Cost-effectiveness analysis of personalised versus standard dosimetry for selective internal radiation therapy with TheraSphere in patients with hepatocellular carcinoma.

Aims: To perform a cost-effectiveness analysis (CEA) comparing personalised dosimetry with standard dosimetry in the context of selective internal radiation therapy (SIRT) with TheraSphere for the management of adult patients with locally advanced hepatocellular carcinoma (HCC) from the Italian Healthcare Service perspective. Materials and methods: A partition survival model was developed to project costs and the quality-adjusted life years (QALYs) over a lifetime horizon. Clinical inputs were retrieved from a published randomised controlled trial. Health resource utilisation inputs were extracted from the questionnaires administered to clinicians in three oncology centres in Italy, respectively. Cost parameters were based on Italian official tariffs. Results: Over a lifetime horizon, the model estimated the average QALYs of 1.292 and 0.578, respectively, for patients undergoing personalised and standard dosimetry approaches. The estimated mean costs per patient were €23,487 and €19,877, respectively. The incremental cost-utility ratio (ICUR) of personalised versus standard dosimetry approaches was €5,056/QALY. Conclusions: Personalised dosimetry may be considered a cost-effective option compared to standard dosimetry for patients undergoing SIRT for HCC in Italy. These findings provide evidence for clinicians and payers on the value of personalised dosimetry as a treatment option for patients with HCC.

Hospital-Based Health Technology Assessment of Machine Perfusion Systems for Human Liver Transplantation.

Based on published data, we have carried out a hospital-based health technology assessment of machine perfusion in adult liver transplantation using cold storage as a comparator, and within the perspective of a national health system-based hospital practice and disease-related group reimbursement policy. A systematic literature review on machine perfusion for adult liver transplantation was conducted exploring the Pubmed, CINAHL, Scopus, Embase, and Cochrane databases. The literature was analyzed with the intent to provide information on 6 dimensions and 19 items of the hospital-based health technology assessment framework derived from previous studies. Out of 705 references, 47 (6.7%) were retained for current analysis. Use of machine perfusion was associated with advantages over cold storage, i.e., a 10%-50% reduced risk for early allograft dysfunction, 7%-15% less ischemia reperfusion injury; 7%-50% fewer ischemic biliary complications, comparable or improved 1-year graft and patient survival, and up to a 50% lower graft discard rate. Hospital stay was not longer, and technical failures were anecdotal. Information on costs of machine perfusion is limited, but this technology is projected to increase hospital costs while cost-effectiveness analysis requires data over the transplant patient lifetime. No hospital-based health technology assessment study on machine perfusion in liver transplantation was previously conducted. From the hospital perspective, there is evidence of the clinical advantages of this novel technology, but strategies to counterbalance the increased costs of liver transplantation are urgently needed. Further studies should focus on the ethical, social, and organizational issues related to machine perfusion.

Impact of MELD 30-allocation policy on liver transplant outcomes in Italy.

BACKGROUND & AIMS: In Italy, since August 2014, liver transplant (LT) candidates with model for end-stage liver disease (MELD) scores ≥30 receive national allocation priority. This multicenter cohort study aims to evaluate time on the waiting list, dropout rate, and graft survival before and after introducing the macro-area sharing policy. METHODS: A total of 4,238 patients registered from 2010 to 2018 were enrolled and categorized into an ERA-1 Group (n = 2,013; before August 2014) and an ERA-2 Group (n = 2,225; during and after August 2014). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of receiving a LT or death between the two eras. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. RESULTS: Patients with MELD ≥30 had a lower median time on the waiting list (4 vs.12 days, p <0.001) and a higher probability of being transplanted (HR 2.27; 95% CI 1.78-2.90; p = 0.001) in ERA-2 compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio 0.56; 95% CI 0.46-0.68; p = 0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high-volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high-volume center and ERA-2, while MELD ≥30 remained related to a higher risk of graft loss. CONCLUSIONS: The national MELD ≥30 priority allocation was associated with improved patient outcomes, although MELD ≥30 was associated with a higher risk of graft loss. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes. CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: Italy introduced a new policy in 2014 to give national allocation priority to patients with a model for end-stage liver disease (MELD) score ≥30 (i.e. very sick patients). This policy has led to more liver transplants, fewer dropouts, and shorter waiting times for patients with MELD ≥30. However, a higher risk of graft loss still burdens these cases. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes.

Comparison between galectin-3 and YKL-40 levels for the assessment of liver fibrosis in cirrhotic patients.

BACKGROUND AND STUDY AIMS: The circulatory levels of Galectin-3 and YKL-40 are considered as candidate biomarkers for the noninvasive assessment of liver fibrosis. This study aimed to evaluate the plasma protein profiles of Galectin-3 and YKL-40 in patients with cirrhosis (with and without hepatocellular carcinoma [HCC]) who underwent deceased-donor liver transplantation (LT), before and after surgery. PATIENTS AND METHODS: The plasma levels of Galectin-3 and YKL-40 were assessed in 46 subjects, including 24 liver graft recipients (before, 1 day after, and 1 month after LT) and 22 healthy controls using enzyme-linked immunosorbent assays. RESULTS: The levels of Galectin-3 and YKL-40 in the LT recipients before the transplant were significantly higher than those in the healthy controls (p < 0.001 and p < 0.01, respectively). YKL-40 levels returned to normal within 1 day after LT, whereas those of Galectin-3 decreased 1 day after LT and returned to normal levels after 1 month. The levels of both proteins did not differ between patients with and without HCC. Unlike YKL-40, the pre-transplant levels of Galectin-3 were directly correlated to that of aspartate aminotransferase (AST; r = 0.473, p = 0.01), alanine aminotransferase (r = 0.395, p = 0.04), total bilirubin (r = 0.545, p = 0.003), and lactate dehydrogenase (r = 0.452, p = 0.02) and to the AST to platelet ratio index (APRI; r = 0.411, p = 0.03) and Child-Pugh score (r = 0.601, p < 0.001). Galectin-3 levels increased significantly according to the severity of cirrhosis (25.9 ± 2.7; 57.4 ± 29.6; and 81 ± 27 ng/mL in Class A, B, and C cirrhosis, respectively), whereas those of YKL-40 tended to be higher in the Class C patients compared to the Class A patients (8.9 ± 2.6 vs. 7.4 ± 0.8 ng/mL). CONCLUSION: Circulating levels of Galectin-3 could be an indicator of liver damage and inflammation that are correlated with fibrosis.

Cost-effectiveness of everolimus plus reduced tacrolimus in de novo liver-recipients in the Italian setting.

INTRODUCTION: Long-term exposure to calcineurin inhibitor-based immunosuppressant (IS) therapy in liver transplant (LT) recipients is associated with renal complications. In the randomized trial H2304, everolimus + reduced-dose tacrolimus (EVR + rTAC) demonstrated equivalent efficacy and superior renal function compared to standard-dose tacrolimus. METHODS: To evaluate the cost-effectiveness of EVR + rTAC vs TAC, in de novo LT patients, a Markov model simulating both liver and kidney function was developed and estimated the long-term outcomes of IS following LT. The analysis used the Italian healthcare payer perspective. RESULTS: Patients treated with EVR + rTAC gained on average 1.92 years and 1.62 quality-adjusted life years (QALYs). The incremental cost-effectiveness ratios (ICER) were €35,851 and €42,567 for LY gained and QALY gained, respectively. For the hepatitis-c sub-population, the ICERs decreased to €22,519 and €30,658, respectively. CONCLUSION: EVR + rTAC improves survival and quality-of-life and is a cost-effective alternative to calcineurin-inhibitor monotherapy for patients requiring LT.

A model for Southern Mediterranean research institute self-assessment: a SWOT analysis-based approach to promote capacity building at Theodor Bilharz Research Institute in Cairo (Egypt).

BACKGROUND AND STUDY AIMS: THEBERA is a project funded by the European Union (EU), as an ERA-WIDE FP7 project, aiming to strengthen the Theodor Bilharz Research Institute (TBRI) capacities. MATERIALS AND METHODS: A SWOT (strength/weakness/opportunities/threats) analysis of human, structural and organisational existing resources was performed in light of an extensive analysis of liver disease research and clinical management in Egypt, for a full understanding of TBRI needs. RESULTS: Strength and weakness features were identified and analysed, so were actions to be implemented and targets to be accomplished, to develop a business plan gathering the required critical mass (political, scientific, industrial, social) to select investment priorities, to sacrifice non-strategic areas of research, to promote national and international connections and industrial innovations, to update diagnostics and research device technologies and clinical management processes at European levels, to implement fundraising activities, to organise and properly assess training activities for young researchers, physicians, nurses, and technicians. CONCLUSIONS: Research institute self assessment is a priority need for sustainable capacity building and for future build-up of a competent health care research institute. Sustainable capacity building strategies must be designed on needs assessment, involving salient requirements: clear strategy, leverage of administrative capacities, industrial support and connections, systematised training programmes and enhancement of mobility of health care staff implemented within ill-defined boundaries and continuously re-evaluated with multiple feedback loops in order to build a complex, adaptable and reliable system based on value.

Quality assurance, efficiency indicators and cost-utility of the evaluation workup for liver transplantation.

We report the results of a retrospective review of the outpatient pretransplantation workup for United Network for Organ Sharing (UNOS) 3 patients adopted at a liver transplantation (LT) center and illustrate the efficiency indicators used for quality evaluation and cost-analysis. A single-center, pre-LT evaluation workup was performed on an outpatient basis at a cost per patient evaluation of 2,770 Euros (). Objective measures were: the number of patients admitted to and excluded from each phase of the algorithm; the rate of patients admitted to pre-LT evaluation out of the total of referred patients (the referral efficiency rate); the rate of waitlisted patients out of those admitted to pre-LT evaluation (the evaluation efficiency rate); the rate of waitlisted patients out of those referred for LT (the process efficiency rate); and the cost per waitlisted patient, as the ratio of the cost per patient evaluation to the evaluation efficiency rate. From January 1, 1996, to October 1, 2004, 1,837 patients were referred for LT on an outpatient basis. Based on preemptive evaluation of the available clinical data, 412 patients (22.4%) were excluded from pre-LT evaluation and 1,425 (77.6%) were admitted to preliminary consultation. Among these, 603 (42.3%) were excluded from and 822 (57.7%) were admitted to pre-LT evaluation with a referral efficiency rate of 44.7% (822 of 1,837). Out of the patients evaluated for LT, 484 were waitlisted with a cost-utility and evaluation efficiency rate of 58.8% each (484 of 822). Of the 1,837 patients originally addressed for LT 484 were waitlisted, yielding a process efficiency rate of 26.3% (484 of 1,837) and a cost per waitlisted patient of 4,710.8. In conclusion, the 3 indicators allowed monitoring of the efficiency of the pre-LT evaluation algorithm. The current process efficiency rate at our center is low (26.3%), but avoiding early referrals we might increase it to 31.6%, with a 12% net saving on costs per waitlisted patient (from 4,710.8 to 4,165.4).