The impact of direct-acting antiviral agents on liver and kidney transplant costs and outcomes.

Direct-acting antiviral medications (DAAs) have revolutionized care for hepatitis C positive (HCV+) liver (LT) and kidney (KT) transplant recipients. Scientific Registry of Transplant Recipients registry data were integrated with national pharmaceutical claims (2007-2016) to identify HCV treatments before January 2014 (pre-DAA) and after (post-DAA), stratified by donor (D) and recipient (R) serostatus and payer. Pre-DAA, 18% of HCV+ LT recipients were treated within 3 years and without differences by donor serostatus or payer. Post-DAA, only 6% of D-/R+ recipients, 19.8% of D+/R+ recipients with public insurance, and 11.3% with private insurance were treated within 3 years (P < .0001). LT recipients treated for HCV pre-DAA experienced higher rates of graft loss (adjusted hazard ratio [aHR] 1.34 1.852.10 , P < .0001) and death (aHR 1.47 1.681.91 , P < .0001). Post-DAA, HCV treatment was not associated with death (aHR 0.34 0.671.32 , P = .25) or graft failure (aHR 0.32 0.641.26 , P = .20) in D+R+ LT recipients. Treatment increased in D+R+ KT recipients (5.5% pre-DAA vs 12.9% post-DAA), but did not differ by payer status. DAAs reduced the risk of death after D+/R+ KT by 57% (0.19 0.430.95 , P = .04) and graft loss by 46% (0.27 0.541.07 , P = .08). HCV treatment with DAAs appears to improve HCV+ LT and KT outcomes; however, access to these medications appears limited in both LT and KT recipients.

Prescription opioid use before and after kidney transplant: Implications for posttransplant outcomes.

Evolving literature suggests that the epidemic of prescription opioid use affects the transplant population. We examined a novel database wherein national U.S. transplant registry records were linked to a large pharmaceutical claims warehouse (2007-2015) to characterize prescription opioid use before and after kidney transplant, and associations (adjusted hazard ratio, 95%LCL aHR95%UCL ) with death and graft loss. Among 75 430 eligible patients, 43.1% filled opioids in the year before transplant. Use was more common among recipients who were women, white, unemployed, publicly insured, and with longer pretransplant dialysis. Of those with the highest level of pretransplant opioid use, 60% continued high-level use posttransplant. Pretransplant opioid use had graded associations with one-year posttransplant outcomes; the highest-level use predicted 46% increased risk of death (aHR 1.28 1.461.66 ) and 28% increased risk of all-cause graft failure (aHR 1.17 1.281.41 ). Effects of high-level opioid use in the first year after transplant were stronger, predicting twice the risk of death (aHR 1.93 2.242.60 ) and 68% higher all-cause graft failure risk (aHR 1.50 1.681.89 ) over the subsequent year; increased risk persisted over five years. While associations may, in part, reflect underlying conditions or behaviors, opioid use history is relevant in assessing and providing care to transplant candidates and recipients.

OPTN/SRTR 2016 Annual Data Report: Economics.

Medicare costs vary for solid organ transplant recipients by outcome: survival with graft function, survival with graft failure, and death. Average per-person per-year reimbursement was $75 thousand for kidney recipients who survived the first year posttransplant with a functioning graft, $171 thousand for those who required a return to dialysis or retransplant, and $350 thousand for those who died with function. For pancreas recipients: $105 thousand for those who survived the first year with a functioning graft, $120 thousand for those who survived pancreas failure, and $443 thousand for those who died with function. For liver recipients: $154 thousand for those who survived with a functioning graft, $388 thousand for those who required retransplant, and $740 thousand who died with function. For intestine recipients: $301 thousand for those who survived with a functioning graft and $1 million for those who died with function. For heart recipients: $272 thousand for those who survived with a functioning graft and $1.2 million for those who died with function. For lung recipients: $196 thousand for those who survived with a functioning graft, $642 thousand for those who required retransplant, and $761 thousand for those who died with function.

OPTN/SRTR 2015 Annual Data Report: Economics.

While the costs to Medicare of solid organ transplants are varied and considerable, the total Medicare expenditure of $4.4 billion for solid organ transplant recipients in 2014 remained less than 1% of all Medicare expenditures. For patients covered by Medicare, the ratio of pre- to posttransplant cost of care varied widely by organ and within some organ categories by patient characteristics. This chapter reports pretransplant costs for all solid organ candidates covered by Medicare to allow investigators to further explore the relative cost of transplant compared with alternative management.

The Changing Financial Landscape of Renal Transplant Practice: A National Cohort Analysis.

Kidney transplantation has become more resource intensive as recipient complexity has increased and average donor quality has diminished over time. A national retrospective cohort study was performed to assess the impact of kidney donor and recipient characteristics on transplant center cost (exclusive of organ acquisition) and Medicare reimbursement. Data from the national transplant registry, University HealthSystem Consortium hospital costs, and Medicare payments for deceased donor (N = 53 862) and living donor (N = 36 715) transplants from 2002 to 2013 were linked and analyzed using multivariate linear regression modeling. Deceased donor kidney transplant costs were correlated with recipient (Expected Post Transplant Survival Score, degree of allosensitization, obesity, cause of renal failure), donor (age, cause of death, donation after cardiac death, terminal creatinine), and transplant (histocompatibility matching) characteristics. Living donor costs rose sharply with higher degrees of allosensitization, and were also associated with obesity, cause of renal failure, recipient work status, and 0-ABDR mismatching. Analysis of Medicare payments for a subsample of 24 809 transplants demonstrated minimal correlation with patient and donor characteristics. In conclusion, the complexity in the landscape of kidney transplantation increases center costs, posing financial disincentives that may reduce organ utilization and limit access for higher-risk populations.

National Variation in Use of Immunosuppression for Kidney Transplantation: A Call for Evidence-Based Regimen Selection.

Immunosuppression management in kidney transplantation has evolved to include an increasingly diverse choice of medications. Although informed by patient and donor characteristics, choice of immunosuppression regimen varies widely across transplant programs. Using a novel database integrating national transplant registry and pharmacy fill records, immunosuppression use at 6-12 and 12-24 mo after transplant was evaluated for 22 453 patients transplanted in 249 U.S. programs in 2005-2010. Use of triple immunosuppression comprising tacrolimus, mycophenolic acid or azathioprine, and steroids varied widely (0-100% of patients per program), as did use of steroid-sparing regimens (0-77%), sirolimus-based regimens (0-100%) and cyclosporine-based regimens (0-78%). Use of triple therapy was more common in highly sensitized patients, women and recipients with dialysis duration >5 years. Sirolimus use appeared to diminish over the study period. Patient and donor characteristics explained only a limited amount of the observed variation in regimen use, whereas center choice explained 30-46% of the use of non-triple-therapy immunosuppression. The majority of patients who received triple-therapy (79%), cyclosporine-based (87.6%) and sirolimus-based (84.3%) regimens continued them in the second year after transplant. This population-based study of immunosuppression practice demonstrates substantial variation in center practice beyond that explained by differences in patient and donor characteristics.

The Impact of Redistricting Proposals on Health Care Expenditures for Liver Transplant Candidates and Recipients.

Redistricting, which means sharing organs in novel districts developed through mathematical optimization, has been proposed to reduce pervasive geographic disparities in access to liver transplantation. The economic impact of redistricting was evaluated with two distinct data sources, Medicare claims and the University HealthSystem Consortium (UHC). We estimated total Medicare payments under (i) the current allocation system (Share 35), (ii) full regional sharing, (iii) an eight-district plan, and (iv) a four-district plan for a simulated population of patients listed for liver transplant over 5 years, using the liver simulated allocation model. The model predicted 5-year transplant volumes (Share 35, 29,267; regional sharing, 29,005; eight districts, 29,034; four districts, 28,265) and a reduction in overall mortality, including listed and posttransplant patients, of up to 676 lives. Compared with current allocation, the eight-district plan was estimated to reduce payments for pretransplant care ($1638 million to $1506 million, p < 0.001), transplant episode ($5607 million to $5569 million, p < 0.03) and posttransplant care ($479 million to $488 million, p < 0.001). The eight-district plan was estimated to increase per-patient transportation costs for organs ($8988 to $11,874 per patient, p < 0.001) and UHC estimated hospital costs ($4699 per case). In summary, redistricting appears to be potentially cost saving for the health care system but will increase the cost of performing liver transplants for some transplant centers.

Economics.

While the costs to Medicare of solid organ transplants are varied and considerable, the total Medicare expenditure of $4.2 billion for solid organ transplant recipients in 2013 remains less than 1% of all Medicare expenditures. Kidney transplant remains one of the most cost-effective surgical interventions in medicine and exhibits a rare feature in that it is generally known to be cost-saving in the long term. For patients covered by Medicare, lung transplant is one of the more costly solid organ transplants performed. This chapter reports pretransplant costs for lung candidates to allow investigators to further explore the relative cost of lung transplant compared with alternative management.

List and liver transplant survival according to waiting time in patients with hepatocellular carcinoma.

The time that patients with hepatocellular carcinoma (HCC) can safely remain on the waiting list for liver transplantation (LT) is unknown. We investigated whether waiting time on the list impacts transplant survival of HCC candidates and transplant recipients. This is a single-center retrospective study of 283 adults with HCC. Patients were divided in groups according to waiting-list time. The main endpoint was survival. The median waiting time for LT was 4.9 months. The dropout rates at 3-, 6-, and 12-months were 6.4%, 12.4%, and 17.7%, respectively. Mortality on the list was 4.8%, but varied depending of the time on the list. Patients who waited less than 3-months had an inferior overall survival when compared to the other groups (p = 0.027). Prolonged time on the list significantly reduced mortality in this analysis (p = 0.02, HR = 0.28). Model for End Stage Liver Disease (MELD) score at transplantation did also independently impact overall survival (p = 0.03, HR = 1.06). MELD was the only factor that independently impacted posttransplant survival (p = 0.048, HR = 1.05). We conclude that waiting time had no relation with posttransplant survival. It is beneficial to prolong the waiting list time for HCC candidates without having a negative impact in posttransplant survival.

OPTN/SRTR 2013 Annual Data Report: economics.

While the costs to Medicare of solid organ transplant are varied and considerable, the total Medicare expenditure of $4.4 billion for solid organ transplant recipients was less than 1 remains one of the most cost-effective surgical interventions in medicine. Heart transplant, the most expensive of the major transplants, is likely cost-effective; SRTR has released an Excel-based tool for investigators to use in exploring this question further. It is likely that most solid organ transplants are cost-effective, given the results presented here and the relatively high cost of heart transplant. However, this must be verified with further study.

Variation in biliary complication rates following liver transplantation: implications for cost and outcome.

Although biliary complications (BCs) have a significant impact on the outcome of liver transplantation (LT), variation in BC rates among transplant centers has not been previously analyzed. BC rate, LT outcome and spending were assessed using linked Scientific Registry of Transplant Recipients and Medicare claims (n = 16,286 LTs). Transplant centers were assigned to BC quartiles based upon risk-adjusted observed to expected (O:E) ratio of BC separately for donation after brain death (DBD) and donation after cardiac death (DCD) donors. The median incidence of BC was 300% greater in the highest versus lowest DBD quartiles (19.0% vs. 5.9%) and varied 250% between DCD quartiles (20.3%-8.4%). Donor and recipient characteristics suggest that high BC centers actually used lower donor risk index organs, fewer split livers and fewer imports (p < 0.001 for all). Transplant at a center in the highest O:E quartile was associated with increased posttransplant mortality (adjusted hazard ratio [aHR] 2.53, p = 0.007) in DCD transplant and increased graft loss (aHR 1.21, p = 0.02) in DBD transplant. Medicare spending was $22,895 (p < 0.0001) higher at centers in highest versus lowest BC quartile. In summary, BC rates vary widely among transplant centers and higher rates are a marker for an increased risk of death, graft failure and health-care spending.

Assessing variation in the costs of care among patients awaiting liver transplantation.

Previous economic analyses of liver transplantation have focused on the cost of the transplant and subsequent care. Accurate characterization of the pretransplant costs, indexed to severity of illness, is needed to assess the economic burden of liver disease. A novel data set linking Medicare claims with transplant registry data for 15,710 liver transplant recipients was used to determine average monthly waitlist spending (N = 249,434 waitlist months) using multivariable linear regression models to adjust for recipient characteristics including Model for End-Stage Liver Disease (MELD) score. Characteristics associated with higher spending included older age, female gender, hepatocellular carcinoma, diabetes, hypertension and increasing MELD score (p < 0.05 for all). Spending increased exponentially with severity of illness: expected monthly spending at a MELD score of 30 was 10 times higher than at MELD of 20 ($22,685 vs. $2030). Monthly spending within MELD strata also varied geographically. For candidates with a MELD score of 35, spending varied from $19,548 (region 10) to $36,099 (region 7). Regional variation in waitlist costs may reflect the impact of longer waiting times on greater pretransplant hospitalization rates among high MELD score patients. Reducing the number of high MELD waitlist patients through improved medical management and novel organ allocation systems could decrease total spending for end-stage liver care.

Addressing geographic disparities in liver transplantation through redistricting.

Severe geographic disparities exist in liver transplantation; for patients with comparable disease severity, 90-day transplant rates range from 18% to 86% and death rates range from 14% to 82% across donation service areas (DSAs). Broader sharing has been proposed to resolve geographic inequity; however, we hypothesized that the efficacy of broader sharing depends on the geographic partitions used. To determine the potential impact of redistricting on geographic disparity in disease severity at transplantation, we combined existing DSAs into novel regions using mathematical redistricting optimization. Optimized maps and current maps were evaluated using the Liver Simulated Allocation Model. Primary analysis was based on 6700 deceased donors, 28 063 liver transplant candidates, and 242 727 Model of End-Stage Liver Disease (MELD) changes in 2010. Fully regional sharing within the current regional map would paradoxically worsen geographic disparity (variance in MELD at transplantation increases from 11.2 to 13.5, p = 0.021), although it would decrease waitlist deaths (from 1368 to 1329, p = 0.002). In contrast, regional sharing within an optimized map would significantly reduce geographic disparity (to 7.0, p = 0.002) while achieving a larger decrease in waitlist deaths (to 1307, p = 0.002). Redistricting optimization, but not broader sharing alone, would reduce geographic disparity in allocation of livers for transplant across the United States.

Optimizing the program-specific reporting of pancreas transplant outcomes.

The Scientific Registry of Transplant Recipients is charged with providing program-specific reports for organ transplant programs in the United States. Monitoring graft survival for pancreas transplant programs has been problematic as there are three different pancreas transplant procedures that may have different outcomes, and analyzing them separately reduces events and statistical power. We combined two consecutive 2.5-year cohorts of transplant recipients to develop Cox proportional hazards models predicting outcomes, and tested these models in the second 2.5-year cohort. We used separate models for 1- and 3-year graft and patient survival for each transplant type: simultaneous pancreas-kidney (SPK), pancreas after kidney (PAK) and pancreas transplant alone (PTA). We first built a predictive model for each pancreas transplant type, and then pooled the transplant types within centers to compare total observed events with total predicted events. Models for 1-year pancreas graft and patient survival yielded C statistics of 0.65 (95% confidence interval, 0.63-0.68) and 0.66 (0.61-0.72), respectively, comparable to C statistics for 1-year patient and graft survival for other organ transplants. Model calibration (Hosmer-Lemeshow method) was also acceptable. We conclude that pooling the results of SPK, PAK and PTA can produce potentially useful models for reporting program-specific pancreas transplant outcomes.