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

Expanding the use of hepatitis C-viremic kidney donors

Direct-acting antivirals have revolutionized the treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease, with implications for the timing of antiviral treatment among kidney transplant candidates and for the use of HCV viremic donors. A recent consensus conference reviewed the available data on the safety and cost-effectiveness of expanding access to HCV-positive organs to HCV-negative recipients. Early trials are promising, but larger trials and a plan for obtaining HCV therapy in the posttransplantation period are needed. Implications for the larger transplant community also need to be considered

Kidney transplantation of highly sensitized recipients under the new kidney allocation system: A reflection from five different transplant centers across the United States

Deceased donor kidney allocation was reorganized in the United States to address several problems, including the highly sensitized patients disadvantaged with large, diverse repertoires of antibodies. Here, five transplant surgeons review their center's experience with the new allocation changes: highlighting areas of accomplishment, opportunities for improvement and, in some cases, stark differences in practice. Across these five centers the highly sensitized patients (CPRA ⩾98%) range from 5.5 to 9.2% of the 12,364 candidates on their collective waitlist. All centers reported greater rates of kidney transplantations in highly sensitized patients (12.4-27%). Three of the programs (Emory, UCSF, UW) relied upon the virtual crossmatch prior to organ acceptance in a majority of cases (70-86%)-the mere presence of antibody on HLA antibody screen was sufficient to exclude the donor in most cases at Emory and UCSF. Penn and UAB relied upon the physical flow crossmatch in almost all cases prior to proceeding with transplantation. Current or historical donor-specific antibody was occasionally crossed in certain cases at UW and UAB necessitating IVIG/plasmapheresis and/or B cell depletion perioperatively. Some authors raised concerns for cost efficiency given the increased need for organ/specimen transportation, and extensive use of hospital resources and ancillary services. In general, we found that the new allocation system has successfully achieved one of its primary goals-increased kidney transplantation in the disadvantaged, highly sensitized patients; the long-term outcomes in all patients and the cost ramifications of these changes will require continued reassessment and clarification

Obesity Impacts Access to Kidney Transplantation

Current billing practices and mandates to report surgical outcomes are disincentives to surgical treatment of obese patients, who are at increased risk for longer hospital stays and higher complication rates. The objective of this study was to quantify the independent association between body mass index (BMI) and waiting time for kidney transplantation to identify potential provider bias against surgical treatment of the obese. A secondary data analysis was performed of a prospective cohort of 132,353 patients who were registered for kidney transplantation in the United States between 1995 and 2006. Among all patients awaiting kidney transplantation, the likelihood of receiving a transplant decreased with increasing degree of obesity, categorized by ranges of BMI (adjusted hazard ratios 0.96 for overweight, 0.93 for obese, 0.72 for severely obese, and 0.56 for morbidly obese, compared with a reference group of patients with normal BMI). Similarly, the likelihood of being bypassed when an organ became available increased in a graded manner with category of obesity (adjusted incidence rate ratio 1.02 for overweight, 1.05 for obese, 1.11 for severely obese, and 1.22 for morbidly obese). Although matching an available organ with an appropriate recipient requires clinical judgment, which could not be fully captured in this study, the observed differences are dramatic and warrant further studies to understand this effect better and to design a system that is less susceptible to unintended bias

Regional Social Vulnerability is Associated With Geographic Disparity in Waitlist Outcomes for Patients With Non-Hepatocellular Carcinoma Model for End-stage Liver Disease Exceptions in the United States

This study was undertaken to evaluate the role of regional social vulnerability in geographic disparity for patients listed for liver transplantation with non-hepatocellular carcinoma (HCC) model for end-stage liver disease (MELD) exceptions. Prior work has demonstrated regional variability in the appropriateness of MELD exceptions for diagnoses other than HCC. Adults listed at a single center for first-time liver-only transplantation without HCC after June 18, 2013 in the Scientific Registry of Transplant Recipients database as of March 2021 were examined. Candidates were mapped to hospital referral regions (HRRs). Adjusted likelihood of mortality and liver transplantation were modeled. Advantaged HRRs were defined as those where exception patients were more likely to be transplanted, yet no more likely to die in adjusted analysis. The Centers for Disease Control's Social Vulnerability Index (SVI) was used as the measure for community health. Higher SVIs indicate poorer community health. There were 49,494 candidates in the cohort, of whom 4337 (8.8%) had MELD exceptions. Among continental US HRRs, 27.3% (n = 78) were identified as advantaged. The mean SVI of advantaged HRRs was 0.42 versus 0.53 in nonadvantaged HRRs ( P = 0.002), indicating better community health in these areas. Only 25.3% of advantaged HRRs were in spatial clusters of high SVI versus 40.7% of nonadvantaged HRRs, whereas 44.6% of advantaged HRRs were in spatial clusters of low SVI versus 38.0% of nonadvantaged HRRs ( P = 0.037). An advantage for non-HCC MELD exception patients is associated with lower social vulnerability on a population level. These findings suggest assigning similar waitlist priority to all non-HCC exception candidates without considering geographic differences in social determinants of health may actually exacerbate rather than ameliorate disparity

Regional Social Vulnerability is Associated with Geographic Disparity in Waitlist Outcomes for Patients with Non-HCC MELD Exceptions in the United States

Background: This study was undertaken to evaluate the role of regional social vulnerability in geographic disparity for patients listed for liver transplant with non-HCC MELD exceptions. Methods: Adults listed at a single center for a first time liver only transplant without HCC after June 18, 2013 in the SRTR database as of March 2021 were examined. Candidates were mapped to hospital referral regions (HRRs). Adjusted likelihood of mortality and liver transplant were modeled. Advantaged HRRs were defined as those where exception patients were more likely to be transplanted, yet no more likely to die in adjusted analysis. The Centers for Disease Control’s Social Vulnerability Index (SVI) was used as the measure for community health. Higher SVIs indicate poorer community health. Results: There were 49,494 candidates in the cohort, of whom 4,337 (8.8%) had MELD exceptions. Among continental US HRRs, 27.3% (n=78) were identified as advantaged. The mean SVI of advantaged HRRs was 0.42 vs. 0.53 in non-advantaged HRRs ( P =0.002), indicating better community health in these areas. Only 25.3% of advantaged HRRs were in spatial clusters of high SVI vs. 40.7% of non-advantaged HRRs, while 44.6% of advantaged HRRs were in spatial clusters of low SVI vs.38.0% of non-advantaged HRRs ( P =0.037). Conclusion: Advantage for non-HCC MELD exception patients is associated with lower social vulnerability on a population level. These findings suggest assigning similar waitlist priority to all non-HCC exception candidates without considering geographic differences in social determinants of health may actually exacerbate rather than ameliorate disparity

Survival following simultaneous liver-lung versus liver alone transplantation: Results of the US National experience

There are little data to compare the post-transplant survival between lung-liver transplant (LLT) and liver-alone recipients. This study was undertaken to compare survival between LLT and liver-alone transplant. UNOS data for patients undergoing LLT from 2002 to 2017 was analyzed. LLT recipients (n = 81) were matched 1:4 to liver-alone recipients (n = 324) by propensity score and patient survival was compared in the matched cohorts. Unadjusted 1, 3, and 5-year patient survival in the matched cohort was significantly worse in the LLT (82.5%, 72.2%, and 62.2%) versus liver-alone (92.2%, 82.8%, and 80.9%; p = 0.005). This difference persisted after adjusting for covariates with residual imbalance (HR 2.05, 95% CI 1.37–3.08; p = 0.001). LLT has significantly worse survival than liver-alone transplant. With an increasing organ shortage, medical necessity criteria such as those developed for simultaneous liver-kidney transplantation should be developed for simultaneous lung-liver transplants to assure liver allografts are only allocated when truly needed. •There are no current criteria to guide allocation of lung-liver transplants.•Lung-liver recipients often have compensated liver disease with a low MELD score.•Survival after lung-liver transplant is inferior to that after liver transplant alone.•Necessity criteria are needed to ensure liver-lung transplants are truly warranted

Addressing ethical confusion in deceased donation and transplantation research: the need for dedicated guidance

Innovative research in deceased donation and transplantation often presents ethical challenges for researchers and those responsible for ethical governance of research. These challenges have been recognized as potential barriers to the conduct of research. We review the literature to identify and describe ethical considerations that may cause confusion or uncertainty in the context of research involving potential deceased donors or deceased donor transplantation. We normatively examine these considerations and discuss their implications for the ethical conduct of research. In addition to the complexities of research involving critically ill, dying or recently deceased individuals, uncertainty may arise regarding the ethical status of various individuals who may be involved in research aimed at improving availability and outcomes of organ transplantation. Consequently, routine ethical guidelines for clinical research may fail to provide clear guidance with regards to the design, conduct and governance of some deceased donation or transplantation studies. Ethical uncertainty may result in delays or barriers to research, or neglect of important ethical considerations. Specific ethical guidance is needed to support research in deceased donation and transplantation as the ethical considerations that arise in the design and conduct of such research may not be addressed in the existing guidelines for human research