Liver transplantation: Expanding the donor and recipient pool

Liver transplantation is an exemplar model of complex surgery and the only curative option for patients with end-stage liver disease. Although historically associated with poor outcomes, liver cancer management has also been revolutionised with liver transplantation and in some instances, survival outcomes are comparable to surgical resection. As such, the key elements underpinning the major advances in surgical technique, immunological therapies and allocation policies combined with improved patient and graft survival outcomes have created a huge demand for organ donation. Despite improvements in donor and recipient selection, there is a persistent disparity between organ supply and demand. Candidate wait-list mortality and dropout rates remain problematic and this concern has resulted in increased efforts to expand the donor pool to meet the unmet needs of the population. This is even more challenging when coupled with an ever-growing recipient pool, candidate waiting lists and an ageing population. Over the past two decades, there has been a considerable focus on extended criteria organs, donations after cardiac death and alternative avenues for marginal liver use. With careful donor selection and recipient matching, these livers may help bridge the gap between supply and demand and placate the ever-expanding recipient pool. Here, we present a summary of recent developments by the transplant community addressing the issues of a growing donor and recipient pool

Role of yttrium-90 selective internal radiation therapy in the treatment of liver-dominant metastatic colorectal cancer: An evidence-based expert consensus algorithm

Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres]. Using a data-driven, modified Delphi process, an expert panel of surgical oncologists, transplant surgeons, and hepatopancreatobiliary (HPB) surgeons convened to create a comprehensive, evidence-based treatment algorithm that includes appropriate treatment options for patients stratified by their eligibility for surgical treatment. The group coined a novel, more inclusive phrase for targeted locoregional tumor treatment (a blanket term for resection, ablation, and other emerging locoregional treatments)

Economic evaluation of the specialized donor care facility for thoracic organ donor management

Background: Over the last decade two alternative models of donor care have emerged in the United States: the conventional model, whereby donors are managed at the hospital where brain death occurs, and the specialized donor care facility (SDCF), in which brain dead donors are transferred to a SDCF for medical optimization and organ procurement. Despite increasing use of the SDCF model, its cost-effectiveness in comparison to the conventional model remains unknown. Methods: We performed an economic evaluation of the SDCF and conventional model of donor care from the perspective of U.S. transplant centers over a 2-year study period. In this analysis, we utilized nationwide data from the Scientific Registry of Transplant Recipients and controlled for donor characteristics and patterns of organ sharing across the nation\u27s organ procurement organizations (OPOs). Subgroup analysis was performed to determine the impact of the SDCF model on thoracic organ transplants. Results: A total of 38,944 organ transplants were performed in the U.S. during the study period from 13,539 donors with an observed total organ cost of $1.36 billion. If every OPO assumed the cost and effectiveness of the SDCF model, a predicted 39,155 organ transplants (+211) would have been performed with a predicted total organ cost of$1.26 billion (-$100 million). Subgroup analysis of thoracic organs revealed that the SDCF model would lead to a predicted 156 additional transplants with a cost saving of$24.6 million. Conclusions: The U.S. SDCF model may be a less costly and more effective means of multi-organ donor management, particularly for thoracic organ donors, compared to the conventional hospital-based model

Liver transplantation as a new standard of care in patients with perihilar cholangiocarcinoma?:Results from an international benchmark study

Objective: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons.Background: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC.Methods: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014–2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥ 50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter &lt;3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers.Results: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤ 5.2%; comprehensive complication index at 1 year of ≤ 33.7; grade ≥ 3 complication rates ≤ 66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n = 106) (62% vs 32%, P &lt; 0.001).Conclusion: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.</p

Optimal Timing of Administration of Direct-Acting Antivirals for Patients with Hepatitis C-Associated Hepatocellular Carcinoma Undergoing Liver Transplantation

Objective: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). Summary of Background Data: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. Methods: The United States HCC LT Consortium (2015–2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). Results: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0–3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0–3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). Conclusions: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results