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

EX SITU END ISCHEMIC HYPOTHERMIC OXYGENATED PERFUSION (HOPE) VERSUS STATIC COLD STORAGE PRIOR TO LIVER TRANSPLANTATION-EARLY RESULTS OF THE BRIDGE TO HOPE PIVOTAL MULTICENTER RANDOMIZED CONTROLLED CLINICAL TRIAL ON THE SAFETY AND EFFECTIVENESS OF THE VITASMART LIVER MACHINE PERFUSION SYSTEM (CLINICALTRIALS.GOV: Nct05045794)

Background: Ex-situ end-ischemic hypothermic oxygenated perfusion (HOPE) is a simple technique to improve liver transplant (LT) results and the donor shortage. HOPE after static cold storage (SCS) reduces ischemia reperfusion injury, early allograft dysfunction (EAD), cholangiopathy and other poor outcomes. A pivotal, US multicenter RCT opened in early 2022 to compare HOPE after SCS to HOPE alone for LT using extended criteria DBD and DCD grafts. Methods: Consented adults matched to a higher risk donor liver that the investigator committed to transplant were randomized 1:1 to SCS followed by HOPE at the transplant center or to SCS only. Livers randomized to the HOPE arm were perfused with the VitaSmart machine, through the portal vein only, at \u3c4 mm Hg pressure, using actively oxygenated (pO2\u3e60 kPa) Belzer machine perfusion solution, for 1.5-5 hr. The primary efficacy endpoint is EAD and the primary safety endpoints are patient and graft survival. Other endpoints include primary non-function (PNF), ischemic cholangiopathy, adverse events, and length of stay (LOS). A centralized, blinded radiologist evaluated cholangiograms for cholangiopathy. Recipients were assessed post-transplantation on days 1-7, 14 and 30, and months 3, 6 and 12 post-LT. Target total enrollment is 244 patients completing transplant. Results: The study has reached the 25% enrollment milestone (61 of 244 targeted LTs, at 11 centers), with key outcomes depicted below. There were no device malfunctions or device-related AEs. Conclusion: Early results of this first US RCT of end-ischemic portal venous HOPE with VitaSmart for LT of extended criteria donor livers reveal promising outcomes, including device safety, lower risk of EAD and shorter hospital LOS

Impact of the new kidney allocation system A2/A2B --> 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-->B DDKT, the likelihood of A2i DDKT among minorities, relative to whites, was not improved. Further discussion regarding A2/A2B-->B policy revisions aiming to improve DDKT access for minorities is warranted

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

Racial Disparities in Liver Transplant for Hepatitis C-Associated Hepatocellular Carcinoma

BACKGROUND: In the United States, hepatitis C virus-associated hepatocellular carcinoma incidence and mortality are highest among minorities. Socioeconomic constraints play a major role in inequitable treatment. We evaluated the association between race/ethnicity and outcomes in a population that overcame treatment barriers. METHODS: We report a retrospective cohort study of 666 patients across 20 institutions in the United States Hepatocellular Carcinoma Liver Transplantation Consortium from 2015 to 2019 with hepatitis C virus-associated hepatocellular carcinoma who completed direct-acting antiviral therapy and underwent liver transplantation. Patients were excluded if they had a prior liver transplantation, hepatocellular carcinoma recurrence, no prior liver-directed therapy, or if race/ethnicity data were unavailable. Patients were stratified by race/ethnicity. Primary outcomes were recurrence-free survival and overall survival, and secondary outcome was major postoperative complication. RESULTS: Race/ethnicity was not associated with differences in 5-year recurrence-free survival (White 90%, Black 88%, Hispanic 92%, Other 87%; p = 0.85), overall survival (White 85%, Black 84%, Hispanic 84%, Other 93%; p = 0.70), or major postoperative complication. CONCLUSIONS: Race/ethnicity was not associated with worse oncologic or postoperative outcomes among those who completed direct-acting antiviral therapy and underwent liver transplantation, suggesting that overcoming socioeconomic constraints equalizes outcomes across racial/ethnic groups. Eliminating barriers that prohibit care access among minorities must be a priority