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

Perceptions and Early Outcomes of the Acuity Circles Allocation Policy Among Liver Transplant Centers in the United States

Background. Recently, a new liver allocation policy called the acuity circles (AC) framework was implemented to decrease geographic disparities in transplant metrics across donor service areas. Early analyses have examined the changes in outcomes because of the AC policy. However, perceptions among transplant surgeons and staff regarding the new policy remain unknown. Methods. A 28-item survey was sent to division chiefs and surgical directors of liver transplantation across the United States. Questions assessed the respondents’ perceptions regarding center-level metrics and staff satisfaction. We used Organ Procurement and Transplantation Network data to study differences in allocation between the pre-AC implementation period (2019) and the post-AC implementation period (2020–2021). Results. A total of 40 participants completed this ongoing survey study. Most responses were from region 8 (13%), region 10 (15%), and region 11 (13%). Sixty-three percent of respondents stated that the wait time for a suitable offer for recipients with model of end-stage liver disease score 30 has increased. However, most respondents (75%) felt that the average cost per transplant had increased and that the rate of surgical complications and 1-y graft survival had remained the same. In most states, an observable decrease in in-state liver transplantations occurred each year between 2019 and 2021. In addition, most allocation regions reported an increase in donations after circulatory deaths between 2019 and 2021. Conclusions. Perceptions of the new AC policy among liver transplant surgeons in the United States remain mixed, highlighting the potential strengths and concerns regarding its future impact. Further studies should assess the effects of the AC policy on clinical outcomes and liver transplantation access

Impact of the new kidney allocation system A2/A2B --\u3e B policy on access to transplantation among minority candidates

Blood group B candidates, many of whom represent ethnic minorities, have historically had diminished access to deceased donor kidney transplantation (DDKT). The new national kidney allocation system (KAS) preferentially allocates blood group A2/A2B deceased donor kidneys to B recipients to address this ethnic and blood group disparity. No study has yet examined the impact of KAS on A2 incompatible (A2i) DDKT for blood group B recipients overall or among minorities. A case-control study of adult blood group B DDKT recipients from 2013 to 2017 was performed, as reported to the Scientific Registry of Transplant Recipients. Cases were defined as recipients of A2/A2B kidneys, whereas controls were all remaining recipients of non-A2/A2B kidneys. A2i DDKT trends were compared from the pre-KAS (1/1/2013-12/3/2014) to the post-KAS period (12/4/2014-2/28/2017) using multivariable logistic regression. Post-KAS, there was a 4.9-fold increase in the likelihood of A2i DDKT, compared to the pre-KAS period (odds ratio [OR] 4.92, 95% confidence interval [CI] 3.67-6.60). However, compared to whites, there was no difference in the likelihood of A2i DDKT among minorities post-KAS. Although KAS resulted in increasing A2/A2B--\u3eB DDKT, the likelihood of A2i DDKT among minorities, relative to whites, was not improved. Further discussion regarding A2/A2B--\u3eB policy revisions aiming to improve DDKT access for minorities is warranted

Donor safety in live donor laparoscopic liver procurement: systematic review and meta-analysis

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Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants: An Analysis From the Randomized TRANSFORM Study

BACKGROUND: The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail. METHODS: TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids. RESULTS: Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.9% versus 59.2% of patients given everolimus or MPA, respectively (P = 0.085). Hyperlipidemia, interstitial lung disease, peripheral edema, proteinuria, stomatitis/mouth ulceration, thrombocytopenia, and wound healing complications were more frequent with everolimus, whereas diarrhea, nausea, vomiting, leukopenia, tremor, and insomnia were more frequent in the MPA group. The incidence of viral infections (17.2% versus 29.2%; P < 0.001), cytomegalovirus (CMV) infections (8.1% versus 20.1%; P < 0.001), CMV syndrome (13.6% versus 23.0%, P = 0.044), and BK virus (BKV) infections (4.3% versus 8.0%, P < 0.001) were less frequent with everolimus. CMV infection was less common with everolimus versus MPA after adjusting for prophylaxis therapy in the D+/R- subgroup (P < 0.001). Study drug was discontinued more frequently due to rejection or impaired healing with everolimus, and more often due to BKV infection or BKV nephropathy with MPA. CONCLUSIONS: De novo everolimus with reduced-exposure CNI yielded a comparable incidence, though a distinctly different pattern, of adverse events versus current standard of care. Both regimens are safe and effective, yet their distinct profiles may enable tailoring for individual kidney transplant recipients.status: publishe