Estimation of lifetime costs for patients receiving a transplant: the case of liver transplantation related to hepatitis B in Italy.

Introduction: In Italy, post-liver transplant (LT) hepatitis B virus (HBV) reinfection prophylaxis is frequently based on a combined regimen of anti-HBV immunoglobulin (HBIG) and oral antivirals. However, little information is available at the national level on the cost of LT and the contribution of HBV prophylaxis. This study aimed to quantify the direct healthcare cost for adult patients undergoing LT for HBV-related disease over a lifetime horizon and from the perspective of a National Healthcare Service. Methods: A pharmaco-economic model was implemented with a 4-tiered approach consisting of 1) preliminary literature research to define the research question; 2) pragmatic literature review to retrieve existing information and inform the model; 3) micro-simulated patient cycles; and 4) validation from a panel of national experts. Results: The average lifetime healthcare cost of LT for HBV-related disease was €395,986. The greatest cost drivers were post-transplant end-stage renal failure (31.9% of the total), immunosuppression (20.6%), and acute transplant phase (15.8%). HBV reinfection prophylaxis with HBIG and antivirals accounted for 12.4% and 6.4% of the total cost, respectively; however, lifetime HBIG prophylaxis was only associated with a 6.6% increase (~€422 k). Various sensitivity analyses have shown that discount rates have the greatest impact on total costs. Conclusion: This analysis showed that the burden of LT due to HBV is not only clinical but also economic.

Impact of Back-to-Base Normothermic Machine Perfusion on Complications and Costs: A Multicenter, Real-World Risk-Matched Analysis.

OBJECTIVE: Assess cost and complication outcomes after liver transplantation (LT) using normothermic machine perfusion (NMP). BACKGROUND: End-ischemic NMP is often used to aid logistics, yet its impact on outcomes after LT remains unclear, as does its true impact on costs associated with transplantation. METHODS: Deceased donor liver recipients at 2 centers (January 1, 2019, to June 30, 2023) were included. Retransplants, splits, and combined grafts were excluded. End-ischemic NMP (OrganOx-Metra) was implemented in October 2022 for extended-criteria donation after brain death (DBDs), all donations after circulatory deaths (DCDs), and logistics. NMP cases were matched 1:2 with static cold storage controls (SCS) using the Balance-of-Risk [donation after brain death (DBD)-grafts] and UK-DCD Score (DCD-grafts). RESULTS: Overall, 803 transplantations were included, 174 (21.7%) receiving NMP. Matching was achieved between 118 NMP-DBDs with 236 SCS; and 37 NMP-DCD with 74 corresponding SCS. For both graft types, median inpatient comprehensive complications index values were comparable between groups. DCD-NMP grafts experienced reduced cumulative 90-day comprehensive complications index (27.6 vs 41.9, P =0.028). NMP also reduced the need for early relaparotomy and renal replacement therapy, with subsequently less frequent major complications (Clavien-Dindo ≥IVa). This effect was more pronounced in DCD transplants. NMP had no protective effect on early biliary complications. Organ acquisition/preservation costs were higher with NMP, yet NMP-treated grafts had lower 90-day pretransplant costs in the context of shorter waiting list times. Overall costs were comparable for both cohorts. CONCLUSIONS: This is the first risk-adjusted outcome and cost analysis comparing NMP and SCS. In addition to logistical benefits, NMP was associated with a reduction in relaparotomy and bleeding in DBD grafts, and overall complications and post-LT renal replacement for DCDs. While organ acquisition/preservation was more costly with NMP, overall 90-day health care costs-per-transplantation were comparable.

Identifying drivers of cost in pediatric liver transplantation.

Understanding the economics of pediatric liver transplantation (LT) is central to high-value care initiatives. We examined cost and resource utilization in pediatric LT nationally to identify drivers of cost and hospital factors associated with greater total cost of care. We reviewed 3295 children (<21 y) receiving an LT from 2010 to 2020 in the Pediatric Health Information System to study cost, both per LT and service line, and associated mortality, complications, and resource utilization. To facilitate comparisons, patients were stratified into high-cost, intermediate-cost, or low-cost tertiles based on LT cost. The median cost per LT was $150,836 [IQR $104,481-$250,129], with marked variance in cost within and between hospital tertiles. High-cost hospitals (HCHs) cared for more patients with the highest severity of illness and mortality risk levels (67% and 29%, respectively), compared to intermediate-cost (60%, 21%; p <0.001) and low-cost (51%, 16%; p <0.001) hospitals. Patients at HCHs experienced a higher prevalence of mechanical ventilation, total parental nutrition use, renal comorbidities, and surgical complications than other tertiles. Clinical (27.5%), laboratory (15.1%), and pharmacy (11.9%) service lines contributed most to the total cost. Renal comorbidities ($69,563) and total parental nutrition use ($33,192) were large, independent contributors to total cost, irrespective of the cost tertile ( p <0.001). There exists a significant variation in pediatric LT cost, with HCHs caring for more patients with higher illness acuity and resource needs. Studies are needed to examine drivers of cost and associated outcomes more granularly, with the goal of defining value and standardizing care. Such efforts may uniquely benefit the sicker patients requiring the strategic resources located within HCHs to achieve the best outcomes.

Caregivers' and providers' perspectives of social and medical care after pediatric liver transplant: Results from the multicenter SOCIAL-Tx study.

Disparities exist in pediatric liver transplant (LT). We characterized barriers and facilitators to providing transplant and social care within pediatric LT clinics. This was a multicenter qualitative study. We oversampled caregivers reporting household financial strain, material economic hardship, or demonstrating poor health literacy. We also enrolled transplant team members. We conducted semistructured interviews with participants. Caregiver interviews focused on challenges addressing transplant and household needs. Transplant provider interviews focused on barriers and facilitators to providing social care within transplant teams. Interviews were recorded, transcribed, and coded according to the Capability, Opportunity, Motivation-Behavior model. We interviewed 27 caregivers and 27 transplant team members. Fifty-two percent of caregivers reported a household income <$60,000, and 62% reported financial resource strain. Caregivers reported experiencing (1) high financial burdens after LT, (2) added caregiving labor that compounds the financial burden, (3) dependency on their social network's generosity for financial and logistical support, and (4) additional support being limited to the perioperative period. Transplant providers reported (1) relying on the pretransplant psychosocial assessment for identifying social risks, (2) discomfort initiating social risk discussions in the post-transplant period, (3) reliance on social workers to address new social risks, and (4) social workers feeling overburdened by quantity and quality of the social work referrals. We identified barriers to providing effective social care in pediatric LT, primarily a lack of comfort in assessing and addressing new social risks in the post-transplant period. Addressing these barriers should enhance social care delivery and improve outcomes for these children.

A cost comparison of liver acquisition fees for donation after circulatory death versus donation after brain death donors.

Donation after circulatory death (DCD) donors now represent over 30% of the deceased donor pool in the United States. Compared to donation after brain death, DCD is less likely to result in transplantation. For each potential donor whose organs cannot be utilized for transplantation (ie, dry run), fees are associated with the attempted donation, which add to the overall costs of organ acquisition. To better characterize the true costs of DCD liver acquisition, we performed a cost comparison of the fees associated with organ acquisition for DCD versus donation after brain death at a single transplant institute that comprises 2 liver transplant centers. Cost, recipient, and transportation data for all cases, including fees associated with liver acquisition from July 1, 2019, to October 31, 2021, were collected. We found that the total cost of DCD liver acquisition per liver transplant was $15,029 more than that for donation after brain death donation, with 18% of the costs of the DCD transplant attributed to dry runs. Overall, the costs associated with DCD transplantation accounted for 34.5% of the total organ acquisition costs; however, DCD transplantation accounted for 30.3% of the transplantation volume. Because the expansion of DCD is essential to increasing the availability of liver grafts for transplantation, strategies need to be implemented to decrease the costs associated with dry runs, including using local recovery, transferring donors to hospitals close to transplant centers, and performing more prerecovery organ analysis. Moreover, these strategies are needed to ensure that financial disincentives to DCD procurement and utilization do not reverse the gains made by expanding the organ donor pool using machine perfusion technologies.

The economic impact of machine perfusion technology in liver transplantation.

INTRODUCTION: Several clinical studies have demonstrated the safety, feasibility, and efficacy of machine perfusion in liver transplantation, although its economic outcomes are still underexplored. This review aimed to examine the costs related to machine perfusion and its associated outcomes. METHODS: Expert opinion of several groups representing different machine perfusion modalities. Critical analysis of the published literature reporting the economic outcomes of the most used techniques of machine perfusion in liver transplantation (normothermic and hypothermic ex situ machine perfusion and in situ normothermic regional perfusion). RESULTS: Machine perfusion costs include disposable components of the perfusion device, perfusate components, personnel and facility fees, and depreciation of the perfusion device or device lease fee. The limited current literature suggests that although this upfront cost varies between perfusion modalities, its use is highly likely to be cost-effective. Optimization of the donor liver utilization rate, local conditions of transplant programs (long waiting list times and higher MELD scores), a decreased rate of complications, changes in logistics, and length of hospital stay are potential cost savings points that must highlight the expected benefits of this intervention. An additional unaccounted factor is that machine perfusion optimizing donor organ utilization allows patients to be transplanted earlier, avoiding clinical deterioration while on the waiting list and the costs associated with hospital admissions and other required procedures. CONCLUSION: So far, the clinical benefits have guided machine perfusion implementation in liver transplantation. Albeit there is data suggesting the economic benefit of the technique, further investigation of its costs to healthcare systems and society and associated outcomes is needed.

Enhanced recovery in liver transplantation: A value-based approach to complex surgical care.

BACKGROUND: Value-based healthcare focuses on improving outcomes relative to cost. We aimed to study the impact of an enhanced recovery pathway for liver transplant recipients on providing value. METHODS: In total, 379 liver recipients were identified: pre-enhanced recovery pathway (2017, n = 57) and post-enhanced recovery pathway (2018-2020, n = 322). The enhanced recovery pathway bundle was defined through multidisciplinary efforts and included optimal fluid management, end-of-case extubation, multimodal analgesia, and a standardized care pathway. Pre- and post-enhanced recovery pathway patients were compared with regard to extubation rates, lengths of stay, complications, readmissions, survival, and costs. RESULTS: Pre- and post-enhanced recovery pathway recipient model for end-stage liver disease score and balance of risk scores were similar, although post-enhanced recovery pathway recipients had a higher median donor risk index (1.55 vs 1.39, P = .003). End-of-case extubation rates were 78% post-enhanced recovery pathway (including 91% in 2020) versus 5% pre-enhanced recovery pathway, with post-enhanced recovery pathway patients having decreased median intraoperative transfusion requirements (1,500 vs 3,000 mL, P < .001). Post-enhanced recovery pathway recipients had shorter median intensive care unit (1.6 vs 2.3 days, P = .01) and hospital stays (5.4 vs 8.0 days, P < .001). Incidence of severe (Clavien-Dindo ≥3) complications during the index hospitalization were similar between pre-enhanced recovery pathway versus post-enhanced recovery pathway groups (33% vs 23%, P = .13), as were 30-day readmissions (26% vs 33%, P = .44) and 1-year survival (93.0% vs 94.5%, P = .58). The post-enhanced recovery pathway cohort demonstrated a significant reduction in median direct cost per case ($11,406; P < .001). CONCLUSION: Implementation of an enhanced recovery pathway in liver transplantation is feasible, safe, and effective in delivering value, even in the setting of complex surgical care.

Health care costs associated with chronic hepatitis C virus infection in Ontario, Canada: a retrospective cohort study.

BACKGROUND: High-quality estimates of health care costs are required to understand the burden of illness and to inform economic models. We estimated the costs associated with hepatitis C virus (HCV) infection from the public payer perspective in Ontario, Canada. METHODS: In this population-based retrospective cohort study, we identified patients aged 18-105 years diagnosed with chronic HCV infection in Ontario from 2003 to 2014 using linked administrative data. We allocated the time from diagnosis until death or the end of follow-up (Dec. 31, 2016) to 9 mutually exclusive health states using validated algorithms: no cirrhosis, no cirrhosis (RNA negative) (i.e., cured HCV infection), compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, both decompensated cirrhosis and hepatocellular carcinoma, liver transplantation, terminal (liver-related) and terminal (non-liver-related). We estimated direct medical costs (in 2018 Canadian dollars) per 30 days per health state and used regression models to identify predictors of the costs. RESULTS: We identified 48 239 patients with chronic hepatitis C, of whom 30 763 (63.8%) were men and 35 891 (74.4%) were aged 30-59 years at diagnosis. The mean 30-day costs were $798 (95% confidence interval [CI] $780-$816) (n = 43 568) for no cirrhosis, $661 (95% CI $630-$692) (n = 6422) for no cirrhosis (RNA negative), $1487 (95% CI $1375-$1599) (n = 4970) for compensated cirrhosis, $3659 (95% CI $3279-$4039) (n = 3151) for decompensated cirrhosis, $4238 (95% CI $3480-$4996) (n = 550) for hepatocellular carcinoma, $8753 (95% CI $7130-$10 377) (n = 485) for both decompensated cirrhosis and hepatocellular carcinoma, $4539 (95% CI $3746-$5333) (n = 372) for liver transplantation, $11 202 (95% CI $10 645-$11 760) (n = 3201) for terminal (liver-related) and $8801 (95% CI $8331-$9271) (n = 5278) for terminal (non-liver-related) health states. Comorbidity was the most significant predictor of total costs for all health states. INTERPRETATION: Our findings suggest that the financial burden of HCV infection is substantially higher than previously estimated in Canada. Our comprehensive, up-to-date cost estimates for clinically defined health states of HCV infection should be useful for future economic evaluations related to this disorder.

Deceased by default: Consent systems and organ-patient mortality.

Previous research shows that countries with opt-out consent systems for organ donation conduct significantly more deceased-donor organ transplantations than those with opt-in systems. This paper investigates whether the higher transplantation rates in opt-out systems translate into equally lower death rates among organ patients registered on a waiting list (i.e., organ-patient mortality rates). We show that the difference between consent systems regarding kidney- and liver-patient mortality rates is significantly smaller than the difference in deceased-donor transplantation rates. This is likely due to different incentives between the consent systems. We find empirical evidence that opt-out systems reduce incentives for living donations, which explains our findings for kidneys. The results imply that focusing on deceased-donor transplantation rates alone paints an incomplete picture of opt-out systems' benefits, and that there are important differences between organs in this respect.

Early Allograft Dysfunction Increases Hospital Associated Costs After Liver Transplantation-A Propensity Score-Matched Analysis.

Concepts to ameliorate the continued mismatch between demand for liver allografts and supply include the acceptance of allografts that meet extended donor criteria (ECD). ECD grafts are generally associated with an increased rate of complications such as early allograft dysfunction (EAD). The costs of liver transplantation for the health care system with respect to specific risk factors remain unclear and are subject to change. We analyzed 317 liver transplant recipients from 2013 to 2018 for outcome after liver transplantation and hospital costs in a German transplant center. In our study period, 1-year survival after transplantation was 80.1% (95% confidence interval: 75.8%-84.6%) and median hospital stay was 33 days (interquartile rage: 24), with mean hospital costs of €115,924 (SD €113,347). There was a positive correlation between costs and laboratory Model for End-Stage Liver Disease score (rs = 0.48, P < 0.001), and the development of EAD increased hospital costs by €26,229. ECD grafts were not associated with a higher risk of EAD in our cohort. When adjusting for recipient-associated risk factors such as laboratory Model for End-Stage Liver Disease score, recipient age, and split liver transplantation with propensity score matching, only EAD and cold ischemia increased total costs. Conclusion: Our data show that EAD leads to significantly higher hospital costs for liver transplantation, which are primarily attributed to recipient health status. Strategies to reduce the incidence of EAD are needed to control costs in liver transplantation.

Racial Disparity in Liver Transplantation Listing.

BACKGROUND: Previous studies have demonstrated disparities in transplantation for women, non-Caucasians, the uninsured or publicly insured, and rural populations. We sought to correlate transplant center characteristics with patient access to the waiting list and liver transplantation. We hypothesized that liver transplant centers vary greatly in providing equitable access to the waiting list and liver transplantation. STUDY DESIGN: Center-specific, adult, deceased-donor liver transplant and waitlist data for the years 2013 to 2018 were obtained from the United Network for Organ Sharing. Waitlist race/ethnicity distributions from liver transplant centers performing ≥ 250 transplants over this period (n = 109) were compared with those of their donor service area, as calculated from 5-year US Census Bureau estimates of 2017. Center-specific characteristics correlating with disparities were analyzed using a linear regression model with a log transformed outcome. RESULTS: Non-Hispanic Blacks (NHBs) are under-represented in liver transplant listing compared with center donation service area (88/109, 81%), whereas, non-Hispanic Whites are over-represented (65/109, 58%) (p < 0.0001). Hispanics were also under-represented on the waitlist at the majority of transplant centers (68/109, 62%) (p = 0.02). Although the racial/ethnic distribution of transplantation is more reflective of the waitlist, there is a higher than expected rate of transplantation for NHBs compared to the waitlist. Predictors of disparity in listing include percentage of transplant recipients at the center who had private insurance, racial composition of the donation service area, and the distance recipients had to travel for transplant. CONCLUSIONS: Non-Hispanic Blacks are listed for liver transplantation less than would be expected. Once listed, however, racial disparities in transplantation are greatly diminished. Improvements in access to adequate health insurance appear to be essential to diminishing disparities in access to this life-saving care.

Do funding sources influence long-term patient survival in pediatric liver transplantation?

BACKGROUND: Socioeconomic status has been associated with inferior outcomes after multiple surgical procedures, but has not been well studied with respect to pediatric liver transplantation. This study evaluated the impact of insurance status (as a proxy for socioeconomic status) on patient and allograft survival in pediatric first-time liver transplant recipients. METHODS: Our retrospective analysis of the UNOS data base from January 2002 through September 2017 revealed 6997 pediatric patients undergoing first-time isolated liver transplantation. A mixed Cox proportional hazards model adjusted for donor, recipient, and program characteristics determined the RR of insurance status on allograft and patient survival. All results were considered significant at P < .05. All statistical results were obtained using R version 3.5.1 and coxme version 2.2-10. RESULTS: Medicaid status had a significant negative impact on long-term survival after controlling for multiple covariates. Pediatric patients undergoing first-time isolated liver transplantation with Medicaid insurance had a RR of 1.42 [confidence interval: 1.18-1.60] of post-transplant death. CONCLUSION: Pediatric patients undergoing first-time isolated liver transplantation have multiple risk factors that may impact long-term survival. Having Medicaid insurance almost doubles the chances of dying post-liver transplant. This patient population may require more global support post-transplant to improve long-term survival.

Cost of illness of Primary Biliary Cholangitis - a population-based study.

BACKGROUND: The economic burden of Primary Biliary Cholangitis (PBC) has not been investigated at population-level. Aim of this study was to estimate the cost of illness of PBC in Lombardy, Italy. METHODS: Individuals with PBC were identified through ICD-9-CM code 571.6 and/or medical exemption code 008.571.6, from the Banca Dati Assistito of Lombardy. Only health services (outpatient, inpatient activities and drugs) related to PBC were considered to estimate direct medical costs in 2017. RESULTS: We identified 970 adult patients (83.5% females) with a mean age of 61 years. Global annual costs were equal to € 913,763 (€ 942 per patient), with € 459,506 (50.3%, € 474 per patient) deriving from hospitalizations (mostly due to liver transplantation, 30.5%, and cirrhosis complications, 20.6%). Costs from outpatient activities were € 109,090 (11.9%, € 112 per patient). CONCLUSIONS: This study provides an overview of the costs attributed to PBC care and management, mainly related to hospitalizations for cirrhosis complications, which is necessary for assuring cost-effective introduction of novel therapies. Additional studies focused on indirect cost, e.g. overall loss of productivity, are warranted.

Socioeconomic Deprivation Does Not Impact Liver Transplantation Outcome for HCC: A Survival Analysis From a National Database.

BACKGROUND: To investigate the value of European deprivation index (EDI) and hepatocellular carcinoma (HCC) characteristics and their relationships with outcome after liver transplantation (LT). METHODS: Patients undergoing LT for HCC were included from a national database (from "Agence de la Biomédecine" between 2006 and 2016. Characteristics of the patients were blindly extracted from the database. Thus, EDI was calculated in 5 quintiles and prognosis factors of survival were determined according to a Cox model. RESULTS: Among the 3865 included patients, 33.9% were in the fifth quintile (quintile 1, N = 562 [14.5%]; quintile 2, N = 647 [16.7%]; quintile 3, N = 654 [16.9%]; quintile 4, N = 688 [17.8%]). Patients in each quintile were comparable regarding HCC history, especially median size of HCC, number of nodules of HCC and alpha-fetoprotein score. In the univariate analysis of the crude survival, having >2 nodules of HCC before LT and time on waiting list were associated with a higher risk of death (P < 0.0001 and P = 0.03, respectively). EDI, size of HCC, model for end-stage liver disease score, Child-Pugh score were not statistically significant in the crude and net survival. In both survival, time on waiting list and number of HCC ≥2 were independent factor of mortality after LT for HCC (P = 0.009 and 0.001, respectively, and P = 0.03 and 0.02, respectively). CONCLUSIONS: EDI does not impact overall survival after LT for HCC. Number of HCC and time on waiting list are independent prognostic factors of survival after LT for HCC.

Immediate Postoperative Extubation Decreases Pulmonary Complications in Liver Transplant Patients.

BACKGROUND: Fast-track anesthesia in liver transplantation (LT) has been discussed over the past few decades; however, factors associated with immediate extubation after LT surgery are not well defined. This study aimed to identify predictive factors and examine impacts of immediate extubation on post-LT outcomes. METHODS: A total of 279 LT patients between January 2014 and May 2017 were included. Primary outcome was immediate extubation after LT. Other postoperative outcomes included reintubation, intensive care unit stay and cost, pulmonary complications within 90 days, and 90-day graft survival. Logistic regression was performed to identify factors that were predictive for immediate extubation. A matched control was used to study immediate extubation effect on the other postoperative outcomes. RESULTS: Of these 279 patients, 80 (28.7%) underwent immediate extubation. Patients with anhepatic time >75 minutes and with total intraoperative blood transfusion ≥12 units were less likely to be immediately extubated (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.89; P = 0.02; OR, 0.11; 95% CI, 0.05-0.21; P < 0.001). The multivariable analysis showed immediate extubation significantly decreased the risk of pulmonary complications (OR, 0.34; 95% CI, 0.15-0.77; P = 0.01). According to a matched case-control model (immediate group [n = 72], delayed group [n = 72]), the immediate group had a significantly lower rate of pulmonary complications (11.1% versus 27.8%; P = 0.012). Intensive care unit stay and cost were relatively lower in the immediate group (2 versus 3 d; P = 0.082; $5700 versus $7710; P = 0.11). Reintubation rates (2.8% versus 2.8%; P > 0.9) and 90-day graft survival rates (95.8% versus 98.6%; P = 0.31) were similar. CONCLUSIONS: Immediate extubation post-LT in appropriate patients is safe and may improve patient outcomes and resource allocation.

Costs Associated With Early Vascular and Biliary Complications in Liver-Transplanted Patients in a Hospital in Antioquia, Colombia 2019: A Case Series.

OBJECTIVES: Vascular and biliary complications associated with liver transplants involve high morbidity and mortality as well as cost overrun for health systems. Efforts to prioritize their prevention require not only clinical information but also information on costs that reflect the economic burden on health systems. The objective of this study was to describe cost overrun incurred from early vascular and biliary complications after liver transplant. METHODS: This cases series included liver transplant patients treated at the San Vicente Foundation University Hospital, Rionegro, Antioquia, from January 1, 2013, to December 31, 2018. All liver transplant patients treated during the above period were included; the absence of clinical records on the variables of interest was considered the exclusion criterion. A probabilistic analysis of patient cost was performed. Monte Carlo simulations as well as a 1-way sensitivity analysis per transplant cost component were performed. RESULTS: Records from 154 patients were assessed. The average patient age was 56.9 (SD 10.9) years; 42.9% of patients were women. Of all, 36.4% patients were classified as Child C, and the average Model for End-Stage Liver Disease score was 19.6. The average cost for patients without complications was $27 834.82, whereas that for patients with early vascular complications was $36 747.83 and for those with early biliary complications was $38 523.74. CONCLUSION: Early vascular and biliary complications after liver transplant increase healthcare costs, with the increase being significant in patients with biliary complications.