses on the drugs that are available, the safety and efficacydata that supports their use and the indications warranting further trailsRecent findings Both TA and EACA are effective in reducing blood loss and transfusion requirements in liver surgery. Analysis of data is complicated as the dosing regimens, especially for tranexamic acid, varies enormously and the agents are highly overdosed in most relevant trials. New data indicates that in a dose-dependent fashion, TA is associated with an increase in adverse events with transient renal failure highlighted as a particular problem. It appears that all the anti-fibrinolyticshave side effects that may impact on morbidity and mortality and it may be that aprotinin is no worse. The use of these agents needs to be balanced against benefitespecially in the management of high risk cases

Donation after Circulatory Death in Paediatric Liver Transplantation: Current Status and Future Perspectives in the Machine Perfusion Era

Efforts have been made by the transplant community to expand the deceased donor pool in paediatric liver transplantation (LT). The growing experience on donation after circulatory death (DCD) for adult LT has encouraged its use also in children, albeit in selective cases, opening new perspectives for paediatric patients. Even though there has recently been a slight increase in the number of DCD livers transplanted in children, with satisfactory graft and patient outcomes, the use of DCD grafts in paediatric recipients is still controversial due to morbid outcomes associated with DCD grafts. In this context, recent advances in the optimization of donor support by extracorporeal membrane oxygenation and in the graft preservation by liver machine perfusion could find application in order to expand the donor pool in paediatric LT. In the present study we review the current literature on DCD liver grafts transplanted in children and on the use of extracorporeal donor support and liver perfusion machines in paediatrics, with the aim of defining the current status and future perspectives of paediatric LT

Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A few lights and many shadows

With the introduction of direct-acting antiviral agents (DAA), the rate of sustained virological response (SVR) in the treatment of hepatitis C virus (HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma (HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4% (maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4% (maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection. \ua9 2018 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved

Superiority of the new sex-adjusted models to remove the female disadvantage restoring equity in liver transplant allocation

Background and Aims: Model for End-stage Liver Disease (MELD) and MELDNa are used worldwide to guide graft allocation in liver transplantation (LT). Evidence exists that females are penalized in the present allocation systems. Recently, new sex-adjusted scores have been proposed with improved performance respect to MELD and MELDNa. GEMA-Na, MELD 3.0, and sex-adjusted MELDNa were developed to improve the 90-day dropout prediction from the list. The present study aimed at evaluating the accuracy and calibration of these scores in an Italian setting. Methods: The primary outcome of the present study was the dropout from the list up to 90 days because of death or clinical deterioration. We retrospectively analysed data from 855 adults enlisted for liver transplantation in the Lazio region (Italy) (2012–2018). Ninety-day prediction of GEMA-Na, MELD 3.0 and sex-adjusted MELDNa with respect to MELD and MELDNa was analysed. Brier score and Brier Skill score were used for accuracy, and the Greenwood-Nam- D'Agostino test was used to evaluate the calibration of the models. Results: GEMA-Na (concordance = .82, 95% CI = .75–. 89), MELD 3.0 (concordance = .81, 95% CI = .74–. 87) and sex-adjusted MELDNa (concordance = .81, 95% CI = .74–.88) showed the best 90-day dropout prediction. GEMA-Na showed a higher increase in accuracy with respect to MELD (p = .03). No superiority was shown with respect to MELDNa. All the tested scores showed a good calibration of the models. Using GEMA-Na instead of MELD would potentially save one in nine dropouts and could save one dropout per 285 patients listed

A Keynesian perspective on the health economics of kidney transplantation would strengthen the value of the whole organ donation and transplantation service

BackgroundIn this study, the Keynesian principle “savings may be used as investments in resources” is applied to Kidney Transplantation (KT), contextualizing the whole Organs Donation and Transplantation (ODT) service as a unique healthcare entity. Our aim was to define the financial resources that may be acquired in the form of savings from the KT activity.MethodsWe analyzed registry and funding data for ODT in our region, between 2015 and 2019. Our hypotheses aimed to evaluate whether the savings would offset the Organ Donation (OD) costs, define the scope for growth, and estimate what savings could be generated by higher KT activity. To facilitate the evaluation of the resources produced by KT, we defined a coefficient generated from the combination of clinical outcomes, activity, and costs.ResultsThe ODT activity reached a peak in 2017, declining through 2018–2019. The savings matured in 2019 from the KT activity exceeded €15 million while the OD costs were less than €9 million. The regional KT activity was superior to the national average but inferior to international benchmarks. The estimated higher KT activity would produce savings between €16 and 20 million.ConclusionThe financial resources produced by KT contribute to defining a comprehensive perspective of ODT finance. The optimization of the funding process may lead to the financial self-sufficiency of the ODT service. The reproducible coefficient allows a reliable estimate of savings, subsequently enabling adequate investments and budgeting. Applying such a perspective jointly with reliable estimates would establish the basis for an in-hospital fee-for-value funding methodology for ODT