Strategies to optimize the use of marginal donors in liver transplantation.

Liver transplantation is the treatment of choice for end stage liver disease, but availability of liver grafts is still the main limitation to its wider use. Extended criteria donors (ECD) are considered not ideal for several reasons but their use has dramatically grown in the last decades in order to augment the donor liver pool. Due to improvement in surgical and medical strategies, results using grafts from these donors have become acceptable in terms of survival and complications; nevertheless a big debate still exists regarding their selection, discharge criteria and allocation policies. Many studies analyzed the use of these grafts from many points of view producing different or contradictory results so that accepted guidelines do not exist and the use of these grafts is still related to non-standardized policies changing from center to center. The aim of this review is to analyze every step of the donation-transplantation process emphasizing all those strategies, both clinical and experimental, that can optimize results using ECD

Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers

Letter to the edito

Viability Criteria during Liver Ex-Situ Normothermic and Hypothermic Perfusion

With the increased use of extended-criteria donors, machine perfusion became a beneficial alternative to cold storage in preservation strategy for donor livers with the intent to expand donor pool. Both normothermic and hypothermic approach achieved good results in terms of mid- and long-term outcome in liver transplantation. Many markers and molecules have been proposed for the assessment of liver, but no definitive criteria for graft viability have been validated in large clinical trials and key parameters during perfusion still require optimization.In this review, we address the current literature of viability criteria during normothermic and hypothermic machine perfusion and discuss about future steps and evolution of these technologies

Implementing a robotic liver resection program does not always require prior laparoscopic experience

Background: Preliminary experience in laparoscopic liver surgery is usually suggested prior to implementation of a robotic liver resection program. Methods: This was a retrospective cohort analysis of patients undergoing robotic (RLR) versus laparoscopic liver resection (LLR) for hepatocellular carcinoma at a center with concomitant initiation of robotic and laparoscopic programs RESULTS: A total of 92 consecutive patients operated on between May 2014 and February 2019 were included: 40 RLR versus 52 LLR. Median age (69 vs. 67; p = 0.74), male sex (62.5% vs. 59.6%; p = 0.96), incidence of chronic liver disease (97.5% vs.98.1%; p = 0.85), median model for end-stage liver disease (MELD) score (8 vs. 9; p = 0.92), and median largest nodule size (22 vs. 24 mm) were similar between RLR and LLR. In the LLR group, there was a numerically higher incidence of nodules located in segment 4 (20.0% vs. 16.6%; p = 0.79); a numerically higher use of Pringle's maneuver (32.7% vs. 20%; p = 0.23), and a shorter duration of surgery (median of 165.5 vs. 217.5 min; p = 0.04). Incidence of complications (25% vs.32.7%; p = 0.49), blood transfusions (2.5% vs.9.6%; p = 0.21), and median length of stay (6 vs. 5; p = 0.54) were similar between RLR and LLR. The overall (OS) and recurrence-free (RFS) survival rates at 1 and 5 years were 100 and 79 and 95 and 26% for RLR versus 96.2 and 76.9 and 84.6 and 26.9% for LLR (log-rank p = 0.65 for OS and 0.72 for RFS). Conclusions: Based on our results, concurrent implementation of a robotic and laparoscopic liver resection program appears feasible and safe, and is associated with similar oncologic long-term outcomes

New Insights in the Setting of Transplant Oncology

: Background and Objectives: Liver transplantation (LT) is the best strategy for curing several primary and secondary hepatic malignancies. In recent years, growing interest has been observed in the enlargement of the transplant oncology indications. This paper aims to review the most recent developments in the setting of LT oncology, with particular attention to LT for unresectable colorectal liver metastases (CRLM) and cholangiocellular carcinoma (CCA). Materials and Methods: A review of the recently published literature was conducted. Results: Growing evidence exists on the efficacy of LT in curing CRLM and peri-hilar and intrahepatic CCA in well-selected patients when integrating this strategy with (neo)-adjuvant chemotherapy, radiotherapy, or locoregional treatments. Conclusion: For unresectable CCA and CRLM management, several prospective protocols are forthcoming to elucidate LT's impact relative to alternative therapies. Advances in diagnosis, treatment protocols, and donor-to-recipient matching are needed to better define the oncological indications for transplantation. Prospective, multicenter trials studying these advances and their impact on outcomes are still required

The perioperative period of liver transplantation from unconventional extended criteria donors: data from two high-volume centres

Background: As literature largely focuses on long-term outcomes, this study aimed at elucidating the perioperative outcomes of liver transplant patients receiving a graft from two groups of unconventional expanded criteria donors: brain dead aged > 80 years and cardiac dead.Methods: Data of 247 cirrhotic patients transplanted at two high volume liver transplant centers were analysed. Confounders were balanced using a stabilized inverse probability therapy weighting and a propensity score for each patient on the original population was generated. The score was created using a multivariate logistic regression model considering a Comprehensive Complication Index & GE; 42 (no versus yes) as the dependent variable and 11 possible clinically relevant confounders as covariate.Results: Forty-four patients received the graft from a cardiac-dead donor and 203 from a brain-dead donor aged > 80 years. Intraoperatively, cardiac-dead donors liver transplant cases required more fresh frozen plasma units (P < 0.0001) with similar reduced need of fibrinogen to old brain-dead donors cases. The incidence of reperfusion syndrome was similar (P = 0.80). In the Intensive Care Unit, both the groups presented a comparable low need for blood transfusions, renal replacement therapy and inotropes. Cardiac-dead donors liver transplantations required more time to tracheal extubation (P < 0.0001) and scored higher Comprehensive Complication Index (P < 0.0001) however the incidence of a severe complication status (Comprehensive Complication Index & GE; 42) was similar (P = 0.52). ICU stay (P = 0.97), total hospital stay (P = 0.57), in hospital (P = 1.00) and 6 months (P = 1.00) death were similar.Conclusion: Selected octogenarian and cardiac-dead donors can be used safely for liver transplantation

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

Hospital-Based Health Technology Assessment of Machine Perfusion Systems for Human Liver Transplantation

Based on published data, we have carried out a hospital-based health technology assessment of machine perfusion in adult liver transplantation using cold storage as a comparator, and within the perspective of a national health system-based hospital practice and disease-related group reimbursement policy. A systematic literature review on machine perfusion for adult liver transplantation was conducted exploring the Pubmed, CINAHL, Scopus, Embase, and Cochrane databases. The literature was analyzed with the intent to provide information on 6 dimensions and 19 items of the hospital-based health technology assessment framework derived from previous studies. Out of 705 references, 47 (6.7%) were retained for current analysis. Use of machine perfusion was associated with advantages over cold storage, i.e., a 10%–50% reduced risk for early allograft dysfunction, 7%–15% less ischemia reperfusion injury; 7%–50% fewer ischemic biliary complications, comparable or improved 1-year graft and patient survival, and up to a 50% lower graft discard rate. Hospital stay was not longer, and technical failures were anecdotal. Information on costs of machine perfusion is limited, but this technology is projected to increase hospital costs while cost-effectiveness analysis requires data over the transplant patient lifetime. No hospital-based health technology assessment study on machine perfusion in liver transplantation was previously conducted. From the hospital perspective, there is evidence of the clinical advantages of this novel technology, but strategies to counterbalance the increased costs of liver transplantation are urgently needed. Further studies should focus on the ethical, social, and organizational issues related to machine perfusion

A call for randomization in clinical trials of liver machine perfusion preservation

Liver transplantation is a lifesaving operation for patients with advanced liver failure. Although mortality from liver disease continues to increase, the number of available grafts remain relatively unchanged, leading to the death of about 15-30% patients on the waiting list. Therefore, transplant teams have resorted to using marginal organs with often poorer outcomes